High HIV prevalence and incidence among women in Southern Mozambique: Evidence from the MDP microbicide feasibility study.

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Sibone Mocumbi

Full Text Available The study aimed to assess the feasibility of conducting large scale HIV prevention clinical trials in Mozambique by measuring HIV prevalence and incidence among women of reproductive age. This paper describes the baseline socio-demographic characteristics of the Mozambique Microbicides Development Programme (MDP feasibility cohort, baseline prevalence of HIV and other STIs, and HIV incidence.The Mozambique MDP feasibility study was conducted from September 2007 to August 2009 in urban Mavalane and rural Manhiça, in Southern Mozambique. Sexually active, HIV negative women aged 18 years and above were recruited to attend the study clinic every 4 weeks for a total of 40 weeks. At baseline, we collected demographic and sexual behaviour data, samples to test for sexually transmitted infections (STI and conducted HIV rapid testing. STI and HIV testing were repeated at clinical follow-up visits. We describe HIV prevalence of women at screening, the demographic, behavioural and clinical characteristics of women at enrolment, and HIV incidence during follow-up.We screened 793 women (369 at Mavalane and 424 at Manhiça and enrolled 505 eligible women (254 at Mavalane and 251 at Manhiça. Overall HIV prevalence at screening was 17%; 10% at Mavalane and 22% at Manhiça. Women screened at Manhiça were twice as likely as women screened at Mavalane to be HIV positive and HIV positive status was associated with younger age (18-34, lower educational level, not using a reliable method of contraception and being Zionist compared to other Christian religions. At enrolment contraceptive use was low in both clinics at 19% in Mavalane and 21% in Manhiça, as was reported condom use at last sex act at 48% in Mavalane and 25% in Manhiça. At enrolment, 8% of women tested positive for Trichomonas vaginalis, 2% for Neisseria gonorrhoeae, 4% for Chlamydia trachomatis and 46% for bacterial vaginosis. In Manhiça, 8% of women had active syphilis at screening. HIV incidence

Obtaining valid laboratory data in clinical trials conducted in resource diverse settings: lessons learned from a microbicide phase III clinical trial.

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Tania Crucitti

2010-10-01

Full Text Available Over the last decade several phase III microbicides trials have been conducted in developing countries. However, laboratories in resource constrained settings do not always have the experience, infrastructure, and the capacity to deliver laboratory data meeting the high standards of clinical trials. This paper describes the design and outcomes of a laboratory quality assurance program which was implemented during a phase III clinical trial evaluating the efficacy of the candidate microbicide Cellulose Sulfate 6% (CS [1].In order to assess the effectiveness of CS for HIV and STI prevention, a phase III clinical trial was conducted in 5 sites: 3 in Africa and 2 in India. The trial sponsor identified an International Central Reference Laboratory (ICRL, responsible for the design and management of a quality assurance program, which would guarantee the reliability of laboratory data. The ICRL provided advice on the tests, assessed local laboratories, organized trainings, conducted supervision visits, performed re-tests, and prepared control panels. Local laboratories were provided with control panels for HIV rapid tests and Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG amplification technique. Aliquots from respective control panels were tested by local laboratories and were compared with results obtained at the ICRL.Overall, good results were observed. However, discordances between the ICRL and site laboratories were identified for HIV and CT/NG results. One particular site experienced difficulties with HIV rapid testing shortly after study initiation. At all sites, DNA contamination was identified as a cause of invalid CT/NG results. Both problems were timely detected and solved. Through immediate feedback, guidance and repeated training of laboratory staff, additional inaccuracies were prevented.Quality control guidelines when applied in field laboratories ensured the reliability and validity of final study data. It is essential that sponsors

The future of HIV prevention: prospects for an effective anti-HIV microbicide.

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Nuttall, Jeremy; Romano, Joseph; Douville, Karen; Galbreath, Caroline; Nel, Annaléne; Heyward, William; Mitchnick, Mark; Walker, Saul; Rosenberg, Zeda

2007-03-01

Topical microbicides are self-administered products for prevention of HIV transmission, and they present one of the most promising strategies for combating the HIV-AIDS epidemic. The development of microbicides is a long and complicated process, with many hurdles that are unique to this class of product, including challenges in product design, in the conduct and design of clinical trials, and in obtaining licensure of a new class of products intended for use almost exclusively in developing countries. Once they have been registered, there are additional challenges to the marketing and distribution of microbicides. An overview of the types of microbicide currently in development, and a summary of the issues and the approaches being taken to address them, are provided.

Vaginal microbicides and teenagers.

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Rupp, Richard E; Rosenthal, Susan L

2003-10-01

Sexually active teens are at significant risk from sexually transmitted infections and girls and women bear the greatest burden of these infections. New methods, such as vaginal microbicides, would provide female controlled options. Microbicides are currently in development and thus it is timely to discuss the progress made and factors that may influence acceptability for teens. Microbicide development presents many challenges, and several different potential mechanisms of action are being explored. There is interest in these products from women and men, and specific preferences are being investigated. Adolescents, due to reproductive system immaturity, developing cognitive abilities and the psychosocial context of their relationships, present a special set of challenges in efforts to foster microbicide use. Vaginal microbicides are on the horizon. Further study into teen issues is required to develop successful strategies for marketing and encouraging adolescent use of microbicides.

Acceptability of a novel vaginal microbicide during a safety trial among low-risk women.

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Bentley, M E; Morrow, K M; Fullem, A; Chesney, M A; Horton, S D; Rosenberg, Z; Mayer, K H

2000-01-01

The increasing recognition that women who are unable or unwilling to discuss or use condoms with their sexual partners need female-controlled methods for preventing sexually transmitted diseases (STDs), including HIV, has led to considerable focus on the development of vaginal microbicides. While many such products are being tested for safety and effectiveness, clinical trials generally overlook another key factor in a product's impact on infection rates-its acceptability to users. A Phase I clinical trial of a microbicidal gel included an assessment of the product's acceptability among 27 low-risk participants. Information on acceptability was gathered from structured interviews, participants' daily diaries and unstructured exit interviews. Participants reported only minor side effects of product use, such as itching, burning and difficulty urinating; two women developed candida infections while participating in the study. None of the side effects could be conclusively linked to use of the gel. Some women noted product discharge and messiness as drawbacks of the method, but this experience varied according to how often the women applied the gel. For example, one-third of those who used it once daily said that at least some of the time, it was too "wet or drippy," compared with two-thirds of women who inserted the gel twice a day. However, participants considered these "nuisance factors" that could be outweighed by the potential protective characteristics of the product. The majority reported that they would use the product if it were available and proven efficacious, and if they perceived that they were at risk of STD infection. Additional testing of this product is urgently needed. Furthermore, as other products approach Phase I testing, acceptability assessments should be a key component of clinical trials.

Young women's contraceptive microbicide preferences: associations with contraceptive behavior and sexual relationship characteristics.

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Best, Candace; Tanner, Amanda E; Hensel, Devon J; Fortenberry, J Dennis; Zimet, Gregory D

2014-03-01

In time, microbicides may provide women with dual prevention against pregnancy and STDs. Although several microbicide dimensions have been evaluated, little is known about women's preferences for contraceptive microbicides and correlates of these preferences. Acceptability of a hypothetical contraceptive microbicide cream or jelly was examined among a -clinic-based sample of 266 women in Indianapolis from 2004 (when participants were aged 14-22) to 2008. Group conjoint analyses and individual conjoint analyses were used to compare preferences with respect to four microbicide -dimensions: contraceptive ability, efficacy in relation to condoms, timing of use and texture. Pearson's product moment correlations were used to examine the relationship between preferences for a contraceptive microbicide and selected characteristics of the women. Overall, the top-rated microbicide dimensions were efficacy in relation to that of condoms and contraceptive ability (importance scores, 40.0 and 35.4 out of 100.0, respectively). When all dimension levels were compared, contraceptive ability was the most strongly preferred (part-worth utility score, 8.9), and lower efficacy than that of -condoms was the least strongly preferred (-11.9). Preference for contraceptive microbicides was positively -associated with current contraceptive use, sexual agency, partner communication, commitment to avoiding pregnancy and -perceived partner agreement about avoiding pregnancy (coefficients, 0.07-0.18). It was negatively associated with current or past nonuse of contraceptives, seeking pregnancy and perceived partner agreement about seeking -pregnancy (-0.08 to -0.14). Microbicides with dual prevention properties may be attractive to young women. Microbicide development and subsequent clinical trials should incorporate contraceptive microbicides. Copyright © 2013 by the Guttmacher Institute.

Vaginal microbicides for reducing the risk of sexual acquisition of HIV infection in women: systematic review and meta-analysis

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Obiero Jael

2012-11-01

Full Text Available Abstract Background Each year more than two million people are newly infected with HIV worldwide, a majority of them through unprotected vaginal sex. More than half of new infections in adults occur in women. Male condoms and male circumcision reduce the risk of HIV acquisition; but the uptake of these methods is out of the control of women. We therefore aimed to determine the effectiveness of vaginal microbicides (a potential female-controlled method for prevention of sexual acquisition of HIV in women. Methods We conducted a comprehensive search of peer-reviewed and grey literature for publications of randomised controlled trials available by September 2012. We screened search outputs, selected studies, assessed risk of bias, and extracted data in duplicate; resolving differences by discussion and consensus. Results We identified 13 eligible trials that compared vaginal microbicides to placebo. These studies enrolled 35,905 sexually active HIV-negative women between 1996 and 2011; in Benin, Cameroon, Cote d’Ivoire, Ghana, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, Zimbabwe, India, Thailand, and the United States of America. A small trial of 889 women found that tenofovir (a nucleotide reverse transcriptase inhibitor significantly reduces the risk of HIV acquisition (risk ratio [RR] 0.63, 95% confidence intervals [CI] 0.43 to 0.93. Effectiveness data are not yet available from follow-up tenofovir trials being conducted in South Africa, Uganda, and Zimbabwe (1 trial and multiple sites in South Africa (1 trial. We found no evidence of a significant effect for nonoxynol-9 (5 trials, cellulose sulphate (2 trials, SAVVY (2 trials, Carraguard (1 trial, PRO 2000 (2 trials, and BufferGel (1 trial microbicides. The pooled RR for the effect of current experimental vaginal microbicides on HIV acquisition in women was 0.97, 95%CI 0.87 to 1.08. Although study results were homogeneous across the different drug classes (heterogeneity P�

Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010

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Uchtenhagen Hannes

2011-04-01

Full Text Available Abstract Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda, and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa.

Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010.

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Brinckmann, Sarah; da Costa, Kelly; van Gils, Marit J; Hallengärd, David; Klein, Katja; Madeira, Luisa; Mainetti, Lara; Palma, Paolo; Raue, Katharina; Reinhart, David; Reudelsterz, Marc; Ruffin, Nicolas; Seifried, Janna; Schäfer, Katrein; Sheik-Khalil, Enas; Sköld, Annette; Uchtenhagen, Hannes; Vabret, Nicolas; Ziglio, Serena; Scarlatti, Gabriella; Shattock, Robin; Wahren, Britta; Gotch, Frances

2011-04-12

Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda), and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa.

Microbicides in the prevention of HIV infection: current status and future directions.

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Nuttall, Jeremy

2010-07-09

More than 28 years since the first cases of HIV/AIDS, there is still no cure or vaccine. The worst affected region is sub-Saharan Africa and, increasingly, it is young women who are bearing the brunt of the epidemic. Consequently, there is an urgent need for HIV prevention options for women in developing countries. Microbicides are topical products that can be used vaginally by women to impede sexual transmission of HIV and thus represent one of the most promising prevention strategies. Efficacy trials with early nonspecific microbicide gels have so far been unsuccessful, but the field has now switched its focus to products containing highly potent and highly specific antiretroviral drugs that are easier to use, and can be formulated in a variety of dosage forms to suit individual and regional preferences. However, these products have their own challenges, with a greater likelihood of absorption, and the potential for systemic toxicities or the development of resistance in infected individuals who are unaware of their HIV status. The conduct of clinical trials is complex for all microbicides, with limited availability of trial sites, difficulties in dose selection and safety monitoring, and a lack of a truly objective measure of adherence. Once a microbicide has been shown to be safe and effective, there will need to be a clear pathway to regulatory approval, and the successful launch of a product will depend on having in place appropriate methods for distribution to the women who need it, along with a strategy for ensuring that they use it correctly. This will require substantial effort in terms of education and community engagement, and these activities need to be initiated well in advance of microbicide rollout.

Short communication: expression of transporters and metabolizing enzymes in the female lower genital tract: implications for microbicide research.

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Zhou, Tian; Hu, Minlu; Cost, Marilyn; Poloyac, Samuel; Rohan, Lisa

2013-11-01

Topical vaginal microbicides have been considered a promising option for preventing the male-to-female sexual transmission of HIV; however, clinical trials to date have not clearly demonstrated robust and reproducible effectiveness results. While multiple approaches may help enhance product effectiveness observed in clinical trials, increasing the drug exposure in lower genital tract tissues is a compelling option, given the difficulty in achieving sufficient drug exposure and positive correlation between tissue exposure and microbicide efficacy. Since many microbicide drug candidates are substrates of transporters and/or metabolizing enzymes, there is emerging interest in improving microbicide exposure and efficacy through local modulation of transporters and enzymes in the female lower genital tract. However, no systematic information on transporter/enzyme expression is available for ectocervical and vaginal tissues of premenopausal women, the genital sites most relevant to microbicide drug delivery. The current study utilized reverse transcriptase polymerase chain reaction (RT-PCR) to examine the mRNA expression profile of 22 transporters and 19 metabolizing enzymes in premenopausal normal human ectocervix and vagina. Efflux and uptake transporters important for antiretroviral drugs, such as P-gp, BCRP, OCT2, and ENT1, were found to be moderately or highly expressed in the lower genital tract as compared to liver. Among the metabolizing enzymes examined, most CYP isoforms were not detected while a number of UGTs such as UGT1A1 were highly expressed. Moderate to high expression of select transporters and enzymes was also observed in mouse cervix and vagina. The implications of this information on microbicide research is also discussed, including microbicide pharmacokinetics, the utilization of the mouse model in microbicide screening, as well as the in vivo functional studies of cervicovaginal transporters and enzymes.

Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa

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Nel, Annalene; Bekker, Linda-Gail; Bukusi, Elizabeth; Hellstrӧm, Elizabeth; Kotze, Philip; Louw, Cheryl; Martinson, Francis; Masenga, Gileard; Montgomery, Elizabeth; Ndaba, Nelisiwe; van der Straten, Ariane; van Niekerk, Neliëtte; Woodsong, Cynthia

2016-01-01

Background This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women. Objectives The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa. Methods 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports. Results No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. Conclusions The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of

Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.

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Roland R Regoes

2005-08-01

Full Text Available Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against "real life" exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses.Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success.Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.

Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa.

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Annalene Nel

Full Text Available This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women.The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa.280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports.No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective.The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches

Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa.

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Nel, Annalene; Bekker, Linda-Gail; Bukusi, Elizabeth; Hellstrӧm, Elizabeth; Kotze, Philip; Louw, Cheryl; Martinson, Francis; Masenga, Gileard; Montgomery, Elizabeth; Ndaba, Nelisiwe; van der Straten, Ariane; van Niekerk, Neliëtte; Woodsong, Cynthia

2016-01-01

This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women. The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa. 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports. No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women

Influences of geo-spatial location on pre-exposure prophylaxis use in South Africa: positioning microbicides for better product uptake.

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Govender, Eliza M; Mansoor, Leila E; Abdool Karim, Quarraisha

2017-06-01

Young women bear a disproportionately high burden of HIV infection in sub-Saharan Africa, prioritising pre-exposure prophylaxis (PrEP) can be an integral part of HIV prevention combination strategies. Women initiated HIV prevention technology options will require consistent adherence, an imperative for product effectiveness. With several PrEP clinical trials underway; exploring women's acceptability to advances in HIV prevention technologies can better facilitate demand creation for future PrEP roll out. This study utilised the opportunity of post-trial access to CAPRISA 008 women (trial) and non-trial women from three geo-spatial settings (urban, rural and peri-urban) to identify microbicide acceptability and how product associations of microbicides can influence future HIV prevention choices. Six participatory workshops using participatory action research with art-based activities and discussion groups were conducted in KwaZulu-Natal with 104 women from various geo-spatial locations and social status to understand microbicide acceptability and product associations. The data were analysed using thematic analysis. The study found that women's acceptability and product association of the tenofovir gel microbicide differed according to rural and urban areas. Most urban women identified confidence, sexiness and classiness as key associations that will encourage microbicide acceptability and use, while rural women identified respect, responsibility and confidence as the key product associations, with increased focus on the individual and collective family/community benefits of product acceptance and use. Urban-rural differences suggest a market segmentation that is contextualised to be locally responsive to promote HIV prevention technologies. Various sexual encounters further determined the types of HIV prevention technologies women would consider. In line with WHO's recommendation that PrEP should be an additional prevention choice for people at risk of HIV, this

Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference.

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Wahren, Britta; Biswas, Priscilla; Borggren, Marie; Coleman, Adam; Da Costa, Kelly; De Haes, Winni; Dieltjens, Tessa; Dispinseri, Stefania; Grupping, Katrijn; Hallengärd, David; Hornig, Julia; Klein, Katja; Mainetti, Lara; Palma, Paolo; Reudelsterz, Marc; Seifried, Janna; Selhorst, Philippe; Sköld, Annette; Uchtenhagen, Hannes; van Gils, Marit J; Weber, Caroline; Shattock, Robin; Scarlatti, Gabriella

2010-07-26

EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur) involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training. EUROPRISE held its second annual conference in Budapest in November, 2009. The conference had 143 participants and their presentations covered aspects of vaccine and microbicide research, development and discovery. Since training is a major task of the Network, the students of the EUROPRISE PhD program summarized certain presentations and their view of the conference in this paper.

Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference

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Mainetti Lara

2010-07-01

Full Text Available Abstract EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training. EUROPRISE held its second annual conference in Budapest in November, 2009. The conference had 143 participants and their presentations covered aspects of vaccine and microbicide research, development and discovery. Since training is a major task of the Network, the students of the EUROPRISE PhD program summarized certain presentations and their view of the conference in this paper.

Compartmental transport model of microbicide delivery by an intravaginal ring

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Geonnotti, Anthony R.; Katz, David F.

2010-01-01

Topical antimicrobials, or microbicides, are being developed to prevent HIV transmission through local, mucosal delivery of antiviral compounds. While hydrogel vehicles deliver the majority of current microbicide products, intravaginal rings (IVRs) are an alternative microbicide modality in preclinical development. IVRs provide a long-term dosing alternative to hydrogel use, and might provide improved user adherence. IVR efficacy requires sustained delivery of antiviral compounds to the entire vaginal compartment. A two-dimensional, compartmental vaginal drug transport model was created to evaluate the delivery of drugs from an intravaginal ring. The model utilized MRI-derived ring geometry and location, experimentally defined ring fluxes and vaginal fluid velocities, and biophysically relevant transport theory. Model outputs indicated the presence of potentially inhibitory concentrations of antiviral compounds along the entire vaginal canal within 24 hours following IVR insertion. Distributions of inhibitory concentrations of antiviral compounds were substantially influenced by vaginal fluid flow and production, while showing little change due to changes in diffusion coefficients or ring fluxes. Additionally, model results were predictive of in vivo concentrations obtained in clinical trials. Overall, this analysis initiates a mechanistic computational framework, heretofore missing, to understand and evaluate the potential of IVRs for effective delivery of antiviral compounds. PMID:20222027

Learning from the private sector: towards a keener understanding of the end-user for microbicide introduction planning.

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Lin, Amy H; Breger, Tiffany L; Barnhart, Matthew; Kim, Ann; Vangsgaard, Charlotte; Harris, Emily

2014-01-01

In planning for the introduction of vaginal microbicides and other new antiretroviral (ARV)-based prevention products for women, an in-depth understanding of potential end-users will be critically important to inform strategies to optimize uptake and long-term adherence. User-centred private sector companies have contributed to the successful launch of many different types of products, employing methods drawn from behavioural and social sciences to shape product designs, marketing messages and communication channels. Examples of how the private sector has adapted and applied these techniques to make decisions around product messaging and targeting may be instructive for adaptation to microbicide introduction. In preparing to introduce a product, user-centred private sector companies employ diverse methods to understand the target population and their lifestyles, values and motivations. ReD Associates' observational research on user behaviours in the packaged food and diabetes fields illustrates how 'tag along' or 'shadowing' techniques can identify sources of non-adherence. Another open-ended method is self-documentation, and IDEO's mammography research utilized this to uncover user motivations that extended beyond health. Mapping the user journey is a quantitative approach for outlining critical decision-making stages, and Monitor Inclusive Markets applied this framework to identify toilet design opportunities for the rural poor. Through an iterative process, these various techniques can generate hypotheses on user drop-off points, quantify where drop-off is highest and prioritize areas of further research to uncover usage barriers. Although research constraints exist, these types of user-centred techniques have helped create effective messaging, product positioning and packaging of health products as well as family planning information. These methods can be applied to microbicide acceptability testing outside of clinical trials to design microbicide marketing

Nanotech-derived topical microbicides for HIV prevention: the road to clinical development.

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Sánchez-Rodríguez, Javier; Vacas-Córdoba, Enrique; Gómez, Rafael; De La Mata, F Javier; Muñoz-Fernández, Ma Ángeles

2015-01-01

More than three decades since its discovery, HIV infection remains one of the most aggressive epidemics worldwide, with more than 35 million people infected. In sub-Saharan Africa, heterosexual transmissions represent nearly 80% of new infections, with 50% of these occurring in women. In an effort to stop the dramatic spread of the HIV epidemic, new preventive treatments, such as microbicides, have been developed. Nanotechnology has revolutionized this field by designing and engineering novel highly effective nano-sized materials as microbicide candidates. This review illustrates the most recent advances in nanotech-derived HIV prevention strategies, as well as the main steps required to translate promising in vitro results into clinical trials. Copyright © 2014 Elsevier B.V. All rights reserved.

Australian men’s experiences during a microbicide male tolerance study

Science.gov (United States)

Rosenthal, Susan L.; Holmes, Wendy; Maher, Lisa

2008-01-01

Microbicides currently in development have the potential to provide new options for the prevention of sexually transmitted infections if proven safe and efficacious. We examined the experiences of healthy male volunteers in a male tolerance study in Victoria, Australia in relation to trial participation and product use. Men (N = 36) enrolled in a seven-day, phase 1 clinical safety trial of SPL7013 were interviewed pre and post-use of the gel using a semi-structured interview guide. Interviews were digitally recorded and transcribed verbatim, and transcripts were analysed using a framework approach. All but one man completed the trial. The median age was 34 years (range 22–67 years). Most men had little pre-study knowledge of microbicides and almost all participated for altruistic or personal reasons. Men expressed few concerns about product safety during the trial and indicated trust in the information received through the consent process and from study staff. Three men were non-adherent to the request to be abstinent and an additional two did not refrain from masturbation. Most were positive about the gel, although they described it as “sticky” and found that it stuck to clothes, bed sheets and pubic hair. The type of applicator used was unfamiliar to the men, and some found it “clinical” in appearance. Men are willing to participate in male tolerance studies, often for altruistic reasons. However, counseling about ways to maintain abstinence and further research to inform anticipatory guidance regarding the “sticky” quality of gels, may be important. PMID:19085229

HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.

Directory of Open Access Journals (Sweden)

Kelly E Seaton

Full Text Available Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to protection and could provide insight for the rational design of HIV-1 vaccines.We first conducted a pilot study to compare three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG antibodies from HIV-1-positive women reacted broadly across the full panel of eight HIV-1 envelope (Env antigens tested, whereas IgA antibodies only reacted to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative women. The three sampling devices yielded equal HIV-1-specific antibody titers, as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs archived from 57 HIV seronegative women who participated in a microbicide efficacy trial in Southern Africa (HPTN 035. We detected vaginal IgA antibodies directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another three women, but did not detect Env-specific IgG antibodies in any women.Vaginal secretions of HIV-1 infected women contained IgG reactivity to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env-binding antibodies in the vaginal secretions of HIV-1 uninfected women participating in the microbicide trial were restricted to the IgA subtype and were mostly directed at HIV-1 gp120/gp140.

Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions.

Science.gov (United States)

McNicholl, Janet M

2016-12-01

Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention.

The influence of social constructs of hegemonic masculinity and sexual behaviour on acceptability of vaginal microbicides in Zambia.

Science.gov (United States)

Mweemba, Oliver; Dixey, Rachael; Bond, Virginia; White, Alan

2018-07-01

Vaginal microbicides are heralded as a woman's HIV prevention method. This study, conducted in a microbicide clinical trial setting in Zambia, explored how the social construction of masculinity and sexual behaviour influenced the acceptability of vaginal microbicides. The data were generated from 18 In-depth Interviews and 8 Focus Group Discussions. The data were analysed thematically. The study found that hegemonic masculinity influenced the use of vaginal microbicides positively and negatively, in multiple ways including: decision to initiate gel use, autonomous use of the gel, and consistent use of the gel. Men were seen as heads of households and decision-makers who approved their partners' intentions to initiate gel use. Autonomous gel use by women was not supported because it challenged men's dominant position in sexual matters and at a family level. The socially accepted notion that men engaged in multiple sexual relationships also influenced women's decision to use the gel. Sustained gel use depended on the perceived effect of the gel on men's sexual desires, sexual performance, fertility, and sexual behaviour. This study suggests that acceptability of microbicides partially lies within the realm of men, with use constrained and dictated by cultural constructs and practice of masculinity and gender.

Microbicides and HIV prevention | Sibeko | Obstetrics and ...

African Journals Online (AJOL)

Microbicide agents come in different preparations and/or formulations. The first generation microbicides are gels and creams; whereas subsequent generations include vaginal rings, films, sponges, gels with barrier devices and suppositories, and work by altering the environment of the genital tract to make it unsuitable for

Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes.

Science.gov (United States)

Notario-Pérez, Fernando; Ruiz-Caro, Roberto; Veiga-Ochoa, María-Dolores

2017-01-01

Infection with human immunodeficiency virus (HIV) remains a global public health concern and is particularly serious in low- and middle-income countries. Widespread sexual violence and poverty, among other factors, increase the risk of infection in women, while currently available prevention methods are outside the control of most. This has driven the study of vaginal microbicides to prevent sexual transmission of HIV from men to women in recent decades. The first microbicides evaluated were formulated as gels for daily use and contained different substances such as surfactants, acidifiers and monoclonal antibodies, which failed to demonstrate efficacy in clinical trials. A gel containing the reverse transcriptase inhibitor tenofovir showed protective efficacy in women. However, the lack of adherence by patients led to the search for dosage forms capable of releasing the active principle for longer periods, and hence to the emergence of the vaginal ring loaded with dapivirine, which requires a monthly application and is able to reduce the sexual transmission of HIV. The future of vaginal microbicides will feature the use of alternative dosage forms, nanosystems for drug release and probiotics, which have emerged as potential microbicides but are still in the early stages of development. Protecting women with vaginal microbicide formulations would, therefore, be a valuable tool for avoiding sexual transmission of HIV.

Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes

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Notario-Pérez F

2017-06-01

Full Text Available Fernando Notario-Pérez, Roberto Ruiz-Caro, María-Dolores Veiga-Ochoa Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain Abstract: Infection with human immunodeficiency virus (HIV remains a global public health concern and is particularly serious in low- and middle-income countries. Widespread sexual violence and poverty, among other factors, increase the risk of infection in women, while currently available prevention methods are outside the control of most. This has driven the study of vaginal microbicides to prevent sexual transmission of HIV from men to women in recent decades. The first microbicides evaluated were formulated as gels for daily use and contained different substances such as surfactants, acidifiers and monoclonal antibodies, which failed to demonstrate efficacy in clinical trials. A gel containing the reverse transcriptase inhibitor tenofovir showed protective efficacy in women. However, the lack of adherence by patients led to the search for dosage forms capable of releasing the active principle for longer periods, and hence to the emergence of the vaginal ring loaded with dapivirine, which requires a monthly application and is able to reduce the sexual transmission of HIV. The future of vaginal microbicides will feature the use of alternative dosage forms, nanosystems for drug release and probiotics, which have emerged as potential microbicides but are still in the early stages of development. Protecting women with vaginal microbicide formulations would, therefore, be a valuable tool for avoiding sexual transmission of HIV. Keywords: vaginal formulations, microbicides, prevention, sexual transmission, acquired immunodeficiency syndrome (AIDS, human immunodeficiency virus (HIV

Stimuli-sensitive nanoparticles for multiple anti-HIV microbicides

International Nuclear Information System (INIS)

Giri, Namita; Oh, Byeongtaek; Lee, Chi H.

2016-01-01

This study is aimed to develop and evaluate an advanced intravaginal formulation for the delivery of multiple anti-HIV microbicides. Novel stimuli-sensitive nanoparticles (NPs) which protected the encapsulated drugs from being degraded in acidic pH conditions were made of Eudragit S-100"® (ES100"®), a pH-sensitive polymer. ES100"® NPs were prepared using the quasi-emulsion solvent diffusion technique and loaded with two microbicides namely Tenofovir (TNF) and Etravirine (ETV). The effects of various fabrication parameters on the formulation properties were evaluated for the optimization of ES100"® NPs. The morphology of the ES100"® NPs was examined by scanning electron microscopy. The cytotoxicity of NPs containing microbicides individually or in a combination was assessed using cell viability and trans-epithelial electrical resistance (TEER) measurements. The cellular uptake rates of the model microbicides by human vaginal epithelial cells, VK2 E6/E7 cells, were evaluated using confocal microscopy and florescence-assisted cell sorting technique. ES100"® NPs had a spherical shape, smooth surface, and uniform texture with a little aggregation. The average particle size for NPs loaded with TNF ranged from 125 to 230 nm, whereas those for ETV-loaded NPs ranged from 160 to 280 nm. ES100"® NPs had zeta potential in the range of −5 to −10 mV. In-vitro release studies displayed the potential benefits of ES100"® NPs in retaining and protecting the loaded microbicides at vaginal pH (acidic), but immediately releasing them as the pH changes to neutral or 7.4 (physiological pH). Cell viability studies demonstrated that ES100"® NPs did not exert any cytotoxicity individually or in a combination of both microbicides. TEER measurements confirmed that ES100"® NPs loaded with TNF and ETV did not cause any changes in the barrier integrity of VK2 E6/E7 cell monolayer. The cellular uptake study revealed that ES100"® NPs were taken by vaginal epithelial cells through

Will dapivirine redeem the promises of anti-HIV microbicides? Overview of product design and clinical testing.

Science.gov (United States)

das Neves, José; Martins, João Pedro; Sarmento, Bruno

2016-08-01

Microbicides are being developed in order to prevent sexual transmission of HIV. Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is one of the leading drug candidates in the field, currently being tested in various dosage forms, namely vaginal rings, gels, and films. In particular, a ring allowing sustained drug release for 1month is in an advanced stage of clinical testing. Two parallel phase III clinical trials are underway in sub-Saharan Africa and results are expected to be released in early 2016. This article overviews the development of dapivirine and its multiple products as potential microbicides, with particular emphasis being placed on clinical evaluation. Also, critical aspects regarding regulatory approval, manufacturing, distribution, and access are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Stimuli-sensitive nanoparticles for multiple anti-HIV microbicides

Energy Technology Data Exchange (ETDEWEB)

Giri, Namita; Oh, Byeongtaek; Lee, Chi H., E-mail: leech@umkc.edu [University of Missouri at Kansas City, Division of Pharmaceutical Sciences (United States)

2016-05-15

This study is aimed to develop and evaluate an advanced intravaginal formulation for the delivery of multiple anti-HIV microbicides. Novel stimuli-sensitive nanoparticles (NPs) which protected the encapsulated drugs from being degraded in acidic pH conditions were made of Eudragit S-100{sup ®} (ES100{sup ®}), a pH-sensitive polymer. ES100{sup ®} NPs were prepared using the quasi-emulsion solvent diffusion technique and loaded with two microbicides namely Tenofovir (TNF) and Etravirine (ETV). The effects of various fabrication parameters on the formulation properties were evaluated for the optimization of ES100{sup ®} NPs. The morphology of the ES100{sup ®} NPs was examined by scanning electron microscopy. The cytotoxicity of NPs containing microbicides individually or in a combination was assessed using cell viability and trans-epithelial electrical resistance (TEER) measurements. The cellular uptake rates of the model microbicides by human vaginal epithelial cells, VK2 E6/E7 cells, were evaluated using confocal microscopy and florescence-assisted cell sorting technique. ES100{sup ®} NPs had a spherical shape, smooth surface, and uniform texture with a little aggregation. The average particle size for NPs loaded with TNF ranged from 125 to 230 nm, whereas those for ETV-loaded NPs ranged from 160 to 280 nm. ES100{sup ®} NPs had zeta potential in the range of −5 to −10 mV. In-vitro release studies displayed the potential benefits of ES100{sup ®} NPs in retaining and protecting the loaded microbicides at vaginal pH (acidic), but immediately releasing them as the pH changes to neutral or 7.4 (physiological pH). Cell viability studies demonstrated that ES100{sup ®} NPs did not exert any cytotoxicity individually or in a combination of both microbicides. TEER measurements confirmed that ES100{sup ®} NPs loaded with TNF and ETV did not cause any changes in the barrier integrity of VK2 E6/E7 cell monolayer. The cellular uptake study revealed that ES100{sup

Perceptions of acceptability and utility of microbicides in Ghana ...

African Journals Online (AJOL)

In addition, gendered negotiation power and the implications of covert use need to be addressed in microbicide education and social marketing. Les microbicides vaginaux, une substance qui pourrait largement réduire les infections sexuellement transmises (IST) et le VIH inclus, font actuellement parti des essais cliniques.

Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides

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Vacas-Córdoba E

2014-07-01

Full Text Available Enrique Vacas-Córdoba,1–3 Marta Galán,3,4 Francisco J de la Mata,3,4 Rafael Gómez,3,4 Marjorie Pion,1–3 M Ángeles Muñoz-Fernández1–3 1Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 2Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain; 3Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN, Madrid, Spain; 4Dendrimers for Biomedical Applications Group (BioInDen, University of Alcalá, Madrid, Spain Abstract: Self-administered topical microbicides or oral preexposure prophylaxis could be very helpful tools for all risk groups to decrease the human immunodeficiency virus (HIV-1 infection rates. Up until now, antiretrovirals (ARVs have been the most advanced microbicide candidates. Nevertheless, the majority of clinical trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane dendrimers, have been shown to be safe and effective compounds against HIV with great potential as topical microbicides. In addition, because most of the attempts to develop effective topical microbicides were unsuccessful, combinatorial strategies could be a valid approach when designing new microbicides. We evaluated various combinations of anionic carbosilane dendrimers with sulfated (G3-S16 and naphthyl sulfonated (G2-NF16 ended groups with different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed a synergistic or additive activity profile with zidovudine, efavirenz, and tenofovir in the majority of the combinations tested against the X4 and R5 tropic HIV-1 in cell lines, as well as in human primary cells. Therefore, the combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral potency of the individual compounds, and our findings support further clinical research on combinational approaches as

Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines.

Science.gov (United States)

Whaley, Kevin J; Hanes, Justin; Shattock, Robin; Cone, Richard A; Friend, David R

2010-12-01

The HIV-1 epidemic remains unchecked despite existing technology; vaccines and microbicides in development may help reverse the epidemic. Reverse transcriptase inhibitors (RTIs) formulated in gels tenofovir (TFV) and IVRs (dapivirine) are under clinical development. While TFV or similar products may prove successful for HIV-1, alternatives to RTIs may provide additional benefits, e.g., broader STI prevention. Biopharmaceutical agents under development as microbicides include cyanovirin, RANTES analogues, commensals, and Mabs. Cost of manufacturing biopharmaceuticals has been reduced and they can be formulated into tablets, films, and IVRs for vaginal delivery. Nanotechnology offers a novel approach to formulate microbicides potentially leading to uniform epithelial delivery. Delivery through vaginal mucus may be possible by controlling nanoparticle size and surface characteristics. Combining prevention modalities may be the most effective means of preventing STI transmission, importantly, codelivery of microbicides and vaccines has demonstrated. Finally, the safety of microbicide preparations and excipients commonly used can be assessed using a mouse/HSV-2 susceptibility model. Screening of new microbicide candidates and formulation excipients may avoid past issues of enhancing HIV-1 transmission. This article forms part of a special supplement covering several presentations on novel microbicide formulations from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA. Copyright © 2010 Elsevier B.V. All rights reserved.

Feasibility of a multicentre, randomised controlled trial of laparoscopic versus open colorectal surgery in the acute setting: the LaCeS feasibility trial protocol.

Science.gov (United States)

Harji, Deena; Marshall, Helen; Gordon, Katie; Crow, Hannah; Hiley, Victoria; Burke, Dermot; Griffiths, Ben; Moriarty, Catherine; Twiddy, Maureen; O'Dwyer, John L; Verjee, Azmina; Brown, Julia; Sagar, Peter

2018-02-22

Acute colorectal surgery forms a significant proportion of emergency admissions within the National Health Service. There is limited evidence to suggest minimally invasive surgery may be associated with improved clinical outcomes in this cohort of patients. Consequently, there is a need to assess the clinical effectiveness and cost-effectiveness of laparoscopic surgery in the acute colorectal setting. However,emergency colorectal surgical trials have previously been difficult to conduct due to issues surrounding recruitment and equipoise. The LaCeS (randomised controlled trial of Laparoscopic versus open Colorectal Surgery in the acute setting) feasibility trial will determine the feasibility of conducting a definitive, phase III trial of laparoscopic versus open acute colorectal resection. The LaCeS feasibility trial is a prospective, multicentre, single-blinded, parallel group, pragmatic randomised controlled feasibility trial. Patients will be randomised on a 1:1 basis to receive eitherlaparoscopic or open surgery. The trial aims to recruit at least 66 patients from five acute general surgical units across the UK. Patients over the age of 18 with a diagnosis of acute colorectal pathology requiring resection on clinical and radiological/endoscopic investigations, with a National Confidential Enquiry into Patient Outcome and Death classification of urgent will be considered eligible for participation. The primary outcome is recruitment. Secondary outcomes include assessing the safety profile of laparoscopic surgery using intraoperative and postoperative complication rates, conversion rates and patient-safety indicators as surrogate markers. Clinical and patient-reported outcomes will also be reported. The trial will contain an embedded qualitative study to assess clinician and patient acceptability of trial processes. The LaCeS feasibility trial is approved by the Yorkshire and The Humber, Bradford Leeds Research Ethics Committee (REC reference: 15/ YH/0542). The

Conducting feasibilities in clinical trials: An investment to ensure a good study

Directory of Open Access Journals (Sweden)

Viraj Rajadhyaksha

2010-01-01

Full Text Available Conducting clinical trial feasibility is one of the first steps in clinical trial conduct. This process includes assessing internal and environmental capacity, alignment of the clinical trial in terms of study design, dose of investigational product, comparator, patient type, with the local environment and assessing potential of conducting clinical trial in a specific country. A robust feasibility also ensures a realistic assessment and capability to conduct the clinical trial. For local affiliates of pharmaceutical organizations, and contract research organizations, this is a precursor to study placement and influences the decision of study placement. This article provides details on different types of feasibilities, information which is to be included and relevance of each. The article also aims to provide practical hands-on suggestions to make feasibilities more realistic and informative.

Conducting feasibilities in clinical trials: an investment to ensure a good study.

Science.gov (United States)

Rajadhyaksha, Viraj

2010-07-01

Conducting clinical trial feasibility is one of the first steps in clinical trial conduct. This process includes assessing internal and environmental capacity, alignment of the clinical trial in terms of study design, dose of investigational product, comparator, patient type, with the local environment and assessing potential of conducting clinical trial in a specific country. A robust feasibility also ensures a realistic assessment and capability to conduct the clinical trial. For local affiliates of pharmaceutical organizations, and contract research organizations, this is a precursor to study placement and influences the decision of study placement. This article provides details on different types of feasibilities, information which is to be included and relevance of each. The article also aims to provide practical hands-on suggestions to make feasibilities more realistic and informative.

Vaginal rings for delivery of HIV microbicides.

Science.gov (United States)

Malcolm, R Karl; Fetherston, Susan M; McCoy, Clare F; Boyd, Peter; Major, Ian

2012-01-01

Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing.

Vaginal microbicides: how do you kick-start a global market?

Science.gov (United States)

1996-10-01

Efforts are underway to develop vaginal microbicides capable of protecting women against HIV and sexually transmitted disease. It was reported at the recent Vancouver international AIDS conference that 20 such products are in the preclinical stage, 13 in the early clinical stage, and two at the late clinical stage. The private sector, however, is not convinced of the commercial viability of vaginal microbicides, especially in developing countries. Johnson & Johnson has estimated there to be a US$40 million world market for vaginal microbicides, too small to garner the interest and involvement of the major research and development-based multinational pharmaceutical companies. The European Commission has therefore contracted Hillmark, a UK consultancy, to assess the market for such products in Cote d'Ivoire, Egypt, Kenya, South Africa, France, Poland, India, Thailand, Philippines, Brazil, and Venezuela. Corporate interest may be sparked by a convincing assessment of a higher market potential. Also at the Vancouver conference, the US Secretary of Health announced grant funding of US$100 million for research into microbicides.

On-demand microbicide products: design matters.

Science.gov (United States)

Patel, Sravan Kumar; Rohan, Lisa Cencia

2017-12-01

Sexual intercourse (vaginal and anal) is the predominant mode of human immunodeficiency virus (HIV) transmission. Topical microbicides used in an on-demand format (i.e., immediately before or after sex) can be part of an effective tool kit utilized to prevent sexual transmission of HIV. The effectiveness of prevention products is positively correlated with adherence, which is likely to depend on user acceptability of the product. The development of an efficacious and acceptable product is therefore paramount for the success of an on-demand product. Acceptability of on-demand products (e.g., gels, films, and tablets) and their attributes is influenced by a multitude of user-specific factors that span behavioral, lifestyle, socio-economic, and cultural aspects. In addition, physicochemical properties of the drug, anatomical and physiological aspects of anorectal and vaginal compartments, issues relating to large-scale production, and cost can impact product development. These factors together with user preferences determine the design space of an effective, acceptable, and feasible on-demand product. In this review, we summarize the interacting factors that together determine product choice and its target product profile.

Potential Use of Antimicrobial Peptides as Vaginal Spermicides/Microbicides

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Nongnuj Tanphaichitr

2016-03-01

Full Text Available The concurrent increases in global population and sexually transmitted infection (STI demand a search for agents with dual spermicidal and microbicidal properties for topical vaginal application. Previous attempts to develop the surfactant spermicide, nonoxynol-9 (N-9, into a vaginal microbicide were unsuccessful largely due to its inefficiency to kill microbes. Furthermore, N-9 causes damage to the vaginal epithelium, thus accelerating microbes to enter the women’s body. For this reason, antimicrobial peptides (AMPs, naturally secreted by all forms of life as part of innate immunity, deserve evaluation for their potential spermicidal effects. To date, twelve spermicidal AMPs have been described including LL-37, magainin 2 and nisin A. Human cathelicidin LL-37 is the most promising spermicidal AMP to be further developed for vaginal use for the following reasons. First, it is a human AMP naturally produced in the vagina after intercourse. Second, LL-37 exerts microbicidal effects to numerous microbes including those that cause STI. Third, its cytotoxicity is selective to sperm and not to the female reproductive tract. Furthermore, the spermicidal effects of LL-37 have been demonstrated in vivo in mice. Therefore, the availability of LL-37 as a vaginal spermicide/microbicide will empower women for self-protection against unwanted pregnancies and STI.

Reverse transcriptase inhibitors as potential colorectal microbicides.

Science.gov (United States)

Herrera, Carolina; Cranage, Martin; McGowan, Ian; Anton, Peter; Shattock, Robin J

2009-05-01

We investigated whether reverse transcriptase (RT) inhibitors (RTI) can be combined to inhibit human immunodeficiency virus type 1 (HIV-1) infection of colorectal tissue ex vivo as part of a strategy to develop an effective rectal microbicide. The nucleotide RTI (NRTI) PMPA (tenofovir) and two nonnucleoside RTI (NNRTI), UC-781 and TMC120 (dapivirine), were evaluated. Each compound inhibited the replication of the HIV isolates tested in TZM-bl cells, peripheral blood mononuclear cells, and colorectal explants. Dual combinations of the three compounds, either NRTI-NNRTI or NNRTI-NNRTI combinations, were more active than any of the individual compounds in both cellular and tissue models. Combinations were key to inhibiting infection by NRTI- and NNRTI-resistant isolates in all models tested. Moreover, we found that the replication capacities of HIV-1 isolates in colorectal explants were affected by single point mutations in RT that confer resistance to RTI. These data demonstrate that colorectal explants can be used to screen compounds for potential efficacy as part of a combination microbicide and to determine the mucosal fitness of RTI-resistant isolates. These findings may have important implications for the rational design of effective rectal microbicides.

A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel.

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Marla J Keller

2011-01-01

Full Text Available Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001 and fit a sigmoid E(max pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development

Plant made anti-HIV microbicides: a field of opportunity

CSIR Research Space (South Africa)

Lotter-Stark, HCT

2012-11-01

Full Text Available -HIV microbicides- a field of opportunity Hester C.T. Lotter-Stark1*, Edward P. Rybicki2 and Rachel K. Chikwamba1 1 Council for Scientific and Industrial Research (CSIR), Biosciences, Pretoria, South Africa. 2 Institute of Infectious Disease and Molecular... efficacious in in vitro and in vivo protection studies. For the purpose of development and access by the relevant 2 population groups, it is crucial that these microbicides be produced at low cost. For the promising protein and peptide candidate...

Neutrophil Leukocyte: Combustive Microbicidal Action and Chemiluminescence

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Robert C. Allen

2015-01-01

Full Text Available Neutrophil leukocytes protect against a varied and complex array of microbes by providing microbicidal action that is simple, potent, and focused. Neutrophils provide such action via redox reactions that change the frontier orbitals of oxygen (O2 facilitating combustion. The spin conservation rules define the symmetry barrier that prevents direct reaction of diradical O2 with nonradical molecules, explaining why combustion is not spontaneous. In burning, the spin barrier is overcome when energy causes homolytic bond cleavage producing radicals capable of reacting with diradical O2 to yield oxygenated radical products that further participate in reactive propagation. Neutrophil mediated combustion is by a different pathway. Changing the spin quantum state of O2 removes the symmetry restriction to reaction. Electronically excited singlet molecular oxygen (O2*1 is a potent electrophilic reactant with a finite lifetime that restricts its radius of reactivity and focuses combustive action on the target microbe. The resulting exergonic dioxygenation reactions produce electronically excited carbonyls that relax by light emission, that is, chemiluminescence. This overview of neutrophil combustive microbicidal action takes the perspectives of spin conservation and bosonic-fermionic frontier orbital considerations. The necessary principles of particle physics and quantum mechanics are developed and integrated into a fundamental explanation of neutrophil microbicidal metabolism.

Microbicidal Effects of Stored Aqueous Ozone Solution Generated by Nano-bubble Technology.

Science.gov (United States)

Seki, Mineaki; Ishikawa, Tatsuya; Terada, Hiroshi; Nashimoto, Masayuki

2017-01-01

Clinically used disinfectants are often irritating and cause skin problems. Ozone water is unique among disinfectants. It does not damage skin cells and readily decomposes to oxygen without generating harmful residues. On the other hand, it rapidly loses its sanitizing activity. Recently developed nano-bubble ozone water (NBOW) can keep its sanitizing activity much longer. This study aimed to examine the microbicidal effects of NBOW after long-term storage. The concentration of ozone in NBOW was examined by measuring the NBOW redox potential. Microbicidal activity was evaluated by colony formation assays, after incubating bacteria with NBOW for set time periods. NBOW lost its microbicidal activity after 1 year of storage at 4°C. Stocked frozen, NBOW retained appreciable microbicidal activity after 1 year of storage. Mycobacterium smegmatis, one of the most disinfectant-resistant bacteria, was killed within 15 min. NBOW was resistant to freeze-thawing. NBOW that had been stored frozen possessed sufficient microbicidal activity to kill bacteria even after 1 year of storage. Moreover, it was shown that NBOW is freeze-thaw resistant. NBOW possesses desirable features rendering it an attractive alternative disinfectant. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Intravaginal rings as delivery systems for microbicides and multipurpose prevention technologies

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Thurman AR

2013-10-01

Full Text Available Andrea Ries Thurman, Meredith R Clark, Jennifer Hurlburt, Gustavo F Doncel CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA Abstract: There is a renewed interest in delivering pharmaceutical products via intravaginal rings (IVRs. IVRs are flexible torus-shaped drug delivery systems that can be easily inserted and removed by the woman and that provide both sustained and controlled drug release, lasting for several weeks to several months. In terms of women's health care products, it has been established that IVRs effectively deliver contraceptive steroids and steroids for the treatment of postmenopausal vaginal atrophy. A novel application for IVRs is the delivery of antiretroviral drugs for the prevention of human immunodeficiency virus (HIV genital infection. Microbicides are antiviral drugs delivered topically for HIV prevention. Recent reviews of microbicide IVRs have focused on technologies in development and optimizing ring design. IVRs have several advantages, including the ability to deliver sustained drug doses for long periods of time while bypassing first pass metabolism in the gut. IVRs are discreet, woman-controlled, and do not require a trained provider for placement or fitting. Previous data support that women and their male sexual partners find IVRs highly acceptable. Multipurpose prevention technology (MPT products provide protection against unintended/mistimed pregnancy and reproductive tract infections, including HIV. Several MPT IVRs are currently in development. Early clinical testing of new microbicide and MPT IVRs will require a focus on safety, pharmacokinetics and pharmacodynamics. Specifically, IVRs will have to deliver tissue concentrations of drugs that are pharmacodynamically active, do not cause mucosal alterations or inflammation, and do not change the resident microbiota. The emergence of resistance to antiretrovirals will need to be investigated. IVRs should not

Pragmatic trial design elements showed a different impact on trial interpretation and feasibility than explanatory elements

NARCIS (Netherlands)

Nieuwenhuis, Joost B.; Irving, Elaine; Oude Rengerink, Katrien; Lloyd, Emily; Goetz, Iris; Grobbee, Diederick E.; Stolk, Pieter; Groenwold, Rolf H H; Zuidgeest, Mira G P

2016-01-01

OBJECTIVE: To illustrate how pragmatic trial design elements, or inserting explanatory trial elements in pragmatic trials affect validity, generalizability, precision and operational feasibility. STUDY DESIGN AND SETTING: From illustrative examples identified through the IMI Get Real Consortium, we

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS

OpenAIRE

Gupta, Satish; Vinu,Nutan

2013-01-01

Satish Kumar Gupta, Nutan Reproductive Cell Biology Laboratory, National Institute of Immunology, New Delhi, India Abstract: Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV. Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl...

Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned.

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Friend, David R; Kiser, Patrick F

2013-09-01

The development of topically applied products capable of preventing vaginal and rectal transmission of HIV-1 has been on-going for nearly 20 years. Despite this, only one clinical trial has demonstrated protection against sexual transmission of HIV-1 in women. This review covers the development of microbicides, also referred to as topical pre-exposure prophylaxis (PrEP), through three stages. The first stage focused on nonspecific agents, including surfactants such as nonoxynol-9 (N-9), to prevent HIV-1 transmission. Unfortunately, N-9 enhanced susceptibility to sexual transmission of HIV-1 when evaluated for efficacy. Soon thereafter, other nonspecific agents (polyanions) were quickly moved into large efficacy trials. Due to a lack of coordination among investigators and funders, a large investment was made in a class of compounds shown ultimately to be ineffective, although poor adherence may have contributed to these findings. The second stage involved the assessment of the antiretroviral drug tenofovir, formulated as a vaginal gel, which was found to be modestly effective in a Phase IIb trial (CAPRISA-004) when dosed in a coitally-dependent manner. In another Phase IIb trial, VOICE (MTN-003), tenofovir gel was found to be ineffective when dosed once-daily in a coitally-independent manner. Based on pharmacokinetic data, it was concluded the participants were poorly adherent to this dosing regimen, leading to a lack of efficacy. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS-001), using the coitally-dependent dosing regimen employed in CAPRISA-004. We are now in the third stage of microbicide research. The antiretroviral drug dapivirine is currently in two Phase III safety and efficacy studies formulated as a vaginal ring. It is hoped that the once-monthly dosing regimen will lead to higher adherence than found in the VOICE study. It is now clear that product adherence could be the greatest challenge to demonstrating

A social ecology of rectal microbicide acceptability among young men who have sex with men and transgender women in Thailand.

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Newman, Peter A; Roungprakhon, Surachet; Tepjan, Suchon

2013-08-01

With HIV-incidence among men who have sex with men (MSM) in Bangkok among the highest in the world, a topical rectal microbicide would be a tremendous asset to prevention. Nevertheless, ubiquitous gaps between clinical trial efficacy and real-world effectiveness of existing HIV preventive interventions highlight the need to address multi-level factors that may impact on rectal microbicide implementation. We explored the social ecology of rectal microbicide acceptability among MSM and transgender women in Chiang Mai and Pattaya, Thailand. We used a qualitative approach guided by a social ecological model. Five focus groups were conducted in Thai using a semi-structured interview guide. All interviews were digitally recorded, transcribed verbatim in Thai and translated into English. We conducted thematic analysis using line-by-line and axial coding and a constant comparative method. Transcripts and codes were uploaded into a customized database programmed in Microsoft Access. We then used content analysis to calculate theme frequencies by group, and Chi-square tests and Fisher's exact test to compare themes by sexual orientation/gender expression and age. Participant's (n=37) mean age was 24.8 years (SD=4.2). The majority (70.3%) self-identified as gay, 24.3% transgender women. Product-level themes (side effects, formulation, efficacy, scent, etc.) accounted for 42%, individual (increased sexual risk, packaging/portability, timing/duration of protection) 29%, interpersonal (trust/communication, power/negotiation, stealth) 8% and social-structural (cost, access, community influence, stigma) 21% of total codes, with significant differences by sexual orientation/gender identity. The intersections of multi-level influences included product formulation and timing of use preferences contingent on interpersonal communication and partner type, in the context of constraints posed by stigma, venues for access and cost. The intersecting influence of multi-level factors on

Key feasibility considerations when conducting vaccine clinical trials in Asia–Pacific countries

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Lansang EZ

2013-03-01

Full Text Available Elvira Zenaida Lansang,1 Kenneth Tan,2 Saumya Nayak,1 Ken J Lee,1 Karen Wai1 1Feasibility and Site Identification – Asia, Quintiles East Asia Pte Ltd, Singapore; 2National University of Singapore, Singapore Introduction: Conducting clinical trial feasibility is an important first step in initiating a clinical trial. A robust feasibility process ensures that a realistic capability assessment is made before conducting a trial. A retrospective analysis of vaccine clinical trials was performed to understand changes which could affect feasibility recommendations. Methods: Feasibilities conducted by Quintiles between January 2011 and August 2012 were reviewed. Vaccine studies only involving Asia–Pacific countries were selected, and common study parameters were identified. Information from Quintiles’ database was retrieved to examine changes in parameters over time. Results: A total of six vaccine studies were identified within the 1.7-year period. Two studies were excluded because they did not contain feasibility information or had involved sites that were sponsor selected. Four studies were analyzed. Three cases required healthy volunteers, while one case involved a specific patient population. Age requirement and seasonality of disease mainly influenced recommendations for Study 1. Sponsor’s marketing strategy influenced the recommendations for Study 2. Study 3 showed the effect of a country’s immunization program and reimbursement of vaccines on a study’s success. In contrast to the other studies, Study 4 demonstrated the impact of eligibility criteria in recruitment recommendations for a vaccine trial requiring specific patient pools. Conclusion: Feasibility recommendations for vaccine trials are largely based on (1 eligibility criteria; (2 cultural beliefs; (3 country’s past recruitment performance; (4 use of advertising; (5 site’s access to subject populations; (6 cooperation with local health professionals and government; (7

Vaginal rings for delivery of HIV microbicides

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McCoy CF

2012-11-01

Full Text Available R Karl Malcolm, Susan M Fetherston, Clare F McCoy, Peter Boyd, Ian MajorSchool of Pharmacy, Queen's University Belfast, Belfast, UKAbstract: Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing.Keywords: controlled release, sustained release, antiretroviral, dapivirine, SILCS diaphragm, silicone elastomer, thermoplastic

How informed is consent in vulnerable populations? Experience using a continuous consent process during the MDP301 vaginal microbicide trial in Mwanza, Tanzania

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Kavit Natujwa

2010-06-01

Full Text Available Abstract Background HIV prevention trials conducted among disadvantaged vulnerable at-risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania. Methods A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs conducted immediately after their 4, 24 and 52 week follow-up visits. Results 99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews. In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy. Conclusions

Adolescent girls' communication with "mothers" about topical microbicides.

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Sunder, Punita K; Ramos, Stephanie; Short, Mary B; Rosenthal, Susan L

2006-12-01

Topical microbicides, a female-initiated method to protect against sexually transmitted infections (STI) and pregnancy, will only be effective if found acceptable. Mothers may have an influence on acceptability and use among adolescent girls. The current study examined the communication between girls and mothers to understand the potential predictors and nature of conversations regarding surrogate microbicide products. Sexually experienced girls, 14 to 21 years, were recruited for a 6-month study examining microbicide acceptability. During face-to-face interviews, qualitative data were collected regarding communication between girls and mothers. Two independent raters coded the responses, which were organized into themes. Themes were interpreted according to the conceptual understanding of mother-daughter communication. Fifty percent of the 171 girls with codable responses had a conversation with their mother. Higher levels of indirect parental monitoring were related to being more likely to have a conversation. Concrete events related to the study (i.e. receiving phone call from the researcher, having an appointment, or seeing the product) or inquiries by mothers appeared to promote conversation. Barriers to conversation included the private nature of the information and relationship issues between the mother and daughter. Conversations often addressed issues related to girls' participation in the study, although some conversations included global issues related to sexuality. Girls may talk to their mothers about new products for STI prevention, and such conversations may provide opportunities to promote use.

Feasibility study of a clinically-integrated randomized trial of modifications to radical prostatectomy

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Vickers Andrew J

2012-02-01

Full Text Available Abstract Background Numerous technical modifications to radical prostatectomy have been proposed. Such modifications are likely to lead to only slight improvements in outcomes. Although small differences would be worthwhile, an appropriately powered randomized trial would need to be very large, and thus of doubtful feasibility given the expense, complexity and regulatory burden of contemporary clinical trials. We have proposed a novel methodology, the clinically-integrated randomized trial, which dramatically streamlines trial procedures in order to reduce the marginal cost of an additional patient towards zero. We aimed to determine the feasibility of implementing such a trial for radical prostatectomy. Methods Patients undergoing radical prostatectomy as initial treatment for prostate cancer were randomized in a factorial design to involvement of the fascia during placement of the anastomotic sutures, urethral irrigation, both or neither. Endpoint data were obtained from routine clinical documentation. Accrual and compliance rates were monitored to determine the feasibility of the trial. Results From a total of 260 eligible patients, 154 (59% consented; 56 patients declined to participate, 20 were not approached on recommendation of the treating surgeon, and 30 were not approached for logistical reasons. Although recording by surgeons of the procedure used was incomplete (~80%, compliance with randomization was excellent when it was recorded, with only 6% of procedures inconsistent with allocation. Outcomes data was received from 71% of patients at one year. This improved to 83% as the trial progressed. Conclusions A clinically-integrated randomized trial was conducted at low cost, with excellent accrual, and acceptable compliance with treatment allocation and outcomes reporting. This demonstrates the feasibility of the methodology. Improved methods to ensure documentation of surgical procedures would be required before wider implementation

Qualitative and quantitative intravaginal targeting: key to anti-HIV-1 microbicide delivery from test tube to in vivo success.

Science.gov (United States)

Pillay, Viness; Mashingaidze, Felix; Choonara, Yahya E; Du Toit, Lisa C; Buchmann, Eckhart; Maharaj, Vinesh; Ndesendo, Valence M K; Kumar, Pradeep

2012-06-01

The past decade has seen several effective anti-HIV-1 agent discoveries, yet microbicides continue to disappoint clinically. Our review expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal microenvironmental factors including pH should be maintained at HIV-1 prohibitive acidic levels simultaneously to ward off other sexually transmitted diseases, which compromise vaginal epithelial barrier properties. Furthermore, choice of receptors to target both on HIV-1 and on target cells is vital in deterring transmission. Appropriate modeling of virus-target cell interactions as well as targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could revolutionize microbicide research, ultimately delivering a female-controlled HIV-1 prevention modality appropriately. Copyright © 2012 Wiley Periodicals, Inc.

Knowledge and perception of microbicides among healthcare ...

African Journals Online (AJOL)

2014-06-02

Jun 2, 2014 ... mankind has tried several prevention options since the onset of the ... Knowledge and perception of microbicides among healthcare providers in Calabar,. Nigeria .... primary source of reproductive health information for ... are a new group of substances that can reduce the risk .... Research process Report.

Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission

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Abusuwwa Raed

2006-06-01

Full Text Available Abstract Background Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9 and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes toxic effects that increase susceptibility. The mouse HSV-2 vaginal transmission model reported here: (a Directly tests for toxic effects that increase susceptibility to HSV-2, (b Determines in vivo whether a microbicide can protect against HSV-2 transmission without causing toxicities that increase susceptibility, and (c Identifies those toxic effects that best correlate with the increased HSV susceptibility. Methods Susceptibility was evaluated in progestin-treated mice by delivering a low-dose viral inoculum (0.1 ID50 at various times after delivering the candidate microbicide to detect whether the candidate increased the fraction of mice infected. Ten agents were tested – five detergents: nonionic (N9, cationic (benzalkonium chloride, BZK, anionic (sodium dodecylsulfate, SDS, the pair of detergents in C31G (C14AO and C16B; one surface active agent (chlorhexidine; two non-detergents (BufferGel®, and sulfonated polystyrene, SPS; and HEC placebo gel (hydroxyethylcellulose. Toxic effects were evaluated by histology, uptake of a 'dead cell' dye, colposcopy, enumeration of vaginal macrophages, and measurement of inflammatory cytokines. Results A single dose of N9 protected against HSV-2 for a few minutes but then rapidly increased susceptibility, which reached maximum at 12 hours. When applied at the minimal concentration needed for brief partial protection, all five detergents caused a subsequent increase in susceptibility at 12 hours of ~20–30-fold. Surprisingly, colposcopy failed to detect visible signs of the N9 toxic effect that increased susceptibility at 12 hours. Toxic

Implementation of a prospective pregnancy registry for antiretroviral based HIV prevention trials.

Science.gov (United States)

Mhlanga, Felix G; Noguchi, Lisa; Balkus, Jennifer E; Kabwigu, Samuel; Scheckter, Rachel; Piper, Jeanna; Watts, Heather; O'Rourke, Colin; Torjesen, Kristine; Brown, Elizabeth R; Hillier, Sharon L; Beigi, Richard

2018-02-01

Safety data on pregnancy and fetal outcomes among women in HIV prevention trials are urgently needed to inform use of effective antiretroviral agents for HIV prevention. We describe an effective, efficient, and novel method to prospectively collect perinatal safety data concurrent with on-going parent clinical trials. The Microbicide Trials Network (MTN)-016 study is a multinational prospective pregnancy exposure registry designed to capture pregnancy and neonatal outcomes. Studies currently contributing data to this registry included phase I and II safety trials with planned exposures to candidate HIV prevention agents, as well as phase IIB and III efficacy trials capturing data on pregnancy and infant outcomes following inadvertent fetal exposure during study participation. To date, participants from two phase I studies and two effectiveness trials have participated in MTN-016, resulting in 420 pregnant women and 381 infants enrolled. Infant retention has been high, with 329 of 381 (86%) infants completing the 12-month follow-up visit. In a research setting context, it is feasible to establish and implement a prospective, multinational HIV chemoprophylaxis pregnancy registry that will generate pregnancy exposure data in a robust fashion.

Time-resolved imaging refractometry of microbicidal films using quantitative phase microscopy.

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Rinehart, Matthew T; Drake, Tyler K; Robles, Francisco E; Rohan, Lisa C; Katz, David; Wax, Adam

2011-12-01

Quantitative phase microscopy is applied to image temporal changes in the refractive index (RI) distributions of solutions created by microbicidal films undergoing hydration. We present a novel method of using an engineered polydimethylsiloxane structure as a static phase reference to facilitate calibration of the absolute RI across the entire field. We present a study of dynamic structural changes in microbicidal films during hydration and subsequent dissolution. With assumptions about the smoothness of the phase changes induced by these films, we calculate absolute changes in the percentage of film in regions across the field of view.

Comparison of the Microbicidal activity of monochloramine and iodine.

Science.gov (United States)

Arnitz, R; Nagl, M; Gottardi, W

2015-12-01

Recently, we showed that monochloramine (NH2 Cl) has a significantly stronger bactericidal and fungicidal activity than chloramine T despite its lower oxidizing power. This phenomenon was explained by increased penetration because of the higher lipophilicity and smaller bulk of NH2 Cl. As iodine (I2 ) has an even fivefold higher bulk than NH2 Cl, a comparison of both compounds regarding their microbicidal activity became the aim of this study. Aqueous solutions of I2 at a concentration of 10·7 μmol l(-1) killed 10(6) colony forming units per millilitre (CFU ml(-1) ) of Escherichia coli, Staphylococcus aureus or Pseudomonas aeruginosa to the detection limit of 10(2) CFU ml(-1) within 1 min at 20°C and pH 7·1, while a concentration of 36-355 μmol l(-1) of NH2 Cl was needed to achieve the same effect. Aspergillus fumigatus was inactivated within 5 min by 36 μmol l(-1) I2 and by 355 μmol l(-1) NH2 Cl, Candida albicans within 1 min by 10·7 μmol l(-1) I2 and by 355 μmol l(-1) NH2 Cl. The lipophilicity of I2 , determined with the octanol/water method, was three powers of 10 higher than that of NH2 Cl. The at least 10-fold stronger microbicidal activity of iodine suggests that the hindrance of penetration of the bulky molecule is outweighed by enhanced lipophilicity. The microbicidal activity of active halogen compounds increases not only with their reactivity, but also with higher lipophilicity and lower bulk, as shown recently. In this study, iodine showed a higher microbicidal activity than monochloramine and a 1000-fold higher lipophilicity. Therefore, the lipophilicity of a disinfectant may be more important than the bulk for bactericidal activity. These facts should be considered upon the design of new antiseptics and their clinical application. © 2015 The Society for Applied Microbiology.

Hypothetical Rectal Microbicide Acceptability and Factors Influencing It among Men Who Have Sex with Men in Tianjin, China.

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Guohong Zhang

Full Text Available To measure potential acceptability of rectal microbicides and to explore factors likely to affect their acceptability among men who have sex with men (MSM.Cross-sectional and retrospective surveys were conducted in this study. A questionnaire and a scale were used to measure the acceptability score for physical and functional characteristics of hypothetical rectal microbicides. We also evaluated the involvement of other factors such as sexual behaviors, social context, etc.MSMs we interviewed showed a high acceptability to rectal microbicides, indicated by the mean acceptability score of 2.92 (SD, 0.54, scale of 1-4. The results also suggested that microbicides were preferred in a cream form that can moisten and lubricate the rectum, prevent HIV infection and go unnoticed by their partners. Multivariate analysis showed that the microbicides acceptability varied significantly by education level (β = 0.135; P = 0.028, having casual partners (β = 0.174; P = 0.007, frequency of lubricant use (β = 0.134; P = 0.031, history of HIV test (β = 0.129; P = 0.036, willingness to use lubricant (β = 0.126; P = 0.045, locus of control by partners regarding STI infection (β = 0.168; P = 0.009.A positive response to rectal microbicides among MSMs was found in our study, suggesting that rectal microbicides might have a potential market in MSMs and they might play an important role in HIV/STIs prevention as a supplement. Further studies may be considered to combine the acceptability study with clinical research together to understand the true feelings of MSMs when they use the products.

The use of supersaturation for the vaginal application of microbicides

DEFF Research Database (Denmark)

Grammen, Carolien; Plum, Jakob; Van Den Brande, Jeroen

2014-01-01

In this study, we investigated the potential of supersaturation for the formulation of the poorly water-soluble microbicide dapivirine (DPV) in an aqueous vaginal gel in order to enhance its vaginal tissue uptake. Different excipients such as hydroxypropylmethylcellulose, polyethylene glycol 1000....... The best performing supersaturated gel containing 500 μM DPV (supersaturation degree of 4) in the presence of sulfobutyl ether-beta-cyclodextrin (2.5%) appeared to be stable for at least 3 months. In addition, the gel generated a significant increase in vaginal drug uptake in rabbits as compared...... with suspension gels. We conclude that supersaturation is a possible strategy to enhance the vaginal concentration of hydrophobic microbicides, thereby increasing permeation into the vaginal submucosa....

In vitro resistance profile of the candidate HIV-1 microbicide drug dapivirine.

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Schader, Susan M; Oliveira, Maureen; Ibanescu, Ruxandra-Ilinca; Moisi, Daniela; Colby-Germinario, Susan P; Wainberg, Mark A

2012-02-01

Antiretroviral-based microbicides may offer a means to reduce the sexual transmission of HIV-1. Suboptimal use of a microbicide may, however, lead to the development of drug resistance in users that are already, or become, infected with HIV-1. In such cases, the efficacy of treatments may be compromised since the same (or similar) antiretrovirals used in treatments are being developed as microbicides. To help predict which drug resistance mutations may develop in the context of suboptimal use, HIV-1 primary isolates of different subtypes and different baseline resistance profiles were used to infect primary cells in vitro in the presence of increasing suboptimal concentrations of the two candidate microbicide antiretrovirals dapivirine (DAP) and tenofovir (TFV) alone or in combination. Infections were ongoing for 25 weeks, after which reverse transcriptase genotypes were determined and scrutinized for the presence of any clinically recognized reverse transcriptase drug resistance mutations. Results indicated that suboptimal concentrations of DAP alone facilitated the emergence of common nonnucleoside reverse transcriptase inhibitor resistance mutations, while suboptimal concentrations of DAP plus TFV gave rise to fewer mutations. Suboptimal concentrations of TFV alone did not frequently result in the development of resistance mutations. Sensitivity evaluations for stavudine (d4T), nevirapine (NVP), and lamivudine (3TC) revealed that the selection of resistance as a consequence of suboptimal concentrations of DAP may compromise the potential for NVP to be used in treatment, a finding of potential relevance in developing countries.

Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.

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Oranat Chuchuen

Full Text Available Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold

Quantitative Analysis of Microbicide Concentrations in Fluids, Gels and Tissues Using Confocal Raman Spectroscopy

Science.gov (United States)

Chuchuen, Oranat; Henderson, Marcus H.; Sykes, Craig; Kim, Min Sung; Kashuba, Angela D. M.; Katz, David F.

2013-01-01

Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry) are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold standard LC-MS/MS data

Gene Expression Profiling of Human Vaginal Cells In Vitro Discriminates Compounds with Pro-Inflammatory and Mucosa-Altering Properties: Novel Biomarkers for Preclinical Testing of HIV Microbicide Candidates.

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Irina A Zalenskaya

Full Text Available Inflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. Therefore, it is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides using a microarray gene expression profiling strategy.To this end, we compared transcriptomes of human vaginal cells (Vk2/E6E7 treated with well-characterized pro-inflammatory (PIC and non-inflammatory (NIC compounds. PICs included compounds with different mechanisms of action. Gene expression was analyzed using Affymetrix U133 Plus 2 arrays. Data processing was performed using GeneSpring 11.5 (Agilent Technologies, Santa Clara, CA.Microarraray comparative analysis allowed us to generate a panel of 20 genes that were consistently deregulated by PICs compared to NICs, thus distinguishing between these two groups. Functional analysis mapped 14 of these genes to immune and inflammatory responses. This was confirmed by the fact that PICs induced NFkB pathway activation in Vk2 cells. By testing microbicide candidates previously characterized in clinical trials we demonstrated that the selected PIC-associated genes properly identified compounds with mucosa-altering effects. The discriminatory power of these genes was further demonstrated after culturing vaginal cells with vaginal bacteria. Prevotella bivia, prevalent bacteria in the disturbed microbiota of bacterial vaginosis, induced strong upregulation of seven selected PIC-associated genes, while a commensal Lactobacillus gasseri associated to vaginal health did not cause any changes.In vitro evaluation of the immunoinflammatory potential of microbicides using the PIC-associated genes defined in this study could help in the initial screening of candidates prior

Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides

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Li Yun-Yao

2006-10-01

Full Text Available Abstract Background Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP, a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined. Methods The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring β-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP, the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured. Results The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate, cellulose sulfate, carrageenan, CAP (in soluble form and polystyrene sulfonate, respectively, was considerably (range ≈ 4 to ≈ 73-fold diminished in the presence of SP (33.3%. Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity. Conclusion The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors.

Perceptions of vaginal microbicides as an HIV prevention method among health care providers in KwaZulu-Natal, South Africa

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Mantell Joanne E

2007-03-01

Full Text Available Abstract Background The promise of microbicides as an HIV prevention method will not be realized if not supported by health care providers. They are the primary source of sexual health information for potential users, in both the public and private health sectors. Therefore, the aim of this study was to determine perceptions of vaginal microbicides as a potential HIV prevention method among health care providers in Durban and Hlabisa, South Africa, using a combination of quantitative and qualitative methods. Results During 2004, semi structured interviews with 149 health care providers were conducted. Fifty seven percent of hospital managers, 40% of pharmacists and 35% of nurses possessed some basic knowledge of microbicides, such as the product being used intra-vaginally before sex to prevent HIV infection. The majority of them were positive about microbicides and were willing to counsel users regarding potential use. Providers from both public and private sectors felt that an effective microbicide should be available to all people, regardless of HIV status. Providers felt that the product should be accessed over-the-counter in pharmacies and in retail stores. They also felt a need for potential microbicides to be available free of charge, and packaged with clear instructions. The media was seen by health care providers as being an effective strategy for promoting microbicides. Conclusion Overall, health care providers were very positive about the possible introduction of an effective microbicide for HIV prevention. The findings generated by this study illustrated the need for training health care providers prior to making the product accessible, as well as the importance of addressing the potential barriers to use of the product by women. These are important concerns in the health care community, and this study also served to educate them for the day when research becomes reality.

Adolescent Girls’ Communication with “Mothers” About Topical Microbicides

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Sunder, Punita K.; Ramos, Stephanie; Short, Mary B.; Rosenthal, Susan L.

2007-01-01

Study Objective Topical microbicides, a female-initiated method to protect against sexually transmitted infections (STIs) and pregnancy, will only be effective if found acceptable. Mothers may have an influence on acceptability and use among adolescent girls. The current study examined the communication between girls and mothers to understand the potential predictors and nature of conversations regarding surrogate microbicide products. Design Sexually experienced girls, 14 to 21 years, were recruited for a 6-month study examining microbicide acceptability. During face-to-face interviews, qualitative data were collected regarding communication between girls and mothers. Two independent raters coded the responses, which were organized into themes. Themes were interpreted according to the conceptual understanding of mother-daughter communication. Results Fifty percent of the 171 girls with codable responses had a conversation with their mother. Higher levels of indirect parental monitoring were related to being more likely to have a conversation. Concrete events related to the study (i.e. receiving phone call from the researcher, having an appointment, or seeing the product) or inquiries by mothers appeared to promote conversation. Barriers to conversation included the private nature of the information and relationship issues between the mother and daughter. Conversations often addressed issues related to girls’ participation in the study, although some conversations included global issues related to sexuality. Conclusions Girls may talk to their mothers about new products for STI prevention, and such conversations may provide opportunities to promote use. PMID:17174825

How important is the myeloperoxidase microbicidal system of phagocytic cells?

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Thong, Y H

1982-03-01

The myeloperoxidase system is presented by most immunology textbooks as a major microbicidal system of phagocytic cells. This theory, however, has not bee subjected to vigorous testing in the clinical arena. Of 14 patients with primary myeloperoxidase deficiency, only 3 had infectious complication. All 3 patients have more plausible explanation than myeloperoxidase deficiency for their infectious complications. Two of these patients were healthy until middle age when they developed systemic candidiasis after the onset of diabetes mellitus. The third patient was an infant with a maturational defect in neutrophil chemotaxis whose infectious complications ceased after the normalization of the chemotactic defect. The results of these "experiments of nature" indicate that the meyloperoxidase system is not a major microbicidal mechanism of phagocytic cells.

Minocycline down-regulates topical mucosal inflammation during the application of microbicide candidates.

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Liangzhu Li

Full Text Available An effective anti-human immunodeficiency virus-1 (HIV-1 microbicide should exert its action in the absence of causing aberrant activation of topical immunity that will increase the risk of HIV acquisition. In the present study, we demonstrated that the vaginal application of cellulose sulfate (CS gel induced topical mucosal inflammatory responses; the addition of minocycline to CS gel could significantly attenuate the inflammation in a mice model. The combined gel of CS plus minocycline not only reduced the production of inflammatory cytokines in cervicovaginal lavages (CVLs, also down-regulated the activation of CD4+ T cells and the recruitment of other immune cells including HIV target cells into vaginal tissues. Furthermore, an In vitro HIV-1 pseudovirus infection inhibition assay showed that the combined gel decreased the infection efficacy of different subtypes of HIV-1 pseudoviruses compared with that of CS gel alone. These results implicate that minocycline could be integrated into microbicide formulation to suppress the aberrant activation of topical mucosal immunity and enhance the safety profile during the application of microbicides.

Acceptability of vaginal microbicides among female sex workers and their intimate male partners in two Mexico-US border cities: a mixed methods analysis.

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Robertson, Angela M; Syvertsen, Jennifer L; Martinez, Gustavo; Rangel, M Gudelia; Palinkas, Lawrence A; Stockman, Jamila K; Ulibarri, Monica D; Strathdee, Steffanie A

2013-01-01

Female sex workers (FSWs) may benefit from pre-exposure prophylaxis (PrEP) including microbicides for HIV prevention. Since adherence is a key factor in PrEP efficacy, we explored microbicide acceptability and potential barriers to use within FSWs' intimate relationships in Tijuana and Ciudad Juárez, Mexico, where HIV prevalence is increasing. FSWs and their verified intimate (non-commercial) male partners completed quantitative and qualitative interviews from 2010 to 2012. Our complementary mixed methods design followed an iterative process to assess microbicide acceptability, explore related relationship dynamics and identify factors associated with concern about male partners' anger regarding microbicide use. Among 185 couples (n=370 individuals), interest in microbicides was high. In qualitative interviews with 28 couples, most participants were enthusiastic about microbicides for sex work contexts but some explained that microbicides could imply mistrust/infidelity within their intimate relationships. In the overall sample, nearly one in six participants (16%) worried that male partners would become angry about microbicides, which was associated with higher self-esteem among FSWs and lower self-esteem and past year conflicts causing injury within relationships among men. HIV prevention interventions should consider intimate relationship dynamics posing potential barriers to PrEP acceptability and adherence, involve male partners and promote risk communication skills.

Moxibustion for cephalic version: a feasibility randomised controlled trial

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Bisits Andrew

2011-09-01

Full Text Available Abstract Background Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin has been used to correct a breech presentation. Evidence of effectiveness and safety from systematic reviews is encouraging although significant heterogeneity has been found among trials. We assessed the feasibility of conducting a randomised controlled trial of moxibustion plus usual care compared with usual care to promote cephalic version in women with a breech presentation, and examined the views of women and health care providers towards implementing a trial within an Australian context. Methods The study was undertaken at a public hospital in Newcastle, New South Wales, Australia. Women at 34-36.5 weeks of gestation with a singleton breech presentation (confirmed by ultrasound, were randomised to moxibustion plus usual care or usual care alone. The intervention was administered over 10 days. Clinical outcomes included cephalic presentation at birth, the need for ECV, mode of birth; perinatal morbidity and mortality, and maternal complications. Feasibility outcomes included: recruitment rate, acceptability, compliance and a sample size for a future study. Interviews were conducted with 19 midwives and obstetricians to examine the acceptability of moxibustion, and views on the trial. Results Twenty women were randomised to the trial. Fifty one percent of women approached accepted randomisation to the trial. A trend towards an increase in cephalic version at delivery (RR 5.0; 95% CI 0.7-35.5 was found for women receiving moxibustion compared with usual care. There was also a trend towards greater success with version following ECV. Two babies were admitted to the neonatal unit from the moxibustion group. Compliance with the moxibustion protocol was acceptable with no reported side effects. Clinicians expressed the need for research to establish the safety and efficacy of moxibustion, and support for the intervention was given to

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011.

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Ruffin, Nicolas; Borggren, Marie; Euler, Zelda; Fiorino, Fabio; Grupping, Katrijn; Hallengärd, David; Javed, Aneele; Mendonca, Kevin; Pollard, Charlotte; Reinhart, David; Saba, Elisa; Sheik-Khalil, Enas; Sköld, Annette; Ziglio, Serena; Scarlatti, Gabriella; Gotch, Frances; Wahren, Britta; Shattock, Robin J

2012-07-11

Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These - necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data.

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011

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Ruffin Nicolas

2012-07-01

Full Text Available Abstract Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines; mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These – necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data.

MABGEL 1: first phase 1 trial of the anti-HIV-1 monoclonal antibodies 2F5, 4E10 and 2G12 as a vaginal microbicide.

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Georgina C Morris

Full Text Available BACKGROUND: Monoclonal antibodies (mAbs which potently neutralize a broad range of HIV isolates are potential microbicide candidates. To date, topical application of mAbs in humans and their stability in vaginal secretions has not been studied. OBJECTIVES: To assess the pharmacokinetics and safety of the mAbs 2F5, 4E10 and 2G12 when applied vaginally in women. DESIGN: A randomized, double-blind, placebo-controlled phase 1 trial. METHODS: Twenty-eight healthy, sexually abstinent women administered 2.5 g of gel daily for 12 days containing either 10 or 20 mg/g of each mAb (MABGEL or placebo. Main clinical evaluations and sampling occurred at baseline, 1, 8, and 24 hours post-1st dose and 12 and 36 hours post-12th dose. RESULTS: After adjustment for dilution factors, median levels of 2F5, 4E10 and 2G12 in vaginal secretions at 1 hour post high-dose MABGEL were 7.74, 5.28 and 7.48 mg/ml respectively. Levels of 2F5 and 4E10 declined exponentially thereafter with similar estimated half-lives (4.6 and 4.3 hours. In contrast, 2G12 levels declined more rapidly in the first 8 hours, with an estimated half-life of 1.4 hours during this period. There was no evidence of systemic absorption. There were no significant differences in local or systemic adverse event rates or vaginal flora changes (by qPCR between active and placebo gel arms. Whilst at least 1 adverse event was recorded in 96% of participants, 95% were mild and none were serious. CONCLUSIONS: Vaginal application of 50 mg of each mAb daily was safe over a 12 day period. Median mAb concentrations detected at 8 hours post dose were potentially sufficient to block HIV transmission.2G12 exhibited more rapid elimination from the human vagina than 4E10 and 2F5, likely due to poor stability of 2G12 in acidic human vaginal secretions. Further research is needed to develop mAb-based vaginal microbicides and delivery systems. TRIAL REGISTRATION: ISRCTN 64808733 UK CRN Portfolio 6470.

Broad Spectrum Microbicidal Activity of Photocatalysis by TiO2

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Yoshinobu Kubota

2013-03-01

Full Text Available Photocatalytically active titanium dioxide (TiO2 is widely used as a self-cleaning and self-disinfecting material in many applications to keep environments biologically clean. Several studies on the inactivation of bacteria and viruses by photocatalytic reactions have also been reported; however, only few studies evaluated the spectrum of the microbicidal activity with photocatalysis for various species. There is a need to confirm the expected effectiveness of disinfection by photocatalysis against multidrug-resistant bacteria and viruses. In this study, microbicidal activity of photocatalysis was evaluated by comparing the inactivation of various species of bacteria and viruses when their suspensions were dropped on the surface of TiO2-coated glass. Gram-positive bacteria, e.g., methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae, were easily inactivated by photocatalysis, whereas some gram-negative bacteria, e.g., Escherichia coli and multidrug-resistant Pseudomonas aeruginosa, were gradually inactivated by photocatalysis. Influenza virus, an enveloped virus, was significantly inactivated by photocatalysis compared with feline calicivirus, a non-enveloped virus. The effectiveness of microbicidal activity by photocatalysis may depend on the surface structure. However, they are effectively inactivated by photocatalysis on the surface of TiO2-coated glass. Our data emphasize that effective cleaning and disinfection by photocatalysis in nosocomial settings prevents pathogen transmission.

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

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Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

Acceptability of vaginal microbicides among female sex workers and their intimate male partners in two Mexico-U.S. border cities: a mixed methods analysis

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Robertson, Angela M.; Syvertsen, Jennifer L.; Martinez, Gustavo; Rangel, M. Gudelia; Palinkas, Lawrence A.; Stockman, Jamila K.; Ulibarri, Monica D.; Strathdee, Steffanie A.

2013-01-01

Background Female sex workers (FSWs) may benefit from pre-exposure prophylaxis (PrEP) including microbicides for HIV prevention. Since adherence is a key factor in PrEP efficacy, we explored microbicide acceptability and potential barriers to use within FSWs’ intimate relationships in Tijuana and Ciudad Juárez, Mexico, where HIV prevalence is increasing. Methods FSWs and their verified intimate (non-commercial) male partners completed quantitative and qualitative interviews from 2010–2012. Our complementary mixed methods design followed an iterative process to assess microbicide acceptability, explore related relationship dynamics, and identify factors associated with concern about male partners’ anger regarding microbicide use. Results Among 185 couples (n=370 individuals), interest in microbicides was high. In qualitative interviews with 28 couples, most participants were enthusiastic about microbicides for sex work contexts but some explained that microbicides could imply mistrust/infidelity within their intimate relationships. In the overall sample, nearly 1 in 6 participants (16%) worried that male partners would become angry about microbicides, which was associated with higher self-esteem among FSWs and lower self-esteem and past year conflict causing injury within relationships among men. Conclusions HIV prevention interventions should consider intimate relationship dynamics posing potential barriers to PrEP acceptability and adherence, involve male partners, and promote risk communication skills. PMID:23398385

Wordless intervention for people with epilepsy and learning disabilities (WIELD): a randomised controlled feasibility trial

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Mengoni, Silvana E; Gates, Bob; Parkes, Georgina; Wellsted, David; Barton, Garry; Ring, Howard; Khoo, Mary Ellen; Monji-Patel, Deela; Friedli, Karin; Zia, Asif; Irvine, Lisa; Durand, Marie-Anne

2016-01-01

Objective To investigate the feasibility of a full-scale randomised controlled trial of a picture booklet to improve quality of life for people with epilepsy and learning disabilities. Trial design A randomised controlled feasibility trial. Randomisation was not blinded and was conducted using a centralised secure database and a blocked 1:1 allocation ratio. Setting Epilepsy clinics in 1 English National Health Service (NHS) Trust. Participants Patients with learning disabilities and epilepsy who had: a seizure within the past 12 months, meaningful communication and a carer with sufficient proficiency in English. Intervention Participants in the intervention group used a picture booklet with a trained researcher, and a carer present. These participants kept the booklet, and were asked to use it at least twice more over 20 weeks. The control group received treatment as usual, and were provided with a booklet at the end of the study. Outcome measures 7 feasibility criteria were used relating to recruitment, data collection, attrition, potential effect on epilepsy-related quality of life (Epilepsy and Learning Disabilities Quality of Life Scale, ELDQOL) at 4-week, 12-week and 20-week follow-ups, feasibility of methodology, acceptability of the intervention and potential to calculate cost-effectiveness. Outcome The recruitment rate of eligible patients was 34% and the target of 40 participants was reached. There was minimal missing data and attrition. An intention-to-treat analysis was performed; data from the outcome measures suggest a benefit from the intervention on the ELDQOL behaviour and mood subscales at 4 and 20 weeks follow-up. The booklet and study methods were positively received, and no adverse events were reported. There was a positive indication of the potential for a cost-effectiveness analysis. Conclusions All feasibility criteria were fully or partially met, therefore confirming feasibility of a definitive trial. Trial registration number ISRCTN

Antiviral and immunological effects of tenofovir microbicide in vaginal herpes simplex virus 2 infection.

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Vibholm, Line; Reinert, Line S; Søgaard, Ole S; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Melchjorsen, Jesper

2012-11-01

The anti-HIV microbicide, tenofovir (TFV) gel, has been shown to decrease HIV-1 acquisition by 39% and reduce herpes simplex virus 2 (HSV-2) transmission by 51%. We evaluated the effect of a 1% TFV gel on genital HSV-2 infection in a mouse vaginal challenge model. In vitro plaque assays and luminex multiplex bead analysis were used, respectively, to measure postinfection vaginal viral shedding (day 1) and cytokine secretion (day 2). To further investigate the anti-HSV-2 properties, we evaluated the direct antiviral effect of TFV and the oral prodrug tenofovir disoproxil fumerate (TDF) in cell culture. Compared to placebo-treated mice, TFV-treated mice had significantly lower clinical scores, developed later genital lesions, and showed reduced vaginal viral shedding. Furthermore, the levels of IFN-γ, IL-2, TNF-α, and other cytokines were altered in the vaginal fluid following topical tenofovir treatment and subsequent HSV-2 challenge. Finally, we found that both TFV and TDF inhibited HSV-2 infection in vitro; TDF showed a 50-fold greater potency than TFV. In conclusion, we confirmed that the microbicide TFV had direct anti-HSV-2 effects in a murine vaginal challenge model. Therefore, this model would be suitable for evaluating present and future microbicide candidates. Furthermore, the present study warrants further investigation of TDF in microbicides.

A novel experience-based internet intervention for smoking cessation: feasibility randomised controlled trial

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John Powell

2016-11-01

Full Text Available Abstract Background The internet is frequently used to share experiences of health and illness, but this phenomenon has not been harnessed as an intervention to achieve health behaviour change. The aim of this study was to determine the feasibility of a randomised trial assessing the effects of a novel, experience-based website as a smoking cessation intervention. The secondary aim was to measure the potential impact on smoking behaviour of both the intervention and a comparator website. Methods A feasibility randomised controlled single-blind trial assessed a novel, experience-based website containing personal accounts of quitting smoking as a cessation intervention, and a comparator website providing factual information. Feasibility measures including recruitment, and usage of the interventions were recorded, and the following participant-reported outcomes were also measured: Smoking Abstinence Self-Efficacy Questionnaire, the single-item Motivation to Stop Scale, self-reported abstinence, quit attempts and health status outcomes. Eligible smokers from two English regions were entered into the trial and given access to their allocated website for two weeks. Results Eighty-seven smokers were randomised, 65 completed follow-up (75 %. Median usage was 15 min for the intervention, and 5 min for the comparator (range 0.5–213 min. Median logins for both sites was 2 (range 1–20. All participant-reported outcomes were similar between groups. Conclusions It was technically feasible to deliver a novel intervention harnessing the online sharing of personal experiences as a tool for smoking cessation, but recruitment was slow and actual use was relatively low, with attrition from the trial. Future work needs to maximize engagement and to understand how best to assess the value of such interventions in everyday use, rather than as an isolated ‘dose of information’. Trial registration ISRCTN29549695 DOI 10.1186/ISRCTN29549695 . Registered 17/05/2013.

Qualitative and quantitative intravaginal targeting: Key to anti-HIV-1 microbicide delivery from test tube to in vivo success

CSIR Research Space (South Africa)

Pillay, V

2012-06-01

Full Text Available employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide...

A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN–based vaginal microbicide

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Shen, Hong; Iwasaki, Akiko

2006-01-01

Topical microbicides represent a promising new approach to preventing HIV and other sexually transmitted infections. TLR agonists are ideal candidates for microbicides, as they trigger a multitude of antiviral genes effective against a broad range of viruses. Although vaginal application of CpG oligodeoxynucleotides (ODNs) and poly I:C has been shown to protect mice from genital herpes infection, the mechanism by which these agents provide protection remains unclear. Here, we show that plasmacytoid DCs (pDCs) are required for CpG ODN–mediated protection against lethal vaginal challenge with herpes simplex virus type 2 (HSV-2). Moreover, we demonstrate that cells of both the hematopoietic and stromal compartments must respond to CpG ODN via TLR9 and to type I IFNs through IFN-αβ receptor (IFN-αβR) for protection. Thus, crosstalk between pDCs and vaginal stromal cells provides for optimal microbicide efficacy. Our results imply that temporally and spatially controlled targeting of CpG ODN to pDCs and epithelial cells can potentially maximize their effectiveness as microbicides while minimizing the associated inflammatory responses. PMID:16878177

Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials.

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Schroen, Anneke T; Petroni, Gina R; Wang, Hongkun; Gray, Robert; Wang, Xiaofei F; Cronin, Walter; Sargent, Daniel J; Benedetti, Jacqueline; Wickerham, Donald L; Djulbegovic, Benjamin; Slingluff, Craig L

2010-08-01

A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual. We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting. A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency. Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (accrual rate) were consistently closed due to insufficient accrual. This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success. Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining

Does microbicide use in consumer products promote antimicrobial resistance? A critical review and recommendations for a cohesive approach to risk assessment.

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Maillard, Jean-Yves; Bloomfield, Sally; Coelho, Joana Rosado; Collier, Phillip; Cookson, Barry; Fanning, Séamus; Hill, Andrew; Hartemann, Philippe; McBain, Andrew J; Oggioni, Marco; Sattar, Syed; Schweizer, Herbert P; Threlfall, John

2013-10-01

The increasing use of microbicides in consumer products is raising concerns related to enhanced microbicide resistance in bacteria and potential cross resistance to antibiotics. The recently published documents on this topic from the European Commission have spawned much interest to better understand the true extent of the putative links for the benefit of the manufacturers, regulators, and consumers alike. This white paper is based on a 2-day workshop (SEAC-Unilever, Bedford, United Kingdom; June 2012) in the fields of microbicide usage and resistance. It identifies gaps in our knowledge and also makes specific recommendations for harmonization of key terms and refinement/standardization of methods for testing microbicide resistance to better assess the impact and possible links with cross resistance to antibiotics. It also calls for a better cohesion in research in this field. Such information is crucial to developing any risk assessment framework on microbicide use notably in consumer products. The article also identifies key research questions where there are inadequate data, which, if addressed, could promote improved knowledge and understanding to assess any related risks for consumer and environmental safety.

In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide.

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Lisa C Rohan

2010-02-01

Full Text Available Tenofovir gel has entered into clinical trials for use as a topical microbicide to prevent HIV-1 infection but has no published data regarding pre-clinical testing using in vitro and ex vivo models. To validate our findings with on-going clinical trial results, we evaluated topical tenofovir gel for safety and efficacy. We also modeled systemic application of tenofovir for efficacy.Formulation assessment of tenofovir gel included osmolality, viscosity, in vitro release, and permeability testing. Safety was evaluated by measuring the effect on the viability of vaginal flora, PBMCs, epithelial cells, and ectocervical and colorectal explant tissues. For efficacy testing, PBMCs were cultured with tenofovir or vehicle control gels and HIV-1 representing subtypes A, B, and C. Additionally, polarized ectocervical and colorectal explant cultures were treated apically with either gel. Tenofovir was added basolaterally to simulate systemic application. All tissues were challenged with HIV-1 applied apically. Infection was assessed by measuring p24 by ELISA on collected supernatants and immunohistochemistry for ectocervical explants. Formulation testing showed the tenofovir and vehicle control gels were >10 times isosmolar. Permeability through ectocervical tissue was variable but in all cases the receptor compartment drug concentration reached levels that inhibit HIV-1 infection in vitro. The gels were non-toxic toward vaginal flora, PBMCs, or epithelial cells. A transient reduction in epithelial monolayer integrity and epithelial fracture for ectocervical and colorectal explants was noted and likely due to the hyperosmolar nature of the formulation. Tenofovir gel prevented HIV-1 infection of PBMCs regardless of HIV-1 subtype. Topical and systemic tenofovir were effective at preventing HIV-1 infection of explant cultures.These studies provide a mechanism for pre-clinical prediction of safety and efficacy of formulated microbicides. Tenofovir was effective

Oral and injectable contraceptive use and HIV acquisition risk among women in four African countries: a secondary analysis of data from a microbicide trial.

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Balkus, Jennifer E; Brown, Elizabeth R; Hillier, Sharon L; Coletti, Anne; Ramjee, Gita; Mgodi, Nyaradzo; Makanani, Bonus; Reid, Cheri; Martinson, Francis; Soto-Torres, Lydia; Abdool Karim, Salim S; Chirenje, Zvavahera M

2016-01-01

To assess the effect of oral and injectable contraceptive use compared to nonhormonal contraceptive use on HIV acquisition among Southern African women enrolled in a microbicide trial. This is a prospective cohort study using data from women enrolled in HIV Prevention Trials Network protocol 035. At each quarterly visit, participants were interviewed about self-reported contraceptive use and sexual behaviors and underwent HIV testing. Cox proportional hazards regression was used to assess the effect of injectable and oral hormonal contraceptive use on HIV acquisition. The analysis included 2830 participants, of whom 106 became HIV infected (4.07 per 100 person-years). At baseline, 1546 (51%) participants reported using injectable contraceptives and 595 (21%) reported using oral contraceptives. HIV incidence among injectable, oral and nonhormonal contraceptive method users was 4.72, 2.68 and 3.83 per 100 person-years, respectively. Injectable contraceptive use was associated with a nonstatistically significant increased risk of HIV acquisition [adjusted hazard ratio (aHR)=1.17; 95% confidence interval (CI) 0.70, 1.96], while oral contraceptive use was associated with a nonstatistically significant decreased risk of HIV acquisition (aHR=0.76; 95% CI 0.37,1.55). In this secondary analysis of randomized trial data, a marginal, but nonstatistically significant, increase in HIV risk among women using injectable hormonal contraceptives was observed. No increased HIV risk was observed among women using oral contraceptives. Our findings support the World Health Organization's recommendation that women at high risk for acquiring HIV, including those using progestogen-only injectable contraception, should be strongly advised to always use condoms and other HIV prevention measures. Among Southern African women participating in an HIV prevention trial, women using injectable hormonal contraceptives had a modest increased risk of HIV acquisition; however, this association was

A novel experience-based internet intervention for smoking cessation: feasibility randomised controlled trial.

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Powell, John; Newhouse, Nikki; Martin, Angela; Jawad, Sena; Yu, Ly-Mee; Davoudianfar, Mina; Locock, Louise; Ziebland, Sue

2016-11-11

The internet is frequently used to share experiences of health and illness, but this phenomenon has not been harnessed as an intervention to achieve health behaviour change. The aim of this study was to determine the feasibility of a randomised trial assessing the effects of a novel, experience-based website as a smoking cessation intervention. The secondary aim was to measure the potential impact on smoking behaviour of both the intervention and a comparator website. A feasibility randomised controlled single-blind trial assessed a novel, experience-based website containing personal accounts of quitting smoking as a cessation intervention, and a comparator website providing factual information. Feasibility measures including recruitment, and usage of the interventions were recorded, and the following participant-reported outcomes were also measured: Smoking Abstinence Self-Efficacy Questionnaire, the single-item Motivation to Stop Scale, self-reported abstinence, quit attempts and health status outcomes. Eligible smokers from two English regions were entered into the trial and given access to their allocated website for two weeks. Eighty-seven smokers were randomised, 65 completed follow-up (75 %). Median usage was 15 min for the intervention, and 5 min for the comparator (range 0.5-213 min). Median logins for both sites was 2 (range 1-20). All participant-reported outcomes were similar between groups. It was technically feasible to deliver a novel intervention harnessing the online sharing of personal experiences as a tool for smoking cessation, but recruitment was slow and actual use was relatively low, with attrition from the trial. Future work needs to maximize engagement and to understand how best to assess the value of such interventions in everyday use, rather than as an isolated 'dose of information'. ISRCTN29549695 DOI 10.1186/ISRCTN29549695 . Registered 17/05/2013.

The use of feasibility studies for stepped-wedge cluster randomised trials: protocol for a review of impact and scope.

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Kristunas, Caroline A; Hemming, Karla; Eborall, Helen C; Gray, Laura J

2017-08-01

The stepped-wedge cluster randomised trial (SW-CRT) is a complex design, for which many decisions about key design parameters must be made during the planning. These include the number of steps and the duration of time needed to embed the intervention. Feasibility studies are likely to be useful for informing these decisions and increasing the likelihood of the main trial's success. However, the number of feasibility studies being conducted for SW-CRTs is currently unknown. This review aims to establish the number of feasibility studies being conducted for SW-CRTs and determine which feasibility issues are commonly investigated. Fully published feasibility studies for SW-CRTs will be identified, according to predefined inclusion criteria, from searches conducted in Ovid MEDLINE, Scopus, Embase and PsycINFO. To also identify and gain information on unpublished feasibility studies the following will be contacted: authors of published SW-CRTs (identified from the most recent systematic reviews); contacts for registered SW-CRTs (identified from clinical trials registries); lead statisticians of UK registered clinical trials units and researchers known to work in the area of SW-CRTs.Data extraction will be conducted independently by two reviewers. For the fully published feasibility studies, data will be extracted on the study characteristics, the rationale for the study, the process for determining progression to a main trial, how the study informed the main trial and whether the main trial went ahead. The researchers involved in the unpublished feasibility studies will be contacted to elicit the same information.A narrative synthesis will be conducted and provided alongside a descriptive analysis of the study characteristics. This review does not require ethical approval, as no individual patient data will be used. The results of this review will be published in an open-access peer-reviewed journal. © Article author(s) (or their employer(s) unless otherwise stated in

Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework.

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Sandra M Eldridge

Full Text Available We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.

Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework.

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Eldridge, Sandra M; Lancaster, Gillian A; Campbell, Michael J; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L; Bond, Christine M

2016-01-01

We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.

Toll-Like Receptors and Cytokines as Surrogate Biomarkers for Evaluating Vaginal Immune Response following Microbicide Administration

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Sadhana M. Gupta

2008-01-01

Full Text Available Topical microbicides are intended for frequent use by women in reproductive age. Hence, it is essential to evaluate their impact on mucosal immune function in the vagina. In the present study, we evaluated nisin, a naturally occurring antimicrobial peptide (AMP, for its efficacy as an intravaginal microbicide. Its effect on the vaginal immune function was determined by localizing Toll-like receptors (TLRs-3, 9 and cytokines (IL-4, 6 , 10 and TNF-α in the rabbit cervicovaginal epithelium following intravaginal administration of high dose of nisin gel for 14 consecutive days. The results revealed no alteration in the expression of TLRs and cytokines at both protein and mRNA levels. However, in SDS gel-treated group, the levels were significantly upregulated with the induction of NF-κB signalling cascade. Thus, TLRs and cytokines appear as sensitive indicators for screening immunotoxic potential of candidate microbicides.

Toll-like receptors and cytokines as surrogate biomarkers for evaluating vaginal immune response following microbicide administration.

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Gupta, Sadhana M; Aranha, Clara C; Mohanty, Madhu C; Reddy, K V R

2008-01-01

Topical microbicides are intended for frequent use by women in reproductive age. Hence, it is essential to evaluate their impact on mucosal immune function in the vagina. In the present study, we evaluated nisin, a naturally occurring antimicrobial peptide (AMP), for its efficacy as an intravaginal microbicide. Its effect on the vaginal immune function was determined by localizing Toll-like receptors (TLRs-3, 9) and cytokines (IL-4, 6 , 10 and TNF-alpha) in the rabbit cervicovaginal epithelium following intravaginal administration of high dose of nisin gel for 14 consecutive days. The results revealed no alteration in the expression of TLRs and cytokines at both protein and mRNA levels. However, in SDS gel-treated group, the levels were significantly upregulated with the induction of NF-kappaB signalling cascade. Thus, TLRs and cytokines appear as sensitive indicators for screening immunotoxic potential of candidate microbicides.

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: protocol for a feasibility randomized pilot trial.

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Johnstone, Jennie; Meade, Maureen; Marshall, John; Heyland, Daren K; Surette, Michael G; Bowdish, Dawn Me; Lauzier, Francois; Thebane, Lehana; Cook, Deborah J

2015-01-01

Probiotics are defined as live microorganisms that may confer health benefits when ingested. Meta-analysis of probiotic trials suggests a 25 % lower ventilator-associated pneumonia (VAP) and 18 % lower infection rates overall when administered to patients in the intensive care unit (ICU). However, prior trials are small, largely single center, and at high risk of bias. Before a large rigorous trial is launched, testing whether probiotics confer benefit, harm, or have no impact, a pilot trial is needed. The aim of the PROSPECT Pilot Trial is to determine the feasibility of performing a larger trial in mechanically ventilated critically ill patients investigating Lactobacillus rhamnosus GG. A priori, we determined that the feasibility of the larger trial would be based on timely recruitment, high protocol adherence, minimal contamination, and an acceptable VAP rate. Patients ≥18 years old in the ICU who are anticipated to receive mechanical ventilation for ≥72 hours will be included. Patients are excluded if they are at increased risk of probiotic-associated infection, have strict enteral medication contraindications, are pregnant, previously enrolled in a related trial, or are receiving palliative care. Following informed consent, patients are randomized in variable unspecified block sizes in a fixed 1:1 ratio, stratified by ICU, and medical, surgical, or trauma admitting diagnosis. Patients receive 1 × 10 10 colony forming units of L. rhamnosus GG (Culturelle, Locin Industries Ltd) or an identical placebo suspended in tap water administered twice daily via nasogastric tube in the ICU. Clinical and research staff, patients, and families are blinded. The primary outcomes for this pilot trial are the following: (1) recruitment success, (2) ≥90 % protocol adherence, (3) ≤5 % contamination, and (4) ~10 % VAP rate. Additional clinical outcomes are VAP, other infections, diarrhea (total, antibiotic associated, and Clostridium difficile), ICU and

A centralised public information resource for randomised trials: a scoping study to explore desirability and feasibility

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Entwistle Vikki A

2005-05-01

Full Text Available Abstract Background There are currently several concerns about the ways in which people are recruited to participate in randomised controlled trials, the low acceptance rates among people invited to participate, and the experiences of trial participants. An information resource about on-going clinical trials designed for potential and current participants could help overcome some of these problems. Methods We carried out a scoping exercise to explore the desirability and feasibility of establishing such a resource. We sought the views of a range of people including people who were considering taking part in a trial, current trial participants, people who had been asked but refused to participate in a trial, consumer group representatives and researchers who design and conduct trials. Results There was broad-based support for the concept of a centralised information resource for members of the public about on-going and recently completed clinical trials. Such an information resource could be based on a database containing standardised information for each trial relating to the purpose of the trial; the interventions being compared; the implications of participation for participants; and features indicative of scientific quality and ethical probity. The usefulness of the database could be enhanced if its search facility could allow people to enter criteria such as a disease and geographic area and be presented with all the trials relevant to them, and if optional display formats could allow them to view information in varying levels of detail. Access via the Internet was considered desirable, with complementary supported access via health information services. The development of such a resource is technically feasible, but the collation of the required information would take a significant investment of resources. Conclusion A centralised participant oriented information resource about clinical trials could serve several purposes. A more detailed

Art participation for psychosocial wellbeing during stroke rehabilitation: a feasibility randomised controlled trial.

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Morris, Jacqui H; Kelly, Chris; Joice, Sara; Kroll, Thilo; Mead, Gillian; Donnan, Peter; Toma, Madalina; Williams, Brian

2017-08-30

To examine the feasibility of undertaking a pragmatic single-blind randomised controlled trial (RCT) of a visual arts participation programme to evaluate effects on survivor wellbeing within stroke rehabilitation. Stroke survivors receiving in-patient rehabilitation were randomised to receive eight art participation sessions (n = 41) or usual care (n = 40). Recruitment, retention, preference for art participation and change in selected outcomes were evaluated at end of intervention outcome assessment and three-month follow-up. Of 315 potentially eligible participants 81 (29%) were recruited. 88% (n = 71) completed outcome and 77% (n = 62) follow-up assessments. Of eight intervention group non-completers, six had no preference for art participation. Outcome completion varied between 97% and 77%. Running groups was difficult because of randomisation timing. Effectiveness cannot be determined from this feasibility study but effects sizes suggested art participation may benefit emotional wellbeing, measured on the positive and negative affect schedule, and self-efficacy for Art (d = 0.24-0.42). Undertaking a RCT of art participation within stroke rehabilitation was feasible. Art participation may enhance self-efficacy and positively influence emotional wellbeing. These should be outcomes in a future definitive trial. A cluster RCT would ensure art groups could be reliably convened. Fewer measures, and better retention strategies are required. Implications for Rehabilitation This feasibility randomised controlled trial (RCT) showed that recruiting and retaining stroke survivors in an RCT of a visual arts participation intervention within stroke rehabilitation was feasible. Preference to participate in art activities may influence recruitment and drop-out rates, and should be addressed and evaluated fully. Art participation as part of rehabilitation may improve some aspects of post-stroke wellbeing, including positive affect and self-efficacy for art

Attitudes and perceptions towards novel objective measures of ARV-based vaginal ring use: Results from a global stakeholder survey.

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Stalter, Randy M; Tharaldson, Jenae; Owen, Derek H; Okumu, Eunice; Moench, Thomas; Mack, Natasha; Tolley, Elizabeth E; MacQueen, Kathleen M

2017-01-01

Results of recent microbicide and pre-exposure prophylaxis clinical trials have shown adherence to be a significant challenge with new HIV prevention technologies. As the vaginal ring containing dapivirine moves into two open label follow-on studies (HOPE/MTN-025 and DREAM) and other antiretroviral-based and multi-purpose prevention technology ring products advance through the development pipeline, there is a need for more accurate and reliable measures of adherence to microbicide ring products. We previously conducted a comprehensive landscape analysis to identify new technologies that could be applied to adherence measurement of vaginal rings containing antiretrovirals. To explore attitudes and perceptions towards the approaches that we identified, we conducted a survey of stakeholders with experience and expertise in microbicide and HIV prevention clinical trials. From May to July 2015 an electronic survey was distributed via email to 894 stakeholders; a total of 206 eligible individuals responded to at least one question and were included in the data analysis. Survey respondents were presented with various objective measures and asked about their perceived acceptability to trial participants, feasibility of implementation by study staff, usefulness for measuring adherence and ethical concerns. Methods that require no additional input from the participant and require no modifications to the existing ring product (i.e., measurement of residual drug or excipient, or a vaginal analyte that enters the ring) were viewed as being more acceptable to trial participants and more feasible to implement in the field. Respondents saw value in using objective measures to provide real-time feedback on adherence. However, approaches that involve unannounced home visits for sample collection or spot checks of ring use, which could provide significant value to adherence feedback efforts, were met with skepticism. Additional research on the acceptability of these methods to

Attitudes and perceptions towards novel objective measures of ARV-based vaginal ring use: Results from a global stakeholder survey.

Directory of Open Access Journals (Sweden)

Randy M Stalter

Full Text Available Results of recent microbicide and pre-exposure prophylaxis clinical trials have shown adherence to be a significant challenge with new HIV prevention technologies. As the vaginal ring containing dapivirine moves into two open label follow-on studies (HOPE/MTN-025 and DREAM and other antiretroviral-based and multi-purpose prevention technology ring products advance through the development pipeline, there is a need for more accurate and reliable measures of adherence to microbicide ring products. We previously conducted a comprehensive landscape analysis to identify new technologies that could be applied to adherence measurement of vaginal rings containing antiretrovirals. To explore attitudes and perceptions towards the approaches that we identified, we conducted a survey of stakeholders with experience and expertise in microbicide and HIV prevention clinical trials. From May to July 2015 an electronic survey was distributed via email to 894 stakeholders; a total of 206 eligible individuals responded to at least one question and were included in the data analysis. Survey respondents were presented with various objective measures and asked about their perceived acceptability to trial participants, feasibility of implementation by study staff, usefulness for measuring adherence and ethical concerns. Methods that require no additional input from the participant and require no modifications to the existing ring product (i.e., measurement of residual drug or excipient, or a vaginal analyte that enters the ring were viewed as being more acceptable to trial participants and more feasible to implement in the field. Respondents saw value in using objective measures to provide real-time feedback on adherence. However, approaches that involve unannounced home visits for sample collection or spot checks of ring use, which could provide significant value to adherence feedback efforts, were met with skepticism. Additional research on the acceptability of these

Couple-Based Psychosexual Support Following Prostate Cancer Surgery: Results of a Feasibility Pilot Randomized Control Trial.

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Robertson, Jane; McNamee, Phillip; Molloy, Gerry; Hubbard, Gill; McNeill, Alan; Bollina, Prasad; Kelly, Daniel; Forbat, Liz

2016-08-01

Surgery for prostate cancer can result in distressing side effects such as sexual difficulties, which are associated with lower levels of dyadic functioning. The study developed and tested an intervention to address sexual, relational, and emotional aspects of the relationship after prostate cancer by incorporating elements of family systems theory and sex therapy. To develop and test the feasibility and acceptability of relational psychosexual treatment for couples with prostate cancer, determine whether a relational-psychosexual intervention is feasible and acceptable for couples affected by prostate cancer, and determine the parameters for a full-scale trial. Forty-three couples were recruited for this pilot randomized controlled trial and received a six-session manual-based psychosexual intervention or usual care. Outcomes were measured before, after, and 6 months after the intervention. Acceptability and feasibility were established from recruitment and retention rates and adherence to the manual. The primary outcome measurement was the sexual bother subdomain of the Expanded Prostate Cancer Index Composite. The Hospital Anxiety and Depression Scale and the 15-item Systemic Clinical Outcome and Routine Evaluation (SCORE-15) were used to measure emotional and relational functioning, respectively. The intervention was feasible and acceptable. The trial achieved adequate recruitment (38%) and retention (74%) rates. The intervention had a clinically and statistically significant effect on sexual bother immediately after the intervention. Small decreases in anxiety and depression were observed for the intervention couples, although these were not statistically significant. Practitioners reported high levels of adherence to the manual. The clinically significant impact on sexual bother and positive feedback on the study's feasibility and acceptability indicate that the intervention should be tested in a multicenter trial. The SCORE-15 lacked specificity for this

Willingness to Use Microbicides Is Affected by the Importance of Product Characteristics, Use Parameters, and Protective Properties

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Morrow, Kathleen M.; Fava, Joseph L.; Rosen, Rochelle K.; Vargas, Sara; Barroso, Candelaria; Christensen, Anna L.; Woodsong, Cynthia; Severy, Lawrence

2008-01-01

Background Along with efficacy, a microbicide’s acceptability will be integral to its impact on the pandemic. Understanding Product Characteristics that users find most acceptable and determining who will use which type of product are key to optimizing use effectiveness. Objectives To evaluate psychometrically the Important Microbicide Characteristics (IMC) instrument and examine its relationship to willingness to use microbicides. Results Exploratory and confirmatory factor analyses revealed 2 IMC subscales (Cronbach’s coefficient α: Product Characteristics subscale (α = 0.84) and Protective Properties subscale (α = 0.89)). Significant differences on Product Characteristics subscale scores were found for history of douching (P = 0.002) and employment status (P = 0.001). Whether a woman used a method to prevent pregnancy or sexually transmitted disease (STD) in the last 3 months (P IMC instrument serves as a template for future studies of candidate microbicides. PMID:17325607

Direct Microbicidal Activity of Cytotoxic T-Lymphocytes

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Paul Oykhman

2010-01-01

Full Text Available Cytotoxic T-lymphocytes (CTL are famous for their ability to kill tumor, allogeneic and virus-infected cells. However, an emerging literature has now demonstrated that CTL also possess the ability to directly recognize and kill bacteria, parasites, and fungi. Here, we review past and recent findings demonstrating the direct microbicidal activity of both CD4+ and CD8+ CTL against various microbial pathogens. Further, this review will outline what is known regarding the mechanisms of direct killing and their underlying signalling pathways.

Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry.

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Rinehart, Matthew; Grab, Sheila; Rohan, Lisa; Katz, David; Wax, Adam

2014-01-01

We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery.

First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy.

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Peter A Anton

Full Text Available Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo.HIV-1 seronegative, sexually-abstinent men and women (N = 36 were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25% with placebo gel (1∶1∶1. Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint.All 36 subjects enrolled completed the 7-14 week trial (100% retention including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm. There were 81 Grade 1 adverse events (AEs and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1(BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration.Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV

Testing of viscous anti-HIV microbicides using Lactobacillus

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Moncla, B.J.; Pryke, K.; Rohan, L. C.; Yang, H.

2011-01-01

The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30 min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To...

Feasibility of a Trial on Improvisational Music Therapy for Children with Autism Spectrum Disorder.

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Geretsegger, Monika; Holck, Ulla; Bieleninik, Łucja; Gold, Christian

2016-01-01

To conduct generalizable, rigorously designed, adequately powered trials investigating music therapy and other complex interventions, it is essential that study procedures are feasible and acceptable for participants. To date, only limited evidence on feasibility of trial designs and strategies to facilitate study implementation is available in the music therapy literature. Using data from a subsample of a multi-center RCT on improvisational music therapy (IMT) for autism spectrum disorder (ASD), this study aims to evaluate feasibility of study procedures, evaluate safety, document concomitant treatment, and report consistency of individuals' trends over time in chosen outcome measures. Children with ASD aged between 4 years, 0 months, and 6 years, 11 months, were randomly assigned to one of three conditions: one (low intensity) vs. three weekly IMT sessions (high intensity) for five months vs. standard care. Feasibility was evaluated by examining recruitment, implementation of study conditions, assessment procedures, blinding, and retention; we also evaluated safety, concomitant treatment, and consistency of changes in standardized scales completed by blinded assessors and parents before and 5 months after randomization. Within this subsample (n = 15), recruitment rates, session attendance in the high-intensity condition, and consistency between outcome measures were lower than expected. Session attendance in the low-intensity and control conditions, treatment fidelity, measurement completion, blinding, retention, and safety met a priori thresholds for feasibility. By discussing strategies to improve recruitment and to minimize potential burden on study participants, referrers, and researchers, this study helps build knowledge about designing and implementing trials successfully. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Transient Ischaemic Attack 999 Emergency Referral (TIER: a cluster randomised feasibility trial facilitated by data linkage

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Anne Seagrove

2017-04-01

Will inform full trial development using criteria: intervention acceptability to practitioners and patients; trial design feasibility; outcome data completeness. Conclusions • If indicated, full trial conducted • If not, but positive results - advise intervention development for immediate implementation • If not, but negative results – advise delivery of intervention should cease.

Post-use assay of vaginal rings (VRs) as a potential measure of clinical trial adherence.

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Spence, Patrick; Nel, Annalene; van Niekerk, Neliëtte; Derrick, Tiffany; Wilder, Susan; Devlin, Bríd

2016-06-05

Adherence measurement for microbicide use within the clinical trial setting remains a challenge for the HIV prevention field. This paper describes an assay method used for determining residual dapivirine levels in post-use vaginal rings from clinical trials conducted with the Dapivirine Vaginal Matrix Ring-004 developed by the International Partnership for Microbicides to prevent male to female HIV transmission. Post-use assay results from three Ring-004 clinical trials showed that of the 25mg drug load, approximately 4mg of dapivirine is released from the matrix ring over a 28-day use period. Data obtained by both in vitro and in vivo studies indicate that dapivirine is released according to a diffusion mechanism, as determined by conformance of both data sets to the Higuchi equation. This, coupled with the low variability associated with batch production over two manufacturing sites and 20 batches of material, provides evidence that post-use ring analysis can contribute to the assessment of adherence to ring use. Limitations of this method include the potential of intra-participant and inter-participant variability and uncertainty associated with measuring the low amount of dapivirine actually released relative to the drug load. Therefore, residual drug levels should not serve as the only direct measurement for microbicide adherence in vaginal ring clinical trials but should preferably be used as part of a multi-pronged approach towards understanding and assessing adherence to vaginal ring use. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Inhibition of Human Immunodeficiency Virus Type 1 Infection by the Candidate Microbicide Dapivirine, a Nonnucleoside Reverse Transcriptase Inhibitor▿

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Fletcher, P.; Harman, S.; Azijn, H.; Armanasco, N.; Manlow, P.; Perumal, D.; de Bethune, M.-P.; Nuttall, J.; Romano, J.; Shattock, R.

2008-01-01

Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal micr...

Facilitating return to work through early specialist health-based interventions (FRESH): protocol for a feasibility randomised controlled trial.

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Radford, Kathryn A; Phillips, Julie; Jones, Trevor; Gibson, Ali; Sutton, Chris; Watkins, Caroline; Sach, Tracey; Duley, Lelia; Walker, Marion; Drummond, Avril; Hoffman, Karen; O'Connor, Rory; Forshaw, Denise; Shakespeare, David

2015-01-01

Over one million people sustain traumatic brain injury each year in the UK and more than 10 % of these are moderate or severe injuries, resulting in cognitive and psychological problems that affect the ability to work. Returning to work is a primary rehabilitation goal but fewer than half of traumatic brain injury survivors achieve this. Work is a recognised health service outcome, yet UK service provision varies widely and there is little robust evidence to inform rehabilitation practice. A single-centre cohort comparison suggested better work outcomes may be achieved through early occupational therapy targeted at job retention. This study aims to determine whether this intervention can be delivered in three new trauma centres and to conduct a feasibility, randomised controlled trial to determine whether its effects and cost effectiveness can be measured to inform a definitive trial. Mixed methods study, including feasibility randomised controlled trial, embedded qualitative studies and feasibility economic evaluation will recruit 102 people with traumatic brain injury and their nominated carers from three English UK National Health Service (NHS) trauma centres. Participants will be randomised to receive either usual NHS rehabilitation or usual rehabilitation plus early specialist traumatic brain injury vocational rehabilitation delivered by an occupational therapist. The primary objective is to assess the feasibility of conducting a definitive trial; secondary objectives include measurement of protocol integrity (inclusion/exclusion criteria, intervention adherence, reasons for non-adherence) recruitment rate, the proportion of eligible patients recruited, reasons for non-recruitment, spectrum of TBI severity, proportion of and reasons for loss to follow-up, completeness of data collection, gains in face-to-face V s postal data collection and the most appropriate methods of measuring primary outcomes (return to work, retention) to determine the sample size for a

Quantitative perceptual differences among over-the-counter vaginal products using a standardized methodology: implications for microbicide development.

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Mahan, Ellen D; Morrow, Kathleen M; Hayes, John E

2011-08-01

Increasing prevalence of HIV infection among women worldwide has motivated the development of female-initiated prevention methods, including gel-based microbicides. User acceptability is vital for microbicide success; however, varying cultural vaginal practices indicate multiple formulations must be developed to appeal to different populations. Perceptual attributes of microbicides have been identified as primary drivers of acceptability; however, previous studies do not allow for direct comparison of these qualities between multiple formulations. Six vaginal products were analyzed ex vivo using descriptive analysis. Perceptual attributes of samples were identified by trained participants (n=10) and rated quantitatively using scales based on a panel-developed lexicon. Data were analyzed using two-way ANOVAs for each attribute; product differences were assessed via Tukey's honestly significant difference test. Significant differences were found between products for multiple attributes. Patterns were also seen for attributes across intended product usage (i.e., contraceptive, moisturizer or lubricant). For example, Options© Gynol II® (Caldwell Consumer Health, LLC) was significantly stickier and grainier than other products. Descriptive analysis, a quantitative approach that is based on consensus lexicon usage among participants, successfully quantified perceptual differences among vaginal products. Since perceptual attributes of products can be directly compared quantitatively, this study represents a novel approach that could be used to inform rational design of microbicides. Copyright © 2011 Elsevier Inc. All rights reserved.

Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry.

Directory of Open Access Journals (Sweden)

Matthew Rinehart

Full Text Available We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery.

Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor.

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Fletcher, P; Harman, S; Azijn, H; Armanasco, N; Manlow, P; Perumal, D; de Bethune, M-P; Nuttall, J; Romano, J; Shattock, R

2009-02-01

Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal microbicide. In tissue compatibility studies, dapivirine was well tolerated by epithelial cells, T cells, macrophages, and cervical tissue explants. Dapivirine demonstrated potent dose-dependent inhibitory effects against a broad panel of HIV type 1 isolates from different clades. Furthermore, dapivirine demonstrated potent activity against a wide range of NNRTI-resistant isolates. In human cervical explant cultures, dapivirine was able not only to inhibit direct infection of mucosal tissue but also to prevent the dissemination of the virus by migratory cells. Activity was retained in the presence of semen or a cervical mucus simulant. Furthermore, dapivirine demonstrated prolonged inhibitory effects: it was able to prevent both localized and disseminated infection for as long as 6 days posttreatment. The prolonged protection observed following pretreatment of genital tissue and the lack of observable toxicity suggest that dapivirine has considerable promise as a potential microbicide candidate.

Inhibition of Human Immunodeficiency Virus Type 1 Infection by the Candidate Microbicide Dapivirine, a Nonnucleoside Reverse Transcriptase Inhibitor▿

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Fletcher, P.; Harman, S.; Azijn, H.; Armanasco, N.; Manlow, P.; Perumal, D.; de Bethune, M.-P.; Nuttall, J.; Romano, J.; Shattock, R.

2009-01-01

Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal microbicide. In tissue compatibility studies, dapivirine was well tolerated by epithelial cells, T cells, macrophages, and cervical tissue explants. Dapivirine demonstrated potent dose-dependent inhibitory effects against a broad panel of HIV type 1 isolates from different clades. Furthermore, dapivirine demonstrated potent activity against a wide range of NNRTI-resistant isolates. In human cervical explant cultures, dapivirine was able not only to inhibit direct infection of mucosal tissue but also to prevent the dissemination of the virus by migratory cells. Activity was retained in the presence of semen or a cervical mucus simulant. Furthermore, dapivirine demonstrated prolonged inhibitory effects: it was able to prevent both localized and disseminated infection for as long as 6 days posttreatment. The prolonged protection observed following pretreatment of genital tissue and the lack of observable toxicity suggest that dapivirine has considerable promise as a potential microbicide candidate. PMID:19029331

Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an HIV microbicide.

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Woolfson, A David; Malcolm, R Karl; Morrow, Ryan J; Toner, Clare F; McCullagh, Stephen D

2006-11-15

TMC 120 (Dapivirine) is a potent non-nucleoside reverse transcriptase inhibitor that is presently being developed as a vaginal HIV microbicide. To date, most vaginal microbicides under clinical investigation have been formulated as single-dose semi-solid gels, designed for application to the vagina before each act of intercourse. However, a clear rationale exists for providing long-term, controlled release of vaginal microbicides in order to afford continuous protection against heterosexually transmitted HIV infection and to improve user compliance. In this study we report on the incorporation of various pharmaceutical excipients into TMC 120 silicone, reservoir-type intravaginal rings (IVRs) in order to modify the controlled release characteristics of the microbicide. The results demonstrate that TMC 120 is released in zero-order fashion from the rings over a 28-day period and that release parameters could be modified by the inclusion of release-modifying excipients in the IVR. The hydrophobic liquid excipient isopropyl myristate had little effect on steady-state daily release rates, but did increase the magnitude and duration of burst release in proportion to excipient loading in the IVR. By comparison, the hydrophobic liquid poly(dimethylsiloxane) had little effect on TMC 120 release parameters. A hydrophilic excipient, lactose, had the surprising effect of decreasing TMC 120 burst release while increasing the apparent steady-state daily release in a concentration-dependent manner. Based on previous cell culture data and vaginal physiology, TMC120 is released from the various ring formulations in amounts potentially capable of maintaining a protective vaginal concentration. It is further predicted that the observed release rates may be maintained for at least a period of 1 year from a single ring device. TMC 120 release profiles and the mechanical properties of rings could be modified by the physicochemical nature of hydrophobic and hydrophilic excipients

Enhancing pediatric clinical trial feasibility through the use of Bayesian statistics.

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Huff, Robin A; Maca, Jeff D; Puri, Mala; Seltzer, Earl W

2017-11-01

BackgroundPediatric clinical trials commonly experience recruitment challenges including limited number of patients and investigators, inclusion/exclusion criteria that further reduce the patient pool, and a competitive research landscape created by pediatric regulatory commitments. To overcome these challenges, innovative approaches are needed.MethodsThis article explores the use of Bayesian statistics to improve pediatric trial feasibility, using pediatric Type-2 diabetes as an example. Data for six therapies approved for adults were used to perform simulations to determine the impact on pediatric trial size.ResultsWhen the number of adult patients contributing to the simulation was assumed to be the same as the number of patients to be enrolled in the pediatric trial, the pediatric trial size was reduced by 75-78% when compared with a frequentist statistical approach, but was associated with a 34-45% false-positive rate. In subsequent simulations, greater control was exerted over the false-positive rate by decreasing the contribution of the adult data. A 30-33% reduction in trial size was achieved when false-positives were held to less than 10%.ConclusionReducing the trial size through the use of Bayesian statistics would facilitate completion of pediatric trials, enabling drugs to be labeled appropriately for children.

Feasibility, Process, and Outcomes of Cardiovascular Clinical Trial Data Sharing: A Reproduction Analysis of the SMART-AF Trial.

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Gay, Hawkins C; Baldridge, Abigail S; Huffman, Mark D

2017-12-01

Data sharing is as an expanding initiative for enhancing trust in the clinical research enterprise. To evaluate the feasibility, process, and outcomes of a reproduction analysis of the THERMOCOOL SMARTTOUCH Catheter for the Treatment of Symptomatic Paroxysmal Atrial Fibrillation (SMART-AF) trial using shared clinical trial data. A reproduction analysis of the SMART-AF trial was performed using the data sets, data dictionary, case report file, and statistical analysis plan from the original trial accessed through the Yale Open Data Access Project using the SAS Clinical Trials Data Transparency platform. SMART-AF was a multicenter, single-arm trial evaluating the effectiveness and safety of an irrigated, contact force-sensing catheter for ablation of drug refractory, symptomatic paroxysmal atrial fibrillation in 172 participants recruited from 21 sites between June 2011 and December 2011. Analysis of the data was conducted between December 2016 and April 2017. Effectiveness outcomes included freedom from atrial arrhythmias after ablation and proportion of participants without any arrhythmia recurrence over the 12 months of follow-up after a 3-month blanking period. Safety outcomes included major adverse device- or procedure-related events. The SMART AF trial participants' mean age was 58.7 (10.8) years, and 72% were men. The time from initial proposal submission to final analysis was 11 months. Freedom from atrial arrhythmias at 12 months postprocedure was similar compared with the primary study report (74.0%; 95% CI, 66.0-82.0 vs 76.4%; 95% CI, 68.7-84.1). The reproduction analysis success rate was higher than the primary study report (65.8%; 95% CI 56.5-74.2 vs 75.6%; 95% CI, 67.2-82.5). Adverse events were minimal and similar between the 2 analyses, but contact force range or regression models could not be reproduced. The feasibility of a reproduction analysis of the SMART-AF trial was demonstrated through an academic data-sharing platform. Data sharing can be

Synergistic activity profile of carbosilane dendrimer G2-STE16 in combination with other dendrimers and antiretrovirals as topical anti-HIV-1 microbicide.

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Sepúlveda-Crespo, Daniel; Lorente, Raquel; Leal, Manuel; Gómez, Rafael; De la Mata, Francisco J; Jiménez, José Luis; Muñoz-Fernández, M Ángeles

2014-04-01

Polyanionic carbosilane dendrimers represent opportunities to develop new anti-HIV microbicides. Dendrimers and antiretrovirals (ARVs) acting at different stages of HIV replication have been proposed as compounds to decrease new HIV infections. Thus, we determined the potential use of our G2-STE16 carbosilane dendrimer in combination with other carbosilane dendrimers and ARVs for the use as topical microbicide against HIV-1. We showed that these combinations obtained 100% inhibition and displayed a synergistic profile against different HIV-1 isolates in our model of TZM.bl cells. Our results also showed their potent activity in the presence of an acidic vaginal or seminal fluid environment and did not activate an inflammatory response. This study is the first step toward exploring the use of different anionic carbosilane dendrimers in combination and toward making a safe microbicide. Therefore, our results support further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicide. This paper describes the first steps toward the use of anionic carbosilane dendrimers in combination with antivirals to address HIV-1, paving the way to further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicides. © 2014.

HIV-1 pseudovirus neutralisation by a natural compound: a potential microbicide

CSIR Research Space (South Africa)

Van den Berg, N

2011-02-01

Full Text Available . The mode of action of the compound is, however, yet to be determined. The aim is to develop a microbicide based on an indigenous plant for people infected with HIV-1. The compound will also be screened against other HIV-1 subtypes to test the neutralisation...

Vaginal microbicides save money: a model of cost-effectiveness in South Africa and the USA.

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Verguet, S; Walsh, J A

2010-06-01

To determine the hypothetical cost-effectiveness of vaginal microbicides preventing male to female HIV transmission. A mathematical epidemiological and cost-effectiveness model using data from South Africa and the USA was used. The prospective 1-year-long intervention targeted a general population of women in a city of 1,000,000 inhabitants in two very different epidemiological settings, South Africa with a male HIV prevalence of 18.80% and the USA with a male HIV prevalence of 0.72%. The base case scenario assumes a microbicide effective at 55%, used in 30% of sexual episodes at a retail price for the public sector in South Africa of US$0.51 per use and in the USA of US$2.23 per use. In South Africa, over 1 year, the intervention would prevent 1908 infections, save US$6712 per infection averted as compared with antiretroviral treatment. In the USA, it would be more costly: over 1 year, the intervention would prevent 21 infections, amounting to a net cost per infection averted of US$405,077. However, in the setting of Washington DC, with a higher HIV prevalence, the same intervention would prevent 93 infections and save US$91,176 per infection averted. Sensitivity analyses were conducted and even a microbicide with a low effectiveness of 30% would still save healthcare costs in South Africa. A microbicide intervention is likely to be very cost-effective in a country undergoing a high-level generalised epidemic such as South Africa, but is unlikely to be cost-effective in a developed country presenting epidemiological features similar to the USA unless the male HIV prevalence exceeds 2.4%.

Entry inhibitor-based microbicides are active in vitro against HIV-1 isolates from multiple genetic subtypes

International Nuclear Information System (INIS)

Ketas, Thomas J.; Schader, Susan M.; Zurita, Juan; Teo, Esther; Polonis, Victoria; Lu Min; Klasse, Per Johan; Moore, John P.

2007-01-01

Inhibitors of viral entry are under consideration as topical microbicides to prevent HIV-1 sexual transmission. Small molecules targeting HIV-1 gp120 (BMS-378806) or CCR5 (CMPD167), and a peptide fusion inhibitor (C52L), each blocks vaginal infection of macaques by a SHIV. A microbicide, however, must be active against multiple HIV-1 variants. We therefore tested BMS-C (a BMS-378806 derivative), CMPD167, C52L and the CXCR4 ligand AMD3465, alone and in combination, against 25 primary R5, 12 X4 and 7 R5X4 isolates from subtypes A-G. At high concentrations (0.1-1 μM), the replication of most R5 isolates in human donor lymphocytes was inhibited by > 90%. At lower concentrations, double and triple combinations were more effective than individual inhibitors. Similar results were obtained with X4 viruses when AMD3465 was substituted for CMPD167. The R5X4 viruses were inhibited by combining AMD3465 with CMPD167, or by the coreceptor-independent compounds. Thus, combining entry inhibitors may improve microbicide effectiveness

Maximising the impact of qualitative research in feasibility studies for randomised controlled trials: guidance for researchers

NARCIS (Netherlands)

O’Cathain, A.; Hoddinott, P.; Lewin, S.; Thomas, K.J.; Young, B.; Adamson, J.; Jansen, J.F.M.; Mills, N.; Moore, G.; Donovan, J.L.

2015-01-01

Feasibility studies are increasingly undertaken in preparation for randomised controlled trials in order to explore uncertainties and enable trialists to optimise the intervention or the conduct of the trial. Qualitative research can be used to examine and address key uncertainties prior to a full

In vitro profiling of the vaginal permeation potential of anti-HIV microbicides and the influence of formulation excipients.

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Grammen, Carolien; Augustijns, Patrick; Brouwers, Joachim

2012-11-01

In the search for an effective anti-HIV microbicidal gel, limited drug penetration into the vaginal submucosa is a possible reason for failed protection against HIV transmission. To address this issue in early development, we here describe a simple in vitro strategy to predict the tissue permeation potential of vaginally applied drugs, based on solubility, permeability and flux assessment. We demonstrated this approach for four model microbicides (tenofovir, darunavir, saquinavir mesylate and dapivirine) and additionally examined the influence of formulation excipients on the permeation potential. When formulated in an aqueous-based HEC gel, high flux values across an HEC-1A cell layer were reached by tenofovir, as a result of its high aqueous solubility. In contrast, saquinavir and dapivirine fluxes remained low due to poor permeability and solubility, respectively. These low fluxes suggest limited in vivo tissue penetration, possibly leading to lack of efficacy. Dapivirine fluxes, however, could be enhanced up to 30-fold, by including formulation excipients such as polyethylene glycol 1000 (20%) or cyclodextrins (5%) in the HEC gels. Alternative formulations, i.e. emulsions or silicone elastomer gels, were less effective in flux enhancement compared to cyclodextrin-HEC gels. In conclusion, implementing the proposed solubility and permeability profiling in early microbicide development may contribute to the successful selection of promising microbicide candidates and appropriate formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Feasibility trial of a film-based educational intervention for increasing boys' and girls' intentions to avoid teenage pregnancy: Study protocol.

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Lohan, Maria; Aventin, Aine; Maguire, Lisa; Clarke, Mike; Linden, Mark; McDaid, Lisa

2014-01-01

The World Health Organisation, amongst others, recognises that adolescent men have a vital yet neglected role in reducing teenage pregnancies and that there is a pressing need for educational interventions designed especially for them. This study seeks to fill this gap by determining the feasibility of conducting an effectiveness trial of the If I Were Jack intervention in post-primary schools. This 4-week intervention aims to increase teenagers' intentions to avoid unintended pregnancy and addresses gender inequalities in sex education by explicitly focusing on young men. A cluster randomised feasibility trial with embedded process evaluation will determine: recruitment, participation and retention rates; quality of implementation; acceptability and feasibility of the intervention and trial procedures; and costs.

Effectiveness of physiotherapy in Parkinson's disease: the feasibility of a randomised controlled trial.

NARCIS (Netherlands)

Keus, S.H.J.; Bloem, B.R.; Hilten, J.J. van; Ashburn, A.; Munneke, M.

2007-01-01

To study the feasibility of a large randomised controlled trial (RCT) evaluating the effectiveness of physiotherapy in Parkinson's disease (PD), 173 patients were asked to participate in a study with random allocation to best practice physiotherapy, or to no physiotherapy. The primary outcome

Are participants concerned about privacy and security when using short message service to report product adherence in a rectal microbicide trial?

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Giguere, Rebecca; Brown, William; Balán, Ivan C; Dolezal, Curtis; Ho, Titcha; Sheinfil, Alan; Ibitoye, Mobolaji; Lama, Javier R; McGowan, Ian; Cranston, Ross D; Carballo-Diéguez, Alex

2018-04-01

During a Phase 2 rectal microbicide trial, men who have sex with men and transgender women (n = 187) in 4 countries (Peru, South Africa, Thailand, United States) reported product use daily via short message service (SMS). To prevent disclosure of study participation, the SMS system program included privacy and security features. We evaluated participants' perceptions of privacy while using the system and acceptability of privacy/security features. To protect privacy, the SMS system: (1) confirmed participant availability before sending the study questions, (2) required a password, and (3) did not reveal product name or study participation. To ensure security, the system reminded participants to lock phone/delete messages. A computer-assisted self-interview (CASI), administered at the final visit, measured burden of privacy and security features and SMS privacy concerns. A subsample of 33 participants underwent an in-depth interview (IDI). Based on CASI, 85% had no privacy concerns; only 5% were very concerned. Most were not bothered by the need for a password (73%) or instructions to delete messages (82%). Based on IDI, reasons for low privacy concerns included sending SMS in private or feeling that texting would not draw attention. A few IDI participants found the password unnecessary and more than half did not delete messages. Most participants were not concerned that the SMS system would compromise their confidentiality. SMS privacy and security features were effective and not burdensome. Short ID-related passwords, ambiguous language, and reminders to implement privacy and security-enhancing behaviors are recommended for SMS systems.

Task-Oriented Training with Computer Games for People with Rheumatoid Arthritis or Hand Osteoarthritis: A Feasibility Randomized Controlled Trial.

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Srikesavan, Cynthia Swarnalatha; Shay, Barbara; Szturm, Tony

2016-09-13

To examine the feasibility of a clinical trial on a novel, home-based task-oriented training with conventional hand exercises in people with rheumatoid arthritis or hand osteoarthritis. To explore the experiences of participants who completed their respective home exercise programmes. Thirty volunteer participants aged between 30 and 60 years and diagnosed with rheumatoid arthritis or hand osteoarthritis were proposed for a single-center, assessor-blinded, randomized controlled trial ( ClinicalTrials.gov : NCT01635582). Participants received task-oriented training with interactive computer games and objects of daily life or finger mobility and strengthening exercises. Both programmes were home based and were done four sessions per week with 20 minutes each session for 6 weeks. Major feasibility outcomes were number of volunteers screened, randomized, and retained; completion of blinded assessments, exercise training, and home exercise sessions; equipment and data management; and clinical outcomes of hand function. Reaching the recruitment target in 18 months and achieving exercise compliance >80% were set as success criteria. Concurrent with the trial, focus group interviews explored experiences of those participants who completed their respective programmes. After trial initiation, revisions in inclusion criteria were required to promote recruitment. A total of 17 participants were randomized and 15 were retained. Completion of assessments, exercise training, and home exercise sessions; equipment and data collection and management demonstrated excellent feasibility. Both groups improved in hand function outcomes and exercise compliance was above 85%. Participants perceived both programmes as appropriate and acceptable. Participants who completed task-oriented training also agreed that playing different computer games was enjoyable, engaging, and motivating. Findings demonstrate initial evidence on recruitment, feasibility of trial procedures, and acceptability of

Feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus™ for frail elderly: study protocol for a feasibility trial.

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Gomes, Gisele Cristine Vieira; Bacha, Jéssica Maria Ribeiro; do Socorro Simões, Maria; Lin, Sumika Mori; Viveiro, Larissa Alamino Pereira; Varise, Eliana Maria; Filho, Wilson Jacob; Pompeu, José Eduardo

2017-01-01

Frailty can be defined as a medical syndrome with multiple causes and contributors, characterized by diminished strength and endurance and reduced physiological function that increases the vulnerability to develop functional dependency and/or death. Studies have shown that the most commonly studied exercise protocol for frail older adults is the multimodal training. Interactive video games (IVGs) involve tasks in virtual environments that combine physical and cognitive demands in an attractive and challenging way. The aim of this study will be to evaluate the feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus TM (NWFP) for frail older adults. The study is a randomized controlled, parallel group, feasibility trial. Participants will be randomly assigned to the experimental group (EG) and control group (CG). The EG will participate in 14 training sessions, each lasting 50 min, twice a week. In each training session, the participants will play five games, with three attempts at each game. The first attempt will be performed with the assistance of a physical therapist to correct the movements and posture of the patients and subsequent attempts will be performed independently. Scores achieved in the games will be recorded. The participants will be evaluated by a blinded physical therapist at three moments: before and after intervention and 30 days after the end of the intervention (follow-up). We will assess the feasibility, acceptability, safety, and clinical outcomes (postural control, gait, cognition, quality of life, mood, and fear of falling). Due to the deficiencies in multiple systems, studies have shown that multimodal interventions including motor-cognitive stimulation can improve the mobility of frail elderly adults. IVGs, among them the NWFP, are considered as a multimodal motor-cognitive intervention that can potentially improve motor and cognitive functions in the frail elderly. However, there is still no evidence

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial.

Science.gov (United States)

Street, Alexander J; Magee, Wendy L; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jorg

2018-01-01

To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Participants' homes across Cambridgeshire, UK. Eleven people with stroke and arm hemiparesis, 3-60 months post stroke, following discharge from community rehabilitation. Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. ClinicalTrials.gov identifier NCT 02310438.

Wordless intervention for people with epilepsy and learning disabilities (WIELD): a randomised controlled feasibility trial.

Science.gov (United States)

Mengoni, Silvana E; Gates, Bob; Parkes, Georgina; Wellsted, David; Barton, Garry; Ring, Howard; Khoo, Mary Ellen; Monji-Patel, Deela; Friedli, Karin; Zia, Asif; Irvine, Lisa; Durand, Marie-Anne

2016-11-10

To investigate the feasibility of a full-scale randomised controlled trial of a picture booklet to improve quality of life for people with epilepsy and learning disabilities. A randomised controlled feasibility trial. Randomisation was not blinded and was conducted using a centralised secure database and a blocked 1:1 allocation ratio. Epilepsy clinics in 1 English National Health Service (NHS) Trust. Patients with learning disabilities and epilepsy who had: a seizure within the past 12 months, meaningful communication and a carer with sufficient proficiency in English. Participants in the intervention group used a picture booklet with a trained researcher, and a carer present. These participants kept the booklet, and were asked to use it at least twice more over 20 weeks. The control group received treatment as usual, and were provided with a booklet at the end of the study. 7 feasibility criteria were used relating to recruitment, data collection, attrition, potential effect on epilepsy-related quality of life (Epilepsy and Learning Disabilities Quality of Life Scale, ELDQOL) at 4-week, 12-week and 20-week follow-ups, feasibility of methodology, acceptability of the intervention and potential to calculate cost-effectiveness. The recruitment rate of eligible patients was 34% and the target of 40 participants was reached. There was minimal missing data and attrition. An intention-to-treat analysis was performed; data from the outcome measures suggest a benefit from the intervention on the ELDQOL behaviour and mood subscales at 4 and 20 weeks follow-up. The booklet and study methods were positively received, and no adverse events were reported. There was a positive indication of the potential for a cost-effectiveness analysis. All feasibility criteria were fully or partially met, therefore confirming feasibility of a definitive trial. ISRCTN80067039. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

Acceptability of microbicidal vaginal rings and oral pre-exposure prophylaxis for HIV prevention among female sex workers in a high-prevalence US city.

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Peitzmeier, Sarah M; Tomko, Catherine; Wingo, Erin; Sawyer, Anne; Sherman, Susan G; Glass, Nancy; Beyrer, Chris; Decker, Michele R

2017-11-01

Biomedical HIV prevention tools including oral pre-exposure prophylaxis (PrEP) and vaginal microbicidal rings hold unique value for high-risk women who may have limited capacity for condom negotiation, including the key populations of sex workers and drug users. Commercial sex is a PrEP indicator in CDC guidelines, yet little is known about female sex workers' (FSWs) knowledge of and attitudes toward PrEP or the recently developed monthly vaginal microbicide rings. We describe knowledge and attitudes toward PrEP and microbicide rings in a sample of 60 mostly drug-using FSWs in Baltimore, Maryland, a high HIV-prevalence US city. Just 33% had heard of PrEP, but 65% were interested in taking daily oral PrEP and 76% were interested in a microbicide vaginal ring; 87% were interested in at least one of the two methods. Results suggest method mix will be important as biomedical tools for HIV prophylaxis are implemented and scaled up in this population, as 12% were interested in PrEP but not vaginal rings, while 19% were interested in vaginal rings but not in PrEP. Self-efficacy for daily oral adherence was high (79%) and 78% were interested in using PrEP even if condoms were still necessary. Women who had experienced recent client-perpetrated violence were significantly more interested in PrEP (86% vs 53%, p = 0.009) and microbicidal rings (91% vs 65%, p = 0.028) than women who had not recently experienced violence. No differences were observed by demographics nor HIV risk behaviors, suggesting broad potential interest in daily PrEP and monthly-use vaginal microbicides in this high-risk population.

Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages.

Directory of Open Access Journals (Sweden)

Ulrike Kuebler

Full Text Available BACKGROUND: Psychological stress delays wound healing but the precise underlying mechanisms are unclear. Macrophages play an important role in wound healing, in particular by killing microbes. We hypothesized that (a acute psychological stress reduces wound-induced activation of microbicidal potential of human monocyte-derived macrophages (HMDM, and (b that these reductions are modulated by stress hormone release. METHODS: Fourty-one healthy men (mean age 35 ± 13 years were randomly assigned to either a stress or stress-control group. While the stress group underwent a standardized short-term psychological stress task after catheter-induced wound infliction, stress-controls did not. Catheter insertion was controlled. Assessing the microbicidal potential, we investigated PMA-activated superoxide anion production by HMDM immediately before and 1, 10 and 60 min after stress/rest. Moreover, plasma norepinephrine and epinephrine and salivary cortisol were repeatedly measured. In subsequent in vitro studies, whole blood was incubated with norepinephrine in the presence or absence of phentolamine (norepinephrine blocker before assessing HMDM microbicidal potential. RESULTS: Compared with stress-controls, HMDM of the stressed subjects displayed decreased superoxide anion-responses after stress (p's <.05. Higher plasma norepinephrine levels statistically mediated lower amounts of superoxide anion-responses (indirect effect 95% CI: 4.14-44.72. Norepinephrine-treated HMDM showed reduced superoxide anion-production (p<.001. This effect was blocked by prior incubation with phentolamine. CONCLUSIONS: Our results suggest that acute psychological stress reduces wound-induced activation of microbicidal potential of HMDM and that this reduction is mediated by norepinephrine. This might have implications for stress-induced impairment in wound healing.

Physiotherapy Post Lumbar Discectomy: Prospective Feasibility and Pilot Randomised Controlled Trial

Science.gov (United States)

Rushton, Alison; Goodwin, Peter C.

2015-01-01

Objectives To evaluate: acceptability and feasibility of trial procedures; distribution of scores on the Roland Morris Disability Questionnaire (RMDQ, planned primary outcome); and efficient working of trial components. Design and Setting A feasibility and external pilot randomised controlled trial (ISRCTN33808269, assigned 10/12/2012) was conducted across 2 UK secondary care outpatient physiotherapy departments associated with regional spinal surgery centres. Participants Consecutive consenting patients aged >18 years; post primary, single level, lumbar discectomy. Interventions Participants were randomised to either 1:1 physiotherapy outpatient management including patient leaflet, or patient leaflet alone. Main Outcome Measures Blinded assessments were made at 4 weeks post surgery (baseline) and 12 weeks post baseline (proposed primary end point). Secondary outcomes included: Global Perceived Effect, back/leg pain, straight leg raise, return to work/function, quality of life, fear avoidance, range of movement, medication, re-operation. Results At discharge, 110 (44%) eligible patients gave consent to be contacted. 59 (54%) patients were recruited. Loss to follow up was 39% at 12 weeks, with one site contributing 83% losses. Mean (SD) RMDQ was 10.07 (5.58) leaflet and 10.52 (5.94) physiotherapy/leaflet at baseline; and 5.37 (4.91) leaflet and 5.53 (4.49) physiotherapy/leaflet at 12 weeks. 5.1% zero scores at 12 weeks illustrated no floor effect. Sensitivity to change was assessed at 12 weeks with mean (SD) change -4.53 (6.41), 95%CI -7.61 to -1.44 for leaflet; and -6.18 (5.59), 95%CI -9.01 to -3.30 for physiotherapy/leaflet. RMDQ mean difference (95%CI) between change from baseline to twelve weeks was 1.65(-2.46 to 5.75). Mean difference (95%CI) between groups at 12 weeks was -0.16 (-3.36 to 3.04). Participant adherence with treatment was good. No adverse events were reported. Conclusions Both interventions were acceptable, and it is promising that they both

Pre-clinical development of a combination microbicide vaginal ring containing dapivirine and darunavir.

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Murphy, Diarmaid J; Desjardins, Delphine; Dereuddre-Bosquet, Nathalie; Brochard, Patricia; Perrot, Ludivine; Pruvost, Alain; Le Grand, Roger; Lagatie, Ole; Vanhooren, Leen; Feyaerts, Maxim; van Roey, Jens; Malcolm, R Karl

2014-09-01

Combination microbicide vaginal rings may be more effective than single microbicide rings at reducing/preventing sexual transmission of HIV. Here, we report the pre-clinical development and macaque pharmacokinetics of matrix-type silicone elastomer vaginal rings containing dapivirine and darunavir. Macaque rings containing 25 mg dapivirine, 100 mg dapivirine, 300 mg darunavir or 100 mg dapivirine+300 mg darunavir were manufactured and characterized by differential scanning calorimetry. In vitro release was assessed into isopropanol/water and simulated vaginal fluid. Macaque vaginal fluid and blood serum concentrations for both antiretrovirals were measured during 28 day ring use. Tissue levels were measured on day 28. Ex vivo challenge studies were performed on vaginal fluid samples and IC50 values were calculated. Darunavir caused a concentration-dependent reduction in the dapivirine melting temperature in both solid drug mixes and in the combination ring. In vitro release from rings was dependent on drug loading, the number of drugs present and the release medium. In macaques, serum concentrations of both microbicides were maintained between 10(1) and 10(2) pg/mL. Vaginal fluid levels ranged between 10(3) and 10(4) ng/g and between 10(4) and 10(5) ng/g for dapivirine and darunavir, respectively. Both dapivirine and darunavir showed very similar concentrations in each tissue type; the range of drug tissue concentrations followed the general rank order: vagina (1.8 × 10(3)-3.8 × 10(3) ng/g)  > cervix (9.4 × 10(1)-3.9 × 10(2) ng/g)  > uterus (0-108 ng/g)  > rectum (0-40 ng/g). Measured IC50 values were >2 ng/mL for both compounds. Based on these results, and in light of recent clinical progress of the 25 mg dapivirine ring, a combination vaginal ring containing dapivirine and darunavir is a viable second-generation HIV microbicide candidate. © The Author 2014. Published by Oxford University Press on behalf of the British Society for

Feasibility and acceptability of TRANSFoRm to improve clinical trial recruitment in primary care.

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Mastellos, Nikolaos; Bliźniuk, Grzegorz; Czopnik, Dorota; McGilchrist, Mark; Misiaszek, Andrzej; Bródka, Piotr; Curcin, Vasa; Car, Josip; Delaney, Brendan C; Andreasson, Anna

2016-04-01

Recruitment of study participants is a challenging process for health professionals and patients. The Translational Medicine and Patient Safety in Europe (TRANSFoRm) clinical trial tools enable automated identification, recruitment and follow-up in clinical trials, potentially saving time, effort and costs for all parties involved. This study evaluates the acceptability and feasibility of TRANSFoRm to improve clinical trial recruitment in primary care. A feasibility study was conducted in three general practices in Poland. Participants were physicians and patients with gastro-oesophageal reflux disease. Semi-structured interviews were held to obtain feedback about the usefulness, ease of use and overall experience with the TRANSFoRm tools and to identify potential usability issues. Data were analysed thematically. A total of 5 physicians and 10 patients participated in the study. Physicians were satisfied with the usefulness of the system, as it enabled easier and faster identification, recruitment and follow-up of patients compared with existing methods. Patients found the TRANSFoRm apps easy to use to report patient outcomes. However, they also felt that the apps may not be useful for patients with limited exposure to smartphone and web technologies. Two main usability issues were identified: physicians could not access the result of the randomization at the end of each visit, and participants could not locate the follow-up reminder email. This study provides new evidence on the acceptability and feasibility of TRANSFoRm to enable automated identification, recruitment and follow-up of study participants in primary care trials. It also helps to better understand and address users' requirements in eHealth-supported clinical research. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Facilitated Extinction Training to Improve Pharmacotherapy for Smoking Cessation: A Pilot Feasibility Trial.

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Brandon, Thomas H; Unrod, Marina; Drobes, David J; Sutton, Steven K; Hawk, Larry W; Simmons, Vani N; Brandon, Karen O; Roetzheim, Richard G; Meltzer, Lauren R; Miller, Ralph R; Cahill, Shawn P

2017-09-12

Varenicline reduces smoking satisfaction during the pre-cessation run-in period, which may contribute to extinction of cravings and smoking behavior. Research indicates that efficacy is enhanced when the run-in period is increased from 1 to 4 weeks, providing a longer extinction opportunity. We hypothesized that efficacy could be further enhanced by harnessing basic and applied research on extinction. We developed a pre-cessation extinction-facilitating intervention and tested its feasibility in a pilot trial. The Facilitated Extinction (FE) intervention comprised brief counseling and a workbook recommending strategies to maximize extinction processes during the run-in, including instructions to smoke at a normal rate across contexts and cues, and use of an extinction cue to enhance generalization. Participants were randomly assigned to 1 of 3 varenicline interventions: standard (1-week run-in), extended (4-week run-in), and extended + FE. Interventions were delivered prior to the target quit date (TQD). Assessments were conducted in weeks 1 and 4 pre-TQD and 1 and 3 months post-TQD, with focus on feasibility indices. Recruitment and retention goals were met (N=58). Treatment satisfaction was high across groups. The majority of FE participants adhered to instructions and maintained their usual smoking rate during the run-in period. Greater decreases in craving and smoking satisfaction were observed among participants in both extended groups versus the standard group (p's<.005). Feasibility was demonstrated. Participants adhered to the FE intervention, thereby optimizing the number and variety of extinction trials. Findings support testing the novel FE smoking cessation intervention in a fully-powered trial. This study expands the research on the clinical benefits of extending the pre-cessation run-in period of varenicline. It introduces the hypothesis that further benefit might be achieved by translating basic behavioral research, as well as cue-exposure research

Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference

NARCIS (Netherlands)

Wahren, Britta; Biswas, Priscilla; Borggren, Marie; Coleman, Adam; Da Costa, Kelly; de Haes, Winni; Dieltjens, Tessa; Dispinseri, Stefania; Grupping, Katrijn; Hallengärd, David; Hornig, Julia; Klein, Katja; Mainetti, Lara; Palma, Paolo; Reudelsterz, Marc; Seifried, Janna; Selhorst, Philippe; Sköld, Annette; Uchtenhagen, Hannes; van Gils, Marit J.; Weber, Caroline; Shattock, Robin; Scarlatti, Gabriella

2010-01-01

EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination

Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota.

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O'Hanlon, Deirdre E; Moench, Thomas R; Cone, Richard A

2013-01-01

Lactic acid at sufficiently acidic pH is a potent microbicide, and lactic acid produced by vaginal lactobacilli may help protect against reproductive tract infections. However, previous observations likely underestimated healthy vaginal acidity and total lactate concentration since they failed to exclude women without a lactobacillus-dominated vaginal microbiota, and also did not account for the high carbon dioxide, low oxygen environment of the vagina. Fifty-six women with low (0-3) Nugent scores (indicating a lactobacillus-dominated vaginal microbiota) and no symptoms of reproductive tract disease or infection, provided a total of 64 cervicovaginal fluid samples using a collection method that avoided the need for sample dilution and rigorously minimized aerobic exposure. The pH of samples was measured by microelectrode immediately after collection and under a physiological vaginal concentration of CO2. Commercial enzymatic assays of total lactate and total acetate concentrations were validated for use in CVF, and compared to the more usual HPLC method. The average pH of the CVF samples was 3.5 ± 0.3 (mean ± SD), range 2.8-4.2, and the average total lactate was 1.0% ± 0.2% w/v; this is a five-fold higher average hydrogen ion concentration (lower pH) and a fivefold higher total lactate concentration than in the prior literature. The microbicidal form of lactic acid (protonated lactic acid) was therefore eleven-fold more concentrated, and a markedly more potent microbicide, than indicated by prior research. This suggests that when lactobacilli dominate the vaginal microbiota, women have significantly more lactic acid-mediated protection against infections than currently believed. Our results invite further evaluations of the prophylactic and therapeutic actions of vaginal lactic acid, whether provided in situ by endogenous lactobacilli, by probiotic lactobacilli, or by products that reinforce vaginal lactic acid.

A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.

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Sandhya Boyapalle

Full Text Available Human immunodeficiency virus (HIV types 1 and 2 (HIV-1 and HIV-2 are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162 viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.

Physiotherapy for sleep disturbance in people with chronic low back pain: results of a feasibility randomized controlled trial

NARCIS (Netherlands)

Eadie, J.; van de Water, A.T.; Lonsdale, C.; Tully, M.A.; van Mechelen, W.; Boreham, C.A.; Daly, L.; McDonough, S.M.; Hurley, D.A.

2013-01-01

Objective: To determine the feasibility of a randomized controlled trial investigating the effectiveness of physiotherapy for sleep disturbance in chronic low back pain (CLBP) (≥12wks). Design: Randomized controlled trial with evaluations at baseline, 3 months, and 6 months. Setting: Outpatient

The HAPPY (Healthy and Active Parenting Programmme for early Years feasibility randomised control trial: acceptability and feasibility of an intervention to reduce infant obesity

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Rosemary R. C. McEachan

2016-03-01

Full Text Available Abstract Background The prevalence of infant obesity is increasing, but there is a lack of evidence-based approaches to prevent obesity at this age. This study tested the acceptability and feasibility of evaluating a theory-based intervention aimed at reducing risk of obesity in infants of overweight/obese women during and after pregnancy: the Healthy and Active Parenting Programme for Early Years (HAPPY. Methods A feasibility randomised controlled trial was conducted in Bradford, England. One hundred twenty overweight/obese pregnant women (Body Mass Index [BMI] ≥25 kg/m2 were recruited between 10–26 weeks gestation. Consenting women were randomly allocated to HAPPY (6 antenatal, 6 postnatal sessions: N = 59 or usual care (N = 61. Appropriate outcome measures for a full trial were explored, including: infant’s length and weight, woman’s BMI, physical activity and dietary intake of the women and infants. Health economic data were collected. Measurement occurred before randomisation and when the infant was aged 6 months and 12 months. Feasibility outcomes were: recruitment/attrition rates, and acceptability of: randomisation, measurement, and intervention. Intra-class correlations for infant weight were calculated. Fidelity was assessed through observations and facilitator feedback. Focus groups and semi-structured interviews explored acceptability of methods, implementation, and intervention content. Results Recruitment targets were met (~20 women/month with a recruitment rate of 30 % of eligible women (120/396. There was 30 % attrition at 12 months; 66 % of recruited women failed to attend intervention sessions, but those who attended the first session were likely to continue to attend (mean 9.4/12 sessions, range 1–12. Reaction to intervention content was positive, and fidelity was high. Group clustering was minimal; an adjusted effect size of −0.25 standard deviation scores for infant weight at 12 months (95 % CI: �

Sham-controlled, randomized, feasibility trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

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Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Wu, Caijun; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2013-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients. Quality of life (QOL) is impaired, and available treatments are of little benefit. This trial determined the feasibility of conducting a sham-controlled trial of acupuncture and whether acupuncture could prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A sham controlled, feasibility trial was conducted at Fudan University Shanghai Cancer Center, Shanghai, China among patients with nasopharyngeal carcinoma undergoing radiotherapy. To determine feasibility of a sham procedure, 23 patients were randomized to real acupuncture (N = 11) or to sham acupuncture (N = 12). Patients were treated 3 times/week during their course of radiotherapy. Subjective measures were the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN). Objective measures were unstimulated whole salivary flow rates (UWSFR) and stimulated salivary flow rates (SSFR). Patients were followed for 1 month after radiotherapy. Results XQ scores for acupuncture were significantly lower than sham controls starting in week 3 and lasted through the 1-month follow-up (all P’s xerostomia symptoms and improved QOL when compared with sham acupuncture. Large-scale, multi-center, randomized, placebo-controlled trials are now needed. PMID:22285177

Video-game based exercises for older people with chronic low back pain: a protocol for a feasibility randomised controlled trial (the GAMEBACK trial).

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Zadro, Joshua Robert; Shirley, Debra; Simic, Milena; Mousavi, Seyed Javad; Ceprnja, Dragana; Maka, Katherine; Ferreira, Paulo

2017-06-01

To investigate the feasibility of implementing a video-game exercise programme for older people with chronic low back pain (LBP). Single-centred single-blinded randomised controlled trial (RCT). Physiotherapy outpatient department in a public hospital in Western Sydney, Australia. We will recruit 60 participants over 55 years old with chronic LBP from the waiting list. Participants will be randomised to receive video-game exercise (n=30) or to remain on the waiting list (n=30) for 8 weeks, with follow up at 3 and 6 months. Participants engaging in video-game exercises will be unsupervised and will complete video-game exercise for 60minutes, 3 times per week. Participants allocated to remain on the waiting list will be encouraged to maintain their usual levels of physical activity. The primary outcomes for this feasibility study will be study processes (recruitment and response rates, adherence to and experience with the intervention, and incidence of adverse events) relevant to the future design of a large RCT. Estimates of treatment efficacy (point estimates and 95% confidence intervals) on pain self-efficacy, care seeking, physical activity, fear of movement/re-injury, pain, physical function, disability, falls-efficacy, strength, and walking speed, will be our secondary outcome measures. Recruitment for this trial began in November 2015. This study describes the rationale and processes of a feasibility study investigating a video-game exercise programme for older people with chronic LBP. Results from the feasibility study will inform on the design and sample required for a large multicentre RCT. Australian New Zealand Clinical Trials Registry: ACTRN12615000703505. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Randomised controlled feasibility trial of an evidence-informed behavioural intervention for obese adults with additional risk factors.

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Falko F Sniehotta

Full Text Available Interventions for dietary and physical activity changes in obese adults may be less effective for participants with additional obesity-related risk factors and co-morbidities than for otherwise healthy individuals. This study aimed to test the feasibility and acceptability of the recruitment, allocation, measurement, retention and intervention procedures of a randomised controlled trial of an intervention to improve physical activity and dietary practices amongst obese adults with additional obesity related risk factors.Pilot single centre open-labelled outcome assessor-blinded randomised controlled trial of obese (Body Mass Index (BMI≥30 kg/m2 adults (age≥18 y with obesity related co-morbidities such as type 2 diabetes, impaired glucose tolerance or hypertension. Participants were randomly allocated to a manual-based group intervention or a leaflet control condition in accordance to a 2∶1 allocation ratio. Primary outcome was acceptability and feasibility of trial procedures, secondary outcomes included measures of body composition, physical activity, food intake and psychological process measures.Out of 806 potentially eligible individuals identified through list searches in two primary care general medical practices N = 81 participants (63% female; mean-age = 56.56(11.44; mean-BMI = 36.73(6.06 with 2.35(1.47 co-morbidities were randomised. Scottish Index of Multiple Deprivation (SIMD was the only significant predictor of providing consent to take part in the study (higher chances of consent for invitees with lower levels of deprivation. Participant flowcharts, qualitative and quantitative feedback suggested good acceptance and feasibility of intervention procedures but 34.6% of randomised participants were lost to follow-up due to overly high measurement burden and sub-optimal retention procedures. Participants in the intervention group showed positive trends for most psychological, behavioural and body composition outcomes

Mathematical model of microbicidal flow dynamics and optimization of rheological properties for intra-vaginal drug delivery: Role of tissue mechanics and fluid rheology.

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Anwar, Md Rajib; Camarda, Kyle V; Kieweg, Sarah L

2015-06-25

Topically applied microbicide gels can provide a self-administered and effective strategy to prevent sexually transmitted infections (STIs). We have investigated the interplay between vaginal tissue elasticity and the yield-stress of non-Newtonian fluids during microbicide deployment. We have developed a mathematical model of tissue deformation driven spreading of microbicidal gels based on thin film lubrication approximation and demonstrated the effect of tissue elasticity and fluid yield-stress on the spreading dynamics. Our results show that both elasticity of tissue and yield-stress rheology of gel are strong determinants of the coating behavior. An optimization framework has been demonstrated which leverages the flow dynamics of yield-stress fluid during deployment to maximize retention while reaching target coating length for a given tissue elasticity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recruiting faith- and non-faith-based schools, adolescents and parents to a cluster randomised sexual-health trial: experiences, challenges and lessons from the mixed-methods Jack Feasibility Trial.

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Aventin, Áine; Lohan, Maria; Maguire, Lisa; Clarke, Mike

2016-07-29

The move toward evidence-based education has led to increasing numbers of randomised trials in schools. However, the literature on recruitment to non-clinical trials is relatively underdeveloped, when compared to that of clinical trials. Recruitment to school-based randomised trials is, however, challenging, even more so when the focus of the study is a sensitive issue such as sexual health. This article reflects on the challenges of recruiting post-primary schools, adolescent pupils and parents to a cluster randomised feasibility trial of a sexual-health intervention, and the strategies employed to address them. The Jack Trial was funded by the UK National Institute for Health Research. It comprised a feasibility study of an interactive film-based sexual-health intervention entitled If I Were Jack, recruiting over 800 adolescents from eight socio-demographically diverse post-primary schools in Northern Ireland. It aimed to determine the facilitators and barriers to recruitment and retention to a school-based sexual-health trial and identify optimal multi-level strategies for an effectiveness study. As part of an embedded process evaluation, we conducted semi-structured interviews and focus groups with principals, vice-principals, teachers, pupils and parents recruited to the study as well as classroom observations and a parents' survey. With reference to social learning theory, we identified a number of individual-, behavioural- and environmental-level factors that influenced recruitment. Commonly identified facilitators included perceptions of the relevance and potential benefit of the intervention to adolescents, the credibility of the organisation and individuals running the study, support offered by trial staff, and financial incentives. Key barriers were prior commitment to other research, lack of time and resources, and perceptions that the intervention was incompatible with pupil or parent needs or the school ethos. Reflecting on the methodological

Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

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Wright, N C; Foster, P J; Mudano, A S; Melnick, J A; Lewiecki, M E; Shergy, W J; Curtis, J R; Cutter, G R; Danila, M I; Kilgore, M L; Lewis, E C; Morgan, S L; Redden, D T; Warriner, A H; Saag, K G

2017-08-01

The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide "drug holiday" clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a

[Effect on the microbicidal efficacy of formaldehyde, glutardialdehyde, peracetic acid, chloramine T (N-chloro-4-toluenesulfonamide), m-cresol, ethanol and benzyldimethyldodecacylammonium bromide by blood (model experiments for chemical disinfection of instruments)].

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Spicher, G; Peters, J

1998-02-01

In a preceding paper (Zbl. Hyg. 191 [1991] 457-477) we reported on the dependence of the microbicidal efficacy of active agents of the disinfection of instruments on the amount of coagulated blood adhering to the instruments. In the present investigation, we were interested in the dependence of the microbicidal effects on the amount of blood in the solutions of the active agents. Test areas of 2 cm2 were contaminated with 50 and 100 microliters coagulating blood, respectively, containing cells of Staphylococcus aureus as test germ. The solutions of the microbicidal agents were contaminated with heparinized blood up to a concentration of 4% immediately before starting the disinfection and 24 hours before, respectively. After a period of action lasting 1 hour at 20 degrees C, the relative number of test germs capable of multiplying (N/N0) was determined. The concentration of the microbicidal substances reducing the relative number of test germs capable to multiply to 10(-4) served for estimating the dependence of the microbicidal efficacy of the agents on the blood content of the solutions. The experimental results depended on the thickness of the layer of coagulated blood. The dependence of the efficacy of the microbicidal substances on the blood content of the solutions was the higher the thinner the blood layer was. At a thickness of the layer of the coagulated blood of 0.25 mm, a blood content of the solution of 4%, and applying it immediately after adding the blood, the concentration of glutardialdehyde had to be 1.6 times that without blood to reach the same microbicidal efficacy. When applying the solution 24 hours after adding the blood, the concentration of glutardialdehyde had to be 4.2 times that without blood. The quaternary ammonium compound reacted faster with the blood than did glutardialdehyde; the respective factors were 2.6 and 4.5. The concentration factors of chloramine T were 3.3 and 3.8. Under the conditions of the test, peracetic acid exhibited

User-identified gel characteristics: a qualitative exploration of perceived product efficacy of topical vaginal microbicides.

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Morrow, Kathleen M; Underhill, Kristen; van den Berg, Jacob J; Vargas, Sara; Rosen, Rochelle K; Katz, David F

2014-10-01

Research has demonstrated that certain vaginal gel products--microbicides containing antiretroviral drugs--may reduce HIV infection risk among women. But for vaginal gels to avert HIV and other sexually transmitted infections (STIs), at-risk women must be willing to use them as directed. These products must therefore be "acceptable" to women and an important component of acceptability is users' perception that the product will work to prevent infection. We sought to understand how women's perceptions of vaginal gel properties may shape their understanding of product efficacy for HIV and STI prevention. Sixteen women completed two in-depth qualitative interviews (k = 32) to identify the range and types of sensory perceptions they experienced when using two vaginal gels. We identified emergent themes and linkages between users' sensory perceptions and their beliefs about product efficacy. Users' predictions about product efficacy for preventing infection corresponded to measurable physical properties, including gel volume, location in the vagina, coating behavior, sensation of the gel in the vagina, leakage, and gel changes during coital acts. Although the women described similar sensory experiences (e.g., gel leaked from the vagina), they interpreted these experiences to have varying implications for product efficacy (e.g., leakage was predicted to increase or decrease efficacy). To improve microbicide acceptability, gel developers should investigate and deliberately incorporate properties that influence users' perceptions of efficacy. When a microbicide is approved for use, providers should educate users to anticipate and understand their sensory experiences; improving users' experience can maximize adherence and product effectiveness.

Developing a placebo-controlled trial in surgery: Issues of design, acceptability and feasibility

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McDonald AM

2011-02-01

Full Text Available Abstract Background Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons; plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists; three focus groups with anaesthetists (one national, two regional; 58 anaesthetists; two focus groups with members of the patient organisation Arthritis Care (7 participants; telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants; interviews with Chairs of UK ethics committees (6 individuals; postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists; two centre pilot (49 patients assessed. Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions proved easier than the method of anaesthesia (general anaesthesia. General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot. Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Conclusions Our study illustrated the opposing and often strongly held opinions about

Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.

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Mukhopadhya, Indrani; Murray, Graeme I; Berry, Susan; Thomson, John; Frank, Bruce; Gwozdz, Garry; Ekeruche-Makinde, Julia; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

2016-02-01

The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between individual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy samples, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of individual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection. © The Author 2015. Published by Oxford University Press on behalf of the

Feasibility, Safety, and Compliance in a Randomized Controlled Trial of Physical Therapy for Parkinson's Disease

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Jennifer L. McGinley

2012-01-01

Full Text Available Both efficacy and clinical feasibility deserve consideration in translation of research outcomes. This study evaluated the feasibility of rehabilitation programs within the context of a large randomized controlled trial of physical therapy. Ambulant participants with Parkinson's disease (PD (n=210 were randomized into three groups: (1 progressive strength training (PST; (2 movement strategy training (MST; or (3 control (“life skills”. PST and MST included fall prevention education. Feasibility was evaluated in terms of safety, retention, adherence, and compliance measures. Time to first fall during the intervention phase did not differ across groups, and adverse effects were minimal. Retention was high; only eight participants withdrew during or after the intervention phase. Strong adherence (attendance >80% did not differ between groups (P=.435. Compliance in the therapy groups was high. All three programs proved feasible, suggesting they may be safely implemented for people with PD in community-based clinical practice.

Culturally adaptive storytelling method to improve hypertension control in Vietnam - "We talk about our hypertension": study protocol for a feasibility cluster-randomized controlled trial.

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Allison, Jeroan J; Nguyen, Hoa L; Ha, Duc A; Chiriboga, Germán; Ly, Ha N; Tran, Hanh T; Phan, Ngoc T; Vu, Nguyen C; Kim, Minjin; Goldberg, Robert J

2016-01-14

Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. At present, the major risk factors for cardiovascular disease (CVD) are either on the rise or at alarming levels in Vietnam; inasmuch, the burden of CVD will continue to increase in this country unless effective prevention and control measures are put in place. A national survey in 2008 found that the prevalence of hypertension (HTN) was approximately 25 % among Vietnamese adults and it increased with advancing age. Therefore, novel, large-scale, and sustainable interventions for public health education to promote engagement in the process of detecting and treating HTN in Vietnam are urgently needed. A feasibility randomized trial will be conducted in Hung Yen province, Vietnam to evaluate the feasibility and acceptability of a novel community-based intervention using the "storytelling" method to enhance the control of HTN in adults residing in four rural communities. The intervention will center on stories about living with HTN, with patients speaking in their own words. The stories will be obtained from particularly eloquent patients, or "video stars," identified during Story Development Groups. The study will involve two phases: (i) developing a HTN intervention using the storytelling method, which is designed to empower patients to facilitate changes in their lifestyle practices, and (ii) conducting a feasibility cluster-randomized trial to investigate the feasibility, acceptability, and potential efficacy of the intervention compared with usual care in HTN control among rural residents. The trial will be conducted at four communes, and within each commune, 25 individuals 50 years or older with HTN will be enrolled in the trial resulting in a total sample size of 100 patients. This feasibility trial will provide the necessary groundwork for a subsequent large-scale, fully powered, cluster-randomized controlled trial to test the efficacy of our novel

Punica granatum (Pomegranate juice provides an HIV-1 entry inhibitor and candidate topical microbicide

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Li Yun-Yao

2004-10-01

Full Text Available Abstract Background For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. Methods Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1 infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2 binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. Results HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. Conclusion These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored.

Project Gel a Randomized Rectal Microbicide Safety and Acceptability Study in Young Men and Transgender Women.

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Ian McGowan

Full Text Available The purpose of Project Gel was to determine the safety and acceptability of rectal microbicides in young men who have sex with men (MSM and transgender women (TGW at risk of HIV infection.MSM and TGW aged 18-30 years were enrolled at three sites; Pittsburgh, PA; Boston, MA; and San Juan, PR. Stage 1A was a cross-sectional assessment of sexual health and behavior in MSM and TGW. A subset of participants from Stage 1A were then enrolled in Stage 1B, a 12-week evaluation of the safety and acceptability of a placebo rectal gel. This was followed by the final phase of the study (Stage 2 in which a subset of participants from Stage 1B were enrolled into a Phase 1 rectal safety and acceptability evaluation of tenofovir (TFV 1% gel.248 participants were enrolled into Stage 1A. Participants' average age was 23.3 years. The most common sexually transmitted infection (STIs at baseline were Herpes simplex (HSV-2 (16.1% by serology and rectal Chlamydia trachomatis (CT (10.1% by NAAT. 134 participants were enrolled into Stage 1B. During the 12 week period of follow-up 2 HIV, 5 rectal CT, and 5 rectal Neisseria gonorrhea infections were detected. The majority of adverse events (AEs were infections (N = 56 or gastrointestinal (N = 46 and were mild (69.6% or moderate (28.0%. Of the participants who completed Stage 1B, 24 were enrolled into Stage 2 and randomized (1:1 to receive TFV or placebo gel. All participants completed Stage 2. The majority of AEs were gastrointestinal (N = 10 and of mild (87.2% or moderate (10.3% severity.In this study we were able to enroll a sexually active population of young MSM and TGW who were willing to use rectal microbicides. TFV gel was safe and acceptable and should be further developed as an alternative HIV prevention intervention for this population.ClinicalTrials.gov NCT01283360.

Practices, patients and (imperfect data - feasibility of a randomised controlled clinical drug trial in German general practices

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Hummers-Pradier Eva

2011-04-01

Full Text Available Abstract Background Randomised controlled clinical (drug trials supply high quality evidence for therapeutic strategies in primary care. Until now, experience with drug trials in German general practice has been sparse. In 2007/2008, the authors conducted an investigator-initiated, non-commercial, double-blind, randomised controlled pilot trial (HWI-01 to assess the clinical equivalence of ibuprofen and ciprofloxacin in the treatment of uncomplicated urinary tract infection (UTI. Here, we report the feasibility of this trial in German general practices and the implementation of Good Clinical Practice (GCP standards as defined by the International Conference on Harmonisation (ICH in mainly inexperienced general practices. Methods This report is based on the experience of the HWI-01 study conducted in 29 German general practices. Feasibility was defined by 1 successful practice recruitment, 2 sufficient patient recruitment, 3 complete and accurate data collection and 4 appropriate protection of patient safety. Results The final practice recruitment rate was 18%. In these practices, 79 of 195 screened UTI patients were enrolled. Recruitment differed strongly between practices (range 0-12, mean 2.8 patients per practice and was below the recruitment goal of approximately 100 patients. As anticipated, practice nurses became the key figures in the screening und recruitment of patients. Clinical trial demands, in particular for completing symptom questionnaires, documentation of source data and reporting of adverse events, did not agree well with GPs' documentation habits and required support from study nurses. In many cases, GPs and practice staff seemed to be overwhelmed by the amount of information and regulations. No sudden unexpected serious adverse reactions (SUSARs were observed during the trial. Conclusions To enable drug trials in general practice, it is necessary to adapt the setup of clinical research infrastructure to the needs of GPs and

77 FR 70167 - Draft Guidance for Industry on Vaginal Microbicides: Development for the Prevention of Human...

Science.gov (United States)

2012-11-23

...] Draft Guidance for Industry on Vaginal Microbicides: Development for the Prevention of Human...: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry... Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New...

CONTRACT Study - CONservative TReatment of Appendicitis in Children (feasibility): study protocol for a randomised controlled Trial.

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Hutchings, Natalie; Wood, Wendy; Reading, Isabel; Walker, Erin; Blazeby, Jane M; Van't Hoff, William; Young, Bridget; Crawley, Esther M; Eaton, Simon; Chorozoglou, Maria; Sherratt, Frances C; Beasant, Lucy; Corbett, Harriet; Stanton, Michael P; Grist, Simon; Dixon, Elizabeth; Hall, Nigel J

2018-03-02

Currently, the routine treatment for acute appendicitis in the United Kingdom is an appendicectomy. However, there is increasing scientific interest and research into non-operative treatment of appendicitis in adults and children. While a number of studies have investigated non-operative treatment of appendicitis in adults, this research cannot be applied to the paediatric population. Ultimately, we aim to perform a UK-based multicentre randomised controlled trial (RCT) to test the clinical and cost effectiveness of non-operative treatment of acute uncomplicated appendicitis in children, as compared with appendicectomy. First, we will undertake a feasibility study to assess the feasibility of performing such a trial. The study involves a feasibility RCT with a nested qualitative research to optimise recruitment as well as a health economic substudy. Children (aged 4-15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Participants will be randomised into one of two arms. Participants in the intervention arm are treated with antibiotics and regular clinical assessment to ensure clinical improvement. Participants in the control arm will receive appendicectomy. Randomisation will be minimised by age, sex, duration of symptoms and centre. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative substudy, which includes recording of recruitment consultants and subsequent interviews with participants and non-participants and their families and recruiters. Analyses of these will inform interventions to optimise recruitment. The main study outcomes include recruitment rate (primary outcome), identification of strategies to optimise recruitment, performance of trial treatment

Feasibility trial of a psychoeducational intervention for parents with personality difficulties: The Helping Families Programme

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Crispin Day

2017-12-01

Full Text Available The Helping Families Programme is a psychoeducational parenting intervention that aims to improve outcomes and engagement for parents affected by clinically significant personality difficulties. This is achieved by working collaboratively with parents to explore ways in which their emotional and relational difficulties impact on parenting and child functioning, and to identify meaningful and realistic goals for change. The intervention is delivered via one-to-one sessions at weekly intervals over a period of 16 weeks. This protocol describes a two-arm parallel RCT in which consenting parents are randomly allocated in a 1:1 ratio to either the Helping Families Programme plus the usual services that the parent may be receiving from their mental health and/or social care providers, or to standard care (usual services plus a brief parenting advice session. The primary clinical outcome will be child behaviour. Secondary clinical outcomes will be child and parental mental health, parenting satisfaction, parenting behaviour and therapeutic alliance. Health economic measures will be collected on quality of life and service use. Outcome measures will be collected at the initial assessment stage, after the intervention is completed and at 6-month follow-up by research staff blind to group allocation. Trial feasibility will be assessed using rates of trial participation at the three time points and intervention uptake, attendance and retention. A parallel process evaluation will use qualitative interviews to ascertain key-workers’ and parent participants' experiences of intervention delivery and trial participation. The results of this feasibility study will determine the appropriateness of proceeding to a full-scale trial.

Engineering soya bean seeds as a scalable platform to produce cyanovirin-N, a non-ARV microbicide against HIV.

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O'Keefe, Barry R; Murad, André M; Vianna, Giovanni R; Ramessar, Koreen; Saucedo, Carrie J; Wilson, Jennifer; Buckheit, Karen W; da Cunha, Nicolau B; Araújo, Ana Claudia G; Lacorte, Cristiano C; Madeira, Luisa; McMahon, James B; Rech, Elibio L

2015-09-01

There is an urgent need to provide effective anti-HIV microbicides to resource-poor areas worldwide. Some of the most promising microbicide candidates are biotherapeutics targeting viral entry. To provide biotherapeutics to poorer areas, it is vital to reduce the cost. Here, we report the production of biologically active recombinant cyanovirin-N (rCV-N), an antiviral protein, in genetically engineered soya bean seeds. Pure, biologically active rCV-N was isolated with a yield of 350 μg/g of dry seed weight. The observed amino acid sequence of rCV-N matched the expected sequence of native CV-N, as did the mass of rCV-N (11 009 Da). Purified rCV-N from soya is active in anti-HIV assays with an EC50 of 0.82-2.7 nM (compared to 0.45-1.8 nM for E. coli-produced CV-N). Standard industrial processing of soya bean seeds to harvest soya bean oil does not diminish the antiviral activity of recovered rCV-N, allowing the use of industrial soya bean processing to generate both soya bean oil and a recombinant protein for anti-HIV microbicide development. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Developing a placebo-controlled trial in surgery: issues of design, acceptability and feasibility.

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Campbell, M K; Entwistle, V A; Cuthbertson, B H; Skea, Z C; Sutherland, A G; McDonald, A M; Norrie, J D; Carlson, R V; Bridgman, S

2011-02-21

Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this

Acceptability and feasibility of repeated mucosal specimen collection in clinical trial participants in Kenya.

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Gloria Omosa-Manyonyi

Full Text Available Mucosal specimens are essential to evaluate compartmentalized immune responses to HIV vaccine candidates and other mucosally targeted investigational products. We studied the acceptability and feasibility of repeated mucosal sampling in East African clinical trial participants at low risk of HIV and other sexually transmitted infections.The Kenya AIDS Vaccine Initiative (KAVI enrolled participants into three Phase 1 trials of preventive HIV candidate vaccines in 2011-2012 at two clinical research centers in Nairobi. After informed consent to a mucosal sub-study, participants were asked to undergo collection of mucosal secretions (saliva, oral fluids, semen, cervico-vaginal and rectal, but could opt out of any collection at any visit. Specimens were collected at baseline and two additional time points. A tolerability questionnaire was administered at the final sub-study visit. Of 105 trial participants, 27 of 34 women (79% and 62 of 71 men (87% enrolled in the mucosal sub-study. Nearly all sub-study participants gave saliva and oral fluids at all visits. Semen was collected from about half the participating men (47-48% at all visits. Cervico-vaginal secretions were collected by Softcup from about two thirds of women (63% at baseline, increasing to 78% at the following visits, with similar numbers for cervical secretion collection by Merocel sponge; about half of women (52% gave cervico-vaginal samples at all visits. Rectal secretions were collected with Merocel sponge from about a quarter of both men and women (24% at all 3 visits, with 16% of men and 19% of women giving rectal samples at all visits.Repeated mucosal sampling in clinical trial participants in Kenya is feasible, with a good proportion of participants consenting to most sampling methods with the exception of rectal samples. Experienced staff members of both sexes and trained counselors with standardized messaging may improve acceptance of rectal sampling.

A cluster randomised feasibility trial evaluating six-month nutritional interventions in the treatment of malnutrition in care home-dwelling adults: recruitment, data collection and protocol.

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Stow, Ruth; Rushton, Alison; Ives, Natalie; Smith, Christina; Rick, Caroline

2015-01-01

Protein energy malnutrition predisposes individuals to disease, delays recovery from illness and reduces quality of life. Care home residents are especially vulnerable, with an estimated 30%-42% at risk. There is no internationally agreed protocol for the nutritional treatment of malnutrition in the care home setting. Widely used techniques include food-based intervention and/or the use of prescribed oral nutritional supplements, but a trial comparing the efficacy of interventions is necessary. In order to define outcomes and optimise the design for an adequately powered, low risk of bias cluster randomised controlled trial, a feasibility trial with 6-month intervention is being run, to assess protocol procedures, recruitment and retention rates, consent processes and resident and staff acceptability. Trial recruitment began in September 2013 and concluded in December 2013. Six privately run care homes in Solihull, England, were selected to establish feasibility within different care home types. Residents with or at risk of malnutrition with no existing dietetic intervention in place were considered for receipt of the allocated intervention. Randomisation took place at the care home level, using a computer-generated random number list to allocate each home to either a dietetic intervention arm (food-based or prescribed supplements) or the standard care arm, continued for 6 months. Dietetic intervention aimed to increase daily calorie intake by 600 kcal and protein by 20-25 g. The primary outcomes will be trial feasibility and acceptability of trial design and allocated interventions. A range of outcome assessments and data collection tools will be evaluated for feasibility, including change in nutrient intake, anthropometric parameters and patient-centric measures, such as quality of life and self-perceived appetite. The complexities inherent in care home research has resulted in the under representation of this population in research trials. The results of this

The feasibility of progressive resistance training in women with polycystic ovary syndrome: a pilot randomized controlled trial.

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Vizza, Lisa; Smith, Caroline A; Swaraj, Soji; Agho, Kingsley; Cheema, Birinder S

2016-01-01

To evaluate the feasibility of executing a randomized controlled trial of progressive resistance training (PRT) in women with polycystic ovary syndrome (PCOS). Women with PCOS were randomized to an experimental (PRT) group or a no-exercise (usual care) control group. The PRT group was prescribed two supervised and two unsupervised (home-based) training sessions per week for 12 weeks. Feasibility outcomes included recruitment and attrition, adherence, adverse events, and completion of assessments. Secondary outcomes, collected pre and post intervention, included a range of pertinent physiological, functional and psychological measures. Fifteen participants were randomised into the PRT group (n = 8) or control group (n = 7); five women (n = 2 in PRT group and n = 3 in control group) withdrew from the study. The most successful recruitment sources were Facebook (40 %) and online advertisement (27 %), while least successful methods were referrals by clinicians, colleagues and flyers. In the PRT group, attendance to supervised sessions was higher (95 %; standard deviation ±6 %) compared to unsupervised sessions (51 %; standard deviation ±28 %). No adverse events were attributed to PRT. Change in menstrual cycle status was not significantly different between groups over time (p = 0.503). However, the PRT group significantly increased body weight (p = 0.01), BMI (p = 0.04), lean mass (p = 0.01), fat-free mass (p = 0.005) and lower body strength (p = 0.03), while reducing waist circumference (p = 0.03) and HbA1c (p = 0.033) versus the control group. The PRT group also significantly improved across several domains of disease-specific and general health-related quality of life, depression, anxiety and exercise self-efficacy. A randomized controlled trial of PRT in PCOS would be feasible, and this mode of exercise may elicit a therapeutic effect on clinically important outcomes in this cohort. The success of a large

Microbicidal activity of neutrophils is inhibited by isolates from recurrent vaginal candidiasis (RVVC) caused by Candida albicans through fungal thioredoxin reductase.

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Ratti, Bianca Altrão; Godoy, Janine Silva Ribeiro; de Souza Bonfim Mendonça, Patrícia; Bidóia, Danielle Lazarin; Nakamura, Tânia Ueda; Nakamura, Celso Vataru; Lopes Consolaro, Marcia Edilaine; Estivalet Svidzinski, Terezinha Inez; de Oliveira Silva, Sueli

2015-01-01

Vulvovaginal candidiasis (VVC) is characterized by an infection of the vulva and vagina, mainly caused by Candida albicans, a commensal microorganism that inhabits the vaginal, digestive, and respiratory mucosae. Vulvovaginal candidiasis affects approximately 75% of women, and 5% develop the recurrent form (RVVC). The aim of the present study was to evaluate whether neutrophils microbicidal response is triggered when activated with RVVC isolates caused by C. albicans. Our results showed that RVVC isolates induced neutrophil migration but significantly decrease the microbicidal activity of neutrophils, compared with VVC and ASS isolates. The microbicidal activity of neutrophils is highly dependent on the production of reactive oxygen species/reactive nitrogen species (ROS/RNS). However, this isolate induced detoxification of ROS/RNS produced by neutrophils, reflected by the high level of thiol groups and by the oxygen consumption. Therefore, RVVC isolates induced biochemical changes in the inflammatory response triggered by neutrophils, and these effects were mainly related to the detoxification of ROS/RNS through the thioredoxin reductase (TR), a key antioxidant enzyme in fungi. This might be one of the resistance mechanisms triggered by RVVC caused by C. albicans. Copyright © 2014 Elsevier Inc. All rights reserved.

Do feasibility studies contribute to, or avoid, waste in research?

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Morgan, Ben; Hejdenberg, Jennie; Hinrichs-Krapels, Saba; Armstrong, David

2018-01-01

In the context of avoiding research waste, the conduct of a feasibility study before a clinical trial should reduce the risk that further resources will be committed to a trial that is likely to 'fail'. However, there is little evidence indicating whether feasibility studies add to or reduce waste in research. Feasibility studies funded by the National Institute for Health Research's (NIHR) Research for Patient Benefit (RfPB) programme were examined to determine how many had published their findings, how many had applied for further funding for a full trial and the timeframe in which both of these occurred. A total of 120 feasibility studies which had closed by May 2016 were identified and each Principal Investigator (PI) was sent a questionnaire of which 89 responses were received and deemed suitable for analysis. Based on self reported answers from the PIs a total of 57 feasibility studies were judged as feasible, 20 were judged not feasible and for 12 it was judged as uncertain whether a full trial was feasible. The RfPB programme had spent approximately £19.5m on the 89 feasibility studies of which 16 further studies had been subsequently funded to a total of £16.8m. The 20 feasibility studies which were judged as not feasible potentially saved up to approximately £20m of further research funding which would likely to have not completed successfully. The average RfPB feasibility study took 31 months (range 18 to 48) to complete and cost £219,048 (range £72,031 to £326,830) and the average full trial funded from an RfPB feasibility study took 42 months (range 26 to 55) to complete and cost £1,163,996 (range £321,403 to £2,099,813). The average timeframe of feasibility study and full trial was 72 months (range 56 to 91), however in addition to this time an average of 10 months (range -7 to 29) was taken between the end of the feasibility study and the application for the full trial, and a further average of 18 months (range 13 to 28) between the

Formulation development of retrocyclin 1 analog RC-101 as an anti-HIV vaginal microbicide product.

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Sassi, A B; Cost, M R; Cole, A L; Cole, A M; Patton, D L; Gupta, P; Rohan, L C

2011-05-01

RC-101 is a synthetic microbicide analog of retrocyclin, which has shown in vitro activity against X4 and R5 HIV-1. In an effort to develop a safe and effective RC-101 vaginal microbicide product, we assessed safety in ex vivo macaque and human models and efficacy using in vitro and ex vivo models. A polyvinyl-alcohol vaginal film containing RC-101 (100 μg/film) was developed. Formulation assessment was conducted by evaluating disintegration, drug content, mechanical properties, and stability. Efficacy was evaluated by in vitro peripheral blood mononuclear cells (PBMC) assay and ex vivo human ectocervical tissue explant model. Ex vivo safety studies were conducted by exposing RC-101 to an excised monkey reproductive tract and excised human ectocervical tissue. RC-101 100 μg films were shown to be safe to human and monkey tissue and effective against HIV-1 in vitro and ex vivo in human ectocervical tissue. The 90% inhibitory concentration (IC90) for RC-101 films at 2,000 μg (IC90=57.5 μM) using an ex vivo model was 10-fold higher than the IC90 observed using an in vitro model (IC90=5.0 μM). RC-101 films were stable for 1 month at 25°C, with in vitro bioactivity maintained for up to 6 months. RC-101 was developed in a quick-dissolve film formulation that was shown to be safe in an ex vivo model and effective in in vitro and ex vivo models. RC-101 film formulations were shown to maintain bioactivity for a period of 6 months. Findings from the present study contribute to the development of a safe and effective topical microbicide product.

The use of supersaturation for the vaginal application of microbicides: a case study with dapivirine.

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Grammen, Carolien; Plum, Jakob; Van Den Brande, Jeroen; Darville, Nicolas; Augustyns, Koen; Augustijns, Patrick; Brouwers, Joachim

2014-11-01

In this study, we investigated the potential of supersaturation for the formulation of the poorly water-soluble microbicide dapivirine (DPV) in an aqueous vaginal gel in order to enhance its vaginal tissue uptake. Different excipients such as hydroxypropylmethylcellulose, polyethylene glycol 1000, and cyclodextrins were evaluated for their ability to inhibit precipitation of supersaturated DPV in the formulation vehicle as such as well as in biorelevant media. In vitro permeation assessment across HEC-1A cell layers demonstrated an enhanced DPV flux from supersaturated gels compared with suspension gels. The best performing supersaturated gel containing 500 μM DPV (supersaturation degree of 4) in the presence of sulfobutyl ether-beta-cyclodextrin (2.5%) appeared to be stable for at least 3 months. In addition, the gel generated a significant increase in vaginal drug uptake in rabbits as compared with suspension gels. We conclude that supersaturation is a possible strategy to enhance the vaginal concentration of hydrophobic microbicides, thereby increasing permeation into the vaginal submucosa. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide

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Conrads Thomas P

2011-07-01

Full Text Available Abstract Background RC-101, a cationic peptide retrocyclin analog, has in vitro activity against HIV-1. Peptide drugs are commonly prone to conformational changes, oxidation and hydrolysis when exposed to excipients in a formulation or biological fluids in the body, this can affect product efficacy. We aimed to investigate RC-101 stability under several conditions including the presence of human vaginal fluids (HVF, enabling the efficient design of a safe and effective microbicide product. Stability studies (temperature, pH, and oxidation were performed by HPLC, Circular Dichroism, and Mass Spectrometry (LC-MS/MS. Additionally, the effect of HVF on formulated RC-101 was evaluated with fluids collected from healthy volunteers, or from subjects with bacterial vaginosis (BV. RC-101 was monitored by LC-MS/MS for up to 72 h. Results RC-101 was stable at pH 3, 4, and 7, at 25 and 37°C. High concentrations of hydrogen peroxide resulted in less than 10% RC-101 reduction over 24 h. RC-101 was detected 48 h after incubation with normal HVF; however, not following incubation with HVF from BV subjects. Conclusions Our results emphasize the importance of preformulation evaluations and highlight the impact of HVF on microbicide product stability and efficacy. RC-101 was stable in normal HVF for at least 48 h, indicating that it is a promising candidate for microbicide product development. However, RC-101 stability appears compromised in individuals with BV, requiring more advanced formulation strategies for stabilization in this environment.

Feasibility randomized-controlled trial of online Acceptance and Commitment Therapy for patients with complex chronic pain in the United Kingdom.

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Scott, W; Chilcot, J; Guildford, B; Daly-Eichenhardt, A; McCracken, L M

2018-04-28

Acceptance and Commitment Therapy (ACT) has growing support for chronic pain. However, more accessible treatment delivery is needed. This study evaluated the feasibility of online ACT for patients with complex chronic pain in the United Kingdom to determine whether a larger trial is justified. Participants with chronic pain and clinically meaningful disability and distress were randomly assigned to ACT online plus specialty medical pain management, or specialty medical management alone. Participants completed questionnaires at baseline, and 3- and 9-month post-randomization. Primary feasibility outcomes included recruitment, retention and treatment completion rates. Secondary outcomes were between-groups effects on treatment outcomes and psychological flexibility. Of 139 potential participants, 63 were eligible and randomized (45% recruitment rate). Retention rates were 76-78% for follow-up assessments. Sixty-one per cent of ACT online participants completed treatment. ACT online was less often completed by employed (44%) compared to unemployed (80%) participants. Fifty-six per cent of ACT online participants rated themselves as 'much improved' or better on a global impression of change rating, compared to only 20 per cent of control participants. Three-month effects favouring ACT online were small for functioning, medication and healthcare use, committed action and decentring, medium for mood, and large for acceptance. Small-to-medium effects were maintained for functioning, healthcare use and committed action at 9 months. Online ACT for patients with chronic pain in the United Kingdom appears feasible to study in a larger efficacy trial. Some adjustments to treatment and trial procedures are warranted, particularly to enhance engagement among employed participants. This study supports the feasibility of online Acceptance and Commitment Therapy for chronic pain in the United Kingdom and a larger efficacy trial. Refinements to treatment delivery, particularly to

Pharmacokinetic modeling of a gel-delivered dapivirine microbicide in humans.

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Halwes, Michael E; Steinbach-Rankins, Jill M; Frieboes, Hermann B

2016-10-10

Although a number of drugs have been developed for the treatment and prevention of human immunodeficiency virus (HIV) infection, it has proven difficult to optimize the drug and dosage parameters. The vaginal tissue, comprised of epithelial, stromal and blood compartments presents a complex system which challenges evaluation of drug kinetics solely through empirical effort. To provide insight into the underlying processes, mathematical modeling and computational simulation have been applied to the study of retroviral microbicide pharmacokinetics. Building upon previous pioneering work that modeled the delivery of Tenofovir (TFV) via topical delivery to the vaginal environment, here we computationally evaluate the performance of the retroviral inhibitor dapivirine released from a microbicide gel. We adapt the TFV model to simulate the multicompartmental diffusion and uptake of dapivirine into the blood plasma and vaginal compartments. The results show that dapivirine is expected to accumulate at the interface between the gel and epithelium compartments due to its hydrophobic characteristics. Hydrophobicity also results in decreased diffusivity, which may impact distribution by up to 2 orders of magnitude compared to TFV. Maximum concentrations of dapivirine in the epithelium, stroma, and blood were 9.9e7, 2.45e6, and 119pg/mL, respectively. This suggests that greater initial doses or longer time frames are required to obtain higher drug concentrations in the epithelium. These observations may have important ramifications if a specific time frame is required for efficacy, or if a minimum/maximum concentration is needed in the mucus, epithelium, or stroma based on combined efficacy and safety data. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive-behavioural therapy (CBT) for renal fatigue (BReF):a feasibility randomised-controlled trial of CBT for the management of fatigue in haemodialysis (HD) patients

OpenAIRE

Picariello, Federica; Moss-Morris, Rona; Macdougall, Iain C.; Norton, Sam; Da Silva-Gane, Maria; Farrington, Ken; Clayton, Hope; Chilcot, Joseph

2018-01-01

Introduction Fatigue is one of the most common and disabling symptoms in end-stage kidney disease, particularly among in-centre haemodialysis patients. This two-arm parallel group feasibility randomised controlled trial will determine whether a fully powered efficacy trial is achievable by examining the feasibility of recruitment, acceptability and potential benefits of a cognitive-behavioural therapy (CBT)-based intervention for fatigue among in-centre haemodialysis patients.Methods We aim t...

Feasibility and preliminary effectiveness of ice therapy in patients with an acute tear in the gastrocnemius muscle: A pilot randomized controlled trial

NARCIS (Netherlands)

Prins, J.C.M.; Stubbe, J.H.; Meeteren, N.L.U. van; Scheffers, F.A.; Dongen, M.C.J.M. van

2011-01-01

Objective: To investigate the feasibility of a randomized controlled trial and the preliminary effectiveness of ice therapy in the acute phase of a gastrocnemius tear for the quality of functional recovery. Design: A pilot version of an intended prospective randomized controlled clinical trial was

Feasibility of Pilates exercise to decrease falls risk: a pilot randomized controlled trial in community-dwelling older people.

Science.gov (United States)

Barker, Anna L; Talevski, Jason; Bohensky, Megan A; Brand, Caroline A; Cameron, Peter A; Morello, Renata T

2016-10-01

To evaluate the feasibility of Pilates exercise in older people to decrease falls risk and inform a larger trial. Pilot Randomized controlled trial. Community physiotherapy clinic. A total of 53 community-dwelling people aged ⩾60 years (mean age, 69.3 years; age range, 61-84). A 60-minute Pilates class incorporating best practice guidelines for exercise to prevent falls, performed twice weekly for 12 weeks. All participants received a letter to their general practitioner with falls risk information, fall and fracture prevention education and home exercises. Indicators of feasibility included: acceptability (recruitment, retention, intervention adherence and participant experience survey); safety (adverse events); and potential effectiveness (fall, fall injury and injurious fall rates; standing balance; lower limb strength; and flexibility) measured at 12 and 24 weeks. Recruitment was achievable but control group drop-outs were high (23%). Of the 20 participants who completed the intervention, 19 (95%) attended ⩾75% of the classes and reported classes were enjoyable and would recommend them to others. The rate of fall injuries at 24 weeks was 42% lower and injurious fall rates 64% lower in the Pilates group, however, was not statistically significant (P = 0.347 and P = 0.136). Standing balance, lower-limb strength and flexibility improved in the Pilates group relative to the control group (P fall injury rates. A definitive randomized controlled trial analysing the effect of Pilates in older people would be feasible and is warranted given the acceptability and potential positive effects of Pilates on fall injuries and fall risk factors. The protocol for this study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN1262000224820). © The Author(s) 2015.

Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

Science.gov (United States)

Planchon, Sarah M; Lingas, Karen T; Reese Koç, Jane; Hooper, Brittney M; Maitra, Basabi; Fox, Robert M; Imrey, Peter B; Drake, Kylie M; Aldred, Micheala A; Lazarus, Hillard M; Cohen, Jeffrey A

2018-01-01

Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10 6 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

Intravaginal insertion in KwaZulu Natal: sexual practices and preferences in the context of microbicide gel use

NARCIS (Netherlands)

Gafos, M.; Mzimela, M.; Sukazi, S.; Pool, R.; Montgomery, C.; Elford, J.

2010-01-01

Intravaginal insertion is often associated with the concept of ‘dry’ sex. All HIV-prevention microbicides tested to date have been vaginally applied lubricant-based gels. In this paper, we examine whether the use of intravaginal insertions could be in conflict with the introduction of vaginal

Protocol for a feasibility trial for improving breast feeding initiation and continuation: assets-based infant feeding help before and after birth (ABA)

Science.gov (United States)

Jolly, Kate; Ingram, Jenny; Clarke, Joanne; Johnson, Debbie; Trickey, Heather; Thomson, Gill; Dombrowski, Stephan U; Sitch, Alice; Dykes, Fiona; Feltham, Max G; Darwent, Kirsty; MacArthur, Christine; Roberts, Tracy

2018-01-01

Introduction Breast feeding improves the health of mothers and infants; the UK has low rates, with marked socioeconomic inequalities. While trials of peer support services have been effective in some settings, UK trials have not improved breast feeding rates. Qualitative research suggests that many women are alienated by the focus on breast feeding. We propose a change from breast feeding-focused interactions to respecting a woman’s feeding choices, inclusion of behaviour change theory and an increased intensity of contacts in the 2 weeks after birth when many women cease to breast feed. This will take place alongside an assets-based approach that focuses on the positive capability of individuals, their social networks and communities. We propose a feasibility study for a multicentre randomised controlled trial of the Assets feeding help Before and After birth (ABA) infant feeding service versus usual care. Methods and analysis A two-arm, non-blinded randomised feasibility study will be conducted in two UK localities. Women expecting their first baby will be eligible, regardless of feeding intention. The ABA infant feeding intervention will apply a proactive, assets-based, woman-centred, non-judgemental approach, delivered antenatally and postnatally tailored through face-to-face contacts, telephone and SMS texts. Outcomes will test the feasibility of delivering the intervention with recommended intensity and duration to disadvantaged women; acceptability to women, feeding helpers and professionals; and feasibility of a future randomised controlled trial (RCT), detailing recruitment rates, willingness to be randomised, follow-up rates at 3 days, 8 weeks and 6 months, and level of outcome completion. Outcomes of the proposed full trial will also be collected. Mixed methods will include qualitative interviews with women/partners, feeding helpers and health service staff; feeding helper logs; and review of audio-recorded helper–women interactions to assess

Protocol for a multicentre randomised feasibility STUdy evaluating the impact of a prognostic model for Management of BLunt chest wall trauma patients: STUMBL trial.

Science.gov (United States)

Battle, Ceri; Abbott, Zoe; Hutchings, Hayley A; O'Neill, Claire; Groves, Sam; Watkins, Alan; Lecky, Fiona E; Jones, Sally; Gagg, James; Body, Richard; Evans, Philip A

2017-07-10

A new prognostic model has been developed and externally validated, the aim of which is to assist in the management of the blunt chest wall trauma patient in the emergency department (ED). A definitive randomised controlled trial (impact trial) is required to assess the clinical and cost effectiveness of the new model before it can be accepted in clinical practice. The purpose of this trial is to assess the feasibility and acceptability of such a definitive trial and inform its design. This feasibility trial is designed to test the methods of a multicentre, cluster-randomised (stepped- wedge) trial, with a substantial qualitative component. Four EDs in England and Wales will collect data for all blunt chest wall trauma patients over a 5-month period; in the initial period acting as the controls (normal care), and in the second period acting as the interventions (in which the new model will be used). Baseline measurements including completion of the SF-12v2 will be obtained on initial assessment in the ED. Patient outcome data will then be collected for any subsequent hospitalisations. Data collection will conclude with a 6-week follow-up completion of two surveys (SF-12v2 and Client Services Receipt Inventory). Analysis of outcomes will focus on feasibility, acceptability and trial processes and will include recruitment and retention rates, attendance at clinician training rates and use of model in the ED. Qualitative feedback will be obtained through clinician interviews and a research nurse focus group. An evaluation of the feasibility of health economics outcomes data will be completed. Wales Research Ethics Committee 6 granted approval for the trial in September 2016. Patient recruitment will commence in February 2017. Planned dissemination is through publication in a peer-reviewed Emergency Medicine Journal , presentation at appropriate conferences and to stakeholders at professional meetings. ISRCTN95571506; Pre-results. © Article author(s) (or their

Mucosal integrity and inflammatory markers in the female lower genital tract as potential screening tools for vaginal microbicides.

Science.gov (United States)

Su, H Irene; Schreiber, Courtney A; Fay, Courtney; Parry, Sam; Elovitz, Michal A; Zhang, Jian; Shaunik, Alka; Barnhart, Kurt

2011-11-01

In the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety. A randomized, blinded crossover trial of 18 subjects comparing effects of nonoxynol-9 vaginal gel (Gynol II; putative inflammatory gel), hydroxyethyl cellulose gel (HEC; putative inert gel) and no gel exposure on endometrial and vaginal epithelial integrity and endometrial and vaginal inflammatory markers [interleukin (IL) 1β, IL-6, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, tumor necrosis factor α, IL-1RA, IL-10, SLPI). Gynol II was associated with more vaginal lesions. No endometrial disruptions were observed across conditions. In the vagina, RANTES (p=.055) and IL-6 (p=.04) were higher after HEC exposure than at baseline. In the endometrium, IL-1β (p=.003) and IL-8 (p=.025) were lower after Gynol II cycles than after no gel. Gynol II and HEC may modulate inflammatory markers in the vagina and endometrium. How these changes relate to infection susceptibility warrants further study. Copyright © 2011 Elsevier Inc. All rights reserved.

Feasibility of a controlled trial aiming to prevent excessive pregnancy-related weight gain in primary health care

Directory of Open Access Journals (Sweden)

Weiderpass Elisabete

2008-08-01

Full Text Available Abstract Background Excessive gestational weight gain and postpartum weight retention may predispose women to long-term overweight and other health problems. Intervention studies aiming at preventing excessive pregnancy-related weight gain are needed. The feasibility of implementing such a study protocol in primary health care setting was evaluated in this pilot study. Methods A non-randomized controlled trial was conducted in three intervention and three control maternity and child health clinics in primary health care in Finland. Altogether, 132 pregnant and 92 postpartum women and 23 public health nurses (PHN participated in the study. The intervention consisted of individual counselling on physical activity and diet at five routine visits to a PHN and of an option for supervised group exercise until 37 weeks' gestation or ten months postpartum. The control clinics continued their usual care. The components of the feasibility evaluation were 1 recruitment and participation, 2 completion of data collection, 3 realization of the intervention and 4 the public health nurses' experiences. Results 1 The recruitment rate was slower than expected and the recruitment period had to be prolonged from the initially planned three months to six months. The average participation rate of eligible women at study enrolment was 77% and the drop-out rate 15%. 2 In total, 99% of the data on weight, physical activity and diet and 96% of the blood samples were obtained. 3 In the intervention clinics, 98% of the counselling sessions were realized, their contents and average durations were as intended, 87% of participants regularly completed the weekly records for physical activity and diet, and the average participation percentage in the group exercise sessions was 45%. 4 The PHNs regarded the extra training as a major advantage and the high additional workload as a disadvantage of the study. Conclusion The study protocol was mostly feasible to implement, which

The Sheep as a Model of Preclinical Safety and Pharmacokinetic Evaluations of Candidate Microbicides

OpenAIRE

Holt, Jonathon D. S.; Cameron, David; Dias, Nicola; Holding, Jeremy; Muntendam, Alex; Oostebring, Freddy; Dreier, Peter; Rohan, Lisa; Nuttall, Jeremy

2015-01-01

When developing novel microbicide products for the prevention of HIV infection, the preclinical safety program must evaluate not only the active pharmaceutical ingredient but also the product itself. To that end, we applied several relatively standard toxicology study methodologies to female sheep, incorporating an assessment of the pharmacokinetics, safety, tolerability, and local toxicity of a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal Ring-004). We performed a...

Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1.

Science.gov (United States)

Telwatte, Sushama; Moore, Katie; Johnson, Adam; Tyssen, David; Sterjovski, Jasminka; Aldunate, Muriel; Gorry, Paul R; Ramsland, Paul A; Lewis, Gareth R; Paull, Jeremy R A; Sonza, Secondo; Tachedjian, Gilda

2011-06-01

Topical microbicides for use by women to prevent the transmission of human immunodeficiency virus (HIV) and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. SPL7013 is a dendrimer with broad-spectrum activity against HIV type I (HIV-1) and -2 (HIV-2), herpes simplex viruses type-1 (HSV-1) and -2 (HSV-2) and human papillomavirus. SPL7013 [3% (w/w)] has been formulated in a mucoadhesive carbopol gel (VivaGel®) for use as a topical microbicide. Previous studies showed that SPL7013 has similar potency against CXCR4-(X4) and CCR5-using (R5) strains of HIV-1 and that it blocks viral entry. However, the ability of SPL7013 to directly inactivate HIV-1 is unknown. We examined whether SPL7013 demonstrates virucidal activity against X4 (NL4.3, MBC200, CMU02 clade EA and 92UG046 clade D), R5 (Ba-L, NB25 and 92RW016 clade A) and dual-tropic (R5X4; MACS1-spln) HIV-1 using a modified HLA-DR viral capture method and by polyethylene glycol precipitation. Evaluation of virion integrity was determined by ultracentrifugation through a sucrose cushion and detection of viral proteins by Western blot analysis. SPL7013 demonstrated potent virucidal activity against X4 and R5X4 strains, although virucidal activity was less potent for the 92UG046 X4 clade D isolate. Where potent virucidal activity was observed, the 50% virucidal concentrations were similar to the 50% effective concentrations previously reported in drug susceptibility assays, indicating that the main mode of action of SPL7013 is by direct viral inactivation for these strains. In contrast, SPL7013 lacked potent virucidal activity against R5 HIV-1 strains. Evaluation of the virucidal mechanism showed that SPL7013-treated NL4.3, 92UG046 and MACS1-spln virions were intact with no significant decrease in gp120 surface protein with respect to p24 capsid content compared to the corresponding untreated virus. These studies demonstrate that SPL

Alcohol and disadvantaged men: A feasibility trial of an intervention delivered by mobile phone.

Science.gov (United States)

Crombie, Iain K; Irvine, Linda; Falconer, Donald W; Williams, Brian; Ricketts, Ian W; Jones, Claire; Humphris, Gerry; Norrie, John; Slane, Peter; Rice, Peter

2017-07-01

Disadvantaged men suffer substantial harm from heavy drinking. This feasibility study developed and evaluated the methods for a trial of a brief intervention delivered by text messages to disadvantaged men. It aimed to test the methods for recruitment and retention, to monitor engagement with the intervention and assess the overall acceptability of study methods. Disadvantaged men aged 25-44 years who had ≥2 episodes of binge drinking (≥8 units in one session) in the preceding month were recruited. Two recruitment strategies were assessed: recruitment from general practice registers and by a community outreach strategy. Theoretically and empirically based text messages were tailored to the target group. The study recruited 67 disadvantaged men at high risk of alcohol-related harm, exceeding the target of 60. Evaluation showed that 95% of text messages were delivered, and the men engaged enthusiastically with the intervention. Retention at follow up was 96%. Outcomes were successfully measured on all men followed up. This provided data for the sample size calculation for the full trial. Post-study evaluation showed high levels of satisfaction with the study. This study has shown that disadvantaged men can be recruited and follow-up data obtained in an alcohol intervention study. The study methods were acceptable to the participants. The men recruited were at high risk of alcohol-related harms. It also clarified ways in which the recruitment strategy, the baseline questionnaire and the intervention could be improved. The full trial is currently underway. [Crombie IK, Irvine L, Falconer DW, Williams B, Ricketts IW, Jones C, Humphris G, Norrie J, Slane P, Rice P. Alcohol and disadvantaged men: A feasibility trial of an intervention delivered by mobile phone. Drug Alcohol Rev 2017;36:468-476]. © 2017 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.

A randomized controlled trial to evaluate the feasibility of the Wii Fit for improving walking in older adults with lower limb amputation.

Science.gov (United States)

Imam, Bita; Miller, William C; Finlayson, Heather; Eng, Janice J; Jarus, Tal

2017-01-01

To assess the feasibility of Wii.n.Walk for improving walking capacity in older adults with lower limb amputation. A parallel, evaluator-blind randomized controlled feasibility trial. Community-living. Individuals who were ⩾50 years old with a unilateral lower limb amputation. Wii.n.Walk consisted of Wii Fit training, 3x/week (40 minute sessions), for 4 weeks. Training started in the clinic in groups of 3 and graduated to unsupervised home training. Control group were trained using cognitive games. Feasibility indicators: trial process (recruitment, retention, participants' perceived benefit from the Wii.n.Walk intervention measured by exit questionnaire), resources (adherence), management (participant processing, blinding), and treatment (adverse event, and Cohen's d effect size and variance). Primary clinical outcome: walking capacity measured using the 2 Minute Walk Test at baseline, end of treatment, and 3-week retention. Of 28 randomized participants, 24 completed the trial (12/arm). Median (range) age was 62.0 (50-78) years. Mean (SD) score for perceived benefit from the Wii.n.Walk intervention was 38.9/45 (6.8). Adherence was 83.4%. The effect sizes for the 2 Minute Walk Test were 0.5 (end of treatment) and 0.6 (3-week retention) based on intention to treat with imputed data; and 0.9 (end of treatment) and 1.2 (3-week retention) based on per protocol analysis. The required sample size for a future larger RCT was deemed to be 72 (36 per arm). The results suggested the feasibility of the Wii.n.Walk with a medium effect size for improving walking capacity. Future larger randomized controlled trials investigating efficacy are warranted.

Texting to increase adolescent physical activity: Feasibility assessment

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Feasibility trials assess whether a behavior change program warrants a definite trial evaluation. This paper reports the feasibility of an intervention consisting of Self Determination Theory-informed text messages, pedometers, and goal prompts to increase adolescent physical activity. A 4-group ran...

Comparison of group-based outpatient physiotherapy with usual care after total knee replacement: a feasibility study for a randomized controlled trial.

Science.gov (United States)

Artz, Neil; Dixon, Samantha; Wylde, Vikki; Marques, Elsa; Beswick, Andrew D; Lenguerrand, Erik; Blom, Ashley W; Gooberman-Hill, Rachael

2017-04-01

To evaluate the feasibility of conducting a randomized controlled trial comparing group-based outpatient physiotherapy with usual care in patients following total knee replacement. A feasibility study for a randomized controlled trial. One secondary-care hospital orthopaedic centre, Bristol, UK. A total of 46 participants undergoing primary total knee replacement. The intervention group were offered six group-based exercise sessions after surgery. The usual care group received standard postoperative care. Participants were not blinded to group allocation. Feasibility was assessed by recruitment, reasons for non-participation, attendance, and completion rates of study questionnaires that included the Lower Extremity Functional Scale and Knee Injury and Osteoarthritis Outcome Score. Recruitment rate was 37%. Five patients withdrew or were no longer eligible to participate. Intervention attendance was high (73%) and 84% of group participants reported they were 'very satisfied' with the exercises. Return of study questionnaires at six months was lower in the usual care (75%) than in the intervention group (100%). Mean (standard deviation) Lower Extremity Functional Scale scores at six months were 45.0 (20.8) in the usual care and 57.8 (15.2) in the intervention groups. Recruitment and retention of participants in this feasibility study was good. Group-based physiotherapy was acceptable to participants. Questionnaire return rates were lower in the usual care group, but might be enhanced by telephone follow-up. The Lower Extremity Functional Scale had high responsiveness and completion rates. Using this outcome measure, 256 participants would be required in a full-scale randomized controlled trial.

Curcumin as a potential non-steroidal contraceptive with spermicidal and microbicidal properties.

Science.gov (United States)

Naz, R K; Lough, M L

2014-05-01

Curcumin, a component of the curry powder turmeric, has immense biological properties, including anticancer effects. The objective of this study was to determine if curcumin can provide a novel non-steroidal contraceptive having both spermicidal and microbicidal properties. The effect of curcumin, with and without photosensitization, was examined on human sperm forward motility and growth of several aerobic (n=8) and anaerobic bacteria (n=4) and yeast (n=7) strains implicated in vaginosis, vaginitis, and vaginal infections in women. The effect of various concentrations of curcumin on human sperm and microbes (aerobic and anaerobic bacteria and yeast) was tested. The effect on sperm was examined by counting the sperm forward motility, and on microbes by agar and broth dilutions and colony counting. Each experiment was repeated using different semen specimens, and bacteria and yeast stocks. Curcumin caused a concentration-dependent inhibition of sperm forward motility with a total block at ≥250μM concentration. After photosensitization, the effective concentration to completely block sperm forward motility decreased 25-fold, now requiring only 10μM concentration for total inhibition. Curcumin concentrations between 100 and 500μM completely blocked the growth of all the bacteria and yeast strains tested. After photosensitization, the effective concentration to completely inhibit microbial growth decreased 10-fold for aerobic bacteria and yeast, and 5-fold for anaerobic bacteria. These findings suggest that curcumin can block sperm function and bacteria/yeast growth. It can potentially provide an ideal non-steroidal contraceptive having both spermicidal and microbicidal properties against vaginal infections. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Feasibility and preliminary effectiveness of ice therapy in patients with an acute tear in the gastrocnemius muscle: a pilot randomized controlled trial.

Science.gov (United States)

Prins, Jan C M; Stubbe, Janine H; van Meeteren, Nico L U; Scheffers, Frans A; van Dongen, Martien C J M

2011-05-01

To investigate the feasibility of a randomized controlled trial and the preliminary effectiveness of ice therapy in the acute phase of a gastrocnemius tear for the quality of functional recovery. A pilot version of an intended prospective randomized controlled clinical trial was conducted. A total of 19 patients with an acute tear in the gastrocnemius muscle were randomly allocated to either active or control treatment. The intervention consisted of the repeated application of crushed ice. Primary outcome measures were functional capacity and reconvalescence time. Secondary outcome measures were pain and work absenteeism. The number of patients we could include within the 6-hour time window and dropping out from the pilot study were regarded as indicators of the feasibility of ice therapy. A total of 16 patients were excluded from the study because diagnosis was not made within 6 hours after onset of the complaint. The 19 patients included completed the treatment. For functional capacity, reconvalescence time, work absenteeism and pain relief, no significant differences between the intervention and control group were found. The execution of a randomized controlled trial on ice therapy for acute gastrocnemius tear is feasible though quite an enterprise. First, it is recommended to improve the recruitment processes. Second, power analysis demands inclusion of 396 participants. Preliminary effectiveness in our limited-sized trial indicates that the use of ice is not beneficial for people who receive ice therapy.

A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

Science.gov (United States)

2012-01-01

Background Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Methods Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets) are the main outcome measures reported. Results There was a high rate of dropout (51%) from the study, and the rates were significantly higher among smokers (64%) than non-smokers (36%). Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout) and non-smokers (18% dropout). Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%), but was associated with the lowest rate of dropout among non-smokers (4%). Conclusions In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials. Trial registration number ISRCTN70410203 PMID:22800470

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention

OpenAIRE

Palanee-Phillips, Thesla; Schwartz, Katie; Brown, Elizabeth R.; Govender, Vaneshree; Mgodi, Nyaradzo; Kiweewa, Flavia Matovu; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Naidoo, Sarita

2015-01-01

Introduction Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. Methods ASPIRE (A Study to Prevent Infe...

What Value Can Qualitative Research Add to Quantitative Research Design? An Example From an Adolescent Idiopathic Scoliosis Trial Feasibility Study.

Science.gov (United States)

Toye, Francine; Williamson, Esther; Williams, Mark A; Fairbank, Jeremy; Lamb, Sarah E

2016-08-09

Using an example of qualitative research embedded in a non-surgical feasibility trial, we explore the benefits of including qualitative research in trial design and reflect on epistemological challenges. We interviewed 18 trial participants and used methods of Interpretive Phenomenological Analysis. Our findings demonstrate that qualitative research can make a valuable contribution by allowing trial stakeholders to see things from alternative perspectives. Specifically, it can help to make specific recommendations for improved trial design, generate questions which contextualize findings, and also explore disease experience beyond the trial. To make the most out of qualitative research embedded in quantitative design it would be useful to (a) agree specific qualitative study aims that underpin research design, (b) understand the impact of differences in epistemological truth claims, (c) provide clear thematic interpretations for trial researchers to utilize, and (d) include qualitative findings that explore experience beyond the trial setting within the impact plan. © The Author(s) 2016.

Restrictive vs Liberal Blood Transfusion for Acute Upper Gastrointestinal Bleeding: Rationale and Protocol for a Cluster Randomized Feasibility Trial

Science.gov (United States)

Jairath, Vipul; Kahan, Brennan C.; Gray, Alasdair; Doré, Caroline J.; Mora, Ana; Dyer, Claire; Stokes, Elizabeth A.; Llewelyn, Charlotte; Bailey, Adam A.; Dallal, Helen; Everett, Simon M.; James, Martin W.; Stanley, Adrian J.; Church, Nicholas; Darwent, Melanie; Greenaway, John; Le Jeune, Ivan; Reckless, Ian; Campbell, Helen E.; Meredith, Sarah; Palmer, Kelvin R.; Logan, Richard F.A.; Travis, Simon P.L.; Walsh, Timothy S.; Murphy, Michael F.

2013-01-01

Acute upper gastrointestinal bleeding (AUGIB) is the commonest reason for hospitalization with hemorrhage in the UK and the leading indication for transfusion of red blood cells (RBCs). Observational studies suggest an association between more liberal RBC transfusion and adverse patient outcomes, and a recent randomised trial reported increased further bleeding and mortality with a liberal transfusion policy. TRIGGER (Transfusion in Gastrointestinal Bleeding) is a pragmatic, cluster randomized trial which aims to evaluate the feasibility and safety of implementing a restrictive versus liberal RBC transfusion policy in adult patients admitted with AUGIB. The trial will take place in 6 UK hospitals, and each centre will be randomly allocated to a transfusion policy. Clinicians throughout each hospital will manage all eligible patients according to the transfusion policy for the 6-month trial recruitment period. In the restrictive centers, patients become eligible for RBC transfusion when their hemoglobin is bleeding, mortality, thromboembolic events, and infections. Quality of life will be measured using the EuroQol EQ-5D at day 28, and the costs associated with hospitalization for AUGIB in the UK will be estimated. Consent will be sought from participants or their representatives according to patient capacity for use of routine hospital data and day 28 follow up. The study has ethical approval for conduct in England and Scotland. Results will be analysed according to a pre-defined statistical analysis plan and disseminated in peer reviewed publications to relevant stakeholders. The results of this study will inform the feasibility and design of a phase III randomized trial. PMID:23706959

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial

Science.gov (United States)

Hollands, Kristen L.; Pelton, Trudy A.; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M.; Wing, Alan M.; Tyson, Sarah F.; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M.

2015-01-01

Objectives Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. Design This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services Participants Community dwelling stroke survivors with walking speed adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Trial Registration Clinicaltrials.gov NCT01600391 PMID:26445137

Update on microbicide research and development-seeking new HIV prevention tools for women

Directory of Open Access Journals (Sweden)

Mertenskoetter T

2011-01-01

Full Text Available Abstract Women and girls are especially vulnerable to HIV infection in sub-Saharan Africa, and in some of those countries, prevalence among young women can be up to 3 times higher than among men of the same age. Effective HIV prevention options for women are clearly needed in this setting. Several ARV-based vaginal microbicides are currently in development for prevention of HIV transmission to women and are discussed here. The concept of pre-exposure prophylaxis for the prevention of HIV transmission to women is introduced.

The feasibility of a home-based sedentary behaviour intervention for hospitalised chronic obstructive pulmonary disease (COPD patients: Sitting and ExacerbAtions Trial (COPD-SEAT

Directory of Open Access Journals (Sweden)

Mark Orme

2015-10-01

COPD-SEAT will be one of the first trials aimed at reducing sedentary behaviour at home in patients hospitalised for an acute exacerbation of COPD. This trial will provide valuable insight into the feasibility of implementing an at-home technology-based feedback intervention for reducing sedentary behaviour into patients existing care. Findings will inform a future large-scale trial acting as an adjuvant to pulmonary rehabilitation.

Vocational rehabilitation services for patients with cancer: design of a feasibility study incorporating a pilot randomised controlled trial among women with breast cancer following surgery

Directory of Open Access Journals (Sweden)

Ayansina Dolapo

2011-03-01

Full Text Available Abstract Background Due to improvements in cancer survival the number of people of working age living with cancer across Europe is likely to increase. UK governments have made commitments to reduce the number of working days lost to ill-health and to improve access to vocational rehabilitation (VR services. Return to work for people with cancer has been identified as a priority. However, there are few services to support people to remain in or return to work after cancer and no associated trials to assess their impact. A pilot randomised controlled trial among women with breast cancer has been designed to assess the feasibility of a larger definitive trial of VR services for people with cancer. Methods Patients are being recruited from three clinical sites in two Scottish National Health Service (NHS Boards for 6 months. Eligible patients are all women who are: (1 aged between 18 and 65 years; (2 in paid employment or self-employed; (3 living or working in Lothian or Tayside, Scotland, UK; (4 diagnosed with an invasive breast cancer tumour; (5 treated first with surgery. Patients are randomly allocated to receive referral to a VR service or usual care, which involves no formal employment support. The primary outcome measure is self-reported sickness absence in the first 6 months following surgery. Secondary outcome measures include changes in quality of life (FACT-B, fatigue (FACIT-Fatigue and employment status between baseline and 6- and 12-months post-surgery. A post-trial evaluation will be conducted to assess the acceptability of the intervention among participants and the feasibility of a larger, more definitive, trial with patients with lung and prostate cancer. Discussion To our knowledge this is the first study to determine the feasibility of a randomised controlled trial of the effectiveness of VR services to enable people with cancer to remain in or return to employment. The study will provide evidence to assess the relevance and

12 A multi-centre randomised feasibility study evaluating the impact of a prognostic model for management of blunt chest wall trauma patients: stumbl trial.

Science.gov (United States)

Battle, Ceri; Hutchings, Hayley; Abbott, Zoe; O'neill, Claire; Groves, Sam; Watkins, Alan; Lecky, Fiona; Jones, Sally; Gagg, James; Body, Rick; Evans, Phillip

2017-12-01

A new prognostic model has been developed and externally validated, the aim of which is to assist in the management of the blunt chest wall trauma patient in the Emergency Department (ED). A definitive randomised controlled trial (impact trial), is required to assess the clinical and cost effectiveness of the new model, before it can be accepted in clinical practice. The purpose of this trial is to assess the feasibility and acceptability of such a definitive trial and inform its design. This feasibility trial is designed to test the methods of a multi-centre, cluster-randomised (stepped wedge) trial, with a substantial qualitative component. Four EDs in England and Wales will collect data for all blunt chest wall trauma patients over a five month period; in the initial period acting as the controls (normal care) and the second period, acting as the interventions (in which the new model will be used). Baseline measurements including completion of the SF-12v2 will be obtained on initial assessment in the ED. Patient outcome data will then be collected for any subsequent hospitalisations. Data collection will conclude with a six week follow-up completion of two surveys (SF-12v2 and Client Services Receipt Inventory).Analysis of outcomes will focus on feasibility, acceptability and trial processes and will include recruitment and retention rates, attendance at clinician training rates and use of model in the ED. Qualitative feedback will be obtained through clinician interviews and a research nurse focus group. An evaluation of the feasibility of health economics outcomes data will be completed. Wales Research Ethics Committee 6 granted approval for the trial in September 2016. Health Care Research Wales Research Permissions and the HRA have granted approval for the study. Patient recruitment commenced in February 2017. Planned dissemination is through publication in a peer-reviewed Emergency Medicine Journal, presentation at appropriate conferences and to

Wordless intervention for epilepsy in learning disabilities (WIELD): study protocol for a randomized controlled feasibility trial.

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Durand, Marie-Anne; Gates, Bob; Parkes, Georgina; Zia, Asif; Friedli, Karin; Barton, Garry; Ring, Howard; Oostendorp, Linda; Wellsted, David

2014-11-20

Epilepsy is the most common neurological problem that affects people with learning disabilities. The high seizure frequency, resistance to treatments, associated skills deficit and co-morbidities make the management of epilepsy particularly challenging for people with learning disabilities. The Books Beyond Words booklet for epilepsy uses images to help people with learning disabilities manage their condition and improve quality of life. Our aim is to conduct a randomized controlled feasibility trial exploring key methodological, design and acceptability issues, in order to subsequently undertake a large-scale randomized controlled trial of the Books Beyond Words booklet for epilepsy. We will use a two-arm, single-centre randomized controlled feasibility design, over a 20-month period, across five epilepsy clinics in Hertfordshire, United Kingdom. We will recruit 40 eligible adults with learning disabilities and a confirmed diagnosis of epilepsy and will randomize them to use either the Books Beyond Words booklet plus usual care (intervention group) or to receive routine information and services (control group). We will collect quantitative data about the number of eligible participants, number of recruited participants, demographic data, discontinuation rates, variability of the primary outcome measure (quality of life: Epilepsy and Learning Disabilities Quality of Life scale), seizure severity, seizure control, intervention's patterns of use, use of other epilepsy-related information, resource use and the EQ-5D-5L health questionnaire. We will also gather qualitative data about the feasibility and acceptability of the study procedures and the Books Beyond Words booklet. Ethical approval for this study was granted on 28 April 2014, by the Wales Research Ethics Committee 5. Recruitment began on 1 July 2014. The outcomes of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the impact of

The Child and Adolescent Trial for Cardiovascular Health (CATCH): intervention, implementation, and feasibility for elementary schools in the United States.

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Perry, C L; Sellers, D E; Johnson, C; Pedersen, S; Bachman, K J; Parcel, G S; Stone, E J; Luepker, R V; Wu, M; Nader, P R; Cook, K

1997-12-01

The Child and Adolescent Trial for Cardiovascular Health (CATCH) was the largest school-based field trial ever sponsored by the National Institutes of Health. The trial demonstrated positive changes in the school food service and physical education program, as well as in students' cardiovascular health behaviors. Because the CATCH intervention programs were implemented in 56 schools (in four states) that were typical of schools throughout the United States, their reception by schools and degree of implementation provide evidence about their feasibility for schools nationally. Extensive process evaluation data were collected from students, teachers, school food service personnel, and physical education specialists throughout the three school years of the CATCH intervention. Four of the CATCH programs--school food service, physical education, classroom curricula, and home programs--were assessed over the three school years. The process data provide information on participation, dose, fidelity, and compatibility of the CATCH programs in the intervention schools for these programs. High levels of participation, dose, fidelity, and compatibility were observed for the four programs during the 3 school years. CATCH emerges as a model of a feasible multilevel health promotion program to improve eating and exercise behaviors for elementary schools in the United States.

Findings of the Chronic Obstructive Pulmonary Disease-Sitting and Exacerbations Trial (COPD-SEAT) in Reducing Sedentary Time Using Wearable and Mobile Technologies With Educational Support: Randomized Controlled Feasibility Trial.

Science.gov (United States)

Orme, Mark W; Weedon, Amie E; Saukko, Paula M; Esliger, Dale W; Morgan, Mike D; Steiner, Michael C; Downey, John W; Sherar, Lauren B; Singh, Sally J

2018-04-11

Targeting sedentary time post exacerbation may be more relevant than targeting structured exercise for individuals with chronic obstructive pulmonary disease. Focusing interventions on sitting less and moving more after an exacerbation may act as a stepping stone to increase uptake to pulmonary rehabilitation. The aim of this paper was to conduct a randomized trial examining trial feasibility and the acceptability of an education and self-monitoring intervention using wearable technology to reduce sedentary behavior for individuals with chronic obstructive pulmonary disease admitted to hospital for an acute exacerbation. Participants were recruited and randomized in hospital into 3 groups, with the intervention lasting 2 weeks post discharge. The Education group received verbal and written information about reducing their time in sedentary behavior, sitting face-to-face with a study researcher. The Education+Feedback group received the same education component along with real-time feedback on their sitting time, stand-ups, and steps at home through a waist-worn inclinometer linked to an app. Patients were shown how to use the technology by the same study researcher. The inclinometer also provided vibration prompts to encourage movement at patient-defined intervals of time. Patients and health care professionals involved in chronic obstructive pulmonary disease exacerbation care were interviewed to investigate trial feasibility and acceptability of trial design and methods. Main quantitative outcomes of trial feasibility were eligibility, uptake, and retention, and for acceptability, were behavioral responses to the vibration prompts. In total, 111 patients were approached with 33 patients recruited (11 Control, 10 Education, and 12 Education+Feedback). Retention at 2-week follow-up was 52% (17/33; n=6 for Control, n=3 for Education, and n=8 for Education+Feedback). No study-related adverse events occurred. Collectively, patients responded to 106 out of 325

Effect of intermediate care on mortality following emergency abdominal surgery. The InCare trial: study protocol, rationale and feasibility of a randomised multicentre trial

Directory of Open Access Journals (Sweden)

Vester-Andersen Morten

2013-02-01

Full Text Available Abstract Background Emergency abdominal surgery carries a 15% to 20% short-term mortality rate. Postoperative medical complications are strongly associated with increased mortality. Recent research suggests that timely recognition and effective management of complications may reduce mortality. The aim of the present trial is to evaluate the effect of postoperative intermediate care following emergency major abdominal surgery in high-risk patients. Methods and design The InCare trial is a randomised, parallel-group, non-blinded clinical trial with 1:1 allocation. Patients undergoing emergency laparotomy or laparoscopic surgery with a perioperative Acute Physiology and Chronic Health Evaluation II score of 10 or above, who are ready to be transferred to the surgical ward within 24 h of surgery are allocated to either intermediate care for 48 h, or surgical ward care. The primary outcome measure is all-cause 30-day mortality. We aim to enrol 400 patients in seven Danish hospitals. The sample size allows us to detect or refute a 34% relative risk reduction of mortality with 80% power. Discussion This trial evaluates the benefits and possible harm of intermediate care. The results may potentially influence the survival of many high-risk surgical patients. As a pioneer trial in the area, it will provide important data on the feasibility of future large-scale randomised clinical trials evaluating different levels of postoperative care. Trial registration Clinicaltrials.gov identifier: NCT01209663

Feasibility of Conducting a Randomized Trial to Promote Healthy Eating, Active Play and Sustainability Awareness in Early Childhood Curricula

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Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie Margaret; Cutter-Mackenzie, Amy; O'Connor, Amanda; Mantilla, Ana; Huang, Terry TK; Lording, Kate Marion; Williams-Smith, Janet

2016-01-01

We sought to evaluate the feasibility of conducting a randomized trial to evaluate the efficacy of a preschool/kindergarten curriculum intervention designed to increase 4-year-old children's knowledge of healthy eating, active play and the sustainability consequences of their food and toy choices. Ninety intervention and 65 control parent/child…

Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial.

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Jairath, Vipul; Kahan, Brennan C; Gray, Alasdair; Doré, Caroline J; Mora, Ana; James, Martin W; Stanley, Adrian J; Everett, Simon M; Bailey, Adam A; Dallal, Helen; Greenaway, John; Le Jeune, Ivan; Darwent, Melanie; Church, Nicholas; Reckless, Ian; Hodge, Renate; Dyer, Claire; Meredith, Sarah; Llewelyn, Charlotte; Palmer, Kelvin R; Logan, Richard F; Travis, Simon P; Walsh, Timothy S; Murphy, Michael F

2015-07-11

Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised trial is a feasible method to substantiate or refute this finding. In this pragmatic, open-label, cluster randomised feasibility trial, done in six university hospitals in the UK, we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding, irrespective of comorbidity, except for exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer-generated randomisation sequence (random permuted block size of 6, without stratification or matching) to either a restrictive (transfusion when haemoglobin concentration fell below 80 g/L) or liberal (transfusion when haemoglobin concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor investigators were masked to treatment allocation. Feasibility outcomes were recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure, selection bias, and information to guide design and economic evaluation of the phase 3 trial. Main exploratory clinical outcomes were further bleeding and mortality at day 28. We did analyses on all enrolled patients for whom an outcome was available. This trial is registered, ISRCTN85757829 and NCT02105532. Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients across six hospitals (403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy). Recruitment rate was significantly higher for the liberal than for the restrictive policy (62% vs 55%; p=0·04). Despite some baseline imbalances, Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% (SD 10) in

Illness Management & Recovery (IMR) in the Netherlands : A naturalistic pilot study to explore the feasibility of a randomized controlled trial

NARCIS (Netherlands)

Roosenschoon, B.J.; Van Weeghel, J.; Bogaards, M.; Deen, M.L.; Mulder, C.L.

2016-01-01

Background Illness Management & Recovery (IMR) is a curriculum-based program for people with severe and persistent mental illness. To date, four randomized controlled trials (RCTs) have been published on it. As these produced mixed results, we conducted a pilot study to test the feasibility of

The Community Navigator Study: a feasibility randomised controlled trial of an intervention to increase community connections and reduce loneliness for people with complex anxiety or depression.

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Lloyd-Evans, Brynmor; Bone, Jessica K; Pinfold, Vanessa; Lewis, Glyn; Billings, Jo; Frerichs, Johanna; Fullarton, Kate; Jones, Rebecca; Johnson, Sonia

2017-10-23

Loneliness is associated with poor health outcomes at all ages, including shorter life expectancy and greater risk of developing depression. People with mental health problems are particularly vulnerable to loneliness and, for those with anxiety or depression, loneliness is associated with poorer outcomes. Interventions which support people to utilise existing networks and access new social contact are advocated in policy but there is little evidence regarding their effectiveness. People with mental health problems have potential to benefit from interventions to reduce loneliness, but evidence is needed regarding their feasibility, acceptability and outcomes. An intervention to reduce loneliness for people with anxiety or depression treated in secondary mental health services was developed for this study, which will test the feasibility and acceptability of delivering and evaluating it through a randomised controlled trial. In this feasibility trial, 40 participants with anxiety or depression will be recruited through two secondary mental health services in London and randomised to an intervention (n = 30) or control group (n = 10). The control group will receive standard care and written information about local community resources. The coproduced intervention, developed in this study, includes up to ten sessions with a 'Community Navigator' over a 6-month period. Community Navigators will work with people individually to increase involvement in social activities, with the aim of reducing feelings of loneliness. Data will be collected at baseline and at 6-month follow-up - the end of the intervention period. The acceptability of the intervention and feasibility of participant recruitment and retention will be assessed. Potential primary and secondary outcomes for a future definitive trial will be completed to assess response and completeness, including measures of loneliness, depression and anxiety. Qualitative interviews with participants, staff and other

Feasibility and acceptability of the DSM-5 Field Trial procedures in the Johns Hopkins Community Psychiatry Programs†

Science.gov (United States)

Clarke, Diana E.; Wilcox, Holly C.; Miller, Leslie; Cullen, Bernadette; Gerring, Joan; Greiner, Lisa H.; Newcomer, Alison; Mckitty, Mellisha V.; Regier, Darrel A.; Narrow, William E.

2014-01-01

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) contains criteria for psychiatric diagnoses that reflect advances in the science and conceptualization of mental disorders and address the needs of clinicians. DSM-5 also recommends research on dimensional measures of cross-cutting symptoms and diagnostic severity, which are expected to better capture patients’ experiences with mental disorders. Prior to its May 2013 release, the American Psychiatric Association (APA) conducted field trials to examine the feasibility, clinical utility, reliability, and where possible, the validity of proposed DSM-5 diagnostic criteria and dimensional measures. The methods and measures proposed for the DSM-5 field trials were pilot tested in adult and child/adolescent clinical samples, with the goal to identify and correct design and procedural problems with the proposed methods before resources were expended for the larger DSM-5 Field Trials. Results allowed for the refinement of the protocols, procedures, and measures, which facilitated recruitment, implementation, and completion of the DSM-5 Field Trials. These results highlight the benefits of pilot studies in planning large multisite studies. PMID:24615761

Isoosmolar enemas demonstrate preferential gastrointestinal distribution, safety, and acceptability compared with hyperosmolar and hypoosmolar enemas as a potential delivery vehicle for rectal microbicides.

Science.gov (United States)

Leyva, Francisco J; Bakshi, Rahul P; Fuchs, Edward J; Li, Liye; Caffo, Brian S; Goldsmith, Arthur J; Ventuneac, Ana; Carballo-Diéguez, Alex; Du, Yong; Leal, Jeffrey P; Lee, Linda A; Torbenson, Michael S; Hendrix, Craig W

2013-11-01

Rectally applied antiretroviral microbicides for preexposure prophylaxis (PrEP) of HIV infection are currently in development. Since enemas (rectal douches) are commonly used by men who have sex with men prior to receptive anal intercourse, a microbicide enema could enhance PrEP adherence by fitting seamlessly within the usual sexual practices. We assessed the distribution, safety, and acceptability of three enema types-hyperosmolar (Fleet), hypoosmolar (distilled water), and isoosmolar (Normosol-R)-in a crossover design. Nine men received each enema type in random order. Enemas were radiolabeled [(99m)Tc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma (99m)Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the (99m)Tc-DTPA. Acceptability was assessed after each product use and at the end of the study. SPECT/CT imaging showed that the isoosmolar enema had greater proximal colonic distribution (up to the splenic flexure) and greater luminal and colon tissue concentrations of (99m)Tc-DTPA when compared to the other enemas (pgood with no clear preferences among the three enema types. The isoosmolar enema was superior or similar to the other enemas in all categories and is a good candidate for further development as a rectal microbicide vehicle.

Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.

Science.gov (United States)

das Neves, José; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

2012-06-01

To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.

Protocol for a feasibility cluster randomised controlled trial of a peer-led school-based intervention to increase the physical activity of adolescent girls (PLAN-A).

Science.gov (United States)

Sebire, Simon J; Edwards, Mark J; Campbell, Rona; Jago, Russell; Kipping, Ruth; Banfield, Kathryn; Tomkinson, Keeley; Garfield, Kirsty; Lyons, Ronan A; Simon, Joanne; Blair, Peter S; Hollingworth, William

2016-01-01

Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels. A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer-supporters. Approximately 15 % of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer-supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer-supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully-powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be largely descriptive and focus on recruitment, attendance and data provision rates. The findings will inform the sample size required for a

A Feasibility Randomised Controlled Trial of the New Orleans Intervention for Infant Mental Health: A Study Protocol

Directory of Open Access Journals (Sweden)

Rachel Pritchett

2013-01-01

Full Text Available Child maltreatment is associated with life-long social, physical, and mental health problems. Intervening early to provide maltreated children with safe, nurturing care can improve outcomes. The need for prompt decisions about permanent placement (i.e., regarding adoption or return home is internationally recognised. However, a recent Glasgow audit showed that many maltreated children “revolve” between birth families and foster carers. This paper describes the protocol of the first exploratory randomised controlled trial of a mental health intervention aimed at improving placement permanency decisions for maltreated children. This trial compares an infant's mental health intervention with the new enhanced service as usual for maltreated children entering care in Glasgow. As both are new services, the trial is being conducted from a position of equipoise. The outcome assessment covers various fields of a child’s neurodevelopment to identify problems in any ESSENCE domain. The feasibility, reliability, and developmental appropriateness of all outcome measures are examined. Additionally, the potential for linkage with routinely collected data on health and social care and, in the future, education is explored. The results will inform a definitive randomised controlled trial that could potentially lead to long lasting benefits for the Scottish population and which may be applicable to other areas of the world. This trial is registered with ClinicalTrials.gov (NC01485510.

Pregabalin versus placebo in targeting pro-nociceptive mechanisms to prevent chronic pain after whiplash injury in at-risk individuals - a feasibility study for a randomised controlled trial.

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Nikles, J; Keijzers, G; Mitchell, G; Schug, S; Ware, R; McLean, S A; Connelly, L; Gibson, S; Farrell, S F; Sterling, M

2018-01-17

Whiplash-associated disorders (WAD) are an enormous and costly burden to Australian society. Up to 50% of people who experience a whiplash injury will never fully recover. Whiplash is resistant to treatment and no early management approach has yet been shown to prevent chronic pain. The early presence of central sensitization is associated with poor recovery. Pregabalin's effects on central sensitization indicate the potential to prevent or modulate these processes after whiplash injury and to improve health outcomes, but this has not been investigated. This paper describes the protocol for a feasibility study for a randomised controlled trial of pregabalin plus evidence-based advice compared to placebo plus evidence-based advice for individuals with acute whiplash injury who are at risk of poor recovery. This double blind, placebo-controlled randomised feasibility study will examine the feasibility and potential effectiveness of pregabalin and evidence-based advice (intervention) compared to placebo and evidence-based advice (control) for individuals with acute whiplash injury at risk of poor recovery. Thirty participants (15 per group) aged 18-65 years with Grade II WAD, within 48 hours of injury and currently experiencing at least moderate pain (NRS: ≥ 5/10) will be recruited from Emergency Departments of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75 mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of weaning. The feasibility of trial procedures will be tested, as well as the potential effect of the intervention on the outcomes. The primary outcome of neck pain intensity at 3 months from randomisation will be compared between the treatment groups using standard analysis of variance techniques. Feasibility and potential effectiveness data will inform an appropriately powered full trial, which if successful, will provide an effective and cost-effective intervention for a costly and treatment

The epidemiology of HIV and HSV-2 infections among women participating in microbicide and vaccine feasibility studies in Northern Tanzania.

Directory of Open Access Journals (Sweden)

Saidi H Kapiga

Full Text Available To prepare for future HIV prevention trials, we conducted prospective cohort studies among women working in food and recreational facilities in northern Tanzania. We examined the prevalence and incidence of HIV and HSV-2, and associated risk factors.Women aged 18-44 years working in food and recreational facilities were screened to determine their eligibility for the studies. Between 2008-2010, HIV-negative women were enrolled and followed for 12 months. At enrolment and 3-monthly, we collected socio-demographic and behavioural data, and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections. Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models.We screened 2,229 and enrolled 1,378 women. The median age was 27 years (interquartile range, IQR 22, 33, and median duration working at current facility was 2 years. The prevalences of HIV at screening and HSV-2 at enrolment were 16% and 67%, respectively. Attendance at the 12-month visit was 86%. HIV and HSV-2 incidence rates were 3.7 (95% confidence interval, CI: 2.8,5.1 and 28.6 (95% CI: 23.5,35.0/100 person-years, respectively. Women who were separated, divorced, or widowed were at increased risk of HIV (adjusted incidence rate ratio, aRR = 6.63; 95% CI: 1.97,22.2 and HSV-2 (aRR = 2.00; 95% CI: 1.15,3.47 compared with married women. Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0-1 partner (aRR = 4.75; 95% CI: 2.10,10.8, while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education (aRR = 0.42; 95% CI: 0.22,0.82.HIV and HSV-2 rates remain substantially higher in this cohort than in the general population, indicating urgent need for effective interventions. These studies demonstrate the feasibility of conducting trials to test new interventions in this

Sugarsquare, a Web-Based Patient Portal for Parents of a Child With Type 1 Diabetes: Multicenter Randomized Controlled Feasibility Trial.

Science.gov (United States)

Boogerd, Emiel; Maas-Van Schaaijk, Nienke M; Sas, Theo C; Clement-de Boers, Agnes; Smallenbroek, Mischa; Nuboer, Roos; Noordam, Cees; Verhaak, Chris M

2017-08-22

Raising a child with type 1 diabetes (T1D) means combining the demands of the disease management with everyday parenting, which is associated with increased levels of distress. A Web-based patient portal, Sugarsquare, was developed to support parents, by providing online parent-professional communication, online peer support and online disease information. The first aim of this study was to assess the feasibility of conducting a multicenter, randomized controlled trial in Dutch parents of a child with T1D. The second aim was to assess the feasibility of implementing Sugarsquare in clinical practice. The parents of 105 children (N=105) with T1D below the age of 13 participated in a 6-month multicenter randomized controlled feasibility trial. They were randomly assigned to an experimental (n=54, usual care and Sugarsquare) or a control group (n=51, usual care). Attrition rates and user statistics were gathered to evaluate feasibility of the trial and implementation. To determine potential efficacy, the parenting stress index (PSI-SF) was assessed at baseline (T0) and after 6 months (T1). Of a potential population of parents of 445 children, 189 were willing to participate (enrollment refusal=57.5%, n=256), 142 filled in the baseline questionnaire (baseline attrition rate=25%, n=47), and 105 also filled in the questionnaire at T1 (post randomization attrition rate during follow-up=26%, n=32). As such, 24% of the potential population participated. Analysis in the experimental group (n=54) revealed a total of 32 (59%) unique users, divided into 12 (38%) frequent users, 9 (28%) incidental users, and 11 (34%) low-frequent users. Of the total of 44 professionals, 34 (77%) logged in, and 32 (73%) logged in repeatedly. Analysis of the user statistics in the experimental group further showed high practicability and integration in all users, moderate acceptability and demand in parents, and high acceptability and demand in health care professionals. Baseline parenting stress

Using conjoint analysis to measure the acceptability of rectal microbicides among men who have sex with men in four South American cities.

Science.gov (United States)

Kinsler, Janni J; Cunningham, William E; Nureña, César R; Nadjat-Haiem, Carsten; Grinsztejn, Beatriz; Casapia, Martin; Montoya-Herrera, Orlando; Sánchez, Jorge; Galea, Jerome T

2012-08-01

Conjoint Analysis (CJA), a statistical market-based technique that assesses the value consumers place on product characteristics, may be used to predict acceptability of hypothetical products. Rectal Microbicides (RM)-substances that would prevent HIV infection during receptive anal intercourse-will require acceptability data from potential users in multiple settings to inform the development process by providing valuable information on desirable product characteristics and issues surrounding potential barriers to product use. This study applied CJA to explore the acceptability of eight different hypothetical RM among 128 MSM in Lima and Iquitos, Peru; Guayaquil, Ecuador; and Rio de Janeiro, Brazil. Overall RM acceptability was highest in Guayaquil and lowest in Rio. Product effectiveness had the greatest impact on acceptability in all four cities, but the impact of other product characteristics varied by city. This study demonstrates that MSM from the same region but from different cities place different values on RM characteristics that could impact uptake of an actual RM. Understanding specific consumer preferences is crucial during RM product development, clinical trials and eventual product dissemination.

Recruiting young people with a visible difference to the YP Face IT feasibility trial: a qualitative exploration of primary care staff experiences.

Science.gov (United States)

Hamlet, Claire; Williamson, Heidi; Harcourt, Diana

2017-11-01

Qualitative research methods embedded within feasibility trials are of significant value as they can provide important information for a definitive trial, often unable to be fulfilled by quantitative methods alone. In addition, such information can aid researchers running other trials or evaluating interventions on a similar topic. Aim This study aimed to explore GP and nurses' experiences of recruiting to a trial exploring the feasibility of evaluating YP Face IT, a novel online psychosocial intervention to support young people with appearance-altering conditions. During the recruitment period, a focus group with participating GPs and nurses explored recruitment challenges. In addition, at the end of the recruitment period, telephone interviews were conducted with eight GPs and nurses involved in recruiting to the study, in order to inform a definitive trial of YP Face IT. Transcripts were subjected to thematic analysis. Findings Despite reporting that the study was valuable and interesting, interviewees struggled to recruit in-consultation. They appeared to lack confidence in raising the sensitive issue of a visible difference and adopted strategies to avoid mentioning the topic. Participants felt the nature of the target population, as well as pressures of the primary care environment presented challenges to recruitment, but welcomed YP Face IT as an intervention that could address unmet support needs. Primary care staff may benefit from training to help them raise the subject of a visible difference with young people in order to identify those that require additional support.

A feasibility randomised controlled trial of pre-operative occupational therapy to optimise recovery for patients undergoing primary total hip replacement for osteoarthritis (PROOF-THR).

Science.gov (United States)

Jepson, Paul; Sands, Gina; Beswick, Andrew D; Davis, Edward T; Blom, Ashley W; Sackley, Catherine M

2016-02-01

To assess the feasibility of a pre-operative occupational therapy intervention for patients undergoing primary total hip replacement. Single blinded feasibility randomised controlled trial, with data collection prior to the intervention, and at 4, 12, and 26 weeks following surgery. Recruitment from two NHS orthopaedic outpatient centres in the West Midlands, UK. Patients awaiting primary total hip replacement due to osteoarthritis were recruited. Following pre-operative assessment, patients were individually randomised to intervention or control by a computer-generated block randomisation algorithm stratified by age and centre. The intervention group received a pre-surgery home visit by an occupational therapist who discussed expectations, assessed home safety, and provided appropriate adaptive equipment. The control group received treatment as usual. The study assessed the feasibility of recruitment procedures, delivery of the intervention, appropriateness of outcome measures and data collection methods. Health related quality of life and resource use were recorded at 4, 12 and 26 weeks. Forty-four participants were recruited, 21 were randomised to the occupational therapy intervention and 23 to usual care. Analysis of 26 week data included 18 participants in the intervention group and 21 in the control. The intervention was delivered successfully with no withdrawals or crossovers; 5/44 were lost to follow-up with further missing data for participation and resource use. The feasibility study provided the information required to conduct a definitive trial. Burden of assessment would need to be addressed. A total of 219 patients would be required in an efficacy trial. © The Author(s) 2015.

Update to a protocol for a feasibility cluster randomised controlled trial of a peer-led school-based intervention to increase the physical activity of adolescent girls (PLAN-A).

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Sebire, Simon J; Edwards, Mark J; Campbell, Rona; Jago, Russell; Kipping, Ruth; Banfield, Kathryn; Kadir, Bryar; Garfield, Kirsty; Lyons, Ronan A; Blair, Peter S; Hollingworth, William

2016-01-01

Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence, and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels. In addition, this paper describes an update that has been made to the protocol for the PLAN-A feasibility cluster randomised controlled trial. A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer supporters. Approximately 15% of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be

Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

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Dezzutti Charlene

2011-03-01

Full Text Available Abstract Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic. Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products.

Feasibility and acceptability of the DSM-5 Field Trial procedures in the Johns Hopkins Community Psychiatry Programs.

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Clarke, Diana E; Wilcox, Holly C; Miller, Leslie; Cullen, Bernadette; Gerring, Joan; Greiner, Lisa H; Newcomer, Alison; McKitty, Mellisha V; Regier, Darrel A; Narrow, William E

2014-06-01

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) contains criteria for psychiatric diagnoses that reflect advances in the science and conceptualization of mental disorders and address the needs of clinicians. DSM-5 also recommends research on dimensional measures of cross-cutting symptoms and diagnostic severity, which are expected to better capture patients' experiences with mental disorders. Prior to its May 2013 release, the American Psychiatric Association (APA) conducted field trials to examine the feasibility, clinical utility, reliability, and where possible, the validity of proposed DSM-5 diagnostic criteria and dimensional measures. The methods and measures proposed for the DSM-5 field trials were pilot tested in adult and child/adolescent clinical samples, with the goal to identify and correct design and procedural problems with the proposed methods before resources were expended for the larger DSM-5 Field Trials. Results allowed for the refinement of the protocols, procedures, and measures, which facilitated recruitment, implementation, and completion of the DSM-5 Field Trials. These results highlight the benefits of pilot studies in planning large multisite studies. Copyright © 2013, American Psychiatric Association. All rights reserved.

Study of Optimal Replacement of Thyroxine in the Elderly (SORTED) - results from the feasibility randomised controlled trial.

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Razvi, Salman; Ingoe, Lorna; Ryan, Vicky; Pearce, Simon H S; Wilkes, Scott

2016-01-01

Hypothyroidism is a common condition, particularly in the older population. Thyroid hormone requirements change with age and serum TSH levels also alter, especially in older patients. However, in practice laboratory reference ranges for thyroid function are not age-specific and treatment in older patients aims to achieve a similar target thyroid function level as younger age groups. A dual centre, single blind, randomised controlled trial was conducted to determine the feasibility of a future definitive RCT in hypothyroid individuals aged 80 years or older who were treated with levothyroxine. Potential participants were identified from 17 research-active GP practices ( n  = 377), by opportunistic invitations ( n  = 9) or in response to publicity ( n  = 4). Participants were randomly allocated to either usual (0.4-4.0 mU/L) or a higher (4.1-8.0 mU/L) target serum TSH range. Information on participants' willingness to enter the trial, acceptability of study design, length of time to complete recruitment and dose titration strategy was collected. Fifteen percent (57/390) of potentially eligible hypothyroid individuals consented to participate in this trial and 48 were randomised to trial medication for 24 weeks, giving a recruitment rate of 12 %. Recruitment averaged 5.5 participants per month over approximately 9 months. Eight participants withdrew (3/24 and 5/24 in the usual and higher TSH arms, respectively) with the commonest reason cited (5 patients) being tiredness. Interestingly, 3/5 participants withdrew from the site that required a visit to a Research Facility whereas only 5/43 participants withdrew from the site that offered home visits. In the higher TSH arm, of those participants who completed the study, approximately half of participants (10/19) reached target TSH. It is feasible to perform a randomised controlled trial of thyroid hormones in hypothyroid patients aged 80 or older. A definitive trial would require collaboration with a

Culturally adaptive storytelling intervention versus didactic intervention to improve hypertension control in Vietnam: a cluster-randomized controlled feasibility trial.

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Nguyen, Hoa L; Allison, Jeroan J; Ha, Duc A; Chiriboga, Germán; Ly, Ha N; Tran, Hanh T; Nguyen, Cuong K; Dang, Diem M; Phan, Ngoc T; Vu, Nguyen C; Nguyen, Quang P; Goldberg, Robert J

2017-01-01

Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. Novel, large-scale, effective, and sustainable interventions to control hypertension in Vietnam are needed. We report the results of a cluster-randomized feasibility trial at 3 months follow-up conducted in Hung Yen province, Vietnam, designed to evaluate the feasibility and acceptability of two community-based interventions to improve hypertension control: a "storytelling" intervention, "We Talk about Our Hypertension," and a didactic intervention. The storytelling intervention included stories about strategies for coping with hypertension, with patients speaking in their own words, and didactic content about the importance of healthy lifestyle behaviors including salt reduction and exercise. The didactic intervention included only didactic content. The storytelling intervention was delivered by two DVDs at 3-month intervals; the didactic intervention included only one installment. The trial was conducted in four communes, equally randomized to the two interventions. The mean age of the 160 study patients was 66 years, and 54% were men. Most participants described both interventions as understandable, informative, and motivational. Between baseline and 3 months, mean systolic blood pressure declined by 8.2 mmHg (95% CI 4.1-12.2) in the storytelling group and by 5.5 mmHg (95% CI 1.4-9.5) in the didactic group. The storytelling group also reported a significant increase in hypertension medication adherence. Both interventions were well accepted in several rural communities and were shown to be potentially effective in lowering blood pressure. A large-scale randomized trial is needed to compare the effectiveness of the two interventions in controlling hypertension. ClinicalTrials.gov, NCT02483780.

Is high-intensity interval cycling feasible and more beneficial than continuous cycling for knee osteoarthritic patients? Results of a randomised control feasibility trial.

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Keogh, Justin W; Grigg, Josephine; Vertullo, Christopher J

2018-01-01

Knee osteoarthritis (OA) patients often suffer joint pain and stiffness, which contributes to negative changes in body composition, strength, physical performance (function), physical activity and health-related quality of life. To reduce these symptoms and side effects of knee OA, moderate-intensity continuous training (MICT) cycling is often recommended. While resistance training is considered the optimal form of training to improve sarcopenic outcomes, it imposes higher joint loads and requires supervision, either initially or continuously by trained exercise professionals. Therefore, this pilot study sought to gain some insight into the feasibility and potential benefits of high-intensity interval training (HIIT) cycling as an alternative exercise option to MICT cycling for individuals with knee OA. Twenty-seven middle-aged and older adults with knee OA were randomly allocated to either MICT or HIIT, with both programs involving four unsupervised home-based cycling sessions (∼25 min per session) each week for eight weeks. Feasibility was assessed by enrolment rate, withdrawal rate, exercise adherence and number of adverse effects. Efficacy was assessed by health-related quality of life (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne index), physical function (Timed Up and Go (TUG), Sit to Stand (STS) and preferred gait speed) and body composition (body mass, BMI, body fat percentage and muscle mass). Twenty-seven of the interested 50 potential participants (54%) enrolled in the study, with 17 of the 27 participants completing the trial (withdrawal rate of 37%); with the primary withdrawal reasons being unrelated injuries or illness or family related issues. Of the 17 participants who completed the trial, exercise adherence was very high (HIIT 94%; MICT 88%). While only three individuals (one in the MICT and two in the HIIT group) reported adverse events, a total of 28 adverse events were reported, with 24 of these

Is high-intensity interval cycling feasible and more beneficial than continuous cycling for knee osteoarthritic patients? Results of a randomised control feasibility trial

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Justin W. Keogh

2018-05-01

Full Text Available Background Knee osteoarthritis (OA patients often suffer joint pain and stiffness, which contributes to negative changes in body composition, strength, physical performance (function, physical activity and health-related quality of life. To reduce these symptoms and side effects of knee OA, moderate-intensity continuous training (MICT cycling is often recommended. While resistance training is considered the optimal form of training to improve sarcopenic outcomes, it imposes higher joint loads and requires supervision, either initially or continuously by trained exercise professionals. Therefore, this pilot study sought to gain some insight into the feasibility and potential benefits of high-intensity interval training (HIIT cycling as an alternative exercise option to MICT cycling for individuals with knee OA. Methods Twenty-seven middle-aged and older adults with knee OA were randomly allocated to either MICT or HIIT, with both programs involving four unsupervised home-based cycling sessions (∼25 min per session each week for eight weeks. Feasibility was assessed by enrolment rate, withdrawal rate, exercise adherence and number of adverse effects. Efficacy was assessed by health-related quality of life (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC and Lequesne index, physical function (Timed Up and Go (TUG, Sit to Stand (STS and preferred gait speed and body composition (body mass, BMI, body fat percentage and muscle mass. Results Twenty-seven of the interested 50 potential participants (54% enrolled in the study, with 17 of the 27 participants completing the trial (withdrawal rate of 37%; with the primary withdrawal reasons being unrelated injuries or illness or family related issues. Of the 17 participants who completed the trial, exercise adherence was very high (HIIT 94%; MICT 88%. While only three individuals (one in the MICT and two in the HIIT group reported adverse events, a total of 28 adverse events were

Measuring skin necrosis in a randomised controlled feasibility trial of heat preconditioning on wound healing after reconstructive breast surgery: study protocol and statistical analysis plan for the PREHEAT trial.

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Cro, Suzie; Mehta, Saahil; Farhadi, Jian; Coomber, Billie; Cornelius, Victoria

2018-01-01

Essential strategies are needed to help reduce the number of post-operative complications and associated costs for breast cancer patients undergoing reconstructive breast surgery. Evidence suggests that local heat preconditioning could help improve the provision of this procedure by reducing skin necrosis. Before testing the effectiveness of heat preconditioning in a definitive randomised controlled trial (RCT), we must first establish the best way to measure skin necrosis and estimate the event rate using this definition. PREHEAT is a single-blind randomised controlled feasibility trial comparing local heat preconditioning, using a hot water bottle, against standard care on skin necrosis among breast cancer patients undergoing reconstructive breast surgery. The primary objective of this study is to determine the best way to measure skin necrosis and to estimate the event rate using this definition in each trial arm. Secondary feasibility objectives include estimating recruitment and 30 day follow-up retention rates, levels of compliance with the heating protocol, length of stay in hospital and the rates of surgical versus conservative management of skin necrosis. The information from these objectives will inform the design of a larger definitive effectiveness and cost-effectiveness RCT. This article describes the PREHEAT trial protocol and detailed statistical analysis plan, which includes the pre-specified criteria and process for establishing the best way to measure necrosis. This study will provide the evidence needed to establish the best way to measure skin necrosis, to use as the primary outcome in a future RCT to definitively test the effectiveness of local heat preconditioning. The pre-specified statistical analysis plan, developed prior to unblinded data extraction, sets out the analysis strategy and a comparative framework to support a committee evaluation of skin necrosis measurements. It will increase the transparency of the data analysis for the

Mixed methods feasibility study for a trial of blood pressure telemonitoring for people who have had stroke/transient ischaemic attack (TIA).

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Hanley, Janet; Fairbrother, Peter; Krishan, Ashma; McCloughan, Lucy; Padfield, Paul; Paterson, Mary; Pinnock, Hilary; Sheikh, Aziz; Sudlow, Cathie; Todd, Allison; McKinstry, Brian

2015-03-25

Good blood pressure (BP) control reduces the risk of recurrence of stroke/transient ischaemic attack (TIA). Although there is strong evidence that BP telemonitoring helps achieve good control, none of the major trials have considered the effectiveness in stroke/TIA survivors. We therefore conducted a feasibility study for a trial of BP telemonitoring for stroke/TIA survivors with uncontrolled BP in primary care. Phase 1 was a pilot trial involving 55 patients stratified by stroke/TIA randomised 3:1 to BP telemonitoring for 6 months or usual care. Phase 2 was a qualitative evaluation and comprised semi-structured interviews with 16 trial participants who received telemonitoring and 3 focus groups with 23 members of stroke support groups and 7 carers. Overall, 125 patients (60 stroke patients, 65 TIA patients) were approached and 55 (44%) patients were randomised including 27 stroke patients and 28 TIA patients. Fifty-two participants (95%) attended the 6-month follow-up appointment, but one declined the second daytime ambulatory blood pressure monitoring (ABPM) measurement resulting in a 93% completion rate for ABPM - the proposed primary outcome measure for a full trial. Adherence to telemonitoring was good; of the 40 participants who were telemonitoring, 38 continued to provide readings throughout the 6 months. There was a mean reduction of 10.1 mmHg in systolic ABPM in the telemonitoring group compared with 3.8 mmHg in the control group, which suggested the potential for a substantial effect from telemonitoring. Our qualitative analysis found that many stroke patients were concerned about their BP and telemonitoring increased their engagement, was easy, convenient and reassuring. A full-scale trial is feasible, likely to recruit well and have good rates of compliance and follow-up. ISRCTN61528726 15/12/2011.

A pilot feasibility randomised controlled trial of an adjunct brief social network intervention in opiate substitution treatment services.

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Day, Ed; Copello, Alex; Seddon, Jennifer L; Christie, Marilyn; Bamber, Deborah; Powell, Charlotte; Bennett, Carmel; Akhtar, Shabana; George, Sanju; Ball, Andrew; Frew, Emma; Goranitis, Ilias; Freemantle, Nick

2018-01-15

Approximately 3% of people receiving opioid substitution therapy (OST) in the UK manage to achieve abstinence from prescribed and illicit drugs within three years of commencing treatment. Involvement of families and wider social networks in supporting psychological treatment may be an effective strategy in facilitating recovery, and this pilot study aimed to evaluate the impact of a social network-focused intervention for patients receiving OST. A two-site, open feasibility trial randomised patients receiving OST for at least 12 months but still reporting illicit opiate use in the past 28 days to one of three treatments: 1) treatment as usual (TAU), 2) Brief Social Behaviour and Network Therapy (B-SBNT) + TAU, or 3) Personal Goal Setting (PGS) + TAU. The two active interventions consisted of 4 sessions. There were 3 aims: 1) test the feasibility of recruiting OST patients to a trial of B-SBNT, and following them up over 12 months; 2) test the feasibility of training clinicians to deliver B-SBNT; 3) test whether B-SBNT reduces heroin use 3 and 12 months after treatment, and to explore potential mediating factors. The primary outcome for aim 3 was number of days of heroin use in the past month, and a range of secondary outcome measures were specified in advance (level of drug dependence, mental health, social satisfaction, therapist rapport, treatment satisfaction, social network size and support). A total of 83 participants were randomised, and 70 (84%) were followed-up at 12 months. Fidelity analysis of showed that B-SBNT sessions were clearly distinguishable from PGS and TAU sessions, suggesting it was possible to train clinical staff to an adequate level of competence. No significant differences were found between the 3 intervention arms in the primary or secondary outcome measures. Attendance at psychosocial treatment intervention sessions was low across all three arms (44% overall). Patients receiving OST can be recruited into a trial of a social

Job retention vocational rehabilitation for employed people with inflammatory arthritis (WORK-IA): a feasibility randomized controlled trial.

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Hammond, Alison; O'Brien, Rachel; Woodbridge, Sarah; Bradshaw, Lucy; Prior, Yeliz; Radford, Kate; Culley, June; Whitham, Diane; Ruth Pulikottil-Jacob

2017-07-21

Inflammatory arthritis leads to work disability, absenteeism and presenteeism (i.e. at-work productivity loss) at high cost to individuals, employers and society. A trial of job retention vocational rehabilitation (VR) in the United States identified this helped people keep working. The effectiveness of this VR in countries with different socioeconomic policies and conditions, and its impact on absenteeism, presenteeism and health, are unknown. This feasibility study tested the acceptability of this VR, modified for the United Kingdom, compared to written advice about managing work problems. To help plan a randomized controlled trial, we tested screening, recruitment, intervention delivery, response rates, applicability of the control intervention and identified the relevant primary outcome. A feasibility randomized controlled trial with rheumatoid, psoriatic or inflammatory arthritis patients randomized to receive either job retention VR or written information only (the WORK-IA trial). Following three days VR training, rheumatology occupational therapists provided individualised VR on a one to one basis. VR included work assessment, activity diaries and action planning, and (as applicable) arthritis self-management in the workplace, ergonomics, fatigue and stress management, orthoses, employment rights and support services, assistive technology, work modifications, psychological and disclosure support, workplace visits and employer liaison. Fifty five (10%) people were recruited from 539 screened. Follow-up response rates were acceptable at 80%. VR was delivered with fidelity. VR was more acceptable than written advice only (7.8 versus 6.7). VR took on average 4 h at a cost of £135 per person. Outcome assessment indicated VR was better than written advice in reducing presenteeism (Work Limitations Questionnaire (WLQ) change score mean: VR = -12.4 (SD 13.2); control = -2.5 (SD 15.9), absenteeism, perceived risk of job loss and improving pain and health status

The feasibility study: a health economics perspective

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Brenda Gannon

2017-02-01

Full Text Available The remit of research funding bodies is to prioritise funding for research that is of relevance and of high quality. This in turn will aim to raise the quality of healthcare and benefit to patients. Researchers are faced with increasing demands and expectations from the public purse and patients. The emphasis is to improve the quality of their research, with the ultimate aim of improving population health. While guidelines on feasibility study methods concentrate heavily on trials, there appears less guidance on application of health economics within feasibility studies, yet these are a less costly way to determine first of all if a full randomised controlled trial (RCT is feasible. A feasibility study assesses if the study can be done in a small RCT type study. Since by definition, a feasibility study does not evaluate the outcome, researchers often omit the health economics aspects but do however include statistical analysis. This leaves a gap in interpretation for policy makers and potential funders. It also means that any resulting publication does not include relevant information and therefore comparison across studies in terms of difficulty in collecting cost data is not possible. The main aim of this commentary therefore, is to demonstrate a suggested health economics analysis within a feasibility study and to recommend to researchers to include these aspects from the conception of their intervention. This paper proposes a number of points, with rationale for each point, to indicate the health economics data and the potential benefits required for coherent interpretation of the feasibility of future economic evaluations in a full trial. Economic evaluation is necessary if implementation into standard care is anticipated. Therefore, collection and summary analysis of relevant data is good practice at each point of the intervention development. Current guidelines for economic evaluation, for example, The Medical Research Guidelines in the

Feasibility randomised controlled trial of Recovery-focused Cognitive Behavioural Therapy for Older Adults with bipolar disorder (RfCBT-OA): study protocol.

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Tyler, Elizabeth; Lobban, Fiona; Sutton, Chris; Depp, Colin; Johnson, Sheri; Laidlaw, Ken; Jones, Steven H

2016-03-03

Bipolar disorder is a severe and chronic mental health problem that persists into older adulthood. The number of people living with this condition is set to rise as the UK experiences a rapid ageing of its population. To date, there has been very little research or service development with respect to psychological therapies for this group of people. A parallel two-arm randomised controlled trial comparing a 14-session, 6-month Recovery-focused Cognitive-Behavioural Therapy for Older Adults with bipolar disorder (RfCBT-OA) plus treatment as usual (TAU) versus TAU alone. Participants will be recruited in the North-West of England via primary and secondary mental health services and through self-referral. The primary objective of the study is to evaluate the feasibility and acceptability of RfCBT-OA; therefore, a formal power calculation is not appropriate. It has been estimated that randomising 25 participants per group will be sufficient to be able to reliably determine the primary feasibility outcomes (eg, recruitment and retention rates), in line with recommendations for sample sizes for feasibility/pilot trials. Participants in both arms will complete assessments at baseline and then every 3 months, over the 12-month follow-up period. We will gain an estimate of the likely effect size of RfCBT-OA on a range of clinical outcomes and estimate parameters needed to determine the appropriate sample size for a definitive, larger trial to evaluate the effectiveness and cost-effectiveness of RfCBT-OA. Data analysis is discussed further in the Analysis section in the main paper. This protocol was approved by the UK National Health Service (NHS) Ethics Committee process (REC ref: 15/NW/0330). The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and local, participating NHS trusts. ISRCTN13875321; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already

A randomised, feasibility trial of a tele-health intervention for Acute Coronary Syndrome patients with depression ('MoodCare': Study protocol

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Hare David L

2011-02-01

Full Text Available Abstract Background Coronary heart disease (CHD and depression are leading causes of disease burden globally and the two often co-exist. Depression is common after Myocardial Infarction (MI and it has been estimated that 15-35% of patients experience depressive symptoms. Co-morbid depression can impair health related quality of life (HRQOL, decrease medication adherence and appropriate utilisation of health services, lead to increased morbidity and suicide risk, and is associated with poorer CHD risk factor profiles and reduced survival. We aim to determine the feasibility of conducting a randomised, multi-centre trial designed to compare a tele-health program (MoodCare for depression and CHD secondary prevention, with Usual Care (UC. Methods Over 1600 patients admitted after index admission for Acute Coronary Syndrome (ACS are being screened for depression at six metropolitan hospitals in the Australian states of Victoria and Queensland. Consenting participants are then contacted at two weeks post-discharge for baseline assessment. One hundred eligible participants are to be randomised to an intervention or a usual medical care control group (50 per group. The intervention consists of up to 10 × 30-40 minute structured telephone sessions, delivered by registered psychologists, commencing within two weeks of baseline screening. The intervention focuses on depression management, lifestyle factors (physical activity, healthy eating, smoking cessation, alcohol intake, medication adherence and managing co-morbidities. Data collection occurs at baseline (Time 1, 6 months (post-intervention (Time 2, 12 months (Time 3 and 24 months follow-up for longer term effects (Time 4. We are comparing depression (Cardiac Depression Scale [CDS] and HRQOL (Short Form-12 [SF-12] scores between treatment and UC groups, assessing the feasibility of the program through patient acceptability and exploring long term maintenance effects. A cost-effectiveness analysis of

Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse

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Sun Mianmian

2010-11-01

Full Text Available Abstract Background Several active ingredients proposed as vaginal microbicides have been shown paradoxically to increase susceptibility to infection in mouse genital herpes (HSV-2 vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients used in topical products to formulate and deliver the active ingredient might also cause epithelial toxicities that increase viral susceptibility. However, excipients have not previously been tested in susceptibility models. Methods Excipients commonly used in topical products were formulated in a non-toxic vehicle (the "HEC universal placebo", or other formulations as specified. Twelve hours after exposure to the excipient or a control treatment, mice were challenged with a vaginal dose of HSV-2, and three days later were assessed for infection by vaginal lavage culture to assess susceptibility. Results The following excipients markedly increased susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML formulated in K-Y® Warming Jelly, 5% GML as a colloidal suspension in phosphate buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent ingredients (neat propylene glycol and neat PEG-8. For excipients formulated in the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1% disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus 0.02% propylparaben, and 1% benzyl alcohol. Conclusions As reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility.

Pharmacokinetics of 2 dapivirine vaginal microbicide gels and their safety vs. Hydroxyethyl cellulose-based universal placebo gel.

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Nel, Annalene M; Smythe, Shanique C; Habibi, Sepideh; Kaptur, Paulina E; Romano, Joseph W

2010-10-01

Dapivirine, a nonnucleoside reverse transcriptase inhibitor, is in development as a microbicide for the protection of women against HIV infection. A randomized, double-blind, phase 1 trial was conducted in 36 healthy HIV-negative women to compare the pharmacokinetics of 2 dapivirine vaginal gel formulations (0.05% each) and their safety with the hydroxyethyl cellulose-based universal placebo gel. Gel was self-administered once daily for a total of 11 days. Blood and vaginal fluid samples were collected sequentially over 24 days for pharmacokinetic analysis. Safety was evaluated by pelvic examination, colposcopy, adverse events, and clinical laboratory assessments. Adverse event profiles were similar for the 3 gels. Most events were mild and not related to study gel. Headache and vaginal hemorrhage (any vaginal bleeding) were most common. Plasma concentrations of dapivirine did not exceed 1.1 ng/mL. Steady-state conditions were reached within approximately 10 days. Dapivirine concentrations in vaginal fluids were slightly higher for Gel 4789, but Cmax values on days 1 and 14 were not significantly different. Terminal half-life was 72-73 hours in plasma and 15-17 hours in vaginal fluids. Both formulations of dapivirine gel were safe and well tolerated. Dapivirine was delivered to the lower genital tract at concentrations at least 5 logs greater than in vitro inhibitory concentrations.

Parents Working Together: development and feasibility trial of a workplace-based program for parents that incorporates general parenting and health behaviour messages

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L. Wilson

2016-11-01

Full Text Available Abstract Background Parenting programs integrating general parenting and health behaviour messaging may be an effective childhood obesity prevention strategy. The current study explored workplaces as an alternate setting to deliver parenting programs. Methods This study involved two phases. The objective of the first phase was to explore interest in and preferred delivery mode of a workplace program that addresses general parenting and health behaviours. The objective of the second phase was to adapt and test the feasibility and acceptability of a pre-existing program that has been successfully run in community settings for parents in their workplace. To achieve the first objective, we conducted 9 individual or small group qualitative interviews with 11 workplace representatives involved in employee wellness/wellness programming from 8 different organizations across Southwestern Ontario. To achieve the second objective, we adapted a pre-existing program incorporating workplace representatives’ suggestions to create Parents Working Together (PWT. We then tested the program using a pre/post uncontrolled feasibility trial with 9 employees of a large manufacturing company located in Guelph, Ontario. Results Results from the qualitative phase showed that a workplace parenting program that addresses general parenting and health behaviour messages is of interest to workplaces. Results from the feasibility trial suggest that PWT is feasible and well received by participants; attendance rates were high with 89 % of the participants attending 5 or more sessions and 44 % attending all 7 sessions offered. All participants stated they would recommend the program to co-workers. Just over half of our parent participants were male (55.6 %, which is a unique finding as the majority of existing parenting programs engage primarily mothers. Impact evaluation results suggest that changes in children’s and parents’ weight-related behaviours, as well as

Parents Working Together: development and feasibility trial of a workplace-based program for parents that incorporates general parenting and health behaviour messages.

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Wilson, L; Lero, Donna; Smofsky, Allan; Gross, Deborah; Haines, Jess

2016-11-10

Parenting programs integrating general parenting and health behaviour messaging may be an effective childhood obesity prevention strategy. The current study explored workplaces as an alternate setting to deliver parenting programs. This study involved two phases. The objective of the first phase was to explore interest in and preferred delivery mode of a workplace program that addresses general parenting and health behaviours. The objective of the second phase was to adapt and test the feasibility and acceptability of a pre-existing program that has been successfully run in community settings for parents in their workplace. To achieve the first objective, we conducted 9 individual or small group qualitative interviews with 11 workplace representatives involved in employee wellness/wellness programming from 8 different organizations across Southwestern Ontario. To achieve the second objective, we adapted a pre-existing program incorporating workplace representatives' suggestions to create Parents Working Together (PWT). We then tested the program using a pre/post uncontrolled feasibility trial with 9 employees of a large manufacturing company located in Guelph, Ontario. Results from the qualitative phase showed that a workplace parenting program that addresses general parenting and health behaviour messages is of interest to workplaces. Results from the feasibility trial suggest that PWT is feasible and well received by participants; attendance rates were high with 89 % of the participants attending 5 or more sessions and 44 % attending all 7 sessions offered. All participants stated they would recommend the program to co-workers. Just over half of our parent participants were male (55.6 %), which is a unique finding as the majority of existing parenting programs engage primarily mothers. Impact evaluation results suggest that changes in children's and parents' weight-related behaviours, as well as parents' reports of family interfering with work were in the

Feasibility and Efficacy of the Nintendo Wii Gaming System to Improve Balance Performance Post-Stroke: Protocol of a Phase II Randomized Controlled Trial in an Inpatient Rehabilitation Setting.

Science.gov (United States)

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2013-04-01

Balance deficits following stroke are common and debilitating. Commercially available gaming systems, such as the Nintendo(®) (Kyoto, Japan) Wii™, have been widely adopted clinically; however, there is limited evidence supporting their feasibility and efficacy for improving balance performance following stroke. The aim of this trial is to investigate the clinical feasibility and efficacy of using the Nintendo Wii gaming system as an adjunct to standard care to improve balance performance following stroke in an inpatient rehabilitation setting. Thirty participants undergoing inpatient stroke rehabilitation will be recruited into this Phase II, single-blind, randomized controlled trial. Participants will be allocated into a Balance or Upper Limb Group, and both groups will perform activities using the Nintendo Wii in addition to their standard care. Participants will attend three 45-minute sessions per week, for a minimum of 2 and a maximum of 4 weeks. The main focus of the study is to investigate the feasibility of the intervention protocol. This will be evaluated through recruitment, retention, adherence, acceptability, and safety. The Step Test and Functional Reach Test will be the primary efficacy outcomes. Secondary outcomes will include force platform, mobility, and upper limb measures. Assessments will occur at baseline, 2 weeks, and 4 weeks after study entry. To the authors' knowledge, this will be the largest randomized clinical trial to investigate the feasibility and efficacy of the Nintendo Wii gaming system for improving balance performance in a stroke population. The results will inform the design of a Phase III multicenter trial.

Plasmid-Mediated Resistance to Thrombin-Induced Platelet Microbicidal Protein in Staphylococci: Role of the qacA Locus

OpenAIRE

Kupferwasser, Leon Iri; Skurray, Ronald A.; Brown, Melissa H.; Firth, Neville; Yeaman, Michael R.; Bayer, Arnold S.

1999-01-01

Thrombin-induced platelet microbicidal protein 1 (tPMP-1) is a small, cationic peptide released from rabbit platelets following thrombin stimulation. In vitro resistance to this peptide among strains of Staphylococcus aureus correlates with the survival advantage of such strains at sites of endothelial damage in humans as well as in experimental endovascular infections. The mechanisms involved in the phenotypic resistance of S. aureus to tPMP-1 are not fully delineated. The plasmid-encoded st...

Thiazide diuretic-caused hyponatremia in the elderly hypertensive: will a bottle of Nepro a day keep hyponatremia and the doctor away? Study protocol for a proof-of-concept feasibility trial.

Science.gov (United States)

Ruzicka, Marcel; McCormick, Brendan; Magner, Peter; Ramsay, Tim; Edwards, Cedric; Bugeja, Ann; Hiremath, Swapnil

2018-01-01

Hypertension is the most common modifiable risk factor for cardiovascular disease, with an increasing prevalence with age, but with easily available medications to control it. Adverse effects of these medications do limit their use, in particular hyponatremia due to thiazide and thiazide-like diuretics. This is more common in the elderly patients due to a combination of inadequate protein intake and impaired urinary dilution capability, made worse by additional thiazide use. Limiting free water intake and increasing protein intake are often not successful resulting in thiazide avoidance. Daily protein supplement is a potential option in this clinical scenario. We describe the protocol for a feasibility study to explore this option. This is a single-arm, prospective, open-label proof-of-concept trial, including elderly patients with thiazide diuretic-induced hyponatremia. Forty patients will be enrolled and receive a bottle of a protein supplement daily, providing 120 mmol of solutes and permitting an extra 163 mL free water loss, for 4 weeks. The main outcome measures will be (1) feasibility for enrollment, (2) safety of the intervention, and (3) potential efficacy of the intervention in improving hyponatremia. Secondary outcome measures will include changes in urine osmolality, body weight, and urea measurements. Thiazide diuretic-induced hyponatremia is an important adverse effect, with significant clinical impact, such as delirium and falls, and limits the use of these potent antihypertensive agents. There are little data on the effect or safety of protein supplementation and also on whether a trial of this is feasible. The results of this proof-of-concept feasibility trial will help plan and execute a larger definitive trial to test protein supplementation as an effective strategy in this condition. The trial is registered with Clinical trials, registration identifier: NCT02614807.

Randomized multicentre feasibility trial of intermediate care versus standard ward care after emergency abdominal surgery (InCare trial)

DEFF Research Database (Denmark)

Vester-Andersen, M; Waldau, T; Wetterslev, J

2015-01-01

BACKGROUND: Emergency abdominal surgery carries a considerable risk of death and postoperative complications. Early detection and timely management of complications may reduce mortality. The aim was to evaluate the effect and feasibility of intermediate care compared with standard ward care...... ward within 24 h of emergency abdominal surgery. Participants were randomized to either intermediate care or standard surgical ward care after surgery. The primary outcome was 30-day mortality. RESULTS: In total, 286 patients were included in the modified intention-to-treat analysis. The trial...... was terminated after the interim analysis owing to slow recruitment and a lower than expected mortality rate. Eleven (7·6 per cent) of 144 patients assigned to intermediate care and 12 (8·5 per cent) of 142 patients assigned to ward care died within 30 days of surgery (odds ratio 0·91, 95 per cent c.i. 0·38 to 2...

Tailored online cognitive behavioural therapy with or without therapist support calls to target psychological distress in adults receiving haemodialysis: A feasibility randomised controlled trial.

Science.gov (United States)

Hudson, Joanna L; Moss-Morris, Rona; Norton, Sam; Picariello, Federica; Game, David; Carroll, Amy; Spencer, Jonathan; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2017-11-01

Psychological distress is prevalent in haemodialysis (HD) patients yet access to psychotherapy remains limited. This study assessed the feasibility and acceptability of online cognitive-behavioural therapy (CBT) tailored for HD patients, with or without therapist support, for managing psychological distress. This feasibility randomised controlled trial recruited patients from a UK HD centre. Following psychological distress screens, patients with mild-moderate psychological distress (Patient Health Questionnaire PHQ-9; score: 5-19 and/or Generalised Anxiety Disorder; GAD-7 score: 5-14) who met remaining inclusion criteria were approached for consent. Consenters were individually randomised (1:1) to online-CBT or online-CBT plus three therapist support calls. Outcomes included recruitment, retention, and adherence rates. Exploratory change analyses were performed for: psychological distress, quality of life (QoL), illness perceptions, and costs. The statistician was blinded to allocation. 182 (44%) out of 410 patients approached completed psychological distress screens. 26% found screening unacceptable; a further 30% found it unfeasible. Psychological distress was detected in 101 (55%) patients, 60 of these met remaining inclusion criteria. The primary reason for ineligibility was poor computer literacy (N=17, 53%). Twenty-five patients were randomised to the supported (N=18) or unsupported arm (N=7); 92% were retained at follow-up. No differences in psychological distress or cost-effectiveness were observed. No trial adverse events occurred. Online CBT appears feasible but only for computer literate patients who identify with the label psychological distress. A definitive trial using the current methods for psychological distress screening and online care delivery is unfeasible. ClinicalTrials.gov Identifier: NCT02352870. Copyright © 2017 Elsevier Inc. All rights reserved.

A qualitative feasibility study to inform a randomised controlled trial of fluid bolus therapy in septic shock

Science.gov (United States)

O’Hara, Caitlin B; Canter, Ruth R; Mouncey, Paul R; Carter, Anjali; Jones, Nicola; Nadel, Simon; Peters, Mark J; Lyttle, Mark D; Harrison, David A; Rowan, Kathryn M; Inwald, David; Woolfall, Kerry

2018-01-01

Objective The Fluids in Shock (FiSh) Trial proposes to evaluate whether restrictive fluid bolus therapy (10 mL/kg) is more beneficial than current recommended practice (20 mL/kg) in the resuscitation of children with septic shock in the UK. This qualitative feasibility study aimed to explore acceptability of the FiSh Trial, including research without prior consent (RWPC), potential barriers to recruitment and participant information for a pilot trial. Design Qualitative interview study involving parents of children who had presented to a UK emergency department or been admitted to a paediatric intensive care unit with severe infection in the previous 3 years. Participants Twenty-one parents (seven bereaved) were interviewed 16 (median) months since their child’s hospital admission (range: 1–41). Results All parents said they would have provided consent for the use of their child’s data in the FiSh Trial. The majority were unfamiliar with RWPC, yet supported its use. Parents were initially concerned about the change from currently recommended treatment, yet were reassured by explanations of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the research discussion and content of participant information. Bereaved parents stated that recruiters should not discuss research immediately after a child’s death, but supported a personalised postal ‘opt-out’ approach to consent. Conclusions Findings show that parents whose child has experienced severe infection supported the proposed FiSh Trial, including the use of RWPC. Parents’ views informed the development of the pilot trial protocol and site staff training. Trial registration number ISRCTN15244462—results. PMID:28847877

The sheep as a model of preclinical safety and pharmacokinetic evaluations of candidate microbicides.

Science.gov (United States)

Holt, Jonathon D S; Cameron, David; Dias, Nicola; Holding, Jeremy; Muntendam, Alex; Oostebring, Freddy; Dreier, Peter; Rohan, Lisa; Nuttall, Jeremy

2015-07-01

When developing novel microbicide products for the prevention of HIV infection, the preclinical safety program must evaluate not only the active pharmaceutical ingredient but also the product itself. To that end, we applied several relatively standard toxicology study methodologies to female sheep, incorporating an assessment of the pharmacokinetics, safety, tolerability, and local toxicity of a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal Ring-004). We performed a 3-month general toxicology study, a preliminary pharmacokinetic study using drug-loaded vaginal gel, and a detailed assessment of the kinetics of dapivirine delivery to plasma, vaginal, and rectal fluid and rectal, vaginal, and cervical tissue over 28 days of exposure and 3 and 7 days after removal of the ring. The findings of the general toxicology study supported the existing data from both preclinical and clinical studies in that there were no signs of toxicity related to dapivirine. In addition, the presence of the physical dapivirine ring did not alter local or systemic toxicity or the pharmacokinetics of dapivirine. Pharmacokinetic studies indicated that the dapivirine ring produced significant vaginal tissue levels of dapivirine. However, no dapivirine was detected in cervical tissue samples using the methods described here. Plasma and vaginal fluid levels were lower than those in previous clinical studies, while there were detectable dapivirine levels in the rectal tissue and fluid. All tissue and fluid levels tailed off rapidly to undetectable levels following removal of the ring. The sheep represents a very useful model for the assessment of the safety and pharmacokinetics of microbicide drug delivery devices, such as the vaginal ring. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Experimental and numerical models of three-dimensional gravity-driven flow of shear-thinning polymer solutions used in vaginal delivery of microbicides.

Science.gov (United States)

Kheyfets, Vitaly O; Kieweg, Sarah L

2013-06-01

HIV/AIDS is a growing global pandemic. A microbicide is a formulation of a pharmaceutical agent suspended in a delivery vehicle, and can be used by women to protect themselves against HIV infection during intercourse. We have developed a three-dimensional (3D) computational model of a shear-thinning power-law fluid spreading under the influence of gravity to represent the distribution of a microbicide gel over the vaginal epithelium. This model, accompanied by a new experimental methodology, is a step in developing a tool for optimizing a delivery vehicle's structure/function relationship for clinical application. We compare our model with experiments in order to identify critical considerations for simulating 3D free-surface flows of shear-thinning fluids. Here we found that neglecting lateral spreading, when modeling gravity-induced flow, resulted in up to 47% overestimation of the experimental axial spreading after 90 s. In contrast, the inclusion of lateral spreading in 3D computational models resulted in rms errors in axial spreading under 7%. In addition, the choice of the initial condition for shape in the numerical simulation influences the model's ability to describe early time spreading behavior. Finally, we present a parametric study and sensitivity analysis of the power-law parameters' influence on axial spreading, and to examine the impact of changing rheological properties as a result of dilution or formulation conditions. Both the shear-thinning index (n) and consistency (m) impacted the spreading length and deceleration of the moving front. The sensitivity analysis showed that gels with midrange m and n values (for the ranges in this study) would be most sensitive (over 8% changes in spreading length) to 10% changes (e.g., from dilution) in both rheological properties. This work is applicable to many industrial and geophysical thin-film flow applications of non-Newtonian fluids; in addition to biological applications in microbicide drug delivery.

Perfusion-CT guided intravenous thrombolysis in patients with unknown-onset stroke: a randomized, double-blind, placebo-controlled, pilot feasibility trial.

Science.gov (United States)

Michel, Patrik; Ntaios, George; Reichhart, Marc; Schindler, Christian; Bogousslavsky, Julien; Maeder, Philip; Meuli, Reto; Wintermark, Max

2012-06-01

Patients with unknown stroke onset are generally excluded from acute recanalisation treatments. We designed a pilot study to assess feasibility of a trial of perfusion computed tomography (PCT)-guided thrombolysis in patients with ischemic tissue at risk of infarction and unknown stroke onset. Patients with a supratentorial stroke of unknown onset in the middle cerebral artery territory and significant volume of at-risk tissue on PCT were randomized to intravenous thrombolysis with alteplase (0.9 mg/kg) or placebo. Feasibility endpoints were randomization and blinded treatment of patients within 2 h after hospital arrival, and the correct application (estimation) of the perfusion imaging criteria. At baseline, there was a trend towards older age [69.5 (57-78) vs. 49 (44-78) years] in the thrombolysis group (n = 6) compared to placebo (n = 6). Regarding feasibility, hospital arrival to treatment delay was above the allowed 2 h in three patients (25%). There were two protocol violations (17%) regarding PCT, both underestimating the predicted infarct in patients randomized in the placebo group. No symptomatic hemorrhage or death occurred during the first 7 days. Three of the four (75%) and one of the five (20%) patients were recanalized in the thrombolysis and placebo group respectively. The volume of non-infarcted at-risk tissue was 84 (44-206) cm(3) in the treatment arm and 29 (8-105) cm(3) in the placebo arm. This pilot study shows that a randomized PCT-guided thrombolysis trial in patients with stroke of unknown onset may be feasible if issues such as treatment delays and reliable identification of tissue at risk of infarction tissue are resolved. Safety and efficiency of such an approach need to be established.

Perfusion-CT guided intravenous thrombolysis in patients with unknown-onset stroke: a randomized, double-blind, placebo-controlled, pilot feasibility trial

International Nuclear Information System (INIS)

Michel, Patrik; Ntaios, George; Reichhart, Marc; Schindler, Christian; Bogousslavsky, Julien; Maeder, Philip; Meuli, Reto; Wintermark, Max

2012-01-01

Patients with unknown stroke onset are generally excluded from acute recanalisation treatments. We designed a pilot study to assess feasibility of a trial of perfusion computed tomography (PCT)-guided thrombolysis in patients with ischemic tissue at risk of infarction and unknown stroke onset. Patients with a supratentorial stroke of unknown onset in the middle cerebral artery territory and significant volume of at-risk tissue on PCT were randomized to intravenous thrombolysis with alteplase (0.9 mg/kg) or placebo. Feasibility endpoints were randomization and blinded treatment of patients within 2 h after hospital arrival, and the correct application (estimation) of the perfusion imaging criteria. At baseline, there was a trend towards older age [69.5 (57-78) vs. 49 (44-78) years] in the thrombolysis group (n = 6) compared to placebo (n = 6). Regarding feasibility, hospital arrival to treatment delay was above the allowed 2 h in three patients (25%). There were two protocol violations (17%) regarding PCT, both underestimating the predicted infarct in patients randomized in the placebo group. No symptomatic hemorrhage or death occurred during the first 7 days. Three of the four (75%) and one of the five (20%) patients were recanalized in the thrombolysis and placebo group respectively. The volume of non-infarcted at-risk tissue was 84 (44-206) cm 3 in the treatment arm and 29 (8-105) cm 3 in the placebo arm. This pilot study shows that a randomized PCT-guided thrombolysis trial in patients with stroke of unknown onset may be feasible if issues such as treatment delays and reliable identification of tissue at risk of infarction tissue are resolved. Safety and efficiency of such an approach need to be established. (orig.)

Effect of undecylenic acid as a topical microbicide against genital herpes infection in mice and guinea pigs.

Science.gov (United States)

Bourne, N; Ireland, J; Stanberry, L R; Bernstein, D I

1999-01-01

There is increasing interest in the use of topical microbicides to help prevent the spread of sexually transmitted diseases (STD). Undecylenic acid (UA), a monosaturated fatty acid, is the active ingredient in a number of over-the-counter (OTC) antifungal spray powders, that also exhibits in vitro antibacterial and antiviral activity, including herpes simplex virus (HSV) activity. We, therefore, evaluated UA as a topical microbicide against genital HSV infection using the murine and guinea pig models of genital herpes. Mice were administered a 20% solution of UA in polyethylene glycol (PEG) vehicle, vehicle alone or phosphate buffered saline (PBS) intravaginally immediately prior to vaginal challenge with HSV-2. Pre-treatment with UA decreased the number of mice that became infected (P < 0.001 vs. PBS or vehicle control), developed symptoms (P <0.001) or died (P <0.001). However, when treatment was extended to either 5 min prior to or after viral inoculation, protection was lost. Similar findings were found using the guinea pig model, where UA treatment completely prevented HSV-2 vaginal infection when given immediately prior to HSV-2 inoculation (P<0.001 vs. PBS or vehicle control). Thus, UA, an approved OTC medication, provided significant protection against HSV disease and infection only when applied immediately before viral inoculation, indicating that better formulations were needed to extend the duration of protection.

A quasi-randomised, controlled, feasibility trial of GLITtER (Green Light Imaging Interpretation to Enhance Recovery—a psychoeducational intervention for adults with low back pain attending secondary care

Directory of Open Access Journals (Sweden)

Emma L. Karran

2018-02-01

Full Text Available Background Although it is broadly accepted that clinicians should endeavour to reassure patients with low back pain, to do so can present a significant clinical challenge. Guidance for how to provide effective reassurance is scarce and there may be a need to counter patient concerns arising from misinterpretation of spinal imaging findings. ‘GLITtER’ (Green Light Imaging Intervention to Enhance Recovery was developed as a standardised method of communicating imaging findings in a manner that is reassuring and promotes engagement in an active recovery. This feasibility study is an important step towards definitive testing of its effect. Methods This feasibility study was a prospective, quasi-randomised, parallel trial with longitudinal follow-up, involving sampling of patients attending a spinal outpatient clinic at a metropolitan hospital. English speaking adults (18–75 years presenting to the clinic with low back pain and prior spinal imaging were considered for inclusion. Eligible patients were allocated to receive a GLITtER consultation or a standard consultation (as determined by appointment scheduling and clinician availability, and were blinded to their allocation. Full details of the GLITtER intervention are described in accordance with the Tidier template.Follow-up data were collected after 1 and 3 months. The primary outcome of this study was the fulfillment of specific feasibility criteria which were established a priori. Determination of a sample size for a definitive randomised controlled trial was a secondary objective. Results Two hundred seventy-six patients underwent preliminary screening and 31 patients met the final eligibility criteria for study inclusion. Seventeen participants were allocated to the intervention group and 14 were allocated to the control group. Three month follow-up data were available from 42% of the 31 enrolled participants (N = 13, six intervention, seven control. Feasibility indicators for consent

Physiotherapy for sleep disturbance in chronic low back pain: a feasibility randomised controlled trial.

LENUS (Irish Health Repository)

Hurley, Deirdre A

2010-01-01

Sleep disturbance is becoming increasingly recognised as a clinically important symptom in people with chronic low back pain (CLBP, low back pain >12 weeks), associated with physical inactivity and depression. Current research and international clinical guidelines recommend people with CLBP assume a physically active role in their recovery to prevent chronicity, but the high prevalence of sleep disturbance in this population may be unknowingly limiting their ability to participate in exercise-based rehabilitation programmes and contributing to poor outcomes. There is currently no knowledge concerning the effectiveness of physiotherapy on sleep disturbance in people with chronic low back pain and no evidence of the feasibility of conducting randomized controlled trials that comprehensively evaluate sleep as an outcome measure in this population.

TIGA-CUB - manualised psychoanalytic child psychotherapy versus treatment as usual for children aged 5-11 years with treatment-resistant conduct disorders and their primary carers: study protocol for a randomised controlled feasibility trial.

Science.gov (United States)

Edginton, Elizabeth; Walwyn, Rebecca; Burton, Kayleigh; Cicero, Robert; Graham, Liz; Reed, Sadie; Tubeuf, Sandy; Twiddy, Maureen; Wright-Hughes, Alex; Ellis, Lynda; Evans, Dot; Hughes, Tom; Midgley, Nick; Wallis, Paul; Cottrell, David

2017-09-15

The National Institute for Health and Care Excellence (NICE) recommends evidence-based parenting programmes as a first-line intervention for conduct disorders (CD) in children aged 5-11 years. As these are not effective in 25-33% of cases, NICE has requested research into second-line interventions. Child and Adolescent Psychotherapists (CAPTs) address highly complex problems where first-line treatments have failed and there have been small-scale studies of Psychoanalytic Child Psychotherapy (PCP) for CD. A feasibility trial is needed to determine whether a confirmatory trial of manualised PCP (mPCP) versus Treatment as Usual (TaU) for CD is practicable or needs refinement. The aim of this paper is to publish the abridged protocol of this feasibility trial. TIGA-CUB (Trial on improving Inter-Generational Attachment for Children Undergoing Behaviour problems) is a two-arm, pragmatic, parallel-group, multicentre, individually randomised (1:1) controlled feasibility trial (target n = 60) with blinded outcome assessment (at 4 and 8 months), which aims to develop an optimum practicable protocol for a confirmatory, pragmatic, randomised controlled trial (RCT) (primary outcome: child's behaviour; secondary outcomes: parental reflective functioning and mental health, child and parent quality of life), comparing mPCP and TaU as second-line treatments for children aged 5-11 years with treatment-resistant CD and inter-generational attachment difficulties, and for their primary carers. Child-primary carer dyads will be recruited following a referral to, or re-referral within, National Health Service (NHS) Child and Adolescent Mental Health Services (CAMHS) after an unsuccessful first-line parenting intervention. PCP will be delivered by qualified CAPTs working in routine NHS clinical practice, using a trial-specific PCP manual (a brief version of established PCP clinical practice). Outcomes are: (1) feasibility of recruitment methods, (2) uptake and follow-up rates, (3

Feasibility and acceptability of group music therapy vs wait-list control for treatment of patients with long-term depression (the SYNCHRONY trial): study protocol for a randomised controlled trial.

Science.gov (United States)

Carr, Catherine Elizabeth; O'Kelly, Julian; Sandford, Stephen; Priebe, Stefan

2017-03-29

Depression is of significant global concern. Despite a range of effective treatment options it is estimated that around one in five diagnosed with an acute depressive episode continue to experience enduring symptoms for more than 2 years. There is evidence for effectiveness of individual music therapy for depression. However, no studies have as yet looked at a group intervention within an NHS context. This study aims to assess the feasibility of conducting a randomised controlled trial of group music therapy for patients with long-term depression (symptom durations of 1 year or longer) within the community. This is a single-centre randomised controlled feasibility trial of group music therapy versus wait-list control with a nested process evaluation. Thirty participants will be randomised with unbalanced allocation (20 to receive the intervention immediately, 10 as wait-list controls). Group music therapy will be offered three times per week in a community centre with a focus on songwriting. Data will be collected post-intervention, 3 and 6 months after the intervention finishes. We will examine the feasibility of recruitment processes including identifying the number of eligible participants, participation and retention rates and the intervention in terms of testing components, measuring adherence and estimation of the likely intervention effect. A nested process evaluation will consist of treatment fidelity analysis, exploratory analysis of process measures and end-of-participation interviews with participants and referring staff. Whilst group music therapy is an option in some community mental health settings, this will be the first study to examine group music therapy for this particular patient group. We will assess symptoms of depression, acceptability of the intervention and quality of life. We anticipate potential challenges in the recruitment and retention of participants. It is unclear whether offering the intervention three times per week will be

Practice brief: adolescents and HIV clinical trials: ethics, culture, and context.

Science.gov (United States)

MacQueen, Kathleen M; Karim, Quarraisha Abdool

2007-01-01

One quarter of HIV infections globally occur among young people 15 to 24 years of age, and more than half of all new infections are in people younger than 25 years. Clearly, there is a need to identify and implement effective HIV prevention strategies among at-risk teens. Some of the most effective options for slowing the epidemic are biomedical, and several promising methods are in development, including microbicides, vaccines, and preexposure prophylaxis (PREP, or the daily use of antiretrovirals to prevent the acquisition of HIV). There is widespread reluctance to enroll minors in such biomedical prevention trials because of concerns about vulnerability related to physical maturity, experiential maturity, and diminished autonomy as well as legal and social challenges that vary across and within nations. However, excluding minors from trials misses an important opportunity to evaluate the effectiveness, acceptability, and safety of innovative interventions under the best conditions for identifying and resolving potential problems. The challenges of including minors in HIV prevention trials are highlighted through the example of one rural South African community that has been particularly devastated by the HIV epidemic.

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting

Science.gov (United States)

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-01-01

Introduction Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Methods and analysis Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). Ethics and dissemination This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). Trial

ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for a single-arm feasibility trial.

Science.gov (United States)

China, Louise; Muirhead, Nicola; Skene, Simon S; Shabir, Zainib; De Maeyer, Roel P H; Maini, Alexander A N; Gilroy, Derek W; O'Brien, Alastair J

2016-01-25

Circulating prostaglandin E2 levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds and inactivates this hormone. Human albumin solution could thus be repurposed as an immune restorative drug in these patients.This feasibility study aims to determine whether it is possible and safe to restore serum albumin to >30 g/L and maintain it at this level in patients admitted with acute decompensated cirrhosis using repeated 20% human albumin infusions according to daily serum albumin levels. Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) stage 1 is a multicentre, open label dose feasibility trial. Patients with acutely decompensated cirrhosis admitted to hospital with a serum albumin of albumin solution will be infused, according to serum albumin levels, for up to 14 days or discharge in all patients. The primary end point is daily serum albumin levels for the duration of the treatment period and the secondary end point is plasma-induced macrophage dysfunction. The trial will recruit 80 patients. Outcomes will be used to assist with study design for an 866 patient randomised controlled trial at more than 30 sites across the UK. Research ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001-0001). Will be disseminated through peer reviewed journals and international conferences. Recruitment of the first participant occurred on 26/05/2015. The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the NIHR (ISRCTN 14174793). This manuscript refers to V.4.0 of the protocol; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Optimized Benzalkonium Chloride Gel: A Potential Vaginal Microbicides

Institute of Scientific and Technical Information of China (English)

Xun-cheng DING; Wei-hua LI; Jie-fei LI; Qiang-yi WANG

2007-01-01

Objective To develop an optimized BZK gel with good pharmaceutical effect and less toxicity to vaginal mucosa.Methods Four methods as below were used to research the spermicidal activity of BZK gel: 1)in vitro spermicidal test; 2) in vivo spermicidal test in rabbits; 3) anti-fertility test in rabbits; 4)contraceptive test in rabbits. Mucosal irritation test was used in rats to evaluate the safety of optimized BZK gel. Microbiological assessments were used to research anti-STI pathogens (including treponema pallidum, neisseria gonorrhoeae, trichomona vaginalis, candida albicans,ureaplama urealyticum, herpes simplex virus type-2, chlamydiae trachomatis) effect of optimized BZK gel.Results In vitro spermicidal test, EC50 of BZK gel was 0.029 mg/ml, a little higher than that of N-9 (0.019 mg/ml). The MIC of BZK gel was 0.25 mg/ml, similar to that of N-9 (0.20 mg/ml).The vaginal mucosal irritation test in rats showed that 0.429% BZK gel showed only minimal vaginal irritation, and did not damage the vaginal epithelium or cause local inflammation in rats. Microbiological assessments showed that optimized BZK gel could inhibit or inactivate common STI pathogens even after 3-fold or 5-fold dilution.Conclusion Optimized BZK gel was an effective microbicides.

Testing of viscous anti-HIV microbicides using Lactobacillus.

Science.gov (United States)

Moncla, B J; Pryke, K; Rohan, L C; Yang, H

2012-02-01

The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To demonstrate the toxicity of formulated products a new assay was developed for use with viscous and non-viscous samples that we have termed the Lactobacillus toxicity test. We found that the vortex mixing of vaginal Lactobacillus species can lead to reductions in bacterial viability. Lactobacillus can survive briefly, about 2s, but viability declines with increased vortex mixing. The addition of heat inactivated serum or bovine serum albumin, but not glycerol, prevented the decrease in bacterial viability. Bacillus atrophaeus spores also demonstrated loss of viability upon extended mixing. We observed that many of the excipients used in film formulation and the films themselves also afford protection from the killing during vortex mixing. This method is of relevance for toxicity for cidal activities of viscous products. Copyright © 2011 Elsevier B.V. All rights reserved.

Integrated psychological therapy for people with bipolar disorder and co-morbid alcohol use: A feasibility and acceptability randomised controlled trial

Directory of Open Access Journals (Sweden)

Steven Jones

2018-06-01

Full Text Available Background: Co-morbid substance misuse, particularly alcohol, is common in bipolar disorder (BD and associated with worse treatment outcomes. Research into psychological interventions for substance misuse in BD is at an early stage and no studies have specifically targeted problematic alcohol use. This paper describes the context and protocol for a feasibility and acceptability randomised controlled trial (RCT evaluating a novel intervention combining motivational interviewing and cognitive behavioural therapy (MI-CBT for participants with BD and problematic alcohol use, developed in collaboration with people with lived experience of both issues. Methods and design: An RCT will assess the feasibility and acceptability of MI-CBT in addition to treatment as usual (TAU compared with TAU alone. Participants will be recruited from across the North West of England through NHS services and self-referral. The primary outcomes will be the feasibility and acceptability of the intervention assessed by recruitment to target, adherence to intervention, retention rate at follow-up, absence of adverse events and qualitative analysis of participants' reported experiences of intervention. The effect size of the impact of the intervention on alcohol use and mood outcomes will also be estimated. In addition, we will explore a number of potential process variables in therapy. Discussion: This is the first RCT evaluating MI-CBT for BD and problematic alcohol use. Given the prevalence and impact of alcohol problems in BD this novel integrated intervention may have potential to offer important improvements in clinical and functional outcomes. Keywords: Bipolar, Alcohol, Substance, Motivational interviewing, Trial registration number: ISRCTN14774583

Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides.

Science.gov (United States)

das Neves, José; Sarmento, Bruno

2015-05-01

Polymeric nanoparticles (NPs) have the potential to provide effective and safe delivery of antiretroviral drugs in the context of prophylactic anti-HIV vaginal microbicides. Dapivirine-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) NPs were produced by an emulsion-solvent evaporation method, optimized for colloidal properties using a 3-factor, 3-level Box-Behnken experimental design, and characterized for drug loading, production yield, morphology, thermal behavior, drug release, in vitro cellular uptake, cytotoxicity and pro-inflammatory potential. Also, drug permeability/membrane retention in well-established HEC-1-A and CaSki cell monolayer models as mediated by NPs was assessed in the absence or presence of mucin. Box-Behnken design allowed optimizing monodisperse 170nm drug-loaded NPs. Drug release experiments showed an initial burst effect up to 4h, followed by sustained 24h release at pH 4.2 and 7.4. NPs were readily taken up by different genital and macrophage cell lines as assessed by fluorescence microscopy. Drug-loaded NPs presented lower or at least similar cytotoxicity as compared to the free drug, with up to around one-log increase in half-maximal cytotoxic concentration values. In all cases, no relevant changes in cell pro-inflammatory cytokine/chemokine production were observed. Dapivirine transport across cell monolayers was significantly decreased when mucin was present at the donor side with either NPs or the free drug, thus evidencing the influence of this natural glycoprotein in membrane permeability. Moreover, drug retention in cell monolayers was significantly higher for NPs in comparison with the free drug. Overall, obtained dapivirine-loaded PLGA NPs possess interesting technological and biological features that may contribute to their use as novel safe and effective vaginal microbicides. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparing open and minimally invasive surgical procedures for oesophagectomy in the treatment of cancer: the ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) feasibility study and pilot trial.

Science.gov (United States)

Metcalfe, Chris; Avery, Kerry; Berrisford, Richard; Barham, Paul; Noble, Sian M; Fernandez, Aida Moure; Hanna, George; Goldin, Robert; Elliott, Jackie; Wheatley, Timothy; Sanders, Grant; Hollowood, Andrew; Falk, Stephen; Titcomb, Dan; Streets, Christopher; Donovan, Jenny L; Blazeby, Jane M

2016-06-01

Localised oesophageal cancer can be curatively treated with surgery (oesophagectomy) but the procedure is complex with a risk of complications, negative effects on quality of life and a recovery period of 6-9 months. Minimal-access surgery may accelerate recovery. The ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) study aimed to establish the feasibility of, and methodology for, a definitive trial comparing minimally invasive and open surgery for oesophagectomy. Objectives were to quantify the number of eligible patients in a pilot trial; develop surgical manuals as the basis for quality assurance; standardise pathological processing; establish a method to blind patients to their allocation in the first week post surgery; identify measures of postsurgical outcome of importance to patients and clinicians; and establish the main cost differences between the surgical approaches. Pilot parallel three-arm randomised controlled trial nested within feasibility work. Two UK NHS departments of upper gastrointestinal surgery. Patients aged ≥ 18 years with histopathological evidence of oesophageal or oesophagogastric junctional adenocarcinoma, squamous cell cancer or high-grade dysplasia, referred for oesophagectomy or oesophagectomy following neoadjuvant chemo(radio)therapy. Oesophagectomy, with patients randomised to open surgery, a hybrid open chest and minimally invasive abdomen or totally minimally invasive access. The primary outcome measure for the pilot trial was the number of patients recruited per month, with the main trial considered feasible if at least 2.5 patients per month were recruited. During 21 months of recruitment, 263 patients were assessed for eligibility; of these, 135 (51%) were found to be eligible and 104 (77%) agreed to participate, an average of five patients per month. In total, 41 patients were allocated to open surgery, 43 to the hybrid procedure and 20 to totally minimally invasive surgery. Recruitment is continuing

Magnetic force nanotherapy: feasibility and tolerance in a trial with residual tumors

International Nuclear Information System (INIS)

Gneveckow, U.; Scholz, R.; Jordan, A.; Cho, C.H.; Feussner, A.; Eckelt, L.; Wust, P.

2005-01-01

Full text: In February 2004 a clinical trial on the feasibility and tolerability of the magnetic force nanotherapy was started. Magnetic force nanotherapy is a new treatment concept for local tumors. The energy deposited by a homogeneous AC magnetic field is transformed into heat by a transducer. This transducer, nanosized superparamagnetic particles dispersed in water (magnetic fluid), is infiltrated into a selected target by minimal invasive intervention. Due to their subdomain size, these particles show no hysteresis behavior. Therefore, the behavior is independent on any previous exposures to magnetic fields. In contrast to hysteresis heating with multidomain-particles, the energy of the magnetic field is transformed to heat by both Brownian rotation and Neel relaxation. In addition, a special 'tumorphil' coating of the ironoxide cores increases the cellular uptake of the particles into tumor cells, which binds the particles in the tumor region. Thus a particular high power density can be achieved in the tumor and directly regulated by the magnetic field amplitude, whereas the normal tissue lacking magnetic fluid is only slightly affected. Both, deep seated and superficial tumors are accessible with a minimum of invasion and a selectable target temperature. To heat the magnetic fluid under clinical conditions, an applicator system has been built to generate a magnetic field in any desired body region. The first results of the feasibility of the magnetic force nanotherapy on different tumor entities are shown here. Until now 18 of 25 patients of the trial were recruited. 4 in the group of CT-guided instillation, 8 with intraoperative instillation of the magnetic nanoparticles and 6 patients with prostate carcinoma under TRUS control. Except of two cases the instillation was successful and at least one thermotherapy could be performed. Temperatures between 40 and 46 o C could be measured whereas calculated temperatures ranged between 42 and 52 o C. Field

Feasibility and Efficacy of an mHealth Game for Managing Anxiety: "Flowy" Randomized Controlled Pilot Trial and Design Evaluation.

Science.gov (United States)

Pham, Quynh; Khatib, Yasmin; Stansfeld, Stephen; Fox, Simon; Green, Tobias

2016-02-01

Meeting the complex needs of patients with chronic common mental health disorders (CMHDs) may be the greatest challenge facing organized medical practice. On the basis of a well-established and proven theoretical foundation for controlled respiration as a behavioral intervention for CMHDs, as well as preliminary evidence that gamification can improve health outcomes through increasing patient engagement, this randomized controlled pilot study evaluated the feasibility and clinical efficacy of a mobile health game called "Flowy" ( www.flowygame.com ) that digitally delivered breathing retraining exercises for anxiety, panic, and hyperventilation symptom management. We designed an unblinded, Web-based, parallel-group randomized controlled trial focusing on feasibility, clinical efficacy, and design proof of concept. In the intervention condition (n = 31), participants received free access to "Flowy" for 4 weeks. In the control condition (n = 32), participants were placed on a waitlist for 4 weeks before being offered free access to "Flowy." Online measurements using psychological self-report questionnaires were made at 2 and 4 weeks post-baseline. At trial conclusion, participants found "Flowy" acceptable as an anxiety management intervention. "Flowy" engaged participants sufficiently to endorse proactive gameplay. Intent-to-treat analysis revealed a reduction in anxiety, panic, and self-report hyperventilation scores in both trial arms, with the intervention arm experiencing greater quality of life. Participants perceived "Flowy" as a fun and useful intervention, proactively used "Flowy" as part of their care, and would recommend "Flowy" to family and friends. Our results suggest that a digital delivery of breathing retraining exercises through a mobile health game can manage anxiety, panic, and hyperventilation symptoms associated with CMHDs.

Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination.

Science.gov (United States)

Schader, Susan M; Colby-Germinario, Susan P; Schachter, Jordana R; Xu, Hongtao; Wainberg, Mark A

2011-08-24

To evaluate the candidate antiretroviral microbicide compounds, dapivirine (DAP) and tenofovir (TFV), alone and in combination against the transmission of wild-type and nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 from different subtypes. We determined single-drug efficacy of the RTIs, DAP and TFV, against subtype B and non-B wild-type and NNRTI-resistant HIV-1 in vitro. To assess breadth of activity, compounds were tested alone and in combination against wild-type and NNRTI-resistant subtype C primary HIV-1 isolates and complimentary clonal HIV-1 from subtypes B, C and CRF02_AG to control for viral variation. Early infection was quantified by counting light units emitted from TZM-bl cells less than 48-h postinfection. Combination ratios were based on drug inhibitory concentrations (IC(50)s) and combined effects were determined by calculating combination indices. Both candidate microbicide antiretrovirals demonstrated potent anti-NNRTI-resistant HIV-1 activity in vitro, albeit the combination protected better than the single-drug treatments. Of particular interest, the DAP with TFV combination exhibited synergy (50% combination index, CI(50) = 0.567) against subtype C NNRTI-resistant HIV-1, whereas additivity (CI(50) = 0.987) was observed against the wild-type counterpart from the same patient. The effect was not compounded by the presence of subdominant viral fractions, as experiments using complimentary clonal subtype C wild-type (CI(50) = 0.968) and NNRTI-resistant (CI(50) = 0.672) HIV-1, in lieu of the patient quasispecies, gave similar results. This study supports the notion that antiretroviral drug combinations may retain antiviral activity against some drug-resistant HIV-1 despite subtype classification and quasispecies diversity.

Job retention vocational rehabilitation for\\ud employed people with inflammatory\\ud arthritis (WORK-IA) : a feasibility randomized\\ud controlled trial

OpenAIRE

Hammond, A; O'Brien, R; Woodbridge, S; Bradshaw, L; Prior, Y; Radford, K; Culley, J; Whitham, D; Pulikottil-Jacob, R

2017-01-01

Background Inflammatory arthritis leads to work disability, absenteeism and presenteeism (i.e. at-work productivity loss) at high cost to individuals, employers and society. A trial of job retention vocational rehabilitation (VR) in the United States identified this helped people keep working. The effectiveness of this VR in countries with different socioeconomic policies and conditions, and its impact on absenteeism, presenteeism and health, are unknown. This feasibility study tested the acc...

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial

Science.gov (United States)

Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-01

Background Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. Objective The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. Methods We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Results Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. Conclusions A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement

Protocol for a feasibility randomised controlled trial of the use of Physical ACtivity monitors in an Exercise Referral Setting: the PACERS study.

Science.gov (United States)

Hawkins, Jemma; Edwards, Michelle; Charles, Joanna; Jago, Russell; Kelson, Mark; Morgan, Kelly; Murphy, Simon; Oliver, Emily; Simpson, Sharon; Edwards, Rhiannon Tudor; Moore, Graham

2017-01-01

Exercise referral schemes are recommended by the National Institute for Clinical Excellence (NICE) for physical activity promotion among inactive patients with health conditions or risk factors. Whilst there is evidence for the initial effectiveness and cost-effectiveness of such schemes for increasing physical activity, evidence of long-term effects is limited. Techniques such as goal setting, self-monitoring and personalised feedback may support motivation for physical activity. Technologies such as activity monitoring devices provide an opportunity to enhance delivery of motivational techniques. This paper describes the PACERS study protocol, which aims to assess the feasibility and acceptability of implementing an activity monitor within the existing Welsh National Exercise Referral Scheme (NERS) and proposed evaluation methodology for a full-scale randomised controlled trial. The PACERS study consists of a pilot randomised controlled trial, process evaluation and exploratory economic analyses. Participants will be recruited from the generic pathway of the Welsh NERS and will be randomly assigned to receive the intervention or usual practice. Usual practice is a 16-week structured exercise programme; the intervention consists of an accelerometry-based activity monitor (MyWellnessKey) and an associated web platform (MyWellnessCloud). The primary outcomes are predefined progression criteria assessing the acceptability and feasibility of the intervention and feasibility of the proposed evaluation methodology. Postal questionnaires will be completed at baseline (time 0: T0), 16 weeks after T0 (T1) and 12 months after T0 (T2). Routinely collected data will also be accessed at the same time points. A sub-sample of intervention participants and exercise referral staff will be interviewed following initiation of intervention delivery and at the end of the study. The PACERS study seeks to assess the feasibility of adding a novel motivational component to an existing

A qualitative feasibility study to inform a randomised controlled trial of fluid bolus therapy in septic shock.

Science.gov (United States)

O'Hara, Caitlin B; Canter, Ruth R; Mouncey, Paul R; Carter, Anjali; Jones, Nicola; Nadel, Simon; Peters, Mark J; Lyttle, Mark D; Harrison, David A; Rowan, Kathryn M; Inwald, David; Woolfall, Kerry

2018-01-01

The Fluids in Shock (FiSh) Trial proposes to evaluate whether restrictive fluid bolus therapy (10 mL/kg) is more beneficial than current recommended practice (20 mL/kg) in the resuscitation of children with septic shock in the UK. This qualitative feasibility study aimed to explore acceptability of the FiSh Trial, including research without prior consent (RWPC), potential barriers to recruitment and participant information for a pilot trial. Qualitative interview study involving parents of children who had presented to a UK emergency department or been admitted to a paediatric intensive care unit with severe infection in the previous 3 years. Twenty-one parents (seven bereaved) were interviewed 16 (median) months since their child's hospital admission (range: 1-41). All parents said they would have provided consent for the use of their child's data in the FiSh Trial. The majority were unfamiliar with RWPC, yet supported its use. Parents were initially concerned about the change from currently recommended treatment, yet were reassured by explanations of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the research discussion and content of participant information. Bereaved parents stated that recruiters should not discuss research immediately after a child's death, but supported a personalised postal 'opt-out' approach to consent. Findings show that parents whose child has experienced severe infection supported the proposed FiSh Trial, including the use of RWPC. Parents' views informed the development of the pilot trial protocol and site staff training. ISRCTN15244462-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Knowledge and acceptability of alternative HIV prevention bio-medical products among MSM who bareback.

Science.gov (United States)

Nodin, N; Carballo-Diéguez, A; Ventuneac, A M; Balan, I C; Remien, R

2008-01-01

Condom use is the best available strategy to prevent HIV infection during sexual intercourse. However, since many people choose not to use condoms in circumstances in which HIV risk exists, alternatives to condom use for HIV prevention are needed. Currently there are several alternative bio-medical HIV-prevention products in different stages of development: microbicides, vaccines, post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Seventy-two men who have sex with men (MSM) who took part in a study on Internet use and intentional condomless anal intercourse were asked about these four products during a semi-structured interview. The questions explored knowledge and acceptability of all the products and willingness to participate in microbicide and vaccine trials. Qualitative analysis of the data suggests that these men had virtually no knowledge of PrEP, very limited knowledge of microbicides, some information about PEP and considerably more knowledge about vaccines. Reactions towards the products were generally positive except for PrEP, for which reactions were polarized as either enthusiastic or negative. With the exception of PrEP, many men expressed willingness to use the products in the future. Most men would be willing to participate in trials for microbicides and vaccines if given basic reassurances. Concerns over negative side effects and preoccupation with possible infection were some of the motives given for non-willingness to participate in a vaccine trial. These results should inform the development of future trials of biomedical prevention products.

Evaluating feasibility and acceptability of a local psycho-educational intervention for pregnant women with common mental problems affected by armed conflict in Swat, Pakistan: A parallel randomized controlled feasibility trial.

Science.gov (United States)

Khan, Muhammad Naseem; Dherani, Mukesh; Chiumento, Anna; Atif, Najia; Bristow, Katie; Sikander, Siham; Rahman, Atif

2017-12-01

The current research was conducted in the Swat valley, where widespread conflict and militancy had been experienced prior to the field activities. The aim of this trial was to evaluate the feasibility and acceptability of a locally developed psycho-educational intervention. This mixed-methods study incorporated a quantitative and qualitative component. For the quantitative component, trial participants were identified from a cross-sectional study conducted in the earlier phase of the research, with Self-Reporting Questionnaire (SRQ) score of ≥9. Participants with suicidal ideation, severe mental or medical illness, recently given birth or living with another woman with an SRQ score of 9 or above were excluded. Participants fulfilling eligibility were randomized on a 1:1 allocation ratio using simple randomization to the psycho-educational intervention or routine care arm. The intervention arm received two psycho-educational sessions at their homes delivered by local community health worker from the study area. The primary outcome was help-seeking for psychological distress, measured by a semi-structured interview by a researcher blind to the allocation status at 2 months post-intervention. Secondary outcomes include psychological distress and social support measured by SRQ and Multidimensional Scale of Perceived Social Support (MSPSS), respectively, at 2 months post-intervention. Intervention acceptability was explored through in-depth interviews. Local community health workers with no mental health experience successfully delivered the psycho-educational sessions in the community. The uptake of intervention was good and the intervention was taken well by the families and the community health workers. The outcome evaluation was not powered; however, more women sought assistance for their distress from their community health workers in the intervention arm, compared to women in the control arm. This trial showed good acceptance and feasible delivery of a

Engineering practice variation through provider agreement: a cluster-randomized feasibility trial.

Science.gov (United States)

McCarren, Madeline; Twedt, Elaine L; Mansuri, Faizmohamed M; Nelson, Philip R; Peek, Brian T

2014-01-01

Minimal-risk randomized trials that can be embedded in practice could facilitate learning health-care systems. A cluster-randomized design was proposed to compare treatment strategies by assigning clusters (eg, providers) to "favor" a particular drug, with providers retaining autonomy for specific patients. Patient informed consent might be waived, broadening inclusion. However, it is not known if providers will adhere to the assignment or whether institutional review boards will waive consent. We evaluated the feasibility of this trial design. Agreeable providers were randomized to "favor" either hydrochlorothiazide or chlorthalidone when starting patients on thiazide-type therapy for hypertension. The assignment applied when the provider had already decided to start a thiazide, and providers could deviate from the strategy as needed. Prescriptions were aggregated to produce a provider strategy-adherence rate. All four institutional review boards waived documentation of patient consent. Providers (n=18) followed their assigned strategy for most of their new thiazide prescriptions (n=138 patients). In the "favor hydrochlorothiazide" group, there was 99% adherence to that strategy. In the "favor chlorthalidone" group, chlorthalidone comprised 77% of new thiazide starts, up from 1% in the pre-study period. When the assigned strategy was followed, dosing in the recommended range was 48% for hydrochlorothiazide (25-50 mg/day) and 100% for chlorthalidone (12.5-25.0 mg/day). Providers were motivated to participate by a desire to contribute to a comparative effectiveness study. A study promotional mug, provider information letter, and interactions with the site investigator were identified as most helpful in reminding providers of their study drug strategy. Providers prescribed according to an assigned drug-choice strategy most of the time for the purpose of a comparative effectiveness study. This simple design could facilitate research participation and behavior change

A quasi-randomised, controlled, feasibility trial of GLITtER (Green Light Imaging Interpretation to Enhance Recovery)-a psychoeducational intervention for adults with low back pain attending secondary care.

Science.gov (United States)

Karran, Emma L; Hillier, Susan L; Yau, Yun-Hom; McAuley, James H; Moseley, G Lorimer

2018-01-01

Although it is broadly accepted that clinicians should endeavour to reassure patients with low back pain, to do so can present a significant clinical challenge. Guidance for how to provide effective reassurance is scarce and there may be a need to counter patient concerns arising from misinterpretation of spinal imaging findings. 'GLITtER' (Green Light Imaging Intervention to Enhance Recovery) was developed as a standardised method of communicating imaging findings in a manner that is reassuring and promotes engagement in an active recovery. This feasibility study is an important step towards definitive testing of its effect. This feasibility study was a prospective, quasi-randomised, parallel trial with longitudinal follow-up, involving sampling of patients attending a spinal outpatient clinic at a metropolitan hospital. English speaking adults (18-75 years) presenting to the clinic with low back pain and prior spinal imaging were considered for inclusion. Eligible patients were allocated to receive a GLITtER consultation or a standard consultation (as determined by appointment scheduling and clinician availability), and were blinded to their allocation. Full details of the GLITtER intervention are described in accordance with the Tidier template.Follow-up data were collected after 1 and 3 months. The primary outcome of this study was the fulfillment of specific feasibility criteria which were established a priori . Determination of a sample size for a definitive randomised controlled trial was a secondary objective. Two hundred seventy-six patients underwent preliminary screening and 31 patients met the final eligibility criteria for study inclusion. Seventeen participants were allocated to the intervention group and 14 were allocated to the control group. Three month follow-up data were available from 42% of the 31 enrolled participants ( N  = 13, six intervention, seven control). Feasibility indicators for consent, resource burden and acceptability of the

Inpatient Massage Therapy Versus Music Therapy Versus Usual Care: A Mixed-methods Feasibility Randomized Controlled Trial.

Science.gov (United States)

Roseen, Eric J; Cornelio-Flores, Oscar; Lemaster, Chelsey; Hernandez, Maria; Fong, Calvin; Resnick, Kirsten; Wardle, Jon; Hanser, Suzanne; Saper, Robert

2017-01-01

Little is known about the feasibility of providing massage or music therapy to medical inpatients at urban safety-net hospitals or the impact these treatments may have on patient experience. To determine the feasibility of providing massage and music therapy to medical inpatients and to assess the impact of these interventions on patient experience. Single-center 3-arm feasibility randomized controlled trial. Urban academic safety-net hospital. Adult inpatients on the Family Medicine ward. Massage therapy consisted of a standardized protocol adapted from a previous perioperative study. Music therapy involved a preference assessment, personalized compact disc, music-facilitated coping, singing/playing music, and/or songwriting. Credentialed therapists provided the interventions. Patient experience was measured with the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) within 7 days of discharge. We compared the proportion of patients in each study arm reporting "top box" scores for the following a priori HCAHPS domains: pain management, recommendation of hospital, and overall hospital rating. Responses to additional open-ended postdischarge questions were transcribed, coded independently, and analyzed for common themes. From July to December 2014, 90 medical inpatients were enrolled; postdischarge data were collected on 68 (76%) medical inpatients. Participants were 70% females, 43% non-Hispanic black, and 23% Hispanic. No differences between groups were observed on HCAHPS. The qualitative analysis found that massage and music therapy were associated with improved overall hospital experience, pain management, and connectedness to the massage or music therapist. Providing music and massage therapy in an urban safety-net inpatient setting was feasible. There was no quantitative impact on HCAHPS. Qualitative findings suggest benefits related to an improved hospital experience, pain management, and connectedness to the massage or music therapist.

Inpatient Massage Therapy Versus Music Therapy Versus Usual Care: A Mixed-methods Feasibility Randomized Controlled Trial

Science.gov (United States)

Cornelio-Flores, Oscar; Lemaster, Chelsey; Hernandez, Maria; Fong, Calvin; Resnick, Kirsten; Wardle, Jon; Hanser, Suzanne; Saper, Robert

2017-01-01

Background Little is known about the feasibility of providing massage or music therapy to medical inpatients at urban safety-net hospitals or the impact these treatments may have on patient experience. Objective To determine the feasibility of providing massage and music therapy to medical inpatients and to assess the impact of these interventions on patient experience. Design Single-center 3-arm feasibility randomized controlled trial. Setting Urban academic safety-net hospital. Patients Adult inpatients on the Family Medicine ward. Interventions Massage therapy consisted of a standardized protocol adapted from a previous perioperative study. Music therapy involved a preference assessment, personalized compact disc, music-facilitated coping, singing/playing music, and/or songwriting. Credentialed therapists provided the interventions. Measurements Patient experience was measured with the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) within 7 days of discharge. We compared the proportion of patients in each study arm reporting “top box” scores for the following a priori HCAHPS domains: pain management, recommendation of hospital, and overall hospital rating. Responses to additional open-ended postdischarge questions were transcribed, coded independently, and analyzed for common themes. Results From July to December 2014, 90 medical inpatients were enrolled; postdischarge data were collected on 68 (76%) medical inpatients. Participants were 70% females, 43% non-Hispanic black, and 23% Hispanic. No differences between groups were observed on HCAHPS. The qualitative analysis found that massage and music therapy were associated with improved overall hospital experience, pain management, and connectedness to the massage or music therapist. Conclusions Providing music and massage therapy in an urban safety-net inpatient setting was feasible. There was no quantitative impact on HCAHPS. Qualitative findings suggest benefits related to an

Randomized feasibility trial to improve hydroxyurea adherence in youth ages 10-18 years through community health workers: The HABIT study.

Science.gov (United States)

Green, Nancy S; Manwani, Deepa; Matos, Sergio; Hicks, April; Soto, Luisa; Castillo, Yina; Ireland, Karen; Stennett, Yvonne; Findley, Sally; Jia, Haomiao; Smaldone, Arlene

2017-12-01

The main therapeutic intervention for sickle cell disease (SCD) is hydroxyurea (HU). The effect of HU is largely through dose-dependent induction of fetal hemoglobin (HbF). Poor HU adherence is common among adolescents. Our 6-month, two-site pilot intervention trial, "HABIT," was led by culturally aligned community health workers (CHWs). CHWs performed support primarily through home visits, augmented by tailored text message reminders. Dyads of youth with SCD ages 10-18 years and a parent were enrolled. A customized HbF biomarker, the percentage decrease from each patients' highest historical HU-induced HbF, "Personal best," was used to qualify for enrollment and assess HU adherence. Two primary outcomes were as follows: (1) intervention feasibility and acceptability and (2) HU adherence measured in three ways: monthly percentage improvement toward HbF Personal best, proportion of days covered (PDC) by HU, and self-report. Twenty-eight dyads were enrolled, of which 89% were retained. Feasibility and acceptability were excellent. Controlling for group assignment and month of intervention, the intervention group improved percentage decrease from Personal best by 2.3% per month during months 0-4 (P = 0.30), with similar improvement in adherence demonstrated using pharmacy records. Self-reported adherence did not correlate. Dyads viewed CHWs as supportive for learning about SCD and HU, living with SCD and making progress in coordinated self-management responsibility to support a daily HU habit. Most parents and youth appreciated text message HU reminders. The HABIT pilot intervention demonstrated feasibility and acceptability with promising effect toward improved medication adherence. Testing in a larger multisite intervention trial is warranted. © 2017 Wiley Periodicals, Inc.

Feasibility of a patient-centred nutrition intervention to improve oral intakes of patients at risk of pressure ulcer: a pilot randomised control trial.

Science.gov (United States)

Roberts, Shelley; Desbrow, Ben; Chaboyer, Wendy

2016-06-01

Nutrition is important for pressure ulcer prevention. This randomised control pilot study assessed the feasibility of conducting a larger trial to test the effectiveness of a patient-centred intervention for improving the dietary intakes of patients at risk of pressure ulcer in hospital. A 3-day intervention targeting patients at risk of pressure ulcer was developed, based on three main foundations: patient education, patient participation and guided goal setting. The intervention was piloted in three wards in a metropolitan hospital in Queensland, Australia. Participants were randomised into control or intervention groups and had their oral intakes monitored. A subset of intervention patients was interviewed on their perceptions of the intervention. Feasibility was tested against three criteria: ≥75% recruitment; ≥80% retention; and ≥80% intervention fidelity. Secondary outcomes related to effects on energy and protein intakes. Eighty patients participated in the study and 66 were included in final analysis. The recruitment rate was 82%, retention rate was 88%, and 100% of intervention patients received the intervention. Patients viewed the intervention as motivating and met significantly more of their estimated energy and protein requirements over time. This pilot study indicates that the intervention is feasible and acceptable by patients at risk of pressure ulcer. A larger trial is needed to confirm the effectiveness of the intervention in the clinical setting. © 2015 Nordic College of Caring Science.

Feasibility of the Enhancing Participation In the Community by improving Wheelchair Skills (EPIC Wheels) program: study protocol for a randomized controlled trial.

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Giesbrecht, Edward M; Miller, William C; Eng, Janice J; Mitchell, Ian M; Woodgate, Roberta L; Goldsmith, Charles H

2013-10-24

Many older adults rely on a manual wheelchair for mobility but typically receive little, if any, training on how to use their wheelchair effectively and independently. Standardized skill training is an effective intervention, but limited access to clinician trainers is a substantive barrier. Enhancing Participation in the Community by Improving Wheelchair Skills (EPIC Wheels) is a 1-month monitored home training program for improving mobility skills in older novice manual wheelchair users, integrating principles from andragogy and social cognitive theory. The purpose of this study is to determine whether feasibility indicators and primary clinical outcome measures of the EPIC Wheels program are sufficiently robust to justify conducting a subsequent multi-site randomized controlled trial. A 2 × 2 factorial randomized controlled trial at two sites will compare improvement in wheelchair mobility skills between an EPIC Wheels treatment group and a computer-game control group, with additional wheelchair use introduced as a second factor. A total of 40 community-dwelling manual wheelchair users at least 55 years old and living in two Canadian metropolitan cities (n = 20 × 2) will be recruited. Feasibility indicators related to study process, resources, management, and treatment issues will be collected during data collection and at the end of the study period, and evaluated against proposed criteria. Clinical outcome measures will be collected at baseline (pre-randomization) and post-intervention. The primary clinical outcome measure is wheelchair skill capacity, as determined by the Wheelchair Skills Test, version 4.1. Secondary clinical outcome measures include wheelchair skill safety, satisfaction with performance, wheelchair confidence, life-space mobility, divided-attention, and health-related quality of life. The EPIC Wheels training program offers several innovative features. The convenient, portable, economical, and adaptable tablet-based, home program model

Influences on visit retention in clinical trials: insights from qualitative research during the VOICE trial in Johannesburg, South Africa.

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Magazi, Busisiwe; Stadler, Jonathan; Delany-Moretlwe, Sinead; Montgomery, Elizabeth; Mathebula, Florence; Hartmann, Miriam; van der Straten, Ariane

2014-07-28

Although significant progress has been made in clinical trials of women-controlled methods of HIV prevention such as microbicides and Pre-exposure Prophylaxis (PrEP), low adherence to experimental study products remains a major obstacle to being able to establish their efficacy in preventing HIV infection. One factor that influences adherence is the ability of trial participants to attend regular clinic visits at which trial products are dispensed, adherence counseling is administered, and participant safety is monitored. We conducted a qualitative study of the social contextual factors that influenced adherence in the VOICE (MTN-003) trial in Johannesburg, South Africa, focusing on study participation in general, and study visits in particular. The research used qualitative methodologies, including in-depth interviews (IDI), serial ethnographic interviews (EI), and focus group discussions (FGD) among a random sub-sample of 102 female trial participants, 18 to 40 years of age. A socio-ecological framework that explored those factors that shaped trial participation and adherence to study products, guided the analysis. Key codes were developed to standardize subsequent coding and a node search was used to identify texts relating to obstacles to visit adherence. Our analysis includes coded transcripts from seven FGD (N = 40), 41 IDI, and 64 serial EI (N = 21 women). Women's kinship, social, and economic roles shaped their ability to participate in the clinical trial. Although participants expressed strong commitments to attend study visits, clinic visit schedules and lengthy waiting times interfered with their multiple obligations as care givers, wage earners, housekeepers, and students. The research findings highlight the importance of the social context in shaping participation in HIV prevention trials, beyond focusing solely on individual characteristics. This points to the need to focus interventions to improve visit attendance by promoting a culture of

Clinical feasibility of the Nintendo Wii™ for balance training post-stroke: a phase II randomized controlled trial in an inpatient setting.

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Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2014-09-01

To investigate the feasibility and potential efficacy of the Nintendo Wii™ for balance rehabilitation after stroke. Phase II, single-blind, randomized controlled trial. Inpatient rehabilitation facility. Thirty adults (mean age 63.6 (14.7) years) undergoing inpatient rehabilitation who were less than three months post-stroke and able to stand unsupported. Participants were allocated to a Balance Group, using the 'Wii Fit Plus' in standing, or Upper Limb Group, using the 'Wii Sports/Sports Resort' in sitting. Both groups undertook three 45 minute sessions per week over two to four weeks in addition to standard care. The primary focus was feasibility, addressed by recruitment, retention, adherence, acceptability and safety. Efficacy was evaluated by balance, mobility and upper limb outcomes. Twenty-one percent of individuals screened were recruited and 86% (n = 30) of eligible people agreed to participate. Study retention and session adherence was 90% and > 99%, respectively, at two weeks; dropping to 70% and 87% at four weeks due to early discharge. All participants reported enjoying the sessions and most felt they were beneficial. No major adverse events occurred. Wii use by the Balance Group was associated with trends for improved balance, with significantly greater improvement in outcomes including the Step Test and Wii Balance Board-derived centre of pressure scores. The Upper Limb Group had larger, non-significant changes in arm function. A Wii-based approach appears feasible and promising for post-stroke balance rehabilitation. A larger randomized controlled trial is recommended to further investigate efficacy. © The Author(s) 2014.

Feasibility of a randomised trial of a continuing medical education program in shared decision-making on the use of antibiotics for acute respiratory infections in primary care: the DECISION+ pilot trial

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Laurier Claudine

2011-01-01

Full Text Available Abstract Background The misuse and limited effectiveness of antibiotics for acute respiratory infections (ARIs are well documented, and current approaches targeting physicians or patients to improve appropriate use have had limited effect. Shared decision-making could be a promising strategy to improve appropriate antibiotic use for ARIs, but very little is known about its implementation processes and outcomes in clinical settings. In this matter, pilot studies have played a key role in health science research over the past years in providing information for the planning, justification, and/or refinement of larger studies. The objective of our study was to assess the feasibility and acceptability of the study design, procedures, and intervention of the DECISION+ program, a continuing medical education program in shared decision-making among family physicians and their patients on the optimal use of antibiotics for treating ARIs in primary care. Methods A pilot clustered randomised trial was conducted. Family medicine groups (FMGs were randomly assigned, to either the DECISION+ program, which included three 3-hour workshops over a four- to six-month period, or a control group that had a delayed exposure to the program. Results Among 21 FMGs contacted, 5 (24% agreed to participate in the pilot study. A total of 39 family physicians (18 in the two experimental and 21 in the three control FMGs and their 544 patients consulting for an ARI were recruited. The proportion of recruited family physicians who participated in all three workshops was 46% (50% for the experimental group and 43% for the control group, and the overall mean level of satisfaction regarding the workshops was 94%. Conclusions This trial, while aiming to demonstrate the feasibility and acceptability of conducting a larger study, has identified important opportunities for improving the design of a definitive trial. This pilot trial is informative for researchers and clinicians

Exploring the feasibility and acceptability of a recovery-focused group therapy intervention for adults with bipolar disorder: trial protocol.

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Beck, Alison K; Baker, Amanda; Jones, Steven; Lobban, Fiona; Kay-Lambkin, Frances; Attia, John; Banfield, Michelle

2018-01-31

Improving accessible, acceptable recovery-oriented service provision for people with bipolar disorder (BD) is an important priority. Mindfulness and acceptance-based cognitive and behavioural therapies (or 'third -wave' CBT) may prove fruitful due to the considerable overlap between these approaches and key features of personal recovery. Groups also confer therapeutic benefits consistent with personal recovery and may improve recovery-oriented service provision by adding another modality for accessing support. The primary objective of this trial is to explore the feasibility and acceptability of a new recovery-focused group therapy (RfGT) intervention for adults with BD. This is the first published feasibility assessment of a time-limited RfGTrecovery-focused group therapy intervention for BD. This protocol describes an open feasibility study, utilising a pre-treatment design versus post- treatment design and nested qualitative evaluation. Participants will be recruited from the Central Coast region of New South Wales, Australia, from primary care providers, specialist mental health services, non-government organisations and via self-referral. The primary outcomes are feasibility and acceptability as indexed by recruitment, retention, intervention adherence, adverse events (if any) and detailed consumer feedback. Clinical outcomes and process measures will be assessed to inform future research. Primary outcome data will utiliseuse descriptive statistics (eg, summarizingsummarising recruitment, demographics, attendance, attrition and intervention adherence). Secondary outcomes will be assessed using repeated-measures analysis of covariance across all time points (including change, effect size and variability). Ethical approval has been granted by the Northern Sydney Local Health District HREChuman research ethics committee (HREC) (HREC/16/HAWKE/69) and The University of Newcastle HREC (H-2016-0107). The Ffindings will be used to improve the intervention per user

Changing physical activity behaviour for people with multiple sclerosis: protocol of a randomised controlled feasibility trial (iStep-MS).

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Ryan, Jennifer M; Fortune, Jennifer; Stennett, Andrea; Kilbride, Cherry; Anokye, Nana; Victor, Christina; Hendrie, Wendy; Abdul, Mohamed; DeSouza, Lorraine; Lavelle, Grace; Brewin, Debbie; David, Lee; Norris, Meriel

2017-11-15

Although physical activity may reduce disease burden, fatigue and disability, and improve quality of life among people with multiple sclerosis (MS), many people with MS are physically inactive and spend significant time in sedentary behaviour. Behaviour change interventions may assist people with MS to increase physical activity and reduce sedentary behaviour. However, few studies have investigated their effectiveness using objective measures of physical activity, particularly in the long term. Further, interventions that have proven effective in the short term may not be feasible in clinical practice because of the large amount of support provided. The iStep-MS trial aims to determine the safety, feasibility and acceptability of a behaviour change intervention to increase physical activity and reduce sedentary behaviour among people with MS. Sixty people with MS will be randomised (1:1 ratio) to receive a 12-week intervention or usual care only. The intervention consists of four physical activity consultations with a physiotherapist supported by a handbook and pedometer. Outcomes assessed at baseline, 12 weeks and 9 months are physical activity (ActiGraph wGT3X-BT accelerometer), sedentary behaviour (activPAL3µ), self-reported activity and sitting time, walking capability, fatigue, self-efficacy, participation, quality of life and health service use. The safety of the intervention will be determined by assessing change in pain and fatigue and the incidence of adverse events during the follow-up period. A parallel process evaluation will assess the feasibility and acceptability of the intervention through assessment of fidelity to the programme and semistructured interviews exploring participants' and therapists' experiences of the intervention. The feasibility of conducting an economic evaluation will be determined by collecting data on quality of life and resource use. Research ethics committee approval has been granted from Brunel University London. Results of

Thermoreversible Gel Formulations Containing Sodium Lauryl Sulfate or n-Lauroylsarcosine as Potential Topical Microbicides against Sexually Transmitted Diseases

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Roy, Sylvie; Gourde, Pierrette; Piret, Jocelyne; Désormeaux, André; Lamontagne, Julie; Haineault, Caroline; Omar, Rabeea F.; Bergeron, Michel G.

2001-01-01

The microbicidal efficacies of two anionic surfactants, sodium lauryl sulfate (SLS) and n-lauroylsarcosine (LS), were evaluated in cultured cells and in a murine model of herpes simplex type 2 (HSV-2) intravaginal infection. In vitro studies showed that SLS and LS were potent inhibitors of the infectivity of HSV-2 strain 333. The concentrations of SLS which inhibit viral infectivity by 50% (50% inhibitory dose) and 90% (90% inhibitory dose) were 32.67 and 46.53 μM, respectively, whereas the corresponding values for LS were 141.76 and 225.30 μM. In addition, intravaginal pretreatment of mice with thermoreversible gel formulations containing 2.5% SLS or 2.5% LS prior to the inoculation of HSV-2 strain 333 completely prevented the development of genital herpetic lesions and the lethality associated with infection. Of prime interest, no infectious virus could be detected in mouse vaginal mucosa. Both formulations still provided significant protection when viral challenge was delayed until 1 h after pretreatment. Finally, intravaginal application of gel formulations containing 2.5% SLS or 2.5% LS once daily for 14 days to rabbits did not induce significant irritations to the genital mucosa, as demonstrated from macroscopic and histopathologic examinations. These results suggest that thermoreversible gel formulations containing SLS or LS could represent potent and safe topical microbicides for the prevention of HSV-2 and possibly other sexually transmitted pathogens, including human immunodeficiency virus. PMID:11353610

Healthy Beyond Pregnancy, a Web-Based Intervention to Improve Adherence to Postpartum Care: Randomized Controlled Feasibility Trial.

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Himes, Katherine Park; Donovan, Heidi; Wang, Stephanie; Weaver, Carrie; Grove, Jillian Rae; Facco, Francesca Lucia

2017-10-10

During the postpartum visit, health care providers address issues with short- and long-term implications for maternal and child health. Women with Medicaid insurance are less likely to return for a postpartum visit compared with women with private insurance. Behavioral economics acknowledges that people do not make exclusively rational choices, rather immediate gratification, cognitive and psychological biases, and social norms influence decision making. Drawing on insights from decision science, behavioral economists have examined how these biases can be modulated through carefully designed interventions. We have developed a Web-based tool, Healthy Beyond Pregnancy, that incorporates empirically derived concepts of behavioral economics to improve adherence rates to the postpartum visit. The primary objectives of this pilot study were to (1) refine and assess the usability of Healthy Beyond Pregnancy and (2) assess the feasibility of a randomized controlled trial (RCT) of the intervention. We used a multistep process and multidisciplinary team of maternal-fetal medicine physicians, a behavioral economist, and researchers with expertise in behavioral interventions to design Healthy Beyond Pregnancy. We assessed the usability of the program with the Post-Study System Usability Questionnaire (PSSUQ), a validated 7-point scale, and semistructured interviews with postpartum women. We then conducted a feasibility trial to determine the proportion of eligible women who were willing to participate in an RCT of Healthy Beyond Pregnancy and the proportion of women willing to complete the Web-based program. Exploratory outcomes of the pilot trial included attendance at the postpartum visit, uptake of long-acting reversible contraception, and uptake of any contraception. The median PSSUQ score for Healthy Beyond Pregnancy was 6.5 (interquartile range: 6.1-7) demonstrating high usability. Semistructured interviews (n=10) provided in-depth comments about users' experience and

Unsupervised progressive elastic band exercises for frail geriatric inpatients objectively monitored by new exercise-integrated technology-a feasibility trial with an embedded qualitative study.

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Rathleff, C R; Bandholm, T; Spaich, E G; Jorgensen, M; Andreasen, J

2017-01-01

Frailty is a serious condition frequently present in geriatric inpatients that potentially causes serious adverse events. Strength training is acknowledged as a means of preventing or delaying frailty and loss of function in these patients. However, limited hospital resources challenge the amount of supervised training, and unsupervised training could possibly supplement supervised training thereby increasing the total exercise dose during admission. A new valid and reliable technology, the BandCizer, objectively measures the exact training dosage performed. The purpose was to investigate feasibility and acceptability of an unsupervised progressive strength training intervention monitored by BandCizer for frail geriatric inpatients. This feasibility trial included 15 frail inpatients at a geriatric ward. At hospitalization, the patients were prescribed two elastic band exercises to be performed unsupervised once daily. A BandCizer Datalogger enabling measurement of the number of sets, repetitions, and time-under-tension was attached to the elastic band. The patients were instructed in performing strength training: 3 sets of 10 repetitions (10-12 repetition maximum (RM)) with a separation of 2-min pauses and a time-under-tension of 8 s. The feasibility criterion for the unsupervised progressive exercises was that 33% of the recommended number of sets would be performed by at least 30% of patients. In addition, patients and staff were interviewed about their experiences with the intervention. Four (27%) out of 15 patients completed 33% of the recommended number of sets. For the total sample, the average percent of performed sets was 23% and for those who actually trained ( n  = 12) 26%. Patients and staff expressed a general positive attitude towards the unsupervised training as an addition to the supervised training sessions. However, barriers were also described-especially constant interruptions. Based on the predefined criterion for feasibility, the

Feasibility and Acceptability of a Web-Based Treatment with Telephone Support for Postpartum Women With Anxiety: Randomized Controlled Trial.

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Ashford, Miriam T; Olander, Ellinor K; Rowe, Heather; Fisher, Jane Rw; Ayers, Susan

2018-04-20

Postpartum anxiety can have adverse effects on the mother and child if left untreated. Time constraints and stigma are common barriers to postpartum treatment. Web-based treatments offer potential flexibility and anonymity. What Am I Worried About (WaWa) is a self-guided treatment based on cognitive-behavioral and mindfulness principles for women experiencing postpartum anxiety. WaWa was developed in Australia and consists of 9 modules with optional weekly telephone support. WaWa was adapted to a Web-based version for use in England (Internet-based What Am I Worried About, iWaWa). This study aimed to investigate the feasibility (engagement and usability) and acceptability (usefulness, satisfaction, and helpfulness) of iWaWa among English postpartum women with anxiety. Postpartum (parenting styles. Despite interest in iWaWa, the results suggest that both the study and iWaWa were not feasible in the current format. However, this first trial provides useful evidence about treatment format and content preferences that can inform iWaWa's future development, as well as research and development of Web-based postpartum anxiety treatments, in general, to optimize adherence. ClinicalTrials.gov NCT02434406; https://clinicaltrials.gov/ct2/show/NCT02434406 (Archived by WebCite at http://www.webcitation.org/6xTq7Bwmd). ©Miriam T Ashford, Ellinor K Olander, Heather Rowe, Jane RW Fisher, Susan Ayers. Originally published in JMIR Mental Health (http://mental.jmir.org), 20.04.2018.

The feasibility of an exercise intervention in males at risk of oesophageal adenocarcinoma: a randomized controlled trial.

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Brooke M Winzer

Full Text Available To investigate the feasibility and safety of a 24-week exercise intervention, compared to control, in males with Barrett's oesophagus, and to estimate the effect of the intervention, compared to control, on risk factors associated with oesophageal adenocarcinoma development.A randomized controlled trial of an exercise intervention (60 minutes moderate-intensity aerobic and resistance exercise five days/week over 24 weeks; one supervised and four unsupervised sessions versus attention control (45 minutes stretching five days/week over 24 weeks; one supervised and four unsupervised sessions in inactive, overweight/obese (25.0-34.9 kg/m2 males with Barrett's oesophagus, aged 18-70 years. Primary outcomes were obesity-associated hormones relevant to oesophageal adenocarcinoma risk (circulating concentrations of leptin, adiponectin, interleukin-6, tumour necrosis factor-alpha, C-reactive protein, and insulin resistance [HOMA]. Secondary outcomes included waist circumference, body composition, fitness, strength and gastro-oesophageal reflux symptoms. Outcomes were measured at baseline and 24-weeks. Intervention effects were analysed using generalised linear models, adjusting for baseline value.Recruitment was difficult in this population with a total of 33 participants recruited (target sample size: n = 80; 97% retention at 24-weeks. Adherence to the exercise protocol was moderate. No serious adverse events were reported. A statistically significant intervention effect (exercise minus control was observed for waist circumference (-4.5 [95% CI -7.5, -1.4] cm; p < 0.01. Effects on primary outcomes were not statistically significant.This small, exploratory trial provides important information to inform future trial development including recruitment rates and estimates of effect sizes on outcomes related to oesophageal adenocarcinoma risk. Future trials should investigate a combined dietary and exercise intervention to achieve greater weight loss in this

An intervention for pulmonary rehabilitators to develop a social identity for patients attending exercise rehabilitation: a feasibility and pilot randomised control trial protocol.

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Levy, Andrew R; Matata, Bashir; Pilsworth, Sam; Mcgonigle, Adrian; Wigelsworth, Lyndsey; Jones, Linda; Pott, Nicola; Bettany, Max; Midgley, Adrian W

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a degenerative condition that can impair health-related quality of life (HRQoL). A number of self-management interventions, employing a variety of behavioural change techniques (BCTs), have been adopted to improve HRQoL for COPD patients. However, a lack of attention has been given to group management interventions with an emphasis on incorporating BCTs into rehabilitators' practice. This study aims to pilot and feasibly explore a social identity group management intervention, delivered by COPD rehabilitation staff to patients attending exercise pulmonary rehabilitation. Doing so will help inform the plausibility of the intervention before conducting a full trial to evaluate its effectiveness to improve HRQoL. This is a two-centre, randomised cross-over controlled trial. Two pulmonary rehabilitation centres based in the UK will be randomly allocated to two treatment arms (standard care and intervention). Outcome measurements relating to HRQoL and social identity will be completed pre- and post-exercise rehabilitation. Focus group interviews will be conducted at the end of exercise rehabilitation to capture participants' contextualised experiences of the intervention. COPD rehabilitators will undertake semi-structured interviews at the end of the trial to garner their holistic perspectives of intervention fidelity and implementation. This is the first study to adopt a social identity approach to develop a rehabilitator-led, group management intervention for COPD patients attending exercise pulmonary rehabilitation. The results of this study will provide evidence for the feasibility and sample size requirements to inform a larger study, which can ascertain the intervention's effectiveness for improving HRQoL for COPD patients. ClinicalTrials.gov NCT02288039. Date 31 October 2014.

A Mixed-Methods, Randomized, Controlled Feasibility Trial to Inform the Design of a Phase III Trial to Test the Effect of the Handheld Fan on Physical Activity and Carer Anxiety in Patients With Refractory Breathlessness.

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Johnson, Miriam J; Booth, Sara; Currow, David C; Lam, Lawrence T; Phillips, Jane L

2016-05-01

The handheld fan is an inexpensive and safe way to provide facial airflow, which may reduce the sensation of chronic refractory breathlessness, a frequently encountered symptom. To test the feasibility of developing an adequately powered, multicenter, multinational randomized controlled trial comparing the efficacy of a handheld fan and exercise advice with advice alone in increasing activity in people with chronic refractory breathlessness from a variety of medical conditions, measuring recruitment rates; data quality; and potential primary outcome measures. This was a Phase II, multisite, international, parallel, nonblinded, mixed-methods randomized controlled trial. Participants were centrally randomized to fan or control. All received breathlessness self-management/exercise advice and were followed up weekly for four weeks. Participants/carers were invited to participate in a semistructured interview at the study's conclusion. Ninety-seven people were screened, 49 randomized (mean age 68 years; 49% men), and 43 completed the study. Site recruitment varied from 0.25 to 3.3/month and screening:randomization from 1.1:1 to 8.5:1. There were few missing data except for the Chronic Obstructive Pulmonary Disease Self-Efficacy Scale (two-thirds of data missing). No harms were observed. Three interview themes included 1) a fan is a helpful self-management strategy, 2) a fan aids recovery, and 3) a symptom control trial was welcome. A definitive, multisite trial to study the use of the handheld fan as part of self-management of chronic refractory breathlessness is feasible. Participants found the fan useful. However, the value of information for changing practice or policy is unlikely to justify the expense of such a trial, given perceived benefits, the minimal costs, and an absence of harms demonstrated in this study. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

A Randomized Clinical Trial of Auricular Point Acupressure for Chronic Low Back Pain: A Feasibility Study

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Chao Hsing Yeh

2013-01-01

Full Text Available Objectives. This prospective, randomized clinical trial (RCT was designed to investigate the feasibility and effects of a 4-week auricular point acupressure (APA for chronic low back pain (CLBP. Methods. Participants were randomized to either true APA (true acupoints with taped seeds on the designated ear points for CLBP or sham APA (sham acupoints with taped seeds but on different locations than those designated for CLBP. The duration of treatment was four weeks. Participants were assessed before treatment, weekly during treatment, and 1 month following treatment. Results. Participants in the true APA group who completed the 4-week APA treatment had a 70% reduction in worst pain intensity, a 75% reduction in overall pain intensity, and a 42% improvement in disability due to back pain from baseline assessment. The reductions of worst pain and overall pain intensity in the true APA group were statistically greater than participants in the sham group (P<0.01 at the completion of a 4-week APA and 1 month followup. Discussion. The preliminary findings of this feasibility study showed a reduction in pain intensity and improvement in physical function suggesting that APA may be a promising treatment for patients with CLBP.

Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm

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Jones Maureen

2010-07-01

Full Text Available Abstract Background At present, there is no effective vaccine or other approved product for the prevention of sexually transmitted human immunodeficiency virus type 1 (HIV-1 infection. It has been reported that women in resource-poor communities use vaginally applied citrus juices as topical microbicides. These easily accessible food products have historically been applied to prevent pregnancy and sexually transmitted diseases. The aim of this study was to evaluate the efficacy and cytotoxicity of these substances using an established topical microbicide testing algorithm. Freshly squeezed lemon and lime juice and household vinegar were tested in their original state or in pH neutralized form for efficacy and cytotoxicity in the CCR5-tropic cell-free entry and cell-associated transmission assays, CXCR4-tropic entry and fusion assays, and in a human PBMC-based anti-HIV-1 assay. These products were also tested for their effect on viability of cervico-vaginal cell lines, human cervical explant tissues, and beneficial Lactobacillus species. Results Natural lime and lemon juice and household vinegar demonstrated anti-HIV-1 activity and cytotoxicity in transformed cell lines. Neutralization of the products reduced both anti-HIV-1 activity and cytotoxicity, resulting in a low therapeutic window for both acidic and neutralized formulations. For the natural juices and vinegar, the IC50 was ≤ 3.5 (0.8-3.5% and the TC50 ≤ 6.3 (1.0-6.3%. All three liquid products inhibited viability of beneficial Lactobacillus species associated with vaginal health. Comparison of three different toxicity endpoints in the cervical HeLa cell line revealed that all three products affected membrane integrity, cytosolic enzyme release, and dehydrogenase enzyme activity in living cells. The juices and vinegar also exerted strong cytotoxicity in cervico-vaginal cell lines, mainly due to their acidic pH. In human cervical explant tissues, treatment with 5% lemon or lime juice

Feasibility trial of a film-based educational intervention for increasing boys’ and girls’ intentions to avoid teenage pregnancy: Study protocol ☆

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Lohan, Maria; Aventin, Áine; Maguire, Lisa; Clarke, Mike; Linden, Mark; McDaid, Lisa

2014-01-01

The World Health Organisation, amongst others, recognises that adolescent men have a vital yet neglected role in reducing teenage pregnancies and that there is a pressing need for educational interventions designed especially for them. This study seeks to fill this gap by determining the feasibility of conducting an effectiveness trial of the If I Were Jack intervention in post-primary schools. This 4-week intervention aims to increase teenagers' intentions to avoid unintended pregnancy and a...

Active Treatment for Idiopathic Adolescent Scoliosis (ACTIvATeS): a feasibility study.

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Williams, Mark A; Heine, Peter J; Williamson, Esther M; Toye, Francine; Dritsaki, Melina; Petrou, Stavros; Crossman, Richard; Lall, Ranjit; Barker, Karen L; Fairbank, Jeremy; Harding, Ian; Gardner, Adrian; Slowther, Anne-Marie; Coulson, Neil; Lamb, Sarah E

2015-07-01

The feasibility of conducting a definitive randomised controlled trial (RCT) evaluating the clinical effectiveness and cost-effectiveness of scoliosis-specific exercises (SSEs) for adolescent idiopathic scoliosis (AIS) is uncertain. The aim of this study was to assess the feasibility of conducting a large, multicentre trial of SSE treatment for patients with AIS, in comparison with standard care, and to refine elements of the study design. The objectives were to (1) update a systematic review of controlled trials evaluating the efficacy of SSE in AIS; (2) survey UK orthopaedic surgeons and physiotherapists to determine current practice, patient populations and equipoise; (3) randomise 50 adolescents to a feasibility trial of either usual care or SSE interventions across a range of sites; (4) develop, document and assess acceptability and adherence of interventions; (5) assess and describe training requirements of physiotherapists; and (6) gain user input in all relevant stages of treatment and protocol design. Multicomponent feasibility study including UK clinician survey, systematic literature review and a randomised feasibility trial. The randomised feasibility study involved four secondary care NHS trusts providing specialist care for patients with AIS. The randomised feasibility study recruited people aged 10-16 years with mild AIS (Cobb angle of physiotherapy SSE programme supported by a home exercise plan. Our choice of intervention was informed by a systematic review of exercise interventions for AIS. The main outcome was feasibility of recruitment to the randomised study. Other elements were to inform choice of outcomes for a definitive trial and included curve severity, quality of life, requirement for surgery/brace, adverse events, psychological symptoms, costs and health utilities. A UK survey of orthopaedic consultants and physiotherapists indicated a wide variation in current provision of exercise therapy through physiotherapy services. It also found

Guided imagery targeting exercise, food cravings, and stress: a multi-modal randomized feasibility trial.

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Giacobbi, Peter; Long, Dustin; Nolan, Richard; Shawley, Samantha; Johnson, Kelsey; Misra, Ranjita

2018-02-01

The purpose of this randomized wait-list controlled trial was to test the feasibility and preliminary efficacy of a guided imagery based multi-behavior intervention intended to address psychological stress, food cravings, and physical activity. Personalized guided imagery scripts were created and participants were instructed to practice guided imagery every day for 35 consecutive days. Of 48 women who enrolled, we report comparisons between 16 randomized to treatment with 19 who were wait-listed (overall M age  = 45.50; M bodymassindex  = 31.43). Study completers reported 89% compliance with practicing guided imagery during the intervention. A significant time-by-group interaction was observed with reductions in food cravings and increases in physical activity compared with wait-list controls. Telephone-based multi-behavior interventions that utilize guided imagery to address food cravings and exercise behavior appear to be acceptable for overweight and obese women. Future phone-based guided imagery research testing this skill to address multiple health behaviors is justified.

Inhibition of HIV-1 infection in ex vivo cervical tissue model of human vagina by palmitic acid; implications for a microbicide development.

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Xudong Lin

Full Text Available BACKGROUND: Approximately 80% of all new HIV-1 infections are acquired through sexual contact. Currently, there is no clinically approved microbicide, indicating a clear and urgent therapeutic need. We recently reported that palmitic acid (PA is a novel and specific inhibitor of HIV-1 fusion and entry. Mechanistically, PA inhibits HIV-1 infection by binding to a novel pocket on the CD4 receptor and blocks efficient gp120-to-CD4 attachment. Here, we wanted to assess the ability of PA to inhibit HIV-1 infection in cervical tissue ex vivo model of human vagina, and determine its effect on Lactobacillus (L species of probiotic vaginal flora. PRINCIPAL FINDINGS: Our results show that treatment with 100-200 µM PA inhibited HIV-1 infection in cervical tissue by up to 50%, and this treatment was not toxic to the tissue or to L. crispatus and jensenii species of vaginal flora. In vitro, in a cell free system that is independent of in vivo cell associated CD4 receptor; we determined inhibition constant (Ki to be ∼2.53 µM. SIGNIFICANCE: These results demonstrate utility of PA as a model molecule for further preclinical development of a safe and potent HIV-1 entry microbicide inhibitor.

'It looks like you just want them when things get rough': civil society perspectives on negative trial results and stakeholder engagement in HIV prevention trials.

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Koen, Jennifer; Essack, Zaynab; Slack, Catherine; Lindegger, Graham; Newman, Peter A

2013-12-01

Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the global HIV epidemic, CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders in HIV research. This study explored the perspectives of CSO representatives involved in HIV prevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents from South African and international CSOs representing activist and advocacy groups, community mobilisation initiatives, and human and legal rights groups were purposively sampled based on involvement in HPTs. Interviews were conducted from February-May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively. CSO representatives largely described positive outcomes of recent microbicide and HIV vaccine trial terminations, particularly in South Africa, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time-points, as well as the need for legitimate alternatives to CABs as mechanisms for engagement. Key issues for CSOs in relation to research were also raised. © 2012 John Wiley & Sons Ltd.

Feasibility and acceptability of a beverage intervention for Hispanic adults: a protocol for a pilot randomized controlled trial.

Science.gov (United States)

Morrill, Kristin E; Aceves, Benjamin; Valdez, Luis A; Thomson, Cynthia A; Hakim, Iman A; Bell, Melanie L; Martinez, Jessica A; Garcia, David O

2018-02-09

-reactive protein (hs-CRP). This pilot study will provide important feasibility, safety, and early efficacy data necessary to design a larger, adequately-powered randomized controlled trial. NCT02911753 ( ClinicalTrials.gov ). Registered September 19, 2016. Last updated November 1, 2017.

The feasibility of a randomised controlled trial to compare the cost-effectiveness of palliative cardiology or usual care in people with advanced heart failure: Two exploratory prospective cohorts.

Science.gov (United States)

Johnson, Miriam J; McSkimming, Paula; McConnachie, Alex; Geue, Claudia; Millerick, Yvonne; Briggs, Andrew; Hogg, Karen

2018-06-01

The effectiveness of cardiology-led palliative care is unknown; we have insufficient information to conduct a full trial. To assess the feasibility (recruitment/retention, data quality, variability/sample size estimation, safety) of a clinical trial of palliative cardiology effectiveness. Non-randomised feasibility. Unmatched symptomatic heart failure patients on optimal cardiac treatment from (1) cardiology-led palliative service (caring together group) and (2) heart failure liaison service (usual care group). Outcomes/safety: Symptoms (Edmonton Symptom Assessment Scale), Kansas City Cardiomyopathy Questionnaire, performance, understanding of disease, anticipatory care planning, cost-effectiveness, survival and carer burden. A total of 77 participants (caring together group = 43; usual care group = 34) were enrolled (53% men; mean age 77 years (33-100)). The caring together group scored worse in Edmonton Symptom Assessment Scale (43.5 vs 35.2) and Kansas City Cardiomyopathy Questionnaire (35.4 vs 39.9). The caring together group had a lower consent/screen ratio (1:1.7 vs 1: 2.8) and few died before approach (0.08% vs 16%) or declined invitation (17% vs 37%). Data quality: At 4 months, 74% in the caring together group and 71% in the usual care group provided data. Most attrition was due to death or deterioration. Data quality in self-report measures was otherwise good. There was no difference in survival. Symptoms and quality of life improved in both groups. A future trial requires 141 (202 allowing 30% attrition) to detect a minimal clinical difference (1 point) in Edmonton Symptom Assessment Scale score for breathlessness (80% power). More participants (176; 252 allowing 30% attrition) are needed to detect a 10.5 change in Kansas City Cardiomyopathy Questionnaire score (80% power; minimum clinical difference = 5). A trial to test the clinical effectiveness (improvement in breathlessness) of cardiology-led palliative care is feasible.

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

Science.gov (United States)

Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

2017-12-01

We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most

"FIND Technology": investigating the feasibility, efficacy and safety of controller-free interactive digital rehabilitation technology in an inpatient stroke population: study protocol for a randomized controlled trial.

Science.gov (United States)

Bird, M L; Cannell, J; Callisaya, M L; Moles, E; Rathjen, A; Lane, K; Tyson, A; Smith, S

2016-04-16

Stroke results in significant disability, which can be reduced by physical rehabilitation. High levels of repetition and activity are required in rehabilitation, but patients are typically sedentary. Using clinically relevant and fun computer games may be one way to achieve increased activity in rehabilitation. A single-blind randomized controlled trial will be conducted to evaluate the feasibility, efficacy and safety of novel stroke-specific rehabilitation software. This software uses controller-free client interaction and inertial motion sensors. Elements of feasibility include recruitment into the trial, ongoing participation (adherence and dropout), perceived benefit, enjoyment and ease of use of the games. Efficacy will be determined by measuring activity and using upper-limb tasks as well as measures of balance and mobility. The hypothesis that the intervention group will have increased levels of physical activity within rehabilitation and improved physical outcomes compared with the control group will be tested. Results from this study will provide a basis for discussion of feasibility of this interactive video technological solution in an inpatient situation. Differences in activity levels between groups will be the primary measure of efficacy. It will also provide data on measures of upper-limb function, balance and mobility. ACTRN12614000427673 . Prospectively registered 17 April 2014.

Feasibility of an online mindfulness-based program for patients with melanoma: study protocol for a randomised controlled trial.

Science.gov (United States)

Russell, Lahiru; Ugalde, Anna; Milne, Donna; Krishnasamy, Meinir; O Seung Chul, Eric; Austin, David W; Chambers, Richard; Orellana, Liliana; Livingston, Patricia M

2018-04-13

People with a melanoma diagnosis are at risk of recurrence, developing a new primary or experiencing disease progression. Previous studies have suggested that fear of a cancer recurrence is clinically relevant in this group of patients and, if not addressed, can lead to distress. Mindfulness-based interventions have been shown to alleviate symptoms of anxiety and depression among various groups of cancer patients. Online mindfulness-based interventions have the potential to reach people unable to attend face-to-face interventions due to limitations such as cancer-related illness, transportation or time constraints. This study aims to (1) examine whether individuals with a melanoma diagnosis are willing to participate and adhere to a 6-week online mindfulness-based intervention and (2) explore potential benefits of the program on fear of cancer recurrence, worries, rumination, perceived stress and trait mindfulness to inform the design of a clinical trial. This is a single-site randomised controlled trial of a feasibility study. Seventy-five participants with stage 2c or 3 melanoma will be recruited from a melanoma outpatient clinic and randomised (2:1) either to an online mindfulness-based program (intervention) or to usual care (control). The intervention is a 6-week program specifically developed for this study. It consists of videos describing the concept of mindfulness, short daily guided meditation practices (5-10 min), automated meditation reminders and instructions for applying mindfulness in daily life to enhance wellbeing. All participants will complete questionnaires at baseline and at 6-week post-randomisation. Participants in the control group will be given access to the online program at the end of the study. Primary outcomes are overall recruitment; retention; extent of questionnaire completion; and usability and acceptability of, and adherence to, the program. The secondary outcomes are fear of cancer recurrence, worries, rumination, perceived

Randomized controlled trial of Family Nurture Intervention in the NICU: assessments of length of stay, feasibility and safety.

Science.gov (United States)

Welch, Martha G; Hofer, Myron A; Stark, Raymond I; Andrews, Howard F; Austin, Judy; Glickstein, Sara B; Ludwig, Robert J; Myers, Michael M

2013-09-24

While survival rates for preterm infants have increased, the risk for adverse long-term neurodevelopmental and behavioral outcomes remains very high. In response to the need for novel, evidence-based interventions that prevent such outcomes, we have assessed Family Nurture Intervention (FNI), a novel dual mother-infant intervention implemented while the infant is in the Neonatal Intensive Care Unit (NICU). Here, we report the first trial results, including the primary outcome measure, length of stay in the NICU and, the feasibility and safety of its implementation in a high acuity level IV NICU. The FNI trial is a single center, parallel-group, randomized controlled trial at Morgan Stanley Children's Hospital for mothers and their singleton or twin infants of 26-34 weeks gestation. Families were randomized to standard care (SC) or (FNI). FNI was implemented by nurture specialists trained to facilitate affective communication between mother and infant during specified calming interactions. These interactions included scent cloth exchange, sustained touch, vocal soothing and eye contact, wrapped or skin-to-skin holding, plus family-based support interactions. A total of 826 infants born between 26 and 34 weeks during the 3.5 year study period were admitted to the NICU. After infant and mother screening plus exclusion due to circumstances that prevented the family from participating, 373 infants were eligible for the study. Of these, we were unable to schedule a consent meeting with 56, and consent was withheld by 165. Consent was obtained for 150 infants from 115 families. The infants were block randomized to groups of N = 78, FNI and N = 72, SC. Sixteen (9.6%) of the randomized infants did not complete the study to home discharge, 7% of those randomized to SC and 12% of FNI infants. Mothers in the intervention group engaged in 3 to 4 facilitated one- to two-hour sessions/week. Intent to treat analyses revealed no significant difference between groups in

Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) - Feasibility testing, pilot randomised controlled trial and mixed methods process evaluation.

Science.gov (United States)

Rahn, A C; Köpke, S; Backhus, I; Kasper, J; Anger, K; Untiedt, B; Alegiani, A; Kleiter, I; Mühlhauser, I; Heesen, C

2018-02-01

Treatment decision-making is complex for people with multiple sclerosis. Profound information on available options is virtually not possible in regular neurologist encounters. The "nurse decision coach model" was developed to redistribute health professionals' tasks in supporting immunotreatment decision-making following the principles of informed shared decision-making. To test the feasibility of a decision coaching programme and recruitment strategies to inform the main trial. Feasibility testing and parallel pilot randomised controlled trial, accompanied by a mixed methods process evaluation. Two German multiple sclerosis university centres. People with suspected or relapsing-remitting multiple sclerosis facing immunotreatment decisions on first line drugs were recruited. Randomisation to the intervention (n = 38) or control group (n = 35) was performed on a daily basis. Quantitative and qualitative process data were collected from people with multiple sclerosis, nurses and physicians. We report on the development and piloting of the decision coaching programme. It comprises a training course for multiple sclerosis nurses and the coaching intervention. The intervention consists of up to three structured nurse-led decision coaching sessions, access to an evidence-based online information platform (DECIMS-Wiki) and a final physician consultation. After feasibility testing, a pilot randomised controlled trial was performed. People with multiple sclerosis were randomised to the intervention or control group. The latter had also access to the DECIMS-Wiki, but received otherwise care as usual. Nurses were not blinded to group assignment, while people with multiple sclerosis and physicians were. The primary outcome was 'informed choice' after six months including the sub-dimensions' risk knowledge (after 14 days), attitude concerning immunotreatment (after physician consultation), and treatment uptake (after six months). Quantitative process evaluation data

Resistance to and killing by the sporicidal microbicide peracetic acid.

Science.gov (United States)

Leggett, Mark J; Schwarz, J Spencer; Burke, Peter A; Mcdonnell, Gerald; Denyer, Stephen P; Maillard, Jean-Yves

2015-03-01

To elucidate the mechanisms of spore resistance to and killing by the oxidizing microbicide peracetic acid (PAA). Mutants of Bacillus subtilis lacking specific spore structures were used to identify resistance properties in spores and to understand the mechanism of action of PAA. We also assessed the effect of PAA treatment on a number of spore properties including heat tolerance, membrane integrity and germination. The spore coat is essential for spore PAA resistance as spores with defective coats were greatly sensitized to PAA treatment. Small acid-soluble spore proteins apparently provide no protection against PAA. Defects in spore germination, specifically in germination via the GerB and GerK but not the GerA germination receptors, as well as leakage of internal components suggest that PAA is active at the spore inner membrane. It is therefore likely that the inner membrane is the major site of PAA's sporicidal activity. PAA treatment targets the spore membrane, with some of its activity directed specifically against the GerB and GerK germination receptors. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: a pilot trial.

Science.gov (United States)

Cook, Deborah J; Johnstone, Jennie; Marshall, John C; Lauzier, Francois; Thabane, Lehana; Mehta, Sangeeta; Dodek, Peter M; McIntyre, Lauralyn; Pagliarello, Joe; Henderson, William; Taylor, Robert W; Cartin-Ceba, Rodrigo; Golan, Eyal; Herridge, Margaret; Wood, Gordon; Ovakim, Daniel; Karachi, Tim; Surette, Michael G; Bowdish, Dawn M E; Lamarche, Daphnee; Verschoor, Chris P; Duan, Erick H; Heels-Ansdell, Diane; Arabi, Yaseen; Meade, Maureen

2016-08-02

Probiotics are live microorganisms that may confer health benefits when ingested. Randomized trials suggest that probiotics significantly decrease the incidence of ventilator-associated pneumonia (VAP) and the overall incidence of infection in critically ill patients. However, these studies are small, largely single-center, and at risk of bias. The aim of the PROSPECT pilot trial was to determine the feasibility of conducting a larger trial of probiotics to prevent VAP in mechanically ventilated patients in the intensive care unit (ICU). In a randomized blinded trial, patients expected to be mechanically ventilated for ≥72 hours were allocated to receive either 1 × 10(10) colony-forming units of Lactobacillus rhamnosus GG or placebo, twice daily. Patients were excluded if they were at increased risk of L. rhamnosus GG infection or had contraindications to enteral medication. Feasibility objectives were: (1) timely recruitment; (2) maximal protocol adherence; (3) minimal contamination; and (4) estimated VAP rate ≥10 %. We also measured other infections, diarrhea, ICU and hospital length of stay, and mortality. Overall, in 14 centers in Canada and the USA, all feasibility goals were met: (1) 150 patients were randomized in 1 year; (2) protocol adherence was 97 %; (3) no patients received open-label probiotics; and (4) the VAP rate was 19 %. Other infections included: bloodstream infection (19.3 %), urinary tract infections (12.7 %), and skin and soft tissue infections (4.0 %). Diarrhea, defined as Bristol type 6 or 7 stools, occurred in 133 (88.7 %) of patients, the median length of stay in ICU was 12 days (quartile 1 to quartile 3, 7-18 days), and in hospital was 26 days (quartile 1 to quartile 3, 14-44 days); 23 patients (15.3 %) died in the ICU. The PROSPECT pilot trial supports the feasibility of a larger trial to investigate the effect of L. rhamnosus GG on VAP and other nosocomial infections in critically ill patients. Clinicaltrials

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

Science.gov (United States)

Treister, Roi; Trudeau, Jeremiah J; Van Inwegen, Richard; Jones, Judith K; Katz, Nathaniel P

2016-12-01

Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651). © 2016 American Academy of Addiction Psychiatry.

Hospital at Home care for older patients with cognitive impairment: a protocol for a randomised controlled feasibility trial.

Science.gov (United States)

Pouw, Maaike A; Calf, Agneta H; van Munster, Barbara C; Ter Maaten, Jan C; Smidt, Nynke; de Rooij, Sophia E

2018-03-27

An acute hospital admission is a stressful life event for older people, particularly for those with cognitive impairment. The hospitalisation is often complicated by hospital-associated geriatric syndromes, including delirium and functional loss, leading to functional decline and nursing home admission. Hospital at Home care aims to avoid hospitalisation-associated adverse outcomes in older patients with cognitive impairment by providing hospital care in the patient's own environment. This randomised, non-blinded feasibility trial aims to assess the feasibility of conducting a randomised controlled trial in terms of the recruitment, use and acceptability of Hospital at Home care for older patients with cognitive impairment. The quality of care will be evaluated and the advantages and disadvantages of the Hospital at Home care programme compared with usual hospital care. Eligible patients will be randomised either to Hospital at Home care in their own environment or usual hospital care. The intervention consists of hospital level care provided at patients' homes, including visits from healthcare professionals, diagnostics (laboratory tests, blood cultures) and treatment. The control group will receive usual hospital care. Measurements will be conducted at baseline, during admission, at discharge and at 3 and 6 months after the baseline assessment. Institutional ethics approval has been granted. The findings will be disseminated through public lectures, professional and scientific conferences, as well as peer-reviewed journal articles. The study findings will contribute to knowledge on the implementation of Hospital at Home care for older patients with cognitive disorders. The results will be used to inform and support strategies to deliver eligible care to older patients with cognitive impairment. e020313; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is

Perceptions among Dutch men who have sex with men and their willingness to use rectal microbicides and oral pre-exposure prophylaxis to reduce HIV risk--a preliminary study

NARCIS (Netherlands)

Marra, Elske; Hankins, Catherine A.

2015-01-01

Oral pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) tablets and topical PrEP or microbicides containing ARV drugs could help to reduce HIV incidence. These methods hold promise for men who have sex with men (MSM) who are at higher risk of acquiring HIV. This mixed-methods study in the

Study protocol for the optimisation, feasibility testing and pilot cluster randomised trial of Positive Choices: a school-based social marketing intervention to promote sexual health, prevent unintended teenage pregnancies and address health inequalities in England.

Science.gov (United States)

Ponsford, Ruth; Allen, Elizabeth; Campbell, Rona; Elbourne, Diana; Hadley, Alison; Lohan, Maria; Melendez-Torres, G J; Mercer, Catherine H; Morris, Steve; Young, Honor; Bonell, Chris

2018-01-01

Since the introduction of the Teenage Pregnancy Strategy (TPS), England's under-18 conception rate has fallen by 55%, but a continued focus on prevention is needed to maintain and accelerate progress. The teenage birth rate remains higher in the UK than comparable Western European countries. Previous trials indicate that school-based social marketing interventions are a promising approach to addressing teenage pregnancy and improving sexual health. Such interventions are yet to be trialled in the UK. This study aims to optimise and establish the feasibility and acceptability of one such intervention: Positive Choices. Design: Optimisation, feasibility testing and pilot cluster randomised trial.Interventions: The Positive Choices intervention comprises a student needs survey, a student/staff led School Health Promotion Council (SHPC), a classroom curriculum for year nine students covering social and emotional skills and sex education, student-led social marketing activities, parent information and a review of school sexual health services.Systematic optimisation of Positive Choices will be carried out with the National Children's Bureau Sex Education Forum (NCB SEF), one state secondary school in England and other youth and policy stakeholders.Feasibility testing will involve the same state secondary school and will assess progression criteria to advance to the pilot cluster RCT.Pilot cluster RCT with integral process evaluation will involve six different state secondary schools (four interventions and two controls) and will assess the feasibility and utility of progressing to a full effectiveness trial.The following outcome measures will be trialled as part of the pilot:Self-reported pregnancy and unintended pregnancy (initiation of pregnancy for boys) and sexually transmitted infections,Age of sexual debut, number of sexual partners, use of contraception at first and last sex and non-volitional sexEducational attainmentThe feasibility of linking administrative

Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints

Science.gov (United States)

Renfro, Lindsay A.; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J.

2014-01-01

Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer. PMID:25061255

Bridges self-management program for people with stroke in the community: A feasibility randomized controlled trial.

Science.gov (United States)

McKenna, Suzanne; Jones, Fiona; Glenfield, Pauline; Lennon, Sheila

2015-07-01

Enabling self-management behaviors is considered important in order to develop coping strategies and confidence for managing life with a long-term condition. However, there is limited research into stroke-specific self-management interventions. The aim of this randomized controlled trial was to evaluate the feasibility of delivering the Bridges stroke self-management program in addition to usual stroke rehabilitation compared with usual rehabilitation only. Participants recruited from the referrals to a community stroke team were randomly allocated to the Bridges stroke self-management program, receiving either one session of up to one-hour per week over a six-week period in addition to usual stroke rehabilitation, or usual rehabilitation only. Feasibility was measured using a range of methods to determine recruitment and retention; adherence to the program; suitability and variability of outcome measures used; application and fidelity of the program; and acceptability of the program to patients, carers and professionals. Twenty-five people were recruited to the study over a 13-month period. Eight out of the 12 participants in the Bridges stroke self-management program received all six sessions; there was one withdrawal from the study. There were changes in outcomes between the two groups. Participants who received the Bridges stroke self-management program appeared to have a greater change in self-efficacy, functional activity, social integration and quality of life over the six-week intervention period and showed less decline in mood and quality of life at the three-month follow-up. Professionals found the program acceptable to use in practice, and feedback from participants was broadly positive. The findings from this study appear promising, but questions remain regarding the feasibility of delivering the Bridges stroke self-management program in addition to usual rehabilitation. The dose response of receiving the program cannot be ruled out, and the next stage

Phase II feasibility trial of adjuvant chemoradiotherapy with 3-weekly cisplatin for Japanese patients with post-operative high-risk squamous cell carcinoma of the head and neck

International Nuclear Information System (INIS)

Kiyota, Naomi; Tahara, Makoto; Okano, Susumu

2012-01-01

The current standard of care for post-operative high-risk squamous cell carcinoma of the head and neck is concurrent chemoradiotherapy with a 3-weekly cycle of cisplatin (3W-CDDP/RT). In previous pivotal trials, the complete delivery rate of three cycles of cisplatin and radiation therapy was only -60%. Here, we evaluated the feasibility and safety of 3W-CDDP/RT in a Japanese population. The study enrolled post-operative high-risk squamous cell carcinoma of the head and neck patients. High-risk factors were a microscopically incomplete resection, extracapsular extension and two or more lymph node metastases. Subjects received three cycles of cisplatin at a dose of 100 mg/m 2 concomitant with radiation therapy (66 Gy/33 Fr). From August 2006 to May 2009, 25 eligible subjects were accrued, including 13 males, with a median age of 59 years, Eastern Cooperative Oncology Group performance status 0/1 (18/7), Stage III/IVA/IVB/recurrent (1/18/1/5) and oral cavity/oropharynx/hypopharynx/larynx (17/4/3/1). Protocol completion rate was 80%. The lower limit of the one-sided 90% confidence interval was 66%, which met the predefined statistical criteria. Grade 3/4 acute and late toxicities were almost identical to those in previous pivotal trials. No treatment-related deaths were observed. With a median follow-up of 39 months, 14 have had progression and 10 have died. Estimated 3-year locoregional control rate, relapse-free survival and overall survival were 74, 43 and 60%, respectively. On univariate analysis, oral cavity cancer and a cumulative cisplatin dose below 240 mg/m 2 appeared to be poor prognostic factors. This is the first Phase II feasibility trial of adjuvant chemoradiotherapy with 3-weekly cisplatin for post-operative high-risk squamous cell carcinoma of the head and neck in a Japanese population. This treatment was feasible and the safety profile was identical to those in pivotal Phase III trials. (author)

Unsupervised progressive elastic band exercises for frail geriatric inpatients objectively monitored by new exercise-integrated technology-a feasibility trial with an embedded qualitative study

DEFF Research Database (Denmark)

Rathleff, C R; Bandholm, T; Spaich, E G

2017-01-01

feasibility and acceptability of an unsupervised progressive strength training intervention monitored by BandCizer for frail geriatric inpatients. Methods: This feasibility trial included 15 frail inpatients at a geriatric ward. At hospitalization, the patients were prescribed two elastic band exercises......Background: Frailty is a serious condition frequently present in geriatric inpatients that potentially causes serious adverse events. Strength training is acknowledged as a means of preventing or delaying frailty and loss of function in these patients. However, limited hospital resources challenge...... the amount of supervised training, and unsupervised training could possibly supplement supervised training thereby increasing the total exercise dose during admission. A new valid and reliable technology, the BandCizer, objectively measures the exact training dosage performed. The purpose was to investigate...

Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T Cells: Implications for HIV Microbicides.

Science.gov (United States)

Mukhopadhya, Indrani; Murray, Graeme I; Duncan, Linda; Yuecel, Raif; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

2016-09-06

CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood samples by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.

Examining self-guided internet-delivered cognitive behavior therapy for older adults with symptoms of anxiety and depression: Two feasibility open trials

Directory of Open Access Journals (Sweden)

Blake F. Dear

2015-03-01

Full Text Available Self-guided internet-delivered cognitive behavior therapy (iCBT has considerable public health potential for treating anxiety and depression. However, no research has examined the use of self-guided iCBT, that is, treatment without contact with a clinician, specifically for older adults. The aim of the present study was to undertake a preliminary examination of the acceptability, efficacy and health economic impact of two entirely self-guided iCBT programs for adults over 60 years of age with anxiety and depression. Two separate single-group feasibility open trials of self-guided iCBT were conducted, the Anxiety Trial (n = 27 and the Depression Trial (n = 20, using the control groups of two randomized controlled trials. The online treatment packages consisted of five online educational lessons, which were delivered over 8 weeks without clinical contact. Participants rated the interventions as acceptable with more than 90% reporting the course was worth their time and more than 70% of participants completing at least 3 of the 5 lessons within the eight weeks. Significant reductions on measures of anxiety (Generalized Anxiety Disorder 7-item; GAD-7 and depression (Patient Health Questionnaire 9-item; PHQ-9 were observed from pre-treatment to post-treatment in both the Anxiety Trial (GAD-7 Cohen's d = 1.17; 95% CI: 0.55 to 1.75 and the Depression Trial (PHQ-9 Cohen's d = 1.06; 95% CI: 0.33 to 1.73. The economic analyses indicated that there was statistically significant improvement in health-related quality of life compared to baseline and marginally higher costs associated with treatment for both the Anxiety Trial ($69.84; 95% CI: $4.24 to $135.45 and the Depression Trial ($54.98; 95% CI: $3.84 to $106.12. The results provide preliminary support for the potential of entirely self-guided iCBT for older adults with anxiety and depression and indicate larger scale and controlled research trials are warranted.

Prediabetes in pregnancy, can early intervention improve outcomes? A feasibility study for a parallel randomised clinical trial.

Science.gov (United States)

Hughes, Ruth C E; Rowan, Janet; Williman, Jonathan

2018-03-03

Measurement of glycated haemoglobin (HbA1c) in early pregnancy is routine in New Zealand to identify women with diabetes and prediabetes. However, the benefit of early intervention in women with prediabetes is inconclusive. Our aim was to test the feasibility of a two-arm parallel randomised controlled trial of standard care versus early intervention in pregnancies complicated by prediabetes. Two tertiary referral centres in New Zealand. Women measured at booking, without pre-existing diabetes. Randomisation was done by remote web-based allocation into one of two groups. Women in the early intervention group attended an antenatal diabetes clinic, commenced daily home blood glucose monitoring, and medication was prescribed if lifestyle measures failed to maintain target blood glucose levels. Controls received lifestyle education, continued standard care with their midwife and/or obstetrician, and were asked to perform a 75 g oral glucose tolerance test at 24 weeks' gestation with a referral to clinic if this test was positive. Both groups received lifestyle questionnaires at recruitment and in late pregnancy. Recruitment rate, adherence to protocol and validation of potential primary outcomes. Recruitment rates were lower than expected, especially in Māori and Pacific women. Non-adherence to allocated treatment protocol was significant, 42% (95% CI 24% to 61%) in the early intervention group and 30% (95% CI 16% to 51%) in controls. Caesarean section and pre-eclampsia were signalled as potential primary outcomes, due to both the high observed incidence in the control group and ease of measurement. For a future definitive trial, extending the gestation of eligibility and stepped-wedge cluster randomisation may overcome the identified feasibility issues. Consistent with published observational data, pre-eclampsia and emergency caesarean section could be included as primary outcome measures, both of which have a significant impact on maternal and neonatal morbidity and

Promoting Physical Activity in Low-Active Adolescents via Facebook: A Pilot Randomized Controlled Trial to Test Feasibility.

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Wójcicki, Thomas R; Grigsby-Toussaint, Diana; Hillman, Charles H; Huhman, Marian; McAuley, Edward

2014-10-30

The World Wide Web is an effective method for delivering health behavior programs, yet major limitations remain (eg, cost of development, time and resource requirements, limited interactivity). Social media, however, has the potential to deliver highly customizable and socially interactive behavioral interventions with fewer constraints. Thus, the evaluation of social media as a means to influence health behaviors is warranted. The objective of this trial was to examine and demonstrate the feasibility of using an established social networking platform (ie, Facebook) to deliver an 8 week physical activity intervention to a sample of low-active adolescents (N=21; estimated marginal mean age 13.48 years). Participants were randomized to either an experimental (ie, Behavioral) or attentional control (ie, Informational) condition. Both conditions received access to a restricted-access, study-specific Facebook group where the group's administrator made two daily wall posts containing youth-based physical activity information and resources. Primary outcomes included physical activity as assessed by accelerometry and self-report. Interactions and main effects were examined, as well as mean differences in effect sizes. Analyses revealed significant improvements over time on subjectively reported weekly leisure-time physical activity (F1,18=8.426, P=.009, η2 = .319). However, there was no interaction between time and condition (F1,18=0.002, P=.968, η2 = .000). There were no significant time or interaction effects among the objectively measured physical activity variables. Examination of effect sizes revealed moderate-to-large changes in physical activity outcomes. Results provide initial support for the feasibility of delivery of a physical activity intervention to low-active adolescents via social media. Whether by employing behavioral interventions via social media can result in statistically meaningful changes in health-related behaviors and outcomes remains to be

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Winnie

Phase III microbicide trial methodology: opinions of experienced ... This study involved a survey of South African women participating in an expanded safety trial of the candidate ... Diseases,Academic Medical Centre, University of Amsterdam. ... National Health Laboratory Service Tertiary Microbiology Laboratory for the ...

Study of Optimal Replacement of Thyroxine in the ElDerly (SORTED): protocol for a mixed methods feasibility study to assess the clinical utility of lower dose thyroxine in elderly hypothyroid patients: study protocol for a randomized controlled trial.

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Wilkes, Scott; Pearce, Simon; Ryan, Vicky; Rapley, Tim; Ingoe, Lorna; Razvi, Salman

2013-03-22

The population of the UK is ageing. There is compelling evidence that thyroid stimulating hormone distribution levels increase with age. Currently, in UK clinical practice elderly hypothyroid patients are treated with levothyroxine to lower their thyroid stimulating hormone levels to a standard non-age-related range. Evidence suggests that mortality is negatively associated with thyroid stimulating hormone levels. We report the protocol of a feasibility study working towards a full-scale randomized controlled trial to test whether lower dose levothyroxine has beneficial cardiovascular outcomes in the oldest old. SORTED is a mixed methods study with three components: SORTED A: A feasibility study of a dual-center single-blinded randomized controlled trial of elderly hypothyroid patients currently treated with levothyroxine. Patients will be recruited from 20 general practices and two hospital trust endocrine units in Northumberland, Tyne and Wear. Target recruitment of 50 elderly hypothyroid patients currently treated with levothyroxine, identified in both primary and secondary care settings. Reduced dose of levothyroxine to achieve an elevated serum thyroid stimulating hormone (target range 4.1 to 8.0 mU/L) versus standard levothyroxine replacement (target range 0.4 to 4.0 mU/L). Using random permuted blocks, in a ratio of 1:1, randomization will be carried out by Newcastle Clinical Trials Unit. Study feasibility (recruitment and retention rates and medication compliance), acceptability of the trial design, assessment of mobility and falls risk, and change in cardiovascular risk factors. Qualitative study using in-depth interviews to understand patients' willingness to take part in a randomized controlled trial and participants' experience of the intervention. Retrospective cohort study of 400 treated hypothyroid patients aged 80 years or over registered in 2008 in primary care practices, studying their 4-year cardiovascular outcomes to inform the power of SORTED

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women.

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Carballo-Diéguez, Alex; Balán, Ivan C; Brown, William; Giguere, Rebecca; Dolezal, Curtis; Leu, Cheng-Shiun; Marzinke, Mark A; Hendrix, Craig W; Piper, Jeanna M; Richardson, Barbra A; Grossman, Cynthia; Johnson, Sherri; Gomez, Kailazarid; Horn, Stephanie; Kunjara Na Ayudhya, Ratiya Pamela; Patterson, Karen; Jacobson, Cindy; Bekker, Linda-Gail; Chariyalertsak, Suwat; Chitwarakorn, Anupong; Gonzales, Pedro; Holtz, Timothy H; Liu, Albert; Mayer, Kenneth H; Zorrilla, Carmen; Lama, Javier; McGowan, Ian; Cranston, Ross D

2017-01-01

Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG-TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive anal intercourse (RAI)-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187) were men who have sex with men and transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%) and South Africa (10%). Mean age was 31.4 years (range 18-64 years). Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL) given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP achieved in MTN-017 among men who have sex with men (MSM and transgender women.

Directory of Open Access Journals (Sweden)

Alex Carballo-Diéguez

Full Text Available Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1 daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, 2 daily use of reduced-glycerin 1% tenofovir (RG-TFV gel applied rectally, and 3 RG-TFV gel applied before and after receptive anal intercourse (RAI-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187 were men who have sex with men and transgender women enrolled in the United States (42%, Thailand (29%, Peru (19% and South Africa (10%. Mean age was 31.4 years (range 18-64 years. Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals

Awareness Enhancing and Monitoring Device plus Habit Reversal in the Treatment of Trichotillomania: An Open Feasibility Trial.

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Himle, Joseph A; Bybee, Deborah; O'Donnell, Lisa A; Weaver, Addie; Vlnka, Sarah; DeSena, Daniel T; Rimer, Jessica M

2018-01-01

Habit Reversal Therapy (HRT) is helpful for many persons suffering from trichotillomania. However successful habit reversal therapy requires awareness of hair pulling behaviors. Available methods to monitor hair pulling behaviors are less than ideal, particularly when sufferers are unaware of their pulling-related behaviors. This open feasibility trial included 20 persons with trichotillomania who were treated with nine weeks of HRT with experienced clinicians following a well-established HRT protocol. HRT was augmented with an electronic Awareness Enhancing and Monitoring Device (AEMD) designed to alert users of hand to head contact and to monitor the frequency of pulling-related behaviors. The AEMD included a neck unit and two wrist units, each equipped with vibrating alert functions. The results of the open trial revealed significant improvements in trichotillomania symptoms as measured by clinician and self-report rating scales. Most participants met study criteria for HRT completion and treatment effects were large. Participants reported that the AEMD, when operational, was effective in alerting participants to TTM-related behaviors. The monitoring function of the AEMD did not operate as designed. Subjective feedback focused on the AEMD concept was positive but AEMD reliability problems and complaints about the wearability the units were common. Recommendations for AEMD design modifications were included.

Safety and feasibility of transcranial direct current stimulation (tDCS) combined with sensorimotor retraining in chronic low back pain: a protocol for a pilot randomised controlled trial.

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Ouellette, Adam Louis; Liston, Matthew B; Chang, Wei-Ju; Walton, David M; Wand, Benedict Martin; Schabrun, Siobhan M

2017-08-21

Chronic low back pain (LBP) is a common and costly health problem yet current treatments demonstrate at best, small effects. The concurrent application of treatments with synergistic clinical and mechanistic effects may improve outcomes in chronic LBP. This pilot trial aims to (1) determine the feasibility, safety and perceived patient response to a combined transcranial direct current stimulation (tDCS) and sensorimotor retraining intervention in chronic LBP and (2) provide data to support a sample size calculation for a fully powered trial should trends of effectiveness be present. A pilot randomised, assessor and participant-blind, sham-controlled trial will be conducted. Eighty participants with chronic LBP will be randomly allocated to receive either (1) active tDCS + sensorimotor retraining or (2) sham tDCS + sensorimotor retraining. tDCS (active or sham) will be applied to the primary motor cortex for 20 min immediately prior to 60 min of supervised sensorimotor retraining twice per week for 10 weeks. Participants in both groups will complete home exercises three times per week. Feasibility, safety, pain, disability and pain system function will be assessed immediately before and after the 10-week intervention. Analysis of feasibility and safety will be performed using descriptive statistics. Statistical analyses will be conducted based on intention-to-treat and per protocol and will be used to determine trends for effectiveness. Ethical approval has been gained from the institutional human research ethics committee (H10184). Written informed consent will be provided by all participants. Results from this pilot study will be submitted for publication in peer-reviewed journals. ACTRN12616000624482. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Feasibility and effectiveness of the implementation of a primary prevention programme for type 2 diabetes in routine primary care practice: a phase IV cluster randomised clinical trial

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Sanchez Alvaro

2012-11-01

Full Text Available Abstract Background The objective of this study is to perform an independent evaluation of the feasibility and effectiveness of an educational programme for the primary prevention of type 2 diabetes (DM2 in high risk populations in primary care settings, implanted within the Basque Health Service - Osakidetza. Methods/design This is a prospective phase IV cluster clinical trial conducted under routine conditions in 14 primary health care centres of Osakidetza, randomly assigned to an intervention or control group. We will recruit a total sample of 1089 individuals, aged between 45 and 70 years old, without diabetes but at high risk of developing the condition (Finnish Diabetes Risk Score, FINDRISC ≥ 14 and follow them up for 2 years. Primary health care nursing teams of the intervention centres will implement DE-PLAN, a structured educational intervention program focused on changing healthy lifestyles (diet and physical activity; while the patients in the control centres will receive the usual care for the prevention and treatment of DM2 currently provided in Osakidetza. The effectiveness attributable to the programme will be assessed by comparing the changes observed in patients exposed to the intervention and those in the control group, with respect to the risk of developing DM2 and lifestyle habits. In terms of feasibility, we will assess indicators of population coverage and programme implementation. Discussion The aim of this study is to provide the scientific basis for disseminate the programme to the remaining primary health centres in Osakidetza, as a novel way of addressing prevention of DM2. The study design will enable us to gather information on the effectiveness of the intervention as well as the feasibility of implementing it in routine practice. Trial registration ClinicalTrials.gov NCT01365013

A randomised controlled trial of six weeks of home enteral nutrition versus standard care after oesophagectomy or total gastrectomy for cancer: report on a pilot and feasibility study.

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Bowrey, David J; Baker, Melanie; Halliday, Vanessa; Thomas, Anne L; Pulikottil-Jacob, Ruth; Smith, Karen; Morris, Tom; Ring, Arne

2015-11-21

Poor nutrition in the first months after oesophago-gastric resection is a contributing factor to the reduced quality of life seen in these patients. The aim of this pilot and feasibility study was to ascertain the feasibility of conducting a multi-centre randomised controlled trial to evaluate routine home enteral nutrition in these patients. Patients undergoing oesophagectomy or total gastrectomy were randomised to either six weeks of home feeding through a jejunostomy (intervention), or treatment as usual (control). Intervention comprised overnight feeding, providing 50 % of energy and protein requirements, in addition to usual oral intake. Primary outcome measures were recruitment and retention rates at six weeks and six months. Nutritional intake, nutritional parameters, quality of life and healthcare costs were also collected. Interviews were conducted with a sample of participants, to ascertain patient and carer experiences. Fifty-four of 112 (48 %) eligible patients participated in the study over the 20 months. Study retention at six weeks was 41/54 patients (76 %) and at six months was 36/54 (67 %). At six weeks, participants in the control group had lost on average 3.9 kg more than participants in the intervention group (95 % confidence interval [CI] 1.6 to 6.2). These differences remained evident at three months (mean difference 2.5 kg, 95 % CI -0.5 to 5.6) and at six months (mean difference 2.5 kg, 95 % CI -1.2 to 6.1). The mean values observed in the intervention group for mid arm circumference, mid arm muscle circumference, triceps skin fold thickness and right hand grip strength were greater than for the control group at all post hospital discharge time points. The economic evaluation suggested that it was feasible to collect resource use and EQ-5D data for a full cost-effectiveness analysis. Thematic analysis of 15 interviews identified three main themes related to the intervention and the trial: 1) a positive experience, 2) the reasons for taking

Feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer.

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Traina, Tiffany A; Rugo, Hope S; Caravelli, James F; Patil, Sujata; Yeh, Benjamin; Melisko, Michele E; Park, John W; Geneus, Stephanie; Paulson, Matthew; Grothusen, Jill; Seidman, Andrew D; Fornier, Monica; Lake, Diana; Dang, Chau; Robson, Mark; Theodoulou, Maria; Flombaum, Carlos D; Norton, Larry; Hudis, Clifford A; Dickler, Maura N

2010-02-01

Preclinical models suggest that the use of anti-vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor-positive metastatic breast cancer (MBC). Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease. Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease >or= 24 weeks was noted in 67%. Median PFS was 17.1 months. Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).

Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: a decade of the PREDICT-HD study

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Jane S Paulsen

2014-04-01

Full Text Available There is growing consensus that intervention and treatment of Huntington disease (HD should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. PREDICT-HD is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest Huntington disease and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease seven to twelve years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

The "Interval Walking in Colorectal Cancer" (I-WALK-CRC) study: Design, methods and recruitment results of a randomized controlled feasibility trial.

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Banck-Petersen, Anna; Olsen, Cecilie K; Djurhuus, Sissal S; Herrstedt, Anita; Thorsen-Streit, Sarah; Ried-Larsen, Mathias; Østerlind, Kell; Osterkamp, Jens; Krarup, Peter-Martin; Vistisen, Kirsten; Mosgaard, Camilla S; Pedersen, Bente K; Højman, Pernille; Christensen, Jesper F

2018-03-01

Low physical activity level is associated with poor prognosis in patients with colorectal cancer (CRC). To increase physical activity, technology-based platforms are emerging and provide intriguing opportunities to prescribe and monitor active lifestyle interventions. The "Interval Walking in Colorectal Cancer"(I-WALK-CRC) study explores the feasibility and efficacy a home-based interval-walking intervention delivered by a smart-phone application in order to improve cardio-metabolic health profile among CRC survivors. The aim of the present report is to describe the design, methods and recruitment results of the I-WALK-CRC study.Methods/Results: The I-WALK-CRC study is a randomized controlled trial designed to evaluate the feasibility and efficacy of a home-based interval walking intervention compared to a waiting-list control group for physiological and patient-reported outcomes. Patients who had completed surgery for local stage disease and patients who had completed surgery and any adjuvant chemotherapy for locally advanced stage disease were eligible for inclusion. Between October 1st , 2015, and February 1st , 2017, 136 inquiries were recorded; 83 patients were eligible for enrollment, and 42 patients accepted participation. Age and employment status were associated with participation, as participants were significantly younger (60.5 vs 70.8 years, P CRC survivors was feasible but we aim to better the recruitment rate in future studies. Further, the study clearly favored younger participants. The I-WALK-CRC study will provide important information regarding feasibility and efficacy of a home-based walking exercise program in CRC survivors.

A randomised controlled feasibility trial for an educational school-based mental health intervention: study protocol

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Chisholm Katharine

2012-03-01

Full Text Available Abstract Background With the burden of mental illness estimated to be costing the English economy alone around £22.5 billion a year 1, coupled with growing evidence that many mental disorders have their origins in adolescence, there is increasing pressure for schools to address the emotional well-being of their students, alongside the stigma and discrimination of mental illness. A number of prior educational interventions have been developed and evaluated for this purpose, but inconsistency of findings, reporting standards, and methodologies have led the majority of reviewers to conclude that the evidence for the efficacy of these programmes remains inconclusive. Methods/Design A cluster randomised controlled trial design has been employed to enable a feasibility study of 'SchoolSpace', an intervention in 7 UK secondary schools addressing stigma of mental illness, mental health literacy, and promotion of mental health. A central aspect of the intervention involves students in the experimental condition interacting with a young person with lived experience of mental illness, a stigma reducing technique designed to facilitate students' engagement in the project. The primary outcome is the level of stigma related to mental illness. Secondary outcomes include mental health literacy, resilience to mental illness, and emotional well-being. Outcomes will be measured pre and post intervention, as well as at 6 month follow-up. Discussion The proposed intervention presents the potential for increased engagement due to its combination of education and contact with a young person with lived experience of mental illness. Contact as a technique to reduce discrimination has been evaluated previously in research with adults, but has been employed in only a minority of research trials investigating the impact on youth. Prior to this study, the effect of contact on mental health literacy, resilience, and emotional well-being has not been evaluated to the authors

Restoring effective sleep tranquility (REST): A feasibility and pilot study.

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Eakman, Aaron M; Schmid, Arlene A; Henry, Kimberly L; Rolle, Natalie R; Schelly, Catherine; Pott, Christine E; Burns, Joshua E

2017-06-01

The purpose of this pilot study was to establish the feasibility of completing a future controlled trial of a multi-component cognitive behavioral therapy for insomnia program for military veterans with sleep disturbance. This was a single-arm feasibility and pilot study. Participants were United States post-9/11 veterans with service-connected injuries, university students, and had self-reported sleep disturbances. Restoring Effective Sleep Tranquility was a multi-component cognitive behavioral therapy for insomnia intervention consisting of seven sessions of group therapy and eight 1:1 sessions delivered by occupational therapists. Feasibility and pilot indicators were process, resources, management, and scientific, including pre-post-assessments of sleep difficulties, dysfunctional sleep beliefs, participation, and pain interference. Indicators were supportive of feasibility, including reduced sleep difficulties (for example Medical Outcomes Study Sleep Measure [ t  = 3.29, p  = .02]), reduced nightmares: t  = 2.79, p  = .03; fewer dysfunctional sleep beliefs: t  = 3.63, p  = .01, and greater ability to participate in social roles: t  = -2.86, p  = .03, along with trends towards improved satisfaction with participation and reduced pain interference. The Restoring Effective Sleep Tranquility program may reduce sleep difficulties and improve participation in US veterans with service-connected injuries, and evidence indicates a controlled trial would be feasible to deliver.

Nevasic audio program for the prevention of chemotherapy induced nausea and vomiting: A feasibility study using a randomized controlled trial design.

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Moradian, Saeed; Walshe, Catherine; Shahidsales, Soodabeh; Ghavam Nasiri, Mohammad Reza; Pilling, Mark; Molassiotis, Alexander

2015-06-01

Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting (CINV). Therefore, exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important. Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction. The aim of this study was to examine the feasibility of conducting a randomized controlled trial (RCT) to evaluate the effectiveness of Nevasic to control CINV. A mixed methods design incorporating an RCT and focus group interviews. For the RCT, female breast cancer patients were randomized to receive either Nevasic plus usual care, music plus usual care, or usual care only. Data were analysed using descriptive statistics and linear mixed-effects models. Five focus group interviews were conducted to obtain participants' views regarding the acceptability of the interventions in the trial. 99 participants were recruited to the RCT and 15 participated in focus group interviews. Recruitment targets were achieved. Issues of Nevasic acceptability were highlighted as weaknesses of the program. This study did not detect any evidence for the effectiveness of Nevasic; however, the results showed statistically significant less use of anti-emetics (p = 0.003) and borderline non-significant improvement in quality of life (p = 0.06). Conducting a non-pharmacological intervention using such an audio program is feasible, although difficulties and limitations exist with its use. Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use, as well as its overall effect on the levels of nausea and vomiting. Copyright © 2014 Elsevier Ltd. All rights reserved.

Feasibility of a multi-modal exercise program on cognition in older adults with Type 2 diabetes - a pilot randomised controlled trial.

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Callisaya, M L; Daly, R M; Sharman, J E; Bruce, D; Davis, T M E; Greenaway, T; Nolan, M; Beare, R; Schultz, M G; Phan, T; Blizzard, L C; Srikanth, V K

2017-10-16

Type 2 Diabetes (T2D) is associated with increased risk of dementia. We aimed to determine the feasibility of a randomised controlled trial (RCT) examining the efficacy of exercise on cognition and brain structure in people with T2D. A 6-month pilot parallel RCT of a progressive aerobic- and resistance-training program versus a gentle movement control group in people with T2D aged 50-75 years (n = 50) at the University of Tasmania, Australia. Assessors were blinded to group allocation. Brain volume (total, white matter, hippocampus), cortical thickness and white matter microstructure (fractional anisotrophy and mean diffusivity) were measured using magnetic resonance imaging, and cognition using a battery of neuropsychological tests. Study design was assessed by any changes (during the pilot or recommended) to the protocol, recruitment by numbers screened and time to enrol 50 participants; randomisation by similarity of characteristics in groups at baseline, adherence by exercise class attendance; safety by number and description of adverse events and retention by numbers withdrawn. The mean age of participants was 66.2 (SD 4.9) years and 48% were women. There were no changes to the design during the study. A total of 114 people were screened for eligibility, with 50 participants with T2D enrolled over 8 months. Forty-seven participants (94%) completed the study (23 of 24 controls; 24 of 26 in the intervention group). Baseline characteristics were reasonably balanced between groups. Exercise class attendance was 79% for the intervention and 75% for the control group. There were 6 serious adverse events assessed as not or unlikely to be due to the intervention. Effect sizes for each outcome variable are provided. This study supports the feasibility of a large scale RCT to test the benefits of multi-modal exercise to prevent cognitive decline in people with T2D. Design changes to the future trial are provided. ANZCTR 12614000222640 ; Registered 3/3/2014; First

Quantitation of microbicidal activity of mononuclear phagocytes: an in vitro technique.

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Rege N

1993-01-01

Full Text Available An in vitro assay technique was set up to determine the phagocytic and microbicidal activity of a monocyte-macrophage cell line using Candida species as test organisms. The norms were determined for the activity of peritoneal macrophages of rats (24.69 +/- 2.6% phagocytosis and 35.4 +/- 5.22% ICK and human (27.89 +/- 3.63% phagocytosis and 50.91 +/- 6.3% ICK. The assay technique was used to test the degree of activation of macrophages induced by metronidazole, Tinospora cordifolia and Asparaqus racemousus and to compare their effects with a standard immunomodulator muramyl-dipeptide. All the three test agents increased the phagocytic and killing capacity of macrophages in a dose dependent manner upto a certain dose, beyond which either these activities were found to have plateaued or decreased. The optimal doses for MDP, Metronidazole, Asparagus racemosus and Tinospora cordifolia were found to be 100 micrograms, 300 mg/kg, 200 mg/kg and 100 mg/kg respectively. Patients with cirrhosis were screened for defects in monocyte function. The depressed monocyte function (20.58 +/- 5% phago and 41.24 +/- 12.19% ICK; P < 0.05 was observed indicating a compromised host defense. The utility of this candidicidal assay in experimental and clinical studies is discussed.

Feasibility and acceptability of training community health workers in ear and hearing care in Malawi: a cluster randomised controlled trial.

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Mulwafu, Wakisa; Kuper, Hannah; Viste, Asgaut; Goplen, Frederik K

2017-10-11

To assess the feasibility and acceptability of training community health workers (CHWs) in ear and hearing care, and their ability to identify patients with ear and hearing disorders. Cluster randomised controlled trial (RCT). Health centres in Thyolo district, Malawi. Ten health centres participated, 5 intervention (29 CHWs) and 5 control (28 CHWs). Intervention CHWs received 3 days of training in primary ear and hearing care, while among control CHWs, training was delayed for 6 months. Both groups were given a pretest that assessed knowledge about ear and hearing care, only the intervention group was given the posttest on the third day of training. The intervention group was given 1 month to identify patients with ear and hearing disorders in their communities, and these people were screened for hearing disorders by ear, nose and throat clinical specialists. Primary outcome measure was improvement in knowledge of ear and hearing care among CHWs after the training. Secondary outcome measures were number of patients with ear or hearing disorders identified by CHWs and number recorded at health centres during routine activities, and the perceived feasibility and acceptability of the intervention. The average overall correct answers increased from 55% to 68% (95% CI 65 to 71) in the intervention group (phearing disorders were identified by CHWs and 860 patients attended the screening camps, of whom 400 had hearing loss (73 patients determined through bilateral fail on otoacoustic emissions, 327 patients through audiometry). Where cause could be determined, the most common cause of ear and hearing disorders was chronic suppurative otitis media followed by impacted wax. The intervention was perceived as feasible and acceptable to implement. Training was effective in improving the knowledge of CHW in ear and hearing care in Malawi and allowing them to identify patients with ear and hearing disorders. This intervention could be scaled up to other CHWs in low-income and

The feasibility of a pragmatic randomised controlled trial to compare usual care with usual care plus individualised homeopathy, in children requiring secondary care for asthma.

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Thompson, E A; Shaw, A; Nichol, J; Hollinghurst, S; Henderson, A J; Thompson, T; Sharp, D

2011-07-01

To test the feasibility of a pragmatic trial design with economic evaluation and nested qualitative study, comparing usual care (UC) with UC plus individualised homeopathy, in children requiring secondary care for asthma. This included recruitment and retention, acceptability of outcome measures patients' and health professionals' views and experiences and a power calculation for a definitive trial. In a pragmatic parallel group randomised controlled trial (RCT) design, children on step 2 or above of the British Thoracic Society Asthma Guidelines (BTG) were randomly allocated to UC or UC plus a five visit package of homeopathic care (HC). Outcome measures included the Juniper Asthma Control Questionnaire, Quality of Life Questionnaire and a resource use questionnaire. Qualitative interviews were used to gain families' and health professionals' views and experiences. 226 children were identified from hospital clinics and related patient databases. 67 showed an interest in participating, 39 children were randomised, 18 to HC and 21 to UC. Evidence in favour of adjunctive homeopathic treatment was lacking. Economic evaluation suggests that the cost of additional consultations was not offset by the reduced cost of homeopathic remedies and the lower use of primary care by children in the homeopathic group. Qualitative data gave insights into the differing perspectives of families and health care professionals within the research process. A future study using this design is not feasible, further investigation of a potential role for homeopathy in asthma management might be better conducted in primary care with children with less severe asthma. Copyright © 2011 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Preventing recurrence of endometriosis by means of long-acting progestogen therapy (PRE-EMPT): report of an internal pilot, multi-arm, randomised controlled trial incorporating flexible entry design and adaption of design based on feasibility of recruitment.

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Middleton, Lee J; Daniels, Jane P; Weckesser, Annalise; Bhattacharya, Siladitya

2017-03-11

Endometriosis is associated with the growth of endometrium in ectopic sites mainly within the pelvis. This results in inflammation and scarring, causing pain and impaired quality of life. Endometriotic lesions can be excised or ablated surgically, but the risk of recurrence is high. A Heath Technology Assessment commissioning call in 2011 sought applications for trials aimed at evaluating long-term effectiveness of postoperative, long-acting, reversible contraceptives (LARCs) in preventing recurrence of endometriosis. A survey of gynaecologists indicated that there was no consensus about which LARC (Levonorgestrel Intrauterine System (LNG-IUS) or depot medroxyprogesterone acetate injection (DMPA)) or comparator (combined oral contraceptive pill (COCP) or no treatment) should be evaluated. Hence, we designed a 'flexible-entry' internal pilot to assess whether a four-arm trial was feasible including a possible design adaption based on pilot findings. In this pilot, women could be randomised to two, three or four treatment options provided that one was a LARC and one was a non-LARC. An assessment of feasibility based on recruitment to these options and a revised substantive trial design was considered by an independent oversight committee. The study ran for 1 year from April 2014 and 77 women were randomised. Only 5 (6%) women accepted randomisation to all groups, with 63 (82%) having a LARC preference and 55 (71%) a non-LARC preference. Four-way and three-way designs were ruled out with a two-way LARC versus COCP design, stratified by prerandomisation choice of LARC and optional subrandomisation to LNG-IUS versus DMPA considered a feasible substantive study. Multi-arm studies are potentially efficient as they can answer multiple questions simultaneously but are difficult to recruit to if there are strong patient or clinician preferences. A flexible approach to randomisation in a pilot phase can be used to assess feasibility of such studies and modify a trial design

Theory-driven group-based complex intervention to support self-management of osteoarthritis and low back pain in primary care physiotherapy: protocol for a cluster randomised controlled feasibility trial (SOLAS).

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Hurley, Deirdre A; Hall, Amanda M; Currie-Murphy, Laura; Pincus, Tamar; Kamper, Steve; Maher, Chris; McDonough, Suzanne M; Lonsdale, Chris; Walsh, Nicola E; Guerin, Suzanne; Segurado, Ricardo; Matthews, James

2016-01-21

International clinical guidelines consistently endorse the promotion of self-management (SM), including physical activity for patients with chronic low back pain (CLBP) and osteoarthritis (OA). Patients frequently receive individual treatment and advice to self-manage from physiotherapists in primary care, but the successful implementation of a clinical and cost-effective group SM programme is a key priority for health service managers in Ireland to maximise long-term outcomes and efficient use of limited and costly resources. This protocol describes an assessor-blinded cluster randomised controlled feasibility trial of a group-based education and exercise intervention underpinned by self-determination theory designed to support an increase in SM behaviour in patients with CLBP and OA in primary care physiotherapy. The primary care clinic will be the unit of randomisation (cluster), with each clinic randomised to 1 of 2 groups providing the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention or usual individual physiotherapy. Patients are followed up at 6 weeks, 2 and 6 months. The primary outcomes are the (1) acceptability and demand of the intervention to patients and physiotherapists, (2) feasibility and optimal study design/procedures and sample size for a definitive trial. Secondary outcomes include exploratory analyses of: point estimates, 95% CIs, change scores and effect sizes in physical function, pain and disability outcomes; process of change in target SM behaviours and selected mediators; and the cost of the intervention to inform a definitive trial. This feasibility trial protocol was approved by the UCD Human Research Ethics-Sciences Committee (LS-13-54 Currie-Hurley) and research access has been granted by the Health Services Executive Primary Care Research Committee in January 2014. The study findings will be disseminated to the research, clinical and health service communities through publication in

An interactive health communication application for supporting parents managing childhood long-term conditions: outcomes of a randomized controlled feasibility trial.

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Swallow, Veronica M; Knafl, Kathleen; Santacroce, Sheila; Campbell, Malcolm; Hall, Andrew G; Smith, Trish; Carolan, Ian

2014-12-03

Families living with chronic or long-term conditions such as chronic kidney disease (CKD), stages 3-5, face multiple challenges and respond to these challenges in various ways. Some families adapt well while others struggle, and family response to a condition is closely related to outcome. With families and professionals, we developed a novel condition-specific interactive health communication app to improve parents' management ability-the online parent information and support (OPIS) program. OPIS consists of a comprehensive mix of clinical caregiving and psychosocial information and support. The purpose of this study was to (1) assess feasibility of a future full-scale randomized controlled trial (RCT) of OPIS in terms of recruitment and retention, data collection procedures, and psychometric performance of the study measures in the target population, and (2) investigate trends in change in outcome measures in a small-scale RCT in parents of children with CKD stages 3-5. Parents were recruited from a pediatric nephrology clinic and randomly assigned to one of two treatment groups: usual support for home-based clinical caregiving (control) or usual support plus password-protected access to OPIS for 20 weeks (intervention). Both groups completed study measures at study entry and exit. We assessed feasibility descriptively in terms of recruitment and retention rates overall; assessed recruitment, retention, and uptake of the intervention between groups; and compared family condition management, empowerment to deliver care, and fathers' involvement between groups. We recruited 55 parents of 39 children (42% of eligible families). Of those, about three-quarters of intervention group parents (19/26, 73%) and control group parents (22/29, 76%) were retained through completion of 20-week data collection. The overall retention rate was 41/55 (75%). The 41 parents completing the trial were asked to respond to the same 10 questionnaire scales at both baseline and 20 weeks

Pregnancy in HIV clinical trials in Sub Saharan Africa: failure of consent or contraception?

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Agnes Ssali

Full Text Available Higher than expected pregnancy rates have been observed in HIV related clinical trials in Sub-Saharan Africa. We designed a qualitative study to explore the factors contributing to high pregnancy rates among participants in two HIV clinical trials in Sub-Saharan Africa.Female and male participants enrolled in one of two clinical HIV trials in south-west Uganda were approached. The trials were a phase III microbicide efficacy trial among HIV negative women using vaginal gel (MDP; and a trial of primary prevention prophylaxis for invasive cryptococcal disease using fluconazole among HIV infected men and women in Uganda (CRYPTOPRO. 14 focus group discussions and 8 in-depth interviews were conducted with HIV positive and negative women and their male partners over a six month period. Areas explored were their experiences about why and when one should get pregnant, factors affecting use of contraceptives, HIV status disclosure and trial product use.All respondents acknowledged being advised of the importance of avoiding pregnancy during the trial. Factors reported to contribute to pregnancy included; trust that the investigational product (oral capsules/vaginal gel would not harm the baby, need for children, side effects that led to inconsistent contraceptive use, low acceptance of condom use among male partners. Attitudes towards getting pregnant are fluid within couples over time and the trials often last for more than a year. Researchers need to account for high pregnancy rates in their sample size calculations, and consider lesser used female initiated contraceptive options e.g. diaphragm or female condoms. In long clinical trials where there is a high fetal or maternal risk due to investigational product, researchers and ethics committees should consider a review of participants contraceptive needs/pregnancy desire review after a fixed period, as need for children, partners and health status of participants may alter over time.

Cognitive Behavioral Analysis System of Psychotherapy as group psychotherapy for chronically depressed inpatients: a naturalistic multicenter feasibility trial.

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Sabaß, Lena; Padberg, Frank; Normann, Claus; Engel, Vera; Konrad, Carsten; Helmle, Kristina; Jobst, Andrea; Worlitz, Andrew; Brakemeier, Eva-Lotta

2017-09-27

The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) is a relatively new approach in the treatment of chronic depression (CD). Adapted as group psychotherapy for inpatients, CBASP is attracting increasing attention. In this naturalistic multicenter trial, we investigated its feasibility after 10 sessions of CBASP group therapy over a treatment time of at least 5 to a maximum of 10 weeks. Treatment outcome was additionally assessed. Across four centers, 116 inpatients with CD (DSM-IV-TR) attended CBASP group psychotherapy. Feasibility was focused on acceptance, and evaluated for patients and therapists after five (t1) and ten sessions (t2) of group psychotherapy. Observer- and self-rating scales (Hamilton Depression Rating Scale-24 items, HDRS 24 ; Beck Depression Inventory-II, BDI-II; World Health Organization Quality of Life assessment, WHOQOL-BREF) were applied before group psychotherapy (t0) and at t2. Dropouts were low (10.3%). Patients' evaluation improved significantly from t1 to t2 with a medium effect size (d = 0.60). Most of the patients stated that the group had enriched their treatment (75.3%), that the size (74.3%) and duration (72.5%) were 'optimal' and 37.3% wished for a higher frequency. Patients gave CBASP group psychotherapy an overall grade of 2 ('good'). Therapists' evaluation was positive throughout, except for size of the group. Outcome scores of HDRS 24 , BDI-II, and WHOQOL-BREF were significantly reduced from t0 to t2 with medium to large effect sizes (d = 1.48; d = 1.11; d = 0.67). In this naturalistic open-label trial, CBASP, when applied as inpatient group psychotherapy, was well accepted by patients and therapists. The results point towards a clinically meaningful effect of inpatient treatment with CBASP group psychotherapy on depression and quality of life. Other potential factors that could have promoted symptom change were discussed. A future controlled study could investigate the safety and efficacy of CBASP

Use of crowdsourcing for cancer clinical trial development.

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Leiter, Amanda; Sablinski, Tomasz; Diefenbach, Michael; Foster, Marc; Greenberg, Alex; Holland, John; Oh, William K; Galsky, Matthew D

2014-10-01

Patient and physician awareness and acceptance of trials and patient ineligibility are major cancer clinical trial accrual barriers. Yet, trials are typically conceived and designed by small teams of researchers with limited patient input. We hypothesized that through crowdsourcing, the intellectual and creative capacity of a large number of researchers, clinicians, and patients could be harnessed to improve the clinical trial design process. In this study, we evaluated the feasibility and utility of using an internet-based crowdsourcing platform to inform the design of a clinical trial exploring an antidiabetic drug, metformin, in prostate cancer. Over a six-week period, crowd-sourced input was collected from 60 physicians/researchers and 42 patients/advocates leading to several major (eg, eligibility) and minor modifications to the clinical trial protocol as originally designed. Crowdsourcing clinical trial design is feasible, adds value to the protocol development process, and may ultimately improve the efficiency of trial conduct. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Design of Phase II Non-inferiority Trials.

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Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

Is clarithromycin a potential treatment for cachexia in people with lung cancer? A feasibility study.

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Awan, Sarah; Crosby, Vincent; Potter, Vanessa; Hennig, Ivo; Baldwin, David; Ndlovu, Mehluli; Paradine, Sharon; Wilcock, Andrew

2017-02-01

Clarithromycin may improve cachexia and survival in non-small cell lung cancer (NSCLC), but adequately controlled data are lacking. This study was undertaken primarily to inform the feasibility and scale of a phase III trial. Eligible consenting patients with stage IV NSCLC and cachexia were to be randomized to receive either clarithromycin 250mg twice daily or placebo for eight weeks. Aspects of trial feasibility recorded included numbers eligible, approached and recruited, together with adherence and completion of treatment and assessments. Over 6 months, none of 125 patients identified fulfilled the entry criteria. The commonest reasons for ineligibility were the use of an excluded concurrent drug (45, 36%), brain metastases (22, 18%), poor performance status (21, 17%) and current chemotherapy (15, 12%). A phase III trial of clarithromycin using these entry criteria is not feasible in this setting. Other macrolides that have a lower risk of a drug-drug interaction may be more practical to pursue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A study protocol of a three-group randomized feasibility trial of an online yoga intervention for mothers after stillbirth (The Mindful Health Study).

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Huberty, Jennifer; Matthews, Jeni; Leiferman, Jenn; Cacciatore, Joanne; Gold, Katherine J

2018-01-01

In the USA, stillbirth (in utero fetal death ≥20 weeks gestation) is a major public health issue. Women who experience stillbirth, compared to women with live birth, have a nearly sevenfold increased risk of a positive screen for post-traumatic stress disorder (PTSD) and a fourfold increased risk of depressive symptoms. Because the majority of women who have experienced the death of their baby become pregnant within 12-18 months and the lack of intervention studies conducted within this population, novel approaches targeting physical and mental health, specific to the needs of this population, are critical. Evidence suggests that yoga is efficacious, safe, acceptable, and cost-effective for improving mental health in a variety of populations, including pregnant and postpartum women. To date, there are no known studies examining online-streaming yoga as a strategy to help mothers cope with PTSD symptoms after stillbirth. The present study is a two-phase randomized controlled trial. Phase 1 will involve (1) an iterative design process to develop the online yoga prescription for phase 2 and (2) qualitative interviews to identify cultural barriers to recruitment in non-Caucasian women (i.e., predominately Hispanic and/or African American) who have experienced stillbirth ( N  = 5). Phase 2 is a three-group randomized feasibility trial with assessments at baseline, and at 12 and 20 weeks post-intervention. Ninety women who have experienced a stillbirth within 6 weeks to 24 months will be randomized into one of the following three arms for 12 weeks: (1) intervention low dose (LD) = 60 min/week online-streaming yoga ( n  = 30), (2) intervention moderate dose (MD) = 150 min/week online-streaming yoga ( n  = 30), or (3) stretch and tone control (STC) group = 60 min/week of stretching/toning exercises ( n  = 30). This study will explore the feasibility and acceptability of a 12-week, home-based, online-streamed yoga intervention, with varying doses

A pilot randomized controlled trial of the feasibility of a self-directed coping skills intervention for couples facing prostate cancer: Rationale and design

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Lambert Sylvie D

2012-09-01

Full Text Available Abstract Background Although it is known both patients’ and partners’ reactions to a prostate cancer diagnosis include fear, uncertainty, anxiety and depression with patients’ partners’ reactions mutually determining how they cope with and adjust to the illness, few psychosocial interventions target couples. Those that are available tend to be led by highly trained professionals, limiting their accessibility and long-term sustainability. In addition, it is recognised that patients who might benefit from conventional face-to-face psychosocial interventions do not access these, either by preference or because of geographical or mobility barriers. Self-directed interventions can overcome some of these limitations and have been shown to contribute to patient well-being. This study will examine the feasibility of a self-directed, coping skills intervention for couples affected by cancer, called Coping-Together, and begin to explore its potential impact on couples’ illness adjustment. The pilot version of Coping-Together includes a series of four booklets, a DVD, and a relaxation audio CD. Methods/design In this double-blind, two-group, parallel, randomized controlled trial, 70 couples will be recruited within 4 months of a prostate cancer diagnosis through urology private practices and randomized to: 1 Coping-Together or 2 a minimal ethical care condition. Minimal ethical care condition couples will be mailed information booklets available at the Cancer Council New South Wales and a brochure for the Cancer Council Helpline. The primary outcome (anxiety and additional secondary outcomes (distress, depression, dyadic adjustment, quality of life, illness or caregiving appraisal, self-efficacy, and dyadic and individual coping will be assessed at baseline (before receiving study material and 2 months post-baseline. Intention-to-treat and per protocol analysis will be conducted. Discussion As partners’ distress rates exceed not only population

General or Spinal Anaesthetic for Vaginal Surgery in Pelvic Floor Disorders (GOSSIP): a feasibility randomised controlled trial.

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Purwar, B; Ismail, K M; Turner, N; Farrell, A; Verzune, M; Annappa, M; Smith, I; El-Gizawy, Zeiad; Cooper, J C

2015-08-01

Spinal anaesthesia (SA) and general anaesthesia (GA) are widely used techniques for vaginal surgery for pelvic floor disorders with inconclusive evidence of the superiority of either. We conducted a randomised controlled trial (RCT) to assess the feasibility of a full scale RCT aiming to examine the effect of anaesthetic mode for vaginal surgery on operative, patient reported and length of hospital stay (LOHS) outcomes. Patients undergoing vaginal surgery, recruited through a urogynaecology service in a University teaching hospital, were randomised to receive either GA or SA. Patients were followed up for 12 weeks postoperatively. Pain was measured on a visual analogue scale; nausea was assessed with a four-point verbal rating scale. Patient's subjective perception of treatment outcome, quality of life (QoL) and functional outcomes were assessed using the International Consultation on Incontinence Modular Questionnaire (ICIQ) on vaginal symptoms and the SF-36 questionnaire. Sixty women were randomised, 29 to GA and 31 to SA. The groups were similar in terms of age and type of vaginal surgery performed. No statistically significant differences were noted between the groups with regard to pain, nausea, quality of life (QoL), functional outcomes as well as length of stay in the postoperative recovery room, use of analgesia postoperatively and LOHS. This study has demonstrated that a full RCT is feasible and should focus on the length of hospital stay in a subgroup of patients undergoing vaginal surgery where SA may help to facilitate enhanced recovery or day surgery.

Making co-enrolment feasible for randomised controlled trials in paediatric intensive care.

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Katie Harron

Full Text Available Enrolling children into several trials could increase recruitment and lead to quicker delivery of optimal care in paediatric intensive care units (PICU. We evaluated decisions taken by clinicians and parents in PICU on co-enrolment for two large pragmatic trials: the CATCH trial (CATheters in CHildren comparing impregnated with standard central venous catheters (CVCs for reducing bloodstream infection in PICU and the CHIP trial comparing tight versus standard control of hyperglycaemia.We recorded the period of trial overlap for all PICUs taking part in both CATCH and CHiP and reasons why clinicians decided to co-enrol children or not into both studies. We examined parental decisions on co-enrolment by measuring recruitment rates and reasons for declining consent.Five PICUs recruited for CATCH and CHiP during the same period (an additional four opened CATCH after having closed CHiP. Of these five, three declined co-enrolment (one of which delayed recruiting elective patients for CATCH whilst CHiP was running, due to concerns about jeopardising CHiP recruitment, asking too much of parents, overwhelming amounts of information to explain to parents for two trials and a policy against co-enrolment. Two units co-enrolled in order to maximise recruitment to both trials. At the first unit, 35 parents were approached for both trials. 17/35 consented to both; 13/35 consented to one trial only; 5/35 declined both. Consent rates during co-enrolment were 29/35 (82% and 18/35 (51% for CATCH and CHiP respectively compared with 78% and 51% respectively for those approached for a single trial within this PICU. The second unit did not record data on approaches or refusals, but successfully co-enrolled one child.Co-enrolment did not appear to jeopardise recruitment or overwhelm parents. Strategies for seeking consent for multiple trials need to be developed and should include how to combine information for parents and patients.

Feasibility and acceptability of a nursing intervention with family caregiver on self-care among heart failure patients: a randomized pilot trial.

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Cossette, Sylvie; Belaid, Hayet; Heppell, Sonia; Mailhot, Tanya; Guertin, Marie-Claude

2016-01-01

. Caregiver involvement was found to be both a feasible and acceptable means of supporting self-care practice in HF patients. This approach presents a potential avenue for enhancing patients' efforts in this regard. However, this pilot study offers preliminary findings only, which need to be replicated in a phase 3 clinical trial.

HIV Prevention and Research Considerations for Women in Sub ...

African Journals Online (AJOL)

AJRH Managing Editor

HIV prevention across the social, behavioral and biomedical spectrum. ... related risk factors that influence HIV infection among women1. ... adolescents, mental health is particularly important, and low ..... Microbicide Trials Network (MTN).

Case series of feasibility considerations that impact operational delivery strategy in the highly competitive rheumatoid arthritis space in Asia

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Wai K

2013-02-01

Full Text Available Karen Wai,1 Lisa Marie Saldanha,1 Elvira Zenaida Lansang,1 Saumya Nayak,1 Anish Sule,2 Ken J Lee31Feasibility and Site Identification Asia, Quintiles East Asia Pte Ltd, Singapore; 2Feasibility and Site Identification India, Quintiles India, Mumbai, India; 3Site Services Asia, Quintiles East Asia Pte Ltd, SingaporeAbstract: The rheumatoid arthritis (RA clinical trial space is very competitive, and recruiting and retaining subjects is of critical importance. Feasibility studies are a central component of ensuring successful recruitment and retention. A feasibility study is an assessment of the practicality of a proposed study protocol, with the goal of understanding challenges and providing risk mitigation strategies leading to better subject enrolment and study start-up should the assessment be favorable. This paper presents findings from a retrospective case series of RA feasibilities, describing important parameters to consider in the highly competitive RA space in Asia. Key parameters identified and discussed are how decisions on clinical development strategy necessitate changes in the clinical operational delivery strategy, with focus on changes in inclusion and exclusion criteria and patient contribution load; how small the patient population becomes when the clinical trial needs to target the patient population that is refractory to standard therapy; regulatory timelines; and the competitive clinical trial landscape. Feasibility assessments are a snapshot in time exercise. Multiple parameters change over time, and, particularly in a space that has become competitive for subjects, one cannot rely on one static feasibility assessment to predict trial performance accurately. Continuous feasibility assessment will also provide insight into the resourcing needs on the part of the sponsor, contract research organization, and investigative site.Keywords: site selection, country selection, clinical operations, risk management, recruitment rates

The feasibility of implementing recovery, psychosocial and pharmacological interventions for psychosis: comparison study.

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van der Krieke, Lian; Bird, Victoria; Leamy, Mary; Bacon, Faye; Dunn, Rebecca; Pesola, Francesca; Janosik, Monika; Le Boutillier, Clair; Williams, Julie; Slade, Mike

2015-05-23

Clinical guidelines for the treatment of people experiencing psychosis have existed for over a decade, but implementation of recommended interventions is limited. Identifying influences on implementation may help to reduce this translational gap. The Structured Assessment of Feasibility (SAFE) measure is a standardised assessment of implementation blocks and enablers. The aim of this study was to characterise and compare the implementation blocks and enablers for recommended psychosis interventions. SAFE was used to evaluate and compare three groups of interventions recommended in the 2014 NICE psychosis guideline: pharmacological (43 trials testing 5 interventions), psychosocial (65 trials testing 5 interventions), and recovery (19 trials testing 5 interventions). The 127 trial reports rated with SAFE were supplemented by published intervention manuals, research protocols, trial registrations and design papers. Differences in the number of blocks and enablers across the three interventions were tested statistically, and feasibility profiles were generated. There was no difference between psychosocial and recovery interventions in the number of blocks or enablers to implementation. Pharmacological interventions (a) had fewer blocks than both psychosocial interventions (χ (2)(3) = 133.77, p Feasibility profiles show that pharmacological interventions are relatively easy to implement but can sometimes involve risks. Psychosocial and recovery interventions are relatively complex but tend to be more flexible and more often manualised. SAFE ratings can contribute to tackling the current implementation challenges in mental health services, by providing a reporting guideline structure for researchers to maximise the potential for implementation and by informing prioritisation decisions by clinical guideline developers and service managers.

Lignosulfonic acid exhibits broadly anti-HIV-1 activity--potential as a microbicide candidate for the prevention of HIV-1 sexual transmission.

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Min Qiu

Full Text Available Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV, herpes simplex virus (HSV, Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA, a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-κB activation and has no significant up-regulation of IL-1α/β and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide.

Reducing electronic media use in 2-3 year-old children: feasibility and efficacy of the Family@play pilot randomised controlled trial.

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Hinkley, Trina; Cliff, Dylan P; Okely, Anthony D

2015-08-14

Participation in electronic media use among 2-3 year olds is high and associated with adverse health and developmental outcomes. This study sought to test the feasibility and potential efficacy of a family-based program to decrease electronic media (EM) use in 2-3-year-old children. Family@play was a six-session pilot randomised controlled trial delivered to parents of 2-3 year-old children from August to September 2012 in a community environment in the Illawarra region of New South Wales, Australia. Development of program content was guided by Social Cognitive and Family Systems Theories. The primary outcome was children's electronic media use. Secondary outcomes included children's time in sitting, standing and stepping. Data collectors were blinded to group allocation. Parents completed comprehensive process evaluation measures and participated in focus group discussions following completion of the program. Regression analyses were undertaken and effect sizes calculated using principles of intention to treat. Twenty-two participants (n = 12 intervention; n = 10 control) provided complete baseline data; complete data from 16 participants (n = 6 intervention; n = 10 control) were available post-intervention. Process evaluation results were high, showing the acceptability of the program. Compared with children in the control group, there were greater decreases in total EM use among children in the intervention group (adjusted difference [95 % CI] = -31.2 mins/day [-71.0-8.6] Cohen's d = 0.70). Differences for other outcomes were in the hypothesised direction and ranged from small for postural (sitting, standing, stepping) outcomes to moderate to large for individual electronic media (e.g. TV viewing, DVD/video viewing). This is the first family-based study to engage families of 2-3 year old children outside the United States and target multiple EM behaviours. Family@play was shown to be a feasible and acceptable intervention to deliver to

Mucosal safety of PHI-443 and stampidine as a combination microbicide to prevent genital transmission of HIV-1.

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D'Cruz, Osmond J; Uckun, Fatih M

2007-10-01

To investigate the in vitro and in vivo mucosal safety of a nonnucleoside reverse transcriptase (RT) inhibitor (PHI-443) and a nucleoside analogue RT inhibitor (stampidine)-based anti-HIV microbicide either alone or in combination. In vitro and in vivo studies using three-dimensional vaginal epithelia integrating Langerhans cells and 16 New Zealand White rabbits, respectively. Research laboratory. Rabbits in groups of four were exposed intravaginally to a gel with and without 1% PHI-443, 1% stampidine, or 1% PHI-443 plus 1% stampidine for 14 days. Cytokine/chemokine release by three-dimensional co-cultures in the presence and absence of PHI-443 or stampidine. Histologic scoring of vaginal tissue for mucosal toxicity at 24 hours after dosing. Simultaneous evaluation of levels of 10 cytokines (granulocyte-macrophage colony-stimulating factor, interleukin-1 alpha, interleukin-13, macrophage inflammatory protein-1 beta, granulocyte colony-stimulating factor, interleukin-18, tumor necrosis factor-alpha, interleukin-6, interleukin-1 beta, and interferon-gamma) and 6 chemokines (epithelial neutrophil-activating peptide-78, interleukin-8, monocyte/macrophage chemoattractant protein-1, macrophage inflammatory protein-3 alpha, interferon-inducible protein-10, and regulated upon activation of normal T-cell expressed and secreted) in culture media by a multiplexed chemiluminescence-based immunoassay. In the rabbit model, repeated intravaginal administration of PHI-443 plus stampidine via a gel formulation at concentrations nearly 2,000 and 10,000 times higher than their respective in vitro anti-HIV IC(50) values did not result in vaginal irritation. The levels of proinflammatory cytokines/chemokines secreted by multilayered human genital epithelia integrating Langerhans cells were unaffected by prolonged exposure to PHI-443 or stampidine. The combination of PHI-443 and stampidine was noncytotoxic to vaginal epithelial cells, nonirritating to vaginal mucosa, and did not induce

The development and feasibility of an online aphasia group intervention and networking program - TeleGAIN.

Science.gov (United States)

Pitt, Rachelle; Theodoros, Deborah; Hill, Anne J; Russell, Trevor

2017-09-04

Aphasia group therapy offers many benefits, however people with aphasia report difficulty accessing groups and speech-language pathologists are faced with many challenges in providing aphasia group therapy. Telerehabilitation may offer an alternative service delivery option. An online aphasia group therapy program - Telerehabilitation Group Aphasia Intervention and Networking (TeleGAIN) - has been developed according to the guidelines of the Medical Research Council (MRC) framework for complex interventions. The purpose of this paper is to describe the development of TeleGAIN and the results of a pilot trial to determine feasibility and acceptability. The development of TeleGAIN was informed through literature reviews in relevant topic areas, consideration of expert opinion and application of the social cognitive theory. TeleGAIN was then modelled through a feasibility pilot trial with four people with aphasia. TeleGAIN appeared to be feasible and acceptable to participants and able to be implemented as planned. Participant satisfaction with treatment was high and results suggested some potential for improvements in language functioning and communication-related quality of life. TeleGAIN appeared to be feasible and acceptable, however the study highlighted issues related to technology, clinical implementation and participant-specific factors that should be addressed prior to a larger trial.

Transdiagnostic internet-delivered cognitive-behaviour therapy (CBT) for adults with functional gastrointestinal disorders (FGID): A feasibility open trial.

Science.gov (United States)

Dear, B F; Fogliati, V J; Fogliati, R; Gandy, M; McDonald, S; Talley, N; Holtmann, G; Titov, N; Jones, M

2018-05-01

Many people with functional gastrointestinal disorders (FGIDs) face significant barriers in accessing psychological treatments that are known to reduce symptoms and their psychological sequelae. This study examined the feasibility and initial outcomes of a transdiagnostic and internet-delivered cognitive behaviour therapy (iCBT) intervention, the Chronic Conditions Course, for adults with functional gastrointestinal disorders (FGIDs). A single-group feasibility open trial design was employed and administered to twenty seven participants. The course ran for 8 weeks and was provided with weekly contact from a Clinical Psychologist. Seventy percent of participants completed the course within the 8 weeks and 81.5% provided data at post-treatment. High levels of satisfaction were observed and relatively little clinician time (M = 42.70 min per participant; SD = 46.25 min) was required. Evidence of clinical improvements in FGID symptoms (ds ≥ 0.46; avg. improvement ≥21%), anxiety symptoms (ds ≥ 0.99; avg. improvement ≥42%), and depression symptoms (ds ≥ 0.75; avg. improvement ≥35%) were observed, which either maintained or continued to improve to 3-month follow-up. Evidence of improvement was also observed in pain catastrophising and mental-health related quality of life, but not physical-health related quality of life. These findings highlight the potential value of transdiagnostic internet-delivered programs for adults with FGIDs and support for the conduct of larger-scale controlled studies. Copyright © 2018 Elsevier Inc. All rights reserved.

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): protocol for a multicentre randomised feasibility trial of non-invasive respiratory support in critically ill children.

Science.gov (United States)

Ramnarayan, Padmanabhan; Lister, Paula; Dominguez, Troy; Habibi, Parviz; Edmonds, Naomi; Canter, Ruth; Mouncey, Paul; Peters, Mark J

2017-06-12

Over 18 000 children are admitted annually to UK paediatric intensive care units (PICUs), of whom nearly 75% receive respiratory support (invasive and/or non-invasive). Continuous positive airway pressure (CPAP) has traditionally been used to provide first-line non-invasive respiratory support (NRS) in PICUs; however, high-flow nasal cannula therapy (HFNC), a novel mode of NRS, has recently gained popularity despite the lack of high-quality trial evidence to support its effectiveness. This feasibility study aims to inform the design and conduct of a future definitive randomised clinical trial (RCT) comparing the two modes of respiratory support. We will conduct a three-centre randomised feasibility study over 12 months. Patients admitted to participating PICUs who satisfy eligibility criteria will be recruited to either group A (primary respiratory failure) or group B (postextubation). Consent will be obtained from parents/guardians prior to randomisation in 'planned' group B, and deferred in emergency situations (group A and 'rescue' group B). Participants will be randomised (1:1) to either CPAP or HFNC using sealed, opaque envelopes, from a computer-generated randomisation sequence with variable block sizes. The study protocol specifies algorithms for the initiation, maintenance and weaning of HFNC and CPAP. The primary outcomes are related to feasibility, including the number of eligible patients in each group, feasibility of randomising >50% of eligible patients and measures of adherence to the treatment protocols. Data will also be collected on patient outcomes (eg, mortality and length of PICU stay) to inform the selection of an appropriate outcome measure in a future RCT. We aim to recruit 120 patients to the study. Ethical approval was granted by the National Research Ethics Service Committee North East-Tyne&Wear South (15/NE/0296). Study findings will be disseminated through peer-reviewed journals, national and international conferences. NCT02612415; pre

Feasibility study of a randomized controlled trial of a telephone-delivered problem-solving-occupational therapy intervention to reduce participation restrictions in rural breast cancer survivors undergoing chemotherapy.

Science.gov (United States)

Hegel, Mark T; Lyons, Kathleen D; Hull, Jay G; Kaufman, Peter; Urquhart, Laura; Li, Zhongze; Ahles, Tim A

2011-10-01

Breast cancer patients receiving adjuvant chemotherapy often experience functional effects of treatment that limit participation in life activities. The purpose of this study was to examine the feasibility of conducting a randomized controlled trial (RCT) of a novel intervention for these restrictions, determine acceptability of the intervention, and preliminarily assess its effects. A pilot RCT of a telephone-delivered Problem-solving and Occupational Therapy intervention (PST-OT) to improve participation restrictions in rural breast cancer patients undergoing chemotherapy. Thirty-one participants with Stages 1-3 breast cancer were randomized to 6 weekly sessions of PST-OT (n = 15) and usual care (n = 16). The primary study outcome was the feasibility of conducting the trial. Secondary outcomes were functional, quality of life and emotional status as assessed at baseline, 6 and 12 weeks. Of 46 patients referred 31 were enrolled (67% recruitment rate), of which 6 participants withdrew (81% retention rate). Twenty-four participants completed all study-related assessments (77%). Ninety-two percent of PST-OT participants were highly satisfied with the intervention, and 92% reported PST-OT to be helpful/very helpful for overcoming participation restrictions. Ninety-seven percent of planned PST-OT treatment sessions were completed. Completion rates for PST-OT homework tasks were high. Measures of functioning, quality of life, and emotional state favored the PST-OT condition. This pilot study suggests that an RCT of the PST-OT intervention is feasible to conduct with rural breast cancer patients undergoing adjuvant chemotherapy and that PST-OT may have positive effects on function, quality of life, and emotional state. 2010 John Wiley & Sons, Ltd.

Study protocol for the 'HelpMeDoIt!' randomised controlled feasibility trial: an app, web and social support-based weight loss intervention for adults with obesity.

Science.gov (United States)

Matthews, Lynsay; Pugmire, Juliana; Moore, Laurence; Kelson, Mark; McConnachie, Alex; McIntosh, Emma; Morgan-Trimmer, Sarah; Murphy, Simon; Hughes, Kathryn; Coulman, Elinor; Utkina-Macaskill, Olga; Simpson, Sharon Anne

2017-10-25

HelpMeDoIt! will test the feasibility of an innovative weight loss intervention using a smartphone app and website. Goal setting, self-monitoring and social support are three key facilitators of behaviour change. HelpMeDoIt! incorporates these features and encourages participants to invite 'helpers' from their social circle to help them achieve their goal(s). To test the feasibility of the intervention in supporting adults with obesity to achieve weight loss goals. 12-month feasibility randomised controlled trial and accompanying process evaluation. Participants (n=120) will be adults interested in losing weight, body mass index (BMI) > 30 kg/m 2 and smartphone users. The intervention group will use the app/website for 12 months. Participants will nominate one or more helpers to support them. Helpers have access to the app/website. The control group will receive a leaflet on healthy lifestyle and will have access to HelpMeDoIt! after follow-up. The key outcome of the study is whether prespecified progression criteria have been met in order to progress to a larger randomised controlled effectiveness trial. Data will be collected at baseline, 6 and 12 months. Outcomes focus on exploring the feasibility of delivering the intervention and include: (i) assessing three primary outcomes (BMI, physical activity and diet); (ii) secondary outcomes of waist/hip circumference, health-related quality of life, social support, self-efficacy, motivation and mental health; (iii) recruitment and retention; (iv) National Health Service (NHS) resource use and participant borne costs; (v) usability and acceptability of the app/website; and (vi) qualitative interviews with up to 50 participants and 20 helpers on their experiences of the intervention. Statistical analyses will focus on feasibility outcomes and provide initial estimates of intervention effects. Thematic analysis of qualitative interviews will assess implementation, acceptability, mechanisms of effect and contextual

MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3 in cynomolgus macaques.

Directory of Open Access Journals (Sweden)

Nathalie Dereuddre-Bosquet

Full Text Available In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1(Ba-L in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP model of mucosal challenge with SHIV(162P3 after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control, the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID(50 of SHIV(162P3. All control animals were infected with a peak plasma viral load of 10(5-10(6 viral RNA (vRNA copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments.

A research protocol for a pilot randomized controlled trial designed to examine the feasibility of a couple-based mind-body intervention for patients with metastatic lung cancer and their partners.

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Milbury, Kathrin; Tsao, Anne S; Liao, Zhongxing; Owns, April; Engle, Rosalinda; Gonzalez, Edrea A; Bruera, Eduardo; Cohen, Lorenzo

2018-01-01

Given the generally incurable nature of metastatic non-small cell lung cancer (mNSCLC), patients and their romantic partners are at risk for existential/spiritual distress. Although a handful of dyadic psychosocial interventions for lung cancer patients and their caregivers exist, none of them target spiritual well-being. Informed by the mindfulness-based intervention literature and our pilot work in couples affected by lung cancer, we developed a brief couple-based mind-body (CBMB) intervention. The primary aim of this research protocol is to determine the feasibility of implementing the CBMB intervention versus an active control (AC) or wait list control (WLC) group in patients with mNSCLC and their partners using a randomized controlled trial design. Seventy-five patients with mNSCLC receiving treatment and their partners are randomized to the CBMB intervention, an AC or a WLC group. Those in the CBMB intervention and AC groups receive four intervention sessions of 60 min each over 4 weeks and complete weekly homework assignments. The first session is delivered in person, and the remaining sessions are delivered via videoconference. The dyads in the AC group discuss cancer-related and personal growth concerns with the interventionist but are not taught coping skills. Patients and partners in all groups complete baseline assessments of quality of life (QOL) prior to randomization. Follow-up assessments are performed 4 weeks and then again 3 months later. The primary outcome is feasibility (i.e., ≥ 30% of eligible couples consent, ≥ 70% of enrolled couples are retained, and ≥ 50% of all CBMB and AC sessions are attended). We will also perform primarily descriptive analyses of the self-reported outcomes (e.g., spiritual well-being and psychological distress) and explore potential intervention mediators (i.e., compassion, communication, mindfulness, and closeness) to inform a larger, future trial. This trial will provide important information

Treating people with intercurrent infection in HIV prevention trials. Report from a WHO/UNAIDS consultation, Geneva 17-18th July 2003.

Science.gov (United States)

2004-10-21

While broad agreement now exists among sponsors of HIV prevention trials that antiretroviral therapy (ART) and a clinical care package should be provided to those who become infected during the conduct of a trial, certain practical issues remain unresolved, including Who should pay for ART? How long should ART be provided for? Does treatment extend outside of ART? What else should be included in the standard of care package and who should pay for it? Who should provide treatment and care? This report summarizes the discussions from a consultation held in Geneva (17-18 July 2003) organized by the World Health Organization (WHO) and the joint United Nations Programme on HIV/AIDS (UNAIDS). The group discussed issues related to the various types of HIV prevention trials covered - vaccines, microbicides, behavioural - the ethics and legal rational for providing treatment and care as well as relevant economic issues and developments around scale-up of treatment and care in middle- and lower-income countries. Also discussed were policies of certain research agencies, countries and international funding agencies. The implementation of the conclusions which came out of these discussions on the treatment and care for people who become infected during HIV prevention trials requires the active participation of members of the research community, funders of research, local and national governments and industry as well as the individuals or communities participating in the trials.

Requirements Elicitation in a Telemedicine Pain-treatment Trial

NARCIS (Netherlands)

Widya, I.A.; Bults, Richard G.A.; van Beijnum, Bernhard J.F.; Sandsjö, L.; Schaake, L.; Huis in 't Veld, M.H.A.; Jones, Valerie M.; Hermens, Hermanus J.; Ryan, K.; Robinson, W.

2009-01-01

This paper presents the early phase requirements elicitation for a work-related neck-shoulder pain teletreatment trial and the assessment of those requirements in respect of their importance to the trial and the feasibility of the needed software adaptations of the telemedicine system within the

Feasibility of progressive sit-to-stand training among older hospitalized patients

DEFF Research Database (Denmark)

Pedersen, Mette Merete; Petersen, Janne; Bean, Jonathan F

2015-01-01

hospitalization and once following discharge in their own homes. A structured interview including assessment of possible modifiers (cognitive status by the Short Orientation Memory test and mobility by the De Morton Mobility Index) was administered both on admission to the hospital and in the home setting...... was independent of cognitive status. Conclusions. We found a simple progression model for loaded sit-to-stands (STAND) feasible in acutely admitted older medical patients (≥65 yrs), based on our pre-specified criteria for feasibility....... and dose for older patients. Therefore, our aim was to test the feasibility of a progression model for loaded sit-to-stand training among older hospitalized patients. Methods. This is a prospective cohort study conducted as a feasibility study prior to a full-scale trial. We included twenty-four older...

A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine.

Science.gov (United States)

Major, Ian; Boyd, Peter; Kilbourne-Brook, Maggie; Saxon, Gene; Cohen, Jessica; Malcolm, R Karl

2013-07-01

There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. This study describes an innovative barrier contraceptive device--based on the SILCS diaphragm--that also provides long-term controlled release of the lead candidate anti-HIV microbicide dapivirine. Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded with a nonmedicated silicone elastomer sheath were fabricated by injection molding processes. In vitro release testing, thermal analysis and mechanical characterization were performed on the devices. A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine provided continuous and controlled release of dapivirine over a 6-month period, with a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the new diaphragm were closely matched to the SILCS diaphragm. The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. In discontinuous clinical use, release of dapivirine may be readily extended over 1 or more years. Copyright © 2013 Elsevier Inc. All rights reserved.

Social Stories™ to alleviate challenging behaviour and social difficulties exhibited by children with autism spectrum disorder in mainstream schools: design of a manualised training toolkit and feasibility study for a cluster randomised controlled trial with nested qualitative and cost-effectiveness components.

Science.gov (United States)

Wright, Barry; Marshall, David; Adamson, Joy; Ainsworth, Hannah; Ali, Shehzad; Allgar, Victoria; Collingridge Moore, Danielle; Cook, Elizabeth; Dempster, Paul; Hackney, Lisa; McMillan, Dean; Trepél, Dominic; Williams, Chris

2016-01-01

A Social Story™ (Carol Gray) is a child-friendly intervention that is used to give children with autism spectrum disorders (ASDs) social information in situations where they have social difficulties. Limited evidence mainly using single-case designs suggests that they can reduce anxiety and challenging behaviour. The objectives were to conduct a systematic review, use this to develop a manualised intervention and run a feasibility trial to inform a fully powered randomised controlled trial (RCT) on their clinical effectiveness and cost-effectiveness in schools. This is a three-stage study following the Medical Research Council framework for complex interventions. Specifically, it involved a theoretical phase, a qualitative stage and a feasibility trial stage. Qualitative interviews and focus groups took place in Child and Adolescent Mental Health Service and primary care settings. The feasibility study took place in 37 local mainstream schools. Fifty children (aged 5-15 years) in mainstream school settings with a diagnosis of ASD were entered into the trial. For each child, an associated teacher and parent was also recruited. The intervention was a goal-setting session followed by a manualised toolkit (including a training session) for creating Social Stories™ for use with school-aged children. The comparator treatment was a goal-setting session followed by an attention control. Both arms received treatment as usual. Outcomes tested as part of the feasibility study included child- and proxy-completed questionnaires for mental health, quality of life and goal-based outcome measures. Adults additionally completed behaviour diaries and the parental stress index. The review found that the research into social stories is predominantly based in the USA, carried out in under-12-year-olds and using single-case designs. Most studies either did not follow established Social Story criteria or did not report if they did. The assessment of effectiveness presents a largely

A randomised controlled trial of a smoking cessation intervention delivered by dental hygienists: a feasibility study

Directory of Open Access Journals (Sweden)

Jenkins William

2007-05-01

Full Text Available Abstract Background Tobacco use continues to be a global public health problem. Helping patients to quit is part of the preventive role of all health professionals. There is now increasing interest in the role that the dental team can play in helping their patients to quit smoking. The aim of this study was to determine the feasibility of undertaking a randomised controlled smoking cessation intervention, utilising dental hygienists to deliver tobacco cessation advice to a cohort of periodontal patients. Methods One hundred and eighteen patients who attended consultant clinics in an outpatient dental hospital department (Periodontology were recruited into a trial. Data were available for 116 participants, 59 intervention and 57 control, and were analysed on an intention-to-treat basis. The intervention group received smoking cessation advice based on the 5As (ask, advise, assess, assist, arrange follow-up and were offered nicotine replacement therapy (NRT, whereas the control group received 'usual care'. Outcome measures included self-reported smoking cessation, verified by salivary cotinine measurement and CO measurements. Self-reported measures in those trial participants who did not quit included number and length of quit attempts and reduction in smoking. Results At 3 months, 9/59 (15% of the intervention group had quit compared to 5/57 (9% of the controls. At 6 months, 6/59 (10% of the intervention group quit compared to 3/57 (5% of the controls. At one year, there were 4/59 (7% intervention quitters, compared to 2/59 (4% control quitters. In participants who described themselves as smokers, at 3 and 6 months, a statistically higher percentage of intervention participants reported that they had had a quit attempt of at least one week in the preceding 3 months (37% and 47%, for the intervention group respectively, compared with 18% and 16% for the control group. Conclusion This study has shown the potential that trained dental hygienists

Combinatorial Approaches to the Prevention and Treatment of HIV-1 Infection▿†

Science.gov (United States)

Pirrone, Vanessa; Thakkar, Nina; Jacobson, Jeffrey M.; Wigdahl, Brian; Krebs, Fred C.

2011-01-01

The discovery of the human immunodeficiency virus type 1 (HIV-1) in 1982 soon led to the identification and development of antiviral compounds to be used in treatment strategies for infected patients. Early in the epidemic, drug monotherapies frequently led to treatment failures because the virus quickly developed resistance to the single drug. Following the advent of highly active antiretroviral therapy (HAART) in 1995, dramatic improvements in HIV-1-infected patient health and survival were realized as more refined combination therapies resulted in reductions in viral loads and increases in CD4+ T-cell counts. In the absence of an effective vaccine, prevention of HIV-1 infection has also gained traction as an approach to curbing the pandemic. The development of compounds as safe and effective microbicides has intensified and has focused on blocking the transmission of HIV-1 during all forms of sexual intercourse. Initial preclinical investigations and clinical trials of microbicides focused on single compounds effective against HIV-1. However, the remarkable successes achieved using combination therapy to treat systemic HIV-1 infection have subsequently stimulated the study and development of combination microbicides that will simultaneously inhibit multiple aspects of the HIV-1 transmission process by targeting incoming viral particles, virus-infected cells, and cells susceptible to HIV-1 infection. This review focuses on existing and developing combination therapies, covering preclinical development, in vitro and in vivo efficacy studies, and subsequent clinical trials. The shift in focus within the microbicide development field from single compounds to combination approaches is also explored. PMID:21343462

Chiropractic treatment including instrument-assisted manipulation for non-specific dizziness and neck pain in community-dwelling older people: a feasibility randomised sham-controlled trial.

Science.gov (United States)

Kendall, Julie C; French, Simon D; Hartvigsen, Jan; Azari, Michael F

2018-01-01

Dizziness in older people is a risk factor for falls. Neck pain is associated with dizziness and responds favourably to neck manipulation. However, it is unknown if chiropractic intervention including instrument-assisted manipulation of the neck in older people with neck pain can also improve dizziness. This parallel two-arm pilot trial was conducted in Melbourne, Australia over nine months (October 2015 to June 2016). Participants aged 65-85 years, with self-reported chronic neck pain and dizziness, were recruited from the general public through advertisements in local community newspapers and via Facebook. Participants were randomised using a permuted block method to one of two groups: 1) Activator II™-instrument-assisted cervical and thoracic spine manipulation plus a combination of: light massage; mobilisation; range of motion exercises; and home advice about the application of heat, or 2) Sham-Activator II™-instrument-assisted manipulation (set to zero impulse) plus gentle touch of cervical and thoracic spinal regions. Participants were blinded to group allocation. The interventions were delivered weekly for four weeks. Assessments were conducted one week pre- and post-intervention. Clinical outcomes were assessed blindly and included: dizziness (dizziness handicap inventory [DHI]); neck pain (neck disability index [NDI]); self-reported concerns of falling; mood; physical function; and treatment satisfaction. Feasibility outcomes included recruitment rates, compliance with intervention and outcome assessment, study location, success of blinding, costs and harms. Out of 162 enquiries, 24 participants were screened as eligible and randomised to either the chiropractic ( n  = 13) or sham ( n  = 11) intervention group. Compliance was satisfactory with only two participants lost to follow up; thus, post-intervention data for 12 chiropractic intervention and 10 sham intervention participants were analysed. Blinding was similar between groups. Mild harms

Feasibility of a randomized controlled trial to evaluate the impact of decision boxes on shared decision-making processes.

Science.gov (United States)

Giguere, Anik Mc; Labrecque, Michel; Légaré, France; Grad, Roland; Cauchon, Michel; Greenway, Matthew; Haynes, R Brian; Pluye, Pierre; Syed, Iqra; Banerjee, Debi; Carmichael, Pierre-Hugues; Martin, Mélanie

2015-02-25

Decision boxes (DBoxes) are two-page evidence summaries to prepare clinicians for shared decision making (SDM). We sought to assess the feasibility of a clustered Randomized Controlled Trial (RCT) to evaluate their impact. A convenience sample of clinicians (nurses, physicians and residents) from six primary healthcare clinics who received eight DBoxes and rated their interest in the topic and satisfaction. After consultations, their patients rated their involvement in decision-making processes (SDM-Q-9 instrument). We measured clinic and clinician recruitment rates, questionnaire completion rates, patient eligibility rates, and estimated the RCT needed sample size. Among the 20 family medicine clinics invited to participate in this study, four agreed to participate, giving an overall recruitment rate of 20%. Of 148 clinicians invited to the study, 93 participated (63%). Clinicians rated an interest in the topics ranging 6.4-8.2 out of 10 (with 10 highest) and a satisfaction with DBoxes of 4 or 5 out of 5 (with 5 highest) for 81% DBoxes. For the future RCT, we estimated that a sample size of 320 patients would allow detecting a 9% mean difference in the SDM-Q-9 ratings between our two arms (0.02 ICC; 0.05 significance level; 80% power). Clinicians' recruitment and questionnaire completion rates support the feasibility of the planned RCT. The level of interest of participants for the DBox topics, and their level of satisfaction with the Dboxes demonstrate the acceptability of the intervention. Processes to recruit clinics and patients should be optimized.

Thrombin-induced rabbit platelet microbicidal protein is fungicidal in vitro.

Science.gov (United States)

Yeaman, M R; Ibrahim, A S; Edwards, J E; Bayer, A S; Ghannoum, M A

1993-03-01

Platelet microbicidal protein (PMP) is released from platelets in response to thrombin stimulation. PMP is known to possess in vitro bactericidal activity against Staphylococcus aureus and viridans group streptococci. To determine whether PMP is active against other intravascular pathogens, we evaluated its potential fungicidal activity against strains of Candida species and Cryptococcus neoformans. Anionic resin adsorption and gel electrophoresis confirmed that the fungicidal activity of PMP resided in a small (approximately 8.5-kDa), cationic protein, identical to previous studies of PMP-induced bacterial killing (M.R. Yeaman, S.M. Puentes, D.C. Norman, and A.S. Bayer, Infect. Immun. 60:1202-1209, 1992). When assayed over a 180-min period in vitro, the susceptibilities of these fungi to PMP varied considerably. Generally, Candida albicans strains (mean survival, 33.5% +/- 6.9% [n = 6]) as well as isolates of Candida glabrata (mean survival, 50.8% +/- 2.9% [n = 2]) were the most susceptible to killing by PMP, while Candida guillermondii and Candida parapsilosis were relatively resistant to PMP-induced killing. Compared with C. albicans, C. neoformans was relatively resistant to the fungicidal activity of PMP, with a mean survival among the isolates studied of 77.4% +/- 12.4% (n = 6). Against C. albicans, PMP-induced fungicidal activity was time dependent (range, 0 to 180 min), PMP concentration dependent (range, 10 to 150 U/ml), and inversely related to the fungal inoculum (range, 5 x 10(3) to 1 x 10(5) CFU/ml). Scanning electron microscopy of PMP-exposed C. albicans and C. neoformans cells revealed extensive surface damage and collapse, suggesting that the site of PMP fungicidal action may directly or indirectly involve the fungal cell envelope.

PERFECTED enhanced recovery (PERFECT-ER) care versus standard acute care for patients admitted to acute settings with hip fracture identified as experiencing confusion: study protocol for a feasibility cluster randomized controlled trial.

Science.gov (United States)

Hammond, Simon P; Cross, Jane L; Shepstone, Lee; Backhouse, Tamara; Henderson, Catherine; Poland, Fiona; Sims, Erika; MacLullich, Alasdair; Penhale, Bridget; Howard, Robert; Lambert, Nigel; Varley, Anna; Smith, Toby O; Sahota, Opinder; Donell, Simon; Patel, Martyn; Ballard, Clive; Young, John; Knapp, Martin; Jackson, Stephen; Waring, Justin; Leavey, Nick; Howard, Gregory; Fox, Chris

2017-12-04

Health and social care provision for an ageing population is a global priority. Provision for those with dementia and hip fracture has specific and growing importance. Older people who break their hip are recognised as exceptionally vulnerable to experiencing confusion (including but not exclusively, dementia and/or delirium and/or cognitive impairment(s)) before, during or after acute admissions. Older people experiencing hip fracture and confusion risk serious complications, linked to delayed recovery and higher mortality post-operatively. Specific care pathways acknowledging the differences in patient presentation and care needs are proposed to improve clinical and process outcomes. This protocol describes a multi-centre, feasibility, cluster-randomised, controlled trial (CRCT) to be undertaken across ten National Health Service hospital trusts in the UK. The trial will explore the feasibility of undertaking a CRCT comparing the multicomponent PERFECTED enhanced recovery intervention (PERFECT-ER), which acknowledges the differences in care needs of confused older patients experiencing hip fracture, with standard care. The trial will also have an integrated process evaluation to explore how PERFECT-ER is implemented and interacts with the local context. The study will recruit 400 hip fracture patients identified as experiencing confusion and will also recruit "suitable informants" (individuals in regular contact with participants who will complete proxy measures). We will also recruit NHS professionals for the process evaluation. This mixed methods design will produce data to inform a definitive evaluation of the intervention via a large-scale pragmatic randomised controlled trial (RCT). The trial will provide a preliminary estimate of potential efficacy of PERFECT-ER versus standard care; assess service delivery variation, inform primary and secondary outcome selection, generate estimates of recruitment and retention rates, data collection difficulties, and

Haptic-based neurorehabilitation in poststroke patients: a feasibility prospective multicentre trial for robotics hand rehabilitation.

Science.gov (United States)

Turolla, Andrea; Daud Albasini, Omar A; Oboe, Roberto; Agostini, Michela; Tonin, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Venneri, Annalena; Piron, Lamberto

2013-01-01

Background. Haptic robots allow the exploitation of known motor learning mechanisms, representing a valuable option for motor treatment after stroke. The aim of this feasibility multicentre study was to test the clinical efficacy of a haptic prototype, for the recovery of hand function after stroke. Methods. A prospective pilot clinical trial was planned on 15 consecutive patients enrolled in 3 rehabilitation centre in Italy. All the framework features of the haptic robot (e.g., control loop, external communication, and graphic rendering for virtual reality) were implemented into a real-time MATLAB/Simulink environment, controlling a five-bar linkage able to provide forces up to 20 [N] at the end effector, used for finger and hand rehabilitation therapies. Clinical (i.e., Fugl-Meyer upper extremity scale; nine hold pegboard test) and kinematics (i.e., time; velocity; jerk metric; normalized jerk of standard movements) outcomes were assessed before and after treatment to detect changes in patients' motor performance. Reorganization of cortical activation was detected in one patient by fMRI. Results and Conclusions. All patients showed significant improvements in both clinical and kinematic outcomes. Additionally, fMRI results suggest that the proposed approach may promote a better cortical activation in the brain.

Haptic-Based Neurorehabilitation in Poststroke Patients: A Feasibility Prospective Multicentre Trial for Robotics Hand Rehabilitation

Directory of Open Access Journals (Sweden)

Andrea Turolla

2013-01-01

Full Text Available Background. Haptic robots allow the exploitation of known motorlearning mechanisms, representing a valuable option for motor treatment after stroke. The aim of this feasibility multicentre study was to test the clinical efficacy of a haptic prototype, for the recovery of hand function after stroke. Methods. A prospective pilot clinical trial was planned on 15 consecutive patients enrolled in 3 rehabilitation centre in Italy. All the framework features of the haptic robot (e.g., control loop, external communication, and graphic rendering for virtual reality were implemented into a real-time MATLAB/Simulink environment, controlling a five-bar linkage able to provide forces up to 20 [N] at the end effector, used for finger and hand rehabilitation therapies. Clinical (i.e., Fugl-Meyer upper extremity scale; nine hold pegboard test and kinematics (i.e., time; velocity; jerk metric; normalized jerk of standard movements outcomes were assessed before and after treatment to detect changes in patients' motor performance. Reorganization of cortical activation was detected in one patient by fMRI. Results and Conclusions. All patients showed significant improvements in both clinical and kinematic outcomes. Additionally, fMRI results suggest that the proposed approach may promote a better cortical activation in the brain.

Surgical timing after chemoradiotherapy for rectal cancer, analysis of technique (STARRCAT): results of a feasibility multi-centre randomized controlled trial.

Science.gov (United States)

Foster, J D; Ewings, P; Falk, S; Cooper, E J; Roach, H; West, N P; Williams-Yesson, B A; Hanna, G B; Francis, N K

2016-10-01

The optimal time of rectal resection after long-course chemoradiotherapy (CRT) remains unclear. A feasibility study was undertaken for a multi-centre randomized controlled trial evaluating the impact of the interval after chemoradiotherapy on the technical complexity of surgery. Patients with rectal cancer were randomized to either a 6- or 12-week interval between CRT and surgery between June 2012 and May 2014 (ISRCTN registration number: 88843062). For blinded technical complexity assessment, the Observational Clinical Human Reliability Analysis technique was used to quantify technical errors enacted within video recordings of operations. Other measured outcomes included resection completeness, specimen quality, radiological down-staging, tumour cell density down-staging and surgeon-reported technical complexity. Thirty-one patients were enrolled: 15 were randomized to 6 and 16-12 weeks across 7 centres. Fewer eligible patients were identified than had been predicted. Of 23 patients who underwent resection, mean 12.3 errors were observed per case at 6 weeks vs. 10.7 at 12 weeks (p = 0.401). Other measured outcomes were similar between groups. The feasibility of measurement of operative performance of rectal cancer surgery as an endpoint was confirmed in this exploratory study. Recruitment of sufficient numbers of patients represented a challenge, and a proportion of patients did not proceed to resection surgery. These results suggest that interval after CRT may not substantially impact upon surgical technical performance.

Transdiagnostic treatment of bipolar disorder and comorbid anxiety using the Unified Protocol for Emotional Disorders: A pilot feasibility and acceptability trial.

Science.gov (United States)

Ellard, Kristen K; Bernstein, Emily E; Hearing, Casey; Baek, Ji Hyun; Sylvia, Louisa G; Nierenberg, Andrew A; Barlow, David H; Deckersbach, Thilo

2017-09-01

Comorbid anxiety in bipolar disorder (BD) is associated with greater illness severity, reduced treatment response, and greater impairment. Treating anxiety in the context of BD is crucial for improving illness course and outcomes. The current study examined the feasibility, acceptability and preliminary efficacy of the Unified Protocol (UP), a transdiagnostic cognitive behavioral therapy, as an adjunctive treatment to pharmacotherapy for BD and comorbid anxiety disorders. Twenty-nine patients with BD and at least one comorbid anxiety disorder were randomized to pharmacotherapy treatment-as-usual (TAU) or TAU with 18 sessions of the UP (UP+TAU). All patients completed assessments every four weeks to track symptoms, functioning, emotion regulation and temperament. Linear mixed-model regressions were conducted to track symptom changes over time and to examine the relationship between emotion-related variables and treatment response. Satisfaction ratings were equivalent for both treatment groups. Patients in the UP+TAU group evidenced significantly greater reductions over time in anxiety and depression symptoms (Cohen's d's>0.80). Baseline levels of neuroticism, perceived affective control, and emotion regulation ability predicted magnitude of symptom change for the UP+TAU group only. Greater change in perceived control of emotions and emotion regulation skills predicted greater change in anxiety related symptoms. This was a pilot feasibility and acceptability trial; results should be interpreted with caution. Treatment with the UP+TAU was rated high in patient satisfaction, and resulted in significantly greater improvement on indices of anxiety and depression relative to TAU. This suggests that the UP may be a feasible treatment approach for BD with comorbid anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.

The Falls In Care Home study: a feasibility randomized controlled trial of the use of a risk assessment and decision support tool to prevent falls in care homes

Science.gov (United States)

Walker, Gemma M; Armstrong, Sarah; Gordon, Adam L; Gladman, John; Robertson, Kate; Ward, Marie; Conroy, Simon; Arnold, Gail; Darby, Janet; Frowd, Nadia; Williams, Wynne; Knowles, Sue; Logan, Pip A

2015-01-01

Objective: To explore the feasibility of implementing and evaluating the Guide to Action Care Home fall prevention intervention. Design: Two-centre, cluster feasibility randomized controlled trial and process evaluation. Setting: Purposive sample of six diverse old age/learning disability, long stay care homes in Nottinghamshire, UK. Subjects: Residents aged over 50 years, who had fallen at least once in the past year, not bed-bound, hoist-dependent or terminally ill. Interventions: Intervention homes (n = 3) received Guide to Action Care Home fall prevention intervention training and support. Control homes (n = 3) received usual care. Outcomes: Recruitment, attrition, baseline and six-month outcome completion, contamination and intervention fidelity, compliance, tolerability, acceptance and impact. Results: A total of 81 of 145 (56%) care homes expressed participatory interest. Six of 22 letter respondent homes (27%) participated. The expected resident recruitment target was achieved by 76% (52/68). Ten (19%) residents did not complete follow-up (seven died, three moved). In intervention homes 36/114 (32%) staff attended training. Two of three (75%) care homes received protocol compliant training. Staff valued the training, but advised greater management involvement to improve intervention implementation. Fall risks were assessed, actioned and recorded in care records. Of 115 recorded falls, 533/570 (93%) of details were complete. Six-month resident fall rates were 1.9 and 4.0 per year for intervention and control homes, respectively. Conclusions: The Guide to Action Care Home is implementable under trial conditions. Recruitment and follow-up rates indicate that a definitive trial can be completed. Falls (primary outcome) can be ascertained reliably from care records. PMID:26385358

A community health worker-led lifestyle behavior intervention for Latina (Hispanic) women: feasibility and outcomes of a randomized controlled trial.

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Koniak-Griffin, Deborah; Brecht, Mary-Lynn; Takayanagi, Sumiko; Villegas, Juan; Melendrez, Marylee; Balcázar, Héctor

2015-01-01

Low-income Latinas (Hispanics) face risk for cardiovascular disease due to high rates of overweight/obesity, sedentary lifestyle, and other factors. Limited access to health care and language barriers may prevent delivery of health promotion messages. Targeted approaches, including the integration of community health workers, may be required to promote healthy lifestyle and prevent chronic disease in underserved ethnic minority groups. The term commonly used to refer to female community health workers in Latino communities is "promotora(s)." This study evaluates the outcomes and feasibility of a promotora-led lifestyle behavior intervention for overweight, immigrant Latinas. A community prevention model was employed in planning and implementing this study. A randomized controlled trial design was used. A Community Advisory Board provided expertise in evaluating feasibility of study implementation in the community and other important guidance. The sample was comprised of 223 women aged 35-64 years, predominantly with low income and ≤8th grade education. The culturally tailored Lifestyle Behavior Intervention included group education (8 classes based upon Su Corazon, Su Vida), followed by 4 months of individual teaching and coaching (home visits and telephone calls). The control group received a comparable length educational program and follow-up contacts. Evaluations were conducted at baseline and at 6 and 9 months using a dietary habits questionnaire, accelerometer readings of physical activity, and clinical measures (body mass index, weight, waist circumference, blood pressure, lipids, blood glucose). Data were collected between January 2010 and August 2012. Women in the intervention group improved significantly in dietary habits, waist circumference, and physical activity in comparison to those in the control group. A treatment dosage effect was observed for weight and waist circumference. Knowledge about heart disease increased. High attendance at classes and

A randomised controlled feasibility trial for an educational school-based mental health intervention: study protocol.

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Chisholm, Katharine Elizabeth; Patterson, Paul; Torgerson, Carole; Turner, Erin; Birchwood, Max

2012-03-22

With the burden of mental illness estimated to be costing the English economy alone around £22.5 billion a year 1, coupled with growing evidence that many mental disorders have their origins in adolescence, there is increasing pressure for schools to address the emotional well-being of their students, alongside the stigma and discrimination of mental illness. A number of prior educational interventions have been developed and evaluated for this purpose, but inconsistency of findings, reporting standards, and methodologies have led the majority of reviewers to conclude that the evidence for the efficacy of these programmes remains inconclusive. A cluster randomised controlled trial design has been employed to enable a feasibility study of 'SchoolSpace', an intervention in 7 UK secondary schools addressing stigma of mental illness, mental health literacy, and promotion of mental health. A central aspect of the intervention involves students in the experimental condition interacting with a young person with lived experience of mental illness, a stigma reducing technique designed to facilitate students' engagement in the project. The primary outcome is the level of stigma related to mental illness. Secondary outcomes include mental health literacy, resilience to mental illness, and emotional well-being. Outcomes will be measured pre and post intervention, as well as at 6 month follow-up. The proposed intervention presents the potential for increased engagement due to its combination of education and contact with a young person with lived experience of mental illness. Contact as a technique to reduce discrimination has been evaluated previously in research with adults, but has been employed in only a minority of research trials investigating the impact on youth. Prior to this study, the effect of contact on mental health literacy, resilience, and emotional well-being has not been evaluated to the authors' knowledge. If efficacious the intervention could provide a

HIV Incidence Remains High in KwaZulu-Natal, South Africa: Evidence from Three Districts

NARCIS (Netherlands)

Nel, Annaléne; Mabude, Zonke; Smit, Jenni; Kotze, Philip; Arbuckle, Derek; Wu, Jian; van Niekerk, Neliëtte; van de Wijgert, Janneke

2012-01-01

Background: HIV prevalence and incidence among sexually active women in peri-urban areas of Ladysmith, Edendale, and Pinetown, KwaZulu-Natal, South Africa, were assessed between October 2007 and February 2010 in preparation for vaginal microbicide trials. Methodology/Principal Findings: Sexually

Pregnant women's attitudes about topical microbicides for the prevention and treatment of bacterial vaginosis during pregnancy.

Science.gov (United States)

Catallozzi, Marina; Fraiz, Lauren Dapena; Hargreaves, Katharine M; Zimet, Gregory D; Stanberry, Lawrence R; Ratner, Adam J; Gelber, Shari E; Rosenthal, Susan L

2017-08-01

We sought to understand pregnant women's product preference and likelihood of use of topical microbicides for bacterial vaginosis (BV) prevention and treatment. Pregnant women (N = 196) in a obstetrics clinic completed a survey between June 2014 and January 2015 about vaginal product use for BV. This cross-sectional study explored product preferences, likelihood of product use for BV management and father of the baby (FOB) involvement. Most participants were under 30 (68%) and underrepresented minorities (47% Hispanic, 21% African-American). Most women preferred the gel (69%). Only 30% were likely to use either product for prevention of BV; 76% if high risk for BV; 83% treatment of BV. Anticipated FOB involvement in decision-making included that 46% would ask his opinion, 38% would inform him of the decision and 7% would need approval. Most (87%) would ask the FOB for reminders and 66% for insertion help. Those under 30 were more likely to agree to ask the FOB for reminders (p Product preferences may be less critical than risk perception. Involvement of the FOB in decision-making may be vital.

Using Mobile Health to Improve Social Support for Low-Income Latino Patients with Diabetes: A Mixed-Methods Analysis of the Feasibility Trial of TExT-MED + FANS.

Science.gov (United States)

Burner, Elizabeth; Lam, Chun Nok; DeRoss, Rebecca; Kagawa-Singer, Marjorie; Menchine, Michael; Arora, Sanjay

2018-01-01

Social support interventions can improve diabetes self-care, particularly for Latinos, but are time and resource intensive. Mobile health may overcome these barriers by engaging and training supporters remotely. We conducted a randomized controlled feasibility trial of emergency department patients with diabetes to determine the feasibility of enrolling patients and supporters, acceptability of the intervention, and preliminary efficacy results to power a larger trial. All patients received an existing mHealth curriculum (TExT-MED). After identifying a supporter, patients were randomized to intervention: supporters receiving FANS (family and friends network support), a text message support curriculum synchronized to patient messages, or control: supporters receiving a mailed pamphlet of the same information. Participants followed up at 3 months. FANS intervention participants came to postintervention interviews as part of a qualitative analysis. We enrolled 44 patients (22 per arm) and followed up 36 at 3 months. Participants were positive about the program. FANS intervention improved HbA1c (intervention mean decreased from 10.4% to 9.0% vs. from 10.1% to 9.5%, delta -0.8%, confidence interval [CI] -0.4 to 2, P = 0.30), self-monitoring of glucose (intervention increased 1.6 days/week vs. control decreased 2 days/week, delta 2.3 days/week, CI 4-0.6, P = 0.02), and physical activity (mean Godin leisure time activity score improved 16.1 vs. decreased 9.6 for control, delta 25.7, CI 49.2-2.3, P = 0.10). In qualitative analysis, patients reported improved motivation, behaviors, and relationships. Supporters reported making healthier decisions for themselves. mHealth is a feasible, acceptable, and promising avenue to improve social support and diabetes outcomes.

Para-aortic lymphadenectomy in advanced stage cervical cancer, a protocol for comparing safety, feasibility and diagnostic accuracy of surgical staging versus PET-CT; PALDISC trial.

Science.gov (United States)

Tax, Casper; Abbink, Karin; Rovers, Maroeska M; Bekkers, Ruud L M; Zusterzeel, Petra L M

2018-01-01

Currently, a PET-CT is used to assess the need for extended field radiotherapy of para-aortic lymph nodes (PALN) in International Federation of Gynaecology and Obstetrics (FIGO) stage IB2, IIA2-IVA (locally advanced stage) cervical cancer. A small study established a sensitivity and specificity estimate for PALN metastases of 50% (95% CI; 7-93%) and 83% (95% CI; 52-98%), respectively. Surgical staging of PALN may lead to a higher diagnostic accuracy. However, surgical staging of para-aortic lymph nodes in locally advanced stage cervical cancer is not common practice. Therefore, a phase 2 randomised controlled trial is needed to assess its safety and feasibility. In addition to standard imaging (MRI or CT scan) with PET-CT, 30 adult women with FIGO stage IB2, IIA2-IVA cervical cancer will be randomised to receive either surgical staging or usual PET-CT staging. Administering extended field radiotherapy will be based on lymphadenectomy results for the intervention group and on the PET-CT results for the control group. Follow-up visits at 0, 3, 6, 9 and 12 months will assess health-related quality of life and progression-free survival.Primary safety and feasibility outcomes of surgical staging will be assessed by calculating means with 95% confidence intervals for duration of surgery, number of complications, blood loss, nodal yield after para-aortic lymphadenectomy and treatment delay due to surgical staging. Secondary patient-centred outcomes on quality of life and first year survival will be documented and compared between the two groups. Estimates of sensitivity, specificity and negative and positive predictive values of MRI, PET-CT and surgical staging will be presented with 95% CI.. All analysis will be performed according to the intention to treat principle. This study will assess safety and feasibility, expressed as the number and severity of complications, effect on quality of life and the treatment delay due to surgically staging para-aortic lymph nodes in

Effects and feasibility of a standardised orientation and mobility training in using an identification cane for older adults with low vision: design of a randomised controlled trial

Directory of Open Access Journals (Sweden)

van der Velde J

2009-08-01

Full Text Available Abstract Background Orientation and mobility training (O&M-training in using an identification cane, also called symbol cane, is provided to people with low vision to facilitate independent participation in the community. In The Netherlands this training is mainly practice-based because a standardised and validly evaluated O&M-training in using the identification cane is lacking. Recently a standardised O&M-training in using the identification cane was developed. This training consists of two face-to-face sessions and one telephone session during which, in addition to usual care, the client's needs regarding mobility are prioritised, and cognitive restructuring techniques, action planning and contracting are applied to facilitate the use of the cane. This paper presents the design of a randomised controlled trial aimed to evaluate this standardised O&M-training in using the identification cane in older adults with low vision. Methods/design A parallel group randomised controlled trial was designed to compare the standardised O&M-training with usual care, i.e. the O&M-training commonly provided by the mobility trainer. Community-dwelling older people who ask for support at a rehabilitation centre for people with visual impairment and who are likely to receive an O&M-training in using the identification cane are included in the trial (N = 190. The primary outcomes of the effect evaluation are ADL self care and visual functioning with respect to distance activities and mobility. Secondary outcomes include quality of life, feelings of anxiety, symptoms of depression, fear of falling, and falls history. Data for the effect evaluation are collected by means of telephone interviews at baseline, and at 5 and 17 weeks after the start of the O&M-training. In addition to an effect evaluation, a process evaluation to study the feasibility of the O&M-training is carried out. Discussion The screening procedure for eligible participants started in November

Improving the large scale purification of the HIV microbicide, griffithsin.

Science.gov (United States)

Fuqua, Joshua L; Wanga, Valentine; Palmer, Kenneth E

2015-02-22

Griffithsin is a broad spectrum antiviral lectin that inhibits viral entry and maturation processes through binding clusters of oligomannose glycans on viral envelope glycoproteins. An efficient, scaleable manufacturing process for griffithsin active pharmaceutical ingredient (API) is essential for particularly cost-sensitive products such as griffithsin -based topical microbicides for HIV-1 prevention in resource poor settings. Our previously published purification method used ceramic filtration followed by two chromatography steps, resulting in a protein recovery of 30%. Our objective was to develop a scalable purification method for griffithsin expressed in Nicotiana benthamiana plants that would increase yield, reduce production costs, and simplify manufacturing techniques. Considering the future need to transfer griffithsin manufacturing technology to resource poor areas, we chose to focus modifying the purification process, paying particular attention to introducing simple, low-cost, and scalable procedures such as use of temperature, pH, ion concentration, and filtration to enhance product recovery. We achieved >99% pure griffithsin API by generating the initial green juice extract in pH 4 buffer, heating the extract to 55°C, incubating overnight with a bentonite MgCl2 mixture, and final purification with Capto™ multimodal chromatography. Griffithsin extracted with this protocol maintains activity comparable to griffithsin purified by the previously published method and we are able to recover a substantially higher yield: 88 ± 5% of griffithsin from the initial extract. The method was scaled to produce gram quantities of griffithsin with high yields, low endotoxin levels, and low purification costs maintained. The methodology developed to purify griffithsin introduces and develops multiple tools for purification of recombinant proteins from plants at an industrial scale. These tools allow for robust cost-effective production and purification of

Evaluation of a Disposable-Diaper Collection Trial in Korea through Comparison with an Absorbent-Hygiene-Product Collection Trial in Scotland

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Kyung-Shin Kim

2018-03-01

Full Text Available This study was designed to analyze the feasibility of economic aspects assuming that the policy of diaper recycling is necessary. With respect to economic feasibility, the collection and transportation of the diaper waste, which accounts for much of the cost, need to be optimized. Starting with the results of a collection trial in Scotland (2012, the method used in a collection trial in Korea (2014 was analyzed to identify problems incurring additional costs. This paper targeted daycare centers in Nowon-Gu, Seoul—because of the quantity of waste diapers they produce and the efficiency of collection—to identify the problems and to predict the cost of collection. This study evaluated multiple scenarios in light of their collection costs, discovering factors that could improve the system and reduce the cost and created the most economically feasible and optimized collection model. This paper will serve as empirical evidence proving the economics of diaper collection when the regulation is revised or amended in the future.

Assessing Clinical Trial-Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool.

Science.gov (United States)

Good, Marjorie J; Hurley, Patricia; Woo, Kaitlin M; Szczepanek, Connie; Stewart, Teresa; Robert, Nicholas; Lyss, Alan; Gönen, Mithat; Lilenbaum, Rogerio

2016-05-01

Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings. Community-based research programs were recruited to collect and enter clinical trial-associated monthly workload data into a web-based tool for 6 consecutive months. Descriptive statistics were computed for self-reported program characteristics and workload data, including staff acuity scores and number of patient encounters. Fifty-one research programs that represented 30 states participated. Median staff acuity scores were highest for staff with patients enrolled in studies and receiving treatment, relative to staff with patients in follow-up status. Treatment trials typically resulted in higher median staff acuity, relative to cancer control, observational/registry, and prevention trials. Industry trials exhibited higher median staff acuity scores than trials sponsored by the National Institutes of Health/National Cancer Institute, academic institutions, or others. The results from this project demonstrate that trial-specific acuity measurement is a better measure of workload than simply counting the number of patients. The tool was shown to be feasible and useable in diverse community-based research settings. Copyright © 2016 by American Society of Clinical Oncology.

Modifying Alcohol Consumption to Reduce Obesity (MACRO): development and feasibility trial of a complex community-based intervention for men.

Science.gov (United States)

Crombie, Iain K; Cunningham, Kathryn B; Irvine, Linda; Williams, Brian; Sniehotta, Falko F; Norrie, John; Melson, Ambrose; Jones, Claire; Briggs, Andrew; Rice, Peter M; Achison, Marcus; McKenzie, Andrew; Dimova, Elena; Slane, Peter W

2017-04-01

Obese men who consume alcohol are at a greatly increased risk of liver disease; those who drink > 14 units of alcohol per week have a 19-fold increased risk of dying from liver disease. To develop an intervention to reduce alcohol consumption in obese men and to assess the feasibility of a randomised controlled trial (RCT) to investigate its effectiveness. The intervention was developed using formative research, public involvement and behaviour change theory. It was organised in two phases, comprising a face-to-face session with trained laypeople (study co-ordinators) followed by a series of text messages. Participants explored how alcohol consumption contributed to weight gain, both through direct calorie consumption and through its effect on increasing food consumption, particularly of high-calorie foodstuffs. Men were encouraged to set goals to reduce their alcohol consumption and to make specific plans to do so. The comparator group received an active control in the form of a conventional alcohol brief intervention. Randomisation was carried out using the secure remote web-based system provided by the Tayside Clinical Trials Unit. Randomisation was stratified by the recruitment method and restricted using block sizes of randomly varying lengths. Members of the public were involved in the development of all study methods. Men were recruited from the community, from primary care registers and by time-space sampling (TSS). The intervention was delivered in community settings such as the participant's home, community centres and libraries. Men aged 35-64 years who had a body mass index (BMI) of > 30 kg/m 2 and who drank > 21 units of alcohol per week. The screening methods successfully identified participants meeting the entry criteria. Trial recruitment was successful, with 69 men (36 from 419 approached in primary care, and 33 from 470 approached via TSS) recruited and randomised in 3 months. Of the 69 men randomised, 35 were allocated to the intervention

Rigorous Clinical Trial Design in Public Health Emergencies Is Essential

DEFF Research Database (Denmark)

Ellenberg, Susan S; Keusch, Gerald T; Babiker, Abdel G

2018-01-01

Randomized clinical trials are the most reliable approaches to evaluating the effects of new treatments and vaccines. During the 2014-15 West African Ebola epidemic, many argued that such trials were neither ethical nor feasible in an environment of limited health infrastructure and severe disease...

Effects and feasibility of a standardised orientation and mobility training in using an identification cane for older adults with low vision: design of a randomised controlled trial.

Science.gov (United States)

Zijlstra, G A R; van Rens, G H M B; Scherder, E J A; Brouwer, D M; van der Velde, J; Verstraten, P F J; Kempen, G I J M

2009-08-27

Orientation and mobility training (O&M-training) in using an identification cane, also called symbol cane, is provided to people with low vision to facilitate independent participation in the community. In The Netherlands this training is mainly practice-based because a standardised and validly evaluated O&M-training in using the identification cane is lacking. Recently a standardised O&M-training in using the identification cane was developed. This training consists of two face-to-face sessions and one telephone session during which, in addition to usual care, the client's needs regarding mobility are prioritised, and cognitive restructuring techniques, action planning and contracting are applied to facilitate the use of the cane. This paper presents the design of a randomised controlled trial aimed to evaluate this standardised O&M-training in using the identification cane in older adults with low vision. A parallel group randomised controlled trial was designed to compare the standardised O&M-training with usual care, i.e. the O&M-training commonly provided by the mobility trainer. Community-dwelling older people who ask for support at a rehabilitation centre for people with visual impairment and who are likely to receive an O&M-training in using the identification cane are included in the trial (N = 190). The primary outcomes of the effect evaluation are ADL self care and visual functioning with respect to distance activities and mobility. Secondary outcomes include quality of life, feelings of anxiety, symptoms of depression, fear of falling, and falls history. Data for the effect evaluation are collected by means of telephone interviews at baseline, and at 5 and 17 weeks after the start of the O&M-training. In addition to an effect evaluation, a process evaluation to study the feasibility of the O&M-training is carried out. The screening procedure for eligible participants started in November 2007 and will continue until October 2009. Preliminary findings

Microbicidal effect of medicinal plant extracts (Psidium guajava Linn. and Carica papaya Linn. upon bacteria isolated from fish muscle and known to induce diarrhea in children Uso de extrato de plantas medicinais (Psidium guajava Linn. e Carica papaya Linn. frente a bactérias isoladas de pescado, causadoras de diarréias infantis

Directory of Open Access Journals (Sweden)

Regine Helena Silva dos Fernandes VIEIRA

2001-06-01

Full Text Available Out of the twenty-four samples of shrimp and fish muscle used for this study, twelve were collected near a large marine sewer for waste disposal, 3 km off the coast of Fortaleza (Brazil and used for the isolation of E. coli. Other twelve were collected at the Mucuripe fresh fish market (Fortaleza, Brazil and used for the isolation of Staphylococcus aureus. Ethanol, water and acetone-diluted extracts of guava and papaya leaf sprouts were tested on the bacteria in order to verify their microbicidal potential. The E. coli strains used in the trials were rated LT positive. The papaya leaf extracts (Carica papaya Linn showed no microbicidal activity while the guava sprout extracts (Psidium guajava Linn displayed halos exceeding 13 mm for both species, an effect considered to be inhibitory by the method employed. Guava sprout extracts by 50% diluted ethanol most effectively inhibited E. coli (EPEC, while those in 50% acetone were less effective. It may be concluded that guava sprout extracts constitute a feasible treatment option for diarrhea caused by E. coli or by S. aureus-produced toxins, due to their quick curative action, easy availability in tropical countries and low cost to the consumer.Foram coletadas doze amostras de camarão e peixes nas imediações do interceptor oceânico, em Fortaleza e igual número na Feira de pescado do Mucuripe, Fortaleza, para isolamento de E. coli e Staphylococcus aureus, respectivamente. Extratos aquosos, alcoólicos e cetônicos de broto de goiabeira e de folha de mamão foram testados frente às bactérias para se verificar suas ações antibióticas. As cepas de E. coli utilizadas nos ensaios foram as classificadas como LT positivas. Os extratos de folhas de mamão (Carica papaya Linn não revelaram quaisquer atividades antibióticas enquanto que os preparados com broto de goiabeira (Psidium guajava Linn apresentaram halos sempre >13 mm para as duas espécies, considerados como de inibição pelo m

A Phase II randomised controlled trial assessing the feasibility, acceptability and potential effectiveness of Dignity Therapy for older people in care homes: Study protocol

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Richardson Alison

2009-03-01

Full Text Available Abstract Background Although most older people living in nursing homes die there, there is a dearth of robust evaluations of interventions to improve their end-of-life care. Residents usually have multiple health problems making them heavily reliant on staff for their care, which can erode their sense of dignity. Dignity Therapy has been developed to help promote dignity and reduce distress. It comprises a recorded interview, which is transcribed, edited then returned to the patient, who can bequeath it to people of their choosing. Piloting has suggested that Dignity Therapy is beneficial to people dying of cancer and their families. The aims of this study are to assess the feasibility, acceptability and potential effectiveness of Dignity Therapy to reduce psychological and spiritual distress in older people reaching the end of life in care homes, and to pilot the methods for a Phase III RCT. Methods/design A randomised controlled open-label trial. Sixty-four residents of care homes for older people are randomly allocated to one of two groups: (i Intervention (Dignity Therapy offered in addition to any standard care, and (ii Control group (standard care. Recipients of the "generativity" documents are asked their views on taking part in the study and the therapy. Both quantitative and qualitative outcomes are assessed in face-to-face interviews at baseline and at approximately one and eight weeks after the intervention (equivalent in the control group. The primary outcome is residents' sense of dignity (potential effectiveness assessed by the Patient Dignity Inventory. Secondary outcomes for residents include depression, hopefulness and quality of life. In view of the relatively small sample size, quantitative analysis is mainly descriptive. The qualitative analysis uses the Framework method. Discussion Dignity Therapy is brief, can be done at the bedside and could help both patients and their families. This detailed exploratory research shows if

Management of irritable bowel syndrome in primary care: feasibility randomised controlled trial of mebeverine, methylcellulose, placebo and a patient self-management cognitive behavioural therapy website. (MIBS trial

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Yardley Lucy

2010-11-01

Full Text Available Abstract Background IBS affects 10-22% of the UK population. Abdominal pain, bloating and altered bowel habit affect quality of life, social functioning and time off work. Current GP treatment relies on a positive diagnosis, reassurance, lifestyle advice and drug therapies, but many suffer ongoing symptoms. A recent Cochrane review highlighted the lack of research evidence for IBS drugs. Neither GPs, nor patients have good evidence to inform prescribing decisions. However, IBS drugs are widely used: In 2005 the NHS costs were nearly £10 million for mebeverine and over £8 million for fibre-based bulking agents. CBT and self-management can be helpful, but poor availability in the NHS restricts their use. We have developed a web-based CBT self-management programme, Regul8, based on an existing evidence based self-management manual and in partnership with patients. This could increase access with minimal increased costs. Methods/Design The aim is to undertake a feasibility factorial RCT to assess the effectiveness of the commonly prescribed medications in UK general practice for IBS: mebeverine (anti-spasmodic and methylcellulose (bulking-agent and Regul8, the CBT based self-management website. 135 patients aged 16 to 60 years with IBS symptoms fulfilling Rome III criteria, recruited via GP practices, will be randomised to 1 of 3 levels of the drug condition: mebeverine, methylcellulose or placebo for 6 weeks and to 1 of 3 levels of the website condition, Regul8 with a nurse telephone session and email support, Regul8 with minimal email support, or no website, thus creating 9 groups. Outcomes: Irritable bowel symptom severity scale and IBS-QOL will be measured at baseline, 6 and 12 weeks as the primary outcomes. An intention to treat analysis will be undertaken by ANCOVA for a factorial trial. Discussion This pilot will provide valuable information for a larger trial. Determining the effectiveness of commonly used drug treatments will help

Reach Out Churches: A Community-Based Participatory Research Pilot Trial to Assess the Feasibility of a Mobile Health Technology Intervention to Reduce Blood Pressure Among African Americans.

Science.gov (United States)

Skolarus, Lesli E; Cowdery, Joan; Dome, Mackenzie; Bailey, Sarah; Baek, Jonggyu; Byrd, James Brian; Hartley, Sarah E; Valley, Staci C; Saberi, Sima; Wheeler, Natalie C; McDermott, Mollie; Hughes, Rebecca; Shanmugasundaram, Krithika; Morgenstern, Lewis B; Brown, Devin L

2017-06-01

Innovative strategies are needed to reduce the hypertension epidemic among African Americans. Reach Out was a faith-collaborative, mobile health, randomized, pilot intervention trial of four mobile health components to reduce high blood pressure (BP) compared to usual care. It was designed and tested within a community-based participatory research framework among African Americans recruited and randomized from churches in Flint, Michigan. The purpose of this pilot study was to assess the feasibility of the Reach Out processes. Feasibility was assessed by willingness to consent (acceptance of randomization), proportion of weeks participants texted their BP readings (intervention use), number lost to follow-up (retention), and responses to postintervention surveys and focus groups (acceptance of intervention). Of the 425 church members who underwent BP screening, 94 enrolled in the study and 73 (78%) completed the 6-month outcome assessment. Median age was 58 years, and 79% were women. Participants responded with their BPs on an average of 13.7 (SD = 10.7) weeks out of 26 weeks that the BP prompts were sent. All participants reported satisfaction with the intervention. Reach Out, a faith-collaborative, mobile health intervention was feasible. Further study of the efficacy of the intervention and additional mobile health strategies should be considered.

Feasibility and efficacy of a multi-factorial intervention to prevent falls in older adults with cognitive impairment living in residential care (ProF-Cog). A feasibility and pilot cluster randomised controlled trial.

Science.gov (United States)

Whitney, Julie; Jackson, Stephen H D; Martin, Finbarr C

2017-05-30

Falls are common in people with dementia living in residential care. The ProF-Cog intervention was developed to address fall risk factors specific to this population. The aim of this study was to evaluate the safety, acceptability, and feasibility of the intervention and provide an estimate of its efficacy. This was a cluster randomised controlled pilot study undertaken in care homes in London, UK. All permanent residents living in participating homes who were not terminally ill were invited to participate. The intervention included an assessment of falls risk factors followed by a tailored intervention which could include dementia care mapping, comprehensive geriatric assessment, occupational therapy input and twice-weekly exercise for 6 months as required to target identified risk factors. The control group received usual care without a falls risk assessment. Standing balance was the primary outcome. This and other outcome measures were collected at baseline and after 6 months. Falls were recorded for this period using incident reports. Changes were analysed using multi-level modelling. Adherence to the interventions, adverse events and trial feasibility were recorded. Nine care homes enrolled in the study with a total 191 participants (51% of those eligible); five homes allocated to the intervention with 103 participants, and four homes to the usual care control group with 88 participants. The intervention was safe with only one reported fall whilst undertaking exercise. Adherence to agreed recommendations on activity and the environment was modest (21 and 45% respectively) and to exercise was poor (41%). Balance scores (score range 0-49) analysed on 100 participants decreased by a mean of 3.9 in the control and 5.1 in the intervention groups, a non-significant difference (p = 0.9). In other measures, both groups declined equally and there was no difference in falls rates (IRR = 1.59 95%, CI 0.67-3.76). The intervention was safe but not clinically

Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes.

Science.gov (United States)

Feldman, Eva L; Boulis, Nicholas M; Hur, Junguk; Johe, Karl; Rutkove, Seward B; Federici, Thais; Polak, Meraida; Bordeau, Jane; Sakowski, Stacey A; Glass, Jonathan D

2014-03-01

The US Food and Drug Administration-approved trial, "A Phase 1, Open-Label, First-in-Human, Feasibility and Safety Study of Human Spinal Cord-Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis, Protocol Number: NS2008-1," is complete. Our overall objective was to assess the safety and feasibility of stem cell transplantation into lumbar and/or cervical spinal cord regions in amyotrophic lateral sclerosis (ALS) subjects. Preliminary results have been reported on the initial trial cohort of 12 ALS subjects. Here, we describe the safety and functional outcome monitoring results for the final trial cohort, consisting of 6 ALS subjects receiving 5 unilateral cervical intraspinal neural stem cell injections. Three of these subjects previously received 10 total bilateral lumbar injections as part of the earlier trial cohort. All injections utilized a novel spinal-mounted stabilization and injection device to deliver 100,000 neural stem cells per injection, for a dosing range up to 1.5 million cells. Subject assessments included detailed pre- and postsurgical neurological outcome measures. The cervical injection procedure was well tolerated and disease progression did not accelerate in any subject, verifying the safety and feasibility of cervical and dual-targeting approaches. Analyses on outcome data revealed preliminary insight into potential windows of stem cell biological activity and identified clinical assessment measures that closely correlate with ALS Functional Rating Scale-Revised scores, a standard assessment for ALS clinical trials. This is the first report of cervical and dual-targeted intraspinal transplantation of neural stem cells in ALS subjects. This approach is feasible and well-tolerated, supporting future trial phases examining therapeutic dosing and efficacy. © 2014 Child Neurology Society/American Neurological Association.

Series: Pragmatic trials and real world evidence: Paper 1. Introduction.

Science.gov (United States)

Zuidgeest, Mira G P; Goetz, Iris; Groenwold, Rolf H H; Irving, Elaine; van Thiel, Ghislaine J M W; Grobbee, Diederick E

2017-08-01

This is the introductory paper in a series of eight papers. In this series, we integrate the theoretical design options with the practice of conducting pragmatic trials. For most new market-approved treatments, the clinical evidence is insufficient to fully guide physicians and policy makers in choosing the optimal treatment for their patients. Pragmatic trials can fill this gap, by providing evidence on the relative effectiveness of a treatment strategy in routine clinical practice, already in an early phase of development, while maintaining the strength of randomized controlled trials. Selecting the setting, study population, mode of intervention, comparator, and outcome are crucial in designing pragmatic trials. In combination with monitoring and data collection that does not change routine care, this will enable appropriate generalization to the target patient group in clinical practice. To benefit from the full potential of pragmatic trials, there is a need for guidance and tools in designing these studies while ensuring operational feasibility. This paper introduces the concept of pragmatic trial design. The complex interplay between pragmatic design options, feasibility, stakeholder acceptability, validity, precision, and generalizability will be clarified. In this way, balanced design choices can be made in pragmatic trials with an optimal chance of success in practice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Pilot trial of a tele-rehab intervention to improve outcomes after stroke in Ghana: A feasibility and user satisfaction study.

Science.gov (United States)

Sarfo, Fred S; Adusei, Nathaniel; Ampofo, Michael; Kpeme, Frank K; Ovbiagele, Bruce

2018-04-15

Tele-rehabilitation after stroke holds promise for under-resourced settings, especially sub-Saharan Africa (SSA), with its immense stroke burden and severely limited physical therapy services. To preliminarily assess the feasibility and outcomes of mobile technology-assisted physical therapy exercises for stroke survivors in Ghana. We conducted a prospective, single arm, pre-post study involving 20 stroke survivors recruited from a tertiary medical center, who received a Smartphone with the 9zest Stroke App® to deliver individualized, goal-targeted 5-days-a-week exercise program that was remotely supervised by a tele-therapist for 12 weeks. Outcome measures included changes in stroke levity scale scores (SLS), Modified Rankin score (MRS), Montreal Cognitive Assessment (MOCA), and feasibility indicators. Among study participants, mean ± SD age was 54.6 ± 10.2 years, 11 (55%) were men, average time from stroke onset was 6 months. No participants dropped out. Compared with baseline status, mean ± SD scores on SLS improved from 7.5 ± 3.1 to 11.8 ± 2.2 at month 1 (p < 0.0001) and 12.2 ± 2.4 at month 3 (p < 0.0001), MOCA scores improved from 18.2 ± 4.3 to 20.4 ± 4.7 at month 1 (p = 0.14), and 22.2 ± 7.6 at month 3 (p = 0.047). Mean ± SD weekly sessions performed by participants per month was 5.7 ± 5.8 and duration of sessions was 25.5 ± 16.2 min. Erratic internet connectivity negatively affected full compliance with the intervention, although satisfaction ratings by study participants were excellent. It is feasible to administer an m-health delivered physical therapy intervention in SSA, with high user satisfaction. Randomized trials to assess the efficacy and cost-effectiveness of this intervention are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

'Test n Treat (TnT)': a cluster-randomised feasibility trial of frequent, rapid-testing and same-day, on-site treatment to reduce rates of chlamydia in high-risk further education college students: statistical analysis plan.

Science.gov (United States)

Phillips, Rachel; Oakeshott, Pippa; Kerry-Barnard, Sarah; Reid, Fiona

2018-06-05

There are high rates of sexually transmitted infections (STIs) in ethnically diverse, sexually active students aged 16-24 years attending London further education (FE) colleges. However, uptake of chlamydia screening remains low. The TnT study aims to assess the feasibility of conducting a future trial in FE colleges to investigate if frequent, rapid, on-site testing and treatment (TnT) reduces chlamydia rates. This article presents the statistical analysis plan for the main study publication as approved and signed off by the Trial Management Group prior to the first data extraction for the final report. TnT is a cluster-randomised feasibility trial conducted over 7 months with parallel qualitative and economic assessments. Colleges will be randomly allocated into the intervention (TnT) or the control group (no TnT). Six FE colleges in London will be included. At each college for 2 days, 80 consecutive sexually active students aged 16-24 years (total 480 students across all six colleges) will be recruited from public areas and asked to provide baseline samples. One and 4 months after recruitment intervention colleges will be visited on two consecutive days by the TnT team where participating students will be texted and invited to come for same-day, on-site, rapid chlamydia testing and, if positive, treatment. Participants in the control colleges will receive 'thank you' texts 1 and 4 months after recruitment. Seven months after recruitment, participants from both groups will be invited to complete questionnaires and provide samples for TnT. All samples will be tested, and same-day treatment offered to participants with positive results. Key feasibility outcomes include: recruitment rates, testing and treatment uptake rates (at 1 and 4 months) and follow-up rates (at 7 months). ISRCTN 58038795 . Registered on 31 August 2016.

The Vaginal Acquisition and Dissemination of HIV-1 Infection in a Novel Transgenic Mouse Model Is Facilitated by Coinfection with Herpes Simplex Virus 2 and Is Inhibited by Microbicide Treatment.

Science.gov (United States)

Seay, Kieran; Khajoueinejad, Nazanin; Zheng, Jian Hua; Kiser, Patrick; Ochsenbauer, Christina; Kappes, John C; Herold, Betsy; Goldstein, Harris

2015-09-01

Epidemiological studies have demonstrated that herpes simplex virus 2 (HSV-2) infection significantly increases the risk of HIV-1 acquisition, thereby contributing to the expanding HIV-1 epidemic. To investigate whether HSV-2 infection directly facilitates mucosal HIV-1 acquisition, we used our transgenic hCD4/R5/cT1 mouse model which circumvents major entry and transcription blocks preventing murine HIV-1 infection by targeting transgenic expression of human CD4, CCR5, and cyclin T1 genes to CD4(+) T cells and myeloid-committed cells. Productive infection of mucosal leukocytes, predominantly CD4(+) T cells, was detected in all hCD4/R5/cT1 mice intravaginally challenged with an HIV-1 infectious molecular clone, HIV-Du151.2env-NLuc, which expresses an env gene (C.Du151.2) cloned from an acute heterosexually infected woman and a NanoLuc luciferase reporter gene. Lower genital tract HIV-1 infection after HIV-Du151.2env-NLuc intravaginal challenge was increased ~4-fold in hCD4/R5/cT1 mice coinfected with HSV-2. Furthermore, HIV-1 dissemination to draining lymph nodes was detected only in HSV-2-coinfected mice. HSV-2 infection stimulated local infiltration and activation of CD4(+) T cells and dendritic cells, likely contributing to the enhanced HIV-1 infection and dissemination in HSV-2-coinfected mice. We then used this model to demonstrate that a novel gel containing tenofovir disoproxil fumarate (TDF), the more potent prodrug of tenofovir (TFV), but not the TFV microbicide gel utilized in the recent CAPRISA 004, VOICE (Vaginal and Oral Interventions to Control the Epidemic), and FACTS 001 clinical trials, was effective as preexposure prophylaxis (PrEP) to completely prevent vaginal HIV-1 infection in almost half of HSV-2-coinfected mice. These results also support utilization of hCD4/R5/cT1 mice as a highly reproducible immunocompetent preclinical model to evaluate HIV-1 acquisition across the female genital tract. Multiple epidemiological studies have reported that

Impact of incident and prevalent herpes simplex virus-2 infection on the incidence of HIV-1 infection among commercial sex workers in South Africa

CSIR Research Space (South Africa)

Ramjee, G

2005-07-01

Full Text Available This study investigated the impact of prevalent and incident HSV-2 infection on the incidence of HIV-1 infection in a cohort of female commercial sex workers in KwaZulu-Natal, South Africa. Prior to a vaginal microbicide trial, 416 women were...

Raising the profile of pilot and feasibility studies in relation to the development, evaluation and implementation of patient-reported outcome measures.

OpenAIRE

Jones, GL

2017-01-01

This editorial introduces a new special series on the pilot and feasibility testing of patient-reported outcome measures (PROMs) in the on-line open access journal Pilot and Feasibility Studies. Pilot and feasibility studies are typically implemented to address issues of uncertainty before undertaking a larger definitive study such as a randomised controlled trial or large scale survey. This editorial considers the role that such pilot and feasibility testing plays in relation to the developm...

Feasibility of a Psychosocial Rehabilitation Intervention to Enhance the Involvement of Relatives in Cancer Rehabilitation: Pilot Study for a Randomized Controlled Trial

DEFF Research Database (Denmark)

L, Ledderer; KI, Cour; O, Mogensen

2013-01-01

. We developed an innovative rehabilitation program to be offered to the patient and a relative as a pair. Objective The aim of the present pilot study was to examine the feasibility of the intervention in a randomized controlled trial (RCT) and to evaluate the impact on quality of life. Methods...... significant difference was observed between the intervention and the control group. Pairs reported that the time of inclusion was inconvenient and that rehabilitation ought to meet their changing needs. Conclusions The pilot study showed that it may be difficult to conduct an RCT of a psychosocial...... rehabilitation intervention for pairs, and difficulties with inclusion and drop out have to be addressed. Interventions need to be carefully developed and tested before evaluating an effect in a large-scale study....

Storytelling in the Early Bereavement Period to Reduce Emotional Distress Among Surrogates Involved in a Decision to Limit Life Support in the ICU: A Pilot Feasibility Trial.

Science.gov (United States)

Barnato, Amber E; Schenker, Yael; Tiver, Greer; Dew, Mary Amanda; Arnold, Robert M; Nunez, Eduardo R; Reynolds, Charles F

2017-01-01

Surrogate decision makers involved in decisions to limit life support for an incapacitated patient in the ICU have high rates of adverse emotional health outcomes distinct from normal processes of grief and bereavement. Narrative self-disclosure (storytelling) reduces emotional distress after other traumatic experiences. We sought to assess the feasibility, acceptability, and tolerability of storytelling among bereaved surrogates involved in a decision to limit life support in the ICU. Pilot single-blind trial. Five ICUs across three hospitals within a single health system between June 2013 and November 2014. Bereaved surrogates of ICU patients. Storytelling and control conditions involved printed bereavement materials and follow-up assessments. Storytelling involved a single 1- to 2-hour home or telephone visit by a trained interventionist who elicited the surrogate's story. The primary outcomes were feasibility (rates of enrollment, intervention receipt, 3- and 6-mo follow-up), acceptability (closed and open-ended end-of-study feedback at 6 mo), and tolerability (acute mental health services referral). Of 53 eligible surrogates, 32 (60%) consented to treatment allocation. Surrogates' mean age was 55.5 (SD, 11.8), and they were making decisions for their parent (47%), spouse (28%), sibling (13%), child (3%), or other relation (8%). We allocated 14 to control and 18 to storytelling, 17 of 18 (94%) received storytelling, 14 of 14 (100%) and 13 of 14 (94%) control subjects and 16 of 18 (89%) and 17 of 18 (94%) storytelling subjects completed their 3- and 6-month telephone assessments. At 6 months, nine of 13 control participants (69%) and 16 of 17 storytelling subjects (94%) reported feeling "better" or "much better," and none felt "much worse." One control subject (8%) and one storytelling subject (6%) said that the study was burdensome, and one control subject (8%) wished they had not participated. No subjects required acute mental health services referral. A

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention.

Science.gov (United States)

Palanee-Phillips, Thesla; Schwartz, Katie; Brown, Elizabeth R; Govender, Vaneshree; Mgodi, Nyaradzo; Kiweewa, Flavia Matovu; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Naidoo, Sarita; Pather, Arendevi; Phillip, Jessica; Husnik, Marla J; van der Straten, Ariane; Soto-Torres, Lydia; Baeten, Jared

2015-01-01

Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22-31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention.

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention.

Directory of Open Access Journals (Sweden)

Thesla Palanee-Phillips

Full Text Available Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges.ASPIRE (A Study to Prevent Infection with a Ring for Extended Use is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial.Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22-31 and the majority (59% were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64% reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis.African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention.

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention

Science.gov (United States)

Palanee-Phillips, Thesla; Schwartz, Katie; Brown, Elizabeth R.; Govender, Vaneshree; Mgodi, Nyaradzo; Kiweewa, Flavia Matovu; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Naidoo, Sarita; Pather, Arendevi; Phillip, Jessica; Husnik, Marla J.; van der Straten, Ariane; Soto-Torres, Lydia; Baeten, Jared

2015-01-01

Introduction Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. Methods ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. Results Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18–45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22–31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. Conclusions African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention. PMID:26061040

Continuous Postoperative Pericardial Flushing: A Pilot Study on Safety, Feasibility, and Effect on Blood Loss

Directory of Open Access Journals (Sweden)

Johan S.J. Manshanden

2015-09-01

Conclusions: CPPF after cardiac surgery was found to be safe and feasible in this experimental setting. The clinically relevant effect on blood loss needs to be confirmed in a randomized clinical trial.

Conductive Education as a Method of Stroke Rehabilitation: A Single Blinded Randomised Controlled Feasibility Study

Directory of Open Access Journals (Sweden)

Judith Bek

2016-01-01

Full Text Available Background. Conductive Education for stroke survivors has shown promise but randomised evidence is unavailable. This study assessed the feasibility of a definitive randomised controlled trial to evaluate efficacy. Methods. Adult stroke survivors were recruited through local community notices. Those completing the baseline assessment were randomised using an online program and group allocation was independent. Intervention group participants received 10 weekly 1.5-hour sessions of Conductive Education at the National Institute of Conductive Education in Birmingham, UK. The control group participants attended two group meetings. The study evaluated the feasibility of recruitment procedures, delivery of the intervention, retention of participants, and appropriateness of outcome measures and data collection methods. Independent assessments included the Barthel Index, the Stroke Impact Scale, the Timed Up and Go test, and the Hospital Anxiety and Depression Scale. Results. Eighty-two patients were enrolled; 77 completed the baseline assessment (46 men, mean age 62.1 yrs. and were randomised. 70 commenced the intervention (n=37 or an equivalent waiting period (n=33. 32/37 completed the 10-week training and 32/33 the waiting period. There were no missing items from completed questionnaires and no adverse events. Discussion. Recruitment, intervention, and assessment methods worked well. Transport issues for intervention and assessment appointments require review. Conclusion. A definitive trial is feasible. This trial is registered with ISRCTN84064492.

Contrast-enhanced ultra-high-field liver MRI: A feasibility trial

Energy Technology Data Exchange (ETDEWEB)

Umutlu, Lale, E-mail: Lale.Umutlu@uk-essen.de [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Bitz, Andreas K.; Maderwald, Stefan; Orzada, Stephan; Kinner, Sonja; Kraff, Oliver; Brote, Irina; Ladd, Susanne C.; Schroeder, Tobias; Forsting, Michael; Antoch, Gerald; Ladd, Mark E. [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Quick, Harald H. [Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Institute of Medical Physics, University Nuernberg-Erlangen (Germany); Lauenstein, Thomas C. [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany)

2013-05-15

The aim of this study was to investigate the feasibility of dynamic contrast-enhanced 7 T MRI of the liver using an eight-channel radiofrequency (RF) transmit/receive body-coil. 16 healthy subjects were examined on a 7 T MR system utilizing a custom-built eight-channel RF body-coil suitable for RF-shimming. The following data were acquired: (1) steady state free precession imaging, (2) T2w turbo spin echo imaging, (3) T1w in and opposed-phase imaging, (4) T1w 3D FLASH images pre-contrast and in arterial, portal-venous and venous phase and (5) a fat-saturated pre- and post-contrast 2D FLASH sequence. Visual evaluation of (1) the delineation of liver vasculature, (2) the overall image quality, and (3) artifact presence and consequent image impairment was performed. SNR of the liver parenchyma was measured for the contrast-enhanced 2D and 3D FLASH sequences. For statistical analysis, a Wilcoxon-Rank Test was used. Best delineation of non-enhanced liver vasculature and overall image quality was found for 2D FLASH MRI, with only slight improvement in vessel conspicuity after the application of contrast media. T2-weighted TSE imaging remained strongly impaired, falling short of diagnostic relevance and precluding a clinical application. Our results demonstrate the feasibility and diagnostic potential of dedicated contrast-enhanced 7 T liver MRI as well as the potential for non-contrast-enhanced angiographic application.

Design Dilemma: The Debate over Using Placebos in Cancer Clinical Trials

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Many patients and researchers assert that in cancer clinical trials, placebos are inappropriate and that all participants should receive active treatment. But with the emergence of molecularly targeted anticancer agents, some cancer researchers believe placebo-controlled trials are now feasible and, in some cases, necessary.

Feasibility and effectiveness of the baby friendly community initiative in rural Kenya: study protocol for a randomized controlled trial.

Science.gov (United States)

Kimani-Murage, Elizabeth W; Kimiywe, Judith; Kabue, Mark; Wekesah, Frederick; Matiri, Evelyn; Muhia, Nelson; Wanjohi, Milka; Muriuki, Peterrock; Samburu, Betty; Kanyuira, James N; Young, Sera L; Griffiths, Paula L; Madise, Nyovani J; McGarvey, Stephen T

2015-09-28

Interventions promoting optimal infant and young child nutrition could prevent a fifth of under-5 deaths in countries with high mortality. Poor infant and young child feeding practices are widely documented in Kenya, with potential detrimental effects on child growth, health and survival. Effective strategies to improve these practices are needed. This study aims to pilot implementation of the Baby Friendly Community Initiative (BFCI), a global initiative aimed at promoting optimal infant and young child feeding practices, to determine its feasibility and effectiveness with regards to infant feeding practices, nutrition and health outcomes in a rural setting in Kenya. The study, employing a cluster-randomized trial design, will be conducted in rural Kenya. A total of 12 clusters, constituting community units within the government's Community Health Strategy, will be randomized, with half allocated to the intervention and the other half to the control arm. A total of 812 pregnant women and their respective children will be recruited into the study. The mother-child pairs will be followed up until the child is 6 months old. Recruitment will last approximately 1 year from January 2015, and the study will run for 3 years, from 2014 to 2016. The intervention will involve regular counseling and support of mothers by trained community health workers and health professionals on maternal, infant and young child nutrition. Regular assessment of knowledge, attitudes and practices on maternal, infant and young child nutrition will be done, coupled with assessment of nutritional status of the mother-child pairs and morbidity for the children. Statistical methods will include analysis of covariance, multinomial logistic regression and multilevel modeling. The study is funded by the NIH and USAID through the Program for Enhanced Research (PEER) Health. Findings from the study outlined in this protocol will inform potential feasibility and effectiveness of a community

ESCAPS study protocol: a feasibility randomised controlled trial of 'Early electrical stimulation to the wrist extensors and wrist flexors to prevent the post-stroke complications of pain and contractures in the paretic arm'.

Science.gov (United States)

Fletcher-Smith, Joanna C; Walker, Dawn-Marie; Sprigg, Nikola; James, Marilyn; Walker, Marion F; Allatt, Kate; Mehta, Rajnikant; Pandyan, Anand D

2016-01-04

Approximately 70% of patients with stroke experience impaired arm function, which is persistent and disabling for an estimated 40%. Loss of function reduces independence in daily activities and impacts on quality of life. Muscles in those who do not recover functional movement in the stroke affected arm are at risk of atrophy and contractures, which can be established as early as 6 weeks following stroke. Pain is also common. This study aims to evaluate the feasibility of a randomised controlled trial to test the efficacy and cost-effectiveness of delivering early intensive electrical stimulation (ES) to prevent post-stroke complications in the paretic upper limb. This is a feasibility randomised controlled trial (n=40) with embedded qualitative studies (patient/carer interviews and therapist focus groups) and feasibility economic evaluation. Patients will be recruited from the Stroke Unit at the Nottingham University Hospitals National Health Service (NHS) Trust within 72 h after stroke. Participants will be randomised to receive usual care or usual care and early ES to the wrist flexors and extensors for 30 min twice a day, 5 days a week for 3 months. The initial treatment(s) will be delivered by an occupational therapist or physiotherapist who will then train the patient and/or their nominated carer to self-manage subsequent treatments. This study has been granted ethical approval by the National Research Ethics Service, East Midlands Nottingham1 Research Ethics Committee (ref: 15/EM/0006). To our knowledge, this is the first study of its kind of the early application (within 72 h post-stroke) of ES to both the wrist extensors and wrist flexors of stroke survivors with upper limb impairment. The results will inform the design of a definitive randomised controlled trial. Dissemination will include 2 peer-reviewed journal publications and presentations at national conferences. ISRCTN1648908; Pre-results. Clinicaltrials.gov ID: NCT02324634. Published by the BMJ

Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain.

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Bennett, Michael I; Johnson, Mark I; Brown, Sarah R; Radford, Helen; Brown, Julia M; Searle, Robert D

2010-04-01

This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain. Cancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial. Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

Contraceptive Use and Pregnancy Incidence Among Women Participating in an HIV Prevention Trial.

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Akello, Carolyne A; Bunge, Katherine E; Nakabiito, Clemensia; Mirembe, Brenda G; Fowler, Mary Glenn; Mishra, Anupam; Marrazzo, Jeanne; Chirenje, Zvavahera M; Celum, Connie; Balkus, Jennifer E

2017-06-01

Recent HIV prevention trials required use of effective contraceptive methods to fulfill eligibility for enrollment. We compared pregnancy rates in a subset of participants enrolled in the Microbicide Trials Network protocol (MTN-003), a randomized trial of chemoprophylaxis to prevent HIV acquisition among women aged 18-45 years who initiated depot medroxyprogesterone acetate (DMPA) or combined oral contraceptives (COCs) at enrollment, relative to those already using DMPA or COCs. Data were analyzed from MTN-003 participants from Uganda. Before enrollment, information on contraceptive type and initiation date was obtained. Urine pregnancy tests were performed at monthly follow-up visits. Cox proportional hazards models were used to compare pregnancy incidence among new users (initiated ≤60 days before enrollment) and established users (initiated >60 days before enrollment). Of 322 women enrolled, 296 were COC or DMPA users, 82 (28%) were new users, and 214 (72%) were established users. Pregnancy incidence was higher among new contraceptive users compared to established users (20.70% vs. 10.55%; adjusted hazard ratio [HR] = 1.66; 95% confidence interval [95% CI] 0.93-2.96). Among DMPA users, pregnancy incidence was 10.20% in new users versus 3.48% in established users (HR = 2.56; 95% CI 0.86-7.65). Among new COC users, pregnancy incidence was 42.67% in new users versus 23.67% in established COC users (adjusted HR = 1.74; 95% CI 0.87-3.48). New contraceptive users, regardless of method, at the Uganda MTN-003 site had an increased pregnancy risk compared to established users, which may be due to contraceptive initiation primarily for trial eligibility. New users may benefit from intensive contraceptive counseling and additional contraceptive options, including longer acting reversible contraceptives.

Feasibility, design and conduct of a pragmatic randomized controlled trial to reduce overweight and obesity in children: The electronic games to aid motivation to exercise (eGAME study

Directory of Open Access Journals (Sweden)

Rodgers Anthony

2009-05-01

Full Text Available Abstract Background Childhood obesity has reached epidemic proportions in developed countries. Sedentary screen-based activities such as video gaming are thought to displace active behaviors and are independently associated with obesity. Active video games, where players physically interact with images onscreen, may have utility as a novel intervention to increase physical activity and improve body composition in children. The aim of the Electronic Games to Aid Motivation to Exercise (eGAME study is to determine the effects of an active video game intervention over 6 months on: body mass index (BMI, percent body fat, waist circumference, cardio-respiratory fitness, and physical activity levels in overweight children. Methods/Design Three hundred and thirty participants aged 10–14 years will be randomized to receive either an active video game upgrade package or to a control group (no intervention. Discussion An overview of the eGAME study is presented, providing an example of a large, pragmatic randomized controlled trial in a community setting. Reflection is offered on key issues encountered during the course of the study. In particular, investigation into the feasibility of the proposed intervention, as well as robust testing of proposed study procedures is a critical step prior to implementation of a large-scale trial. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12607000632493

Feasibility of personalised remote long-term follow-up of people with cochlear implants: a randomised controlled trial.

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Cullington, Helen; Kitterick, Padraig; Weal, Mark; Margol-Gromada, Magdalena

2018-04-20

Substantial resources are required to provide lifelong postoperative care to people with cochlear implants. Most patients visit the clinic annually. We introduced a person-centred remote follow-up pathway, giving patients telemedicine tools to use at home so they would only visit the centre when intervention was required. To assess the feasibility of comparing a remote care pathway with the standard pathway in adults using cochlear implants. Two-arm randomised controlled trial. Randomisation used a minimisation approach, controlling for potential confounding factors. Participant blinding was not possible, but baseline measures occurred before allocation. University of Southampton Auditory Implant Service: provider of National Health Service care. 60 adults who had used cochlear implants for at least 6 months. Control group (n=30) followed usual care pathway.Remote care group (n=30) received care remotely for 6 months incorporating: home hearing in noise test, online support tool and self-adjustment of device (only 10 had compatible equipment). Primary: change in patient activation; measured using the Patient Activation Measure.Secondary: change in hearing and quality of life; qualitative feedback from patients and clinicians. One participant in the remote care group dropped out. The remote care group showed a greater increase in patient activation than the control group. Changes in hearing differed between the groups. The remote care group improved on the Triple Digit Test hearing test; the control group perceived their hearing was worse on the Speech, Spatial and Qualities of Hearing Scale questionnaire. Quality of life remained unchanged in both groups. Patients and clinicians were generally positive about remote care tools and wanted to continue. Adults with cochlear implants were willing to be randomised and complied with the protocol. Personalised remote care for long-term follow-up is feasible and acceptable, leading to more empowered patients. ISRCTN14644286

OS7.7 Feasibility and toxicity of concomitant radiochemotherapy with vincristine in adult patients with medulloblastoma - results from the NOA-07 trial

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Seidel, C.; Reimers, C.; Beier, D.; Pietsch, T.; Warmuth-Metz, M.; Bogdahn, U.; Kortmann, R.; Hau, P.

2016-01-01

Abstract Introduction: Medulloblastoma is a tumor of the cerebellum that is rare in adults with an incidence of about 0.6 cases per million per year. In children the introduction of chemotherapy with cisplatin, lomustine and vincristine in combination with craniospinal radiotherapy led to a significant improvement of overall survival. In adults, this regimen was never prospectively investigated in a clinical trial. Methods. The NOA-07 trial is a prospective single arm Phase II study to evaluate toxicity of craniospinal irradiation (1.6 Gy/35.2 Gy, posterior fossa boost 1.8 Gy/55.0 Gy) in combination with vincristine (1.5 mg/m2 weekly, ceiling dose 2.0 mg) followed by adjuvant chemotherapy with a maximum 8 of 6-weekly cycles of cisplatin (70 mg/m2, day 1), lomustine (75 mg/m2, day 1) and vincristine (1.5 g/m2, ceiling dose 2.0 mg, day 1, 8, 15) in adults with medulloblastoma. Here, we report on feasibility and toxicity of the concomitant radiochemotherapy. Results. 30 patients with medulloblastoma were recruited in 15 German centers. Radiotherapy was completed in all patients. Treatment interruptions occurred in 3/30 patients (toxicity related: 2, compliance: 1). Leukopenia was the major toxicity with grade 3 and 4 (CTC Version 3.0) occurring in 11 of 30 patients and 1 of 30 patients, respectively. Grade 3 to 4 thrombocytopenia occurred in 1 patient. Grade 3 to 4 infections occurred in 3 patients. Polyneuropathy due to vincristine was the most prevalent adverse event (Grade 1: 5, Grade 2: 4, Grade 3: 5 of 30 patients). Frequent but less severe toxicities involved sickness, dermatitis and alopecia. Conclusion. Concomitant radiochemotherapy with vincristine was feasible in adults with medulloblastoma. Leukopenia and polyneuropathy are major complications, pointing out that polyneuropathy occurs already early in treatment after application of only 1 to 6 doses in a substantial number of patients. Toxicity of the complete treatment protocol including

In Vitro Cross-Resistance Profiles of Rilpivirine, Dapivirine, and MIV-150, Nonnucleoside Reverse Transcriptase Inhibitor Microbicides in Clinical Development for the Prevention of HIV-1 Infection.

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Giacobbi, Nicholas S; Sluis-Cremer, Nicolas

2017-07-01

Rilpivirine (RPV), dapivirine (DPV), and MIV-150 are in development as microbicides. It is not known whether they will block infection of circulating nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant human immunodeficiency virus type 1 (HIV-1) variants. Here, we demonstrate that the activity of DPV and MIV-150 is compromised by many resistant viruses containing single or double substitutions. High DPV genital tract concentrations from DPV ring use may block replication of resistant viruses. However, MIV-150 genital tract concentrations may be insufficient to inhibit many resistant viruses, including those harboring K103N or Y181C. Copyright © 2017 American Society for Microbiology.

Perceptions among Dutch men who have sex with men and their willingness to use rectal microbicides and oral pre-exposure prophylaxis to reduce HIV risk--a preliminary study.

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Marra, Elske; Hankins, Catherine A

2015-01-01

Oral pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) tablets and topical PrEP or microbicides containing ARV drugs could help to reduce HIV incidence. These methods hold promise for men who have sex with men (MSM) who are at higher risk of acquiring HIV. This mixed-methods study in the Netherlands explored perceptions of MSM and their willingness to use oral PrEP and rectal microbicides (RM) if made available. Recruited through social media (Facebook and Twitter), 108 MSM completed online questionnaires. Seven of them consented to discuss the survey results in semi-structured interviews. Survey participants preferred a RM that could be applied before and after anal intercourse (60.8%) to daily oral PrEP (20.3%). This preference was based on anticipated user friendliness, hypothetically fewer expected adverse events, and perceptions that RM would be less likely to be confused with ARVs for treatment. Those who preferred oral PrEP had stronger beliefs in the effectiveness of pills, perceived its use as easy, and viewed not requiring sexual partner awareness as advantages. No predictive factors were found for the choice of one prevention method over the other. Although Dutch MSM perceive both oral and topical PrEP positively, many barriers exist to the introduction of these products in the Netherlands. These include lack of regulatory approval of oral PrEP, no proven efficacy as yet for RM, and strong HIV stigma within the MSM population. In-depth qualitative research is needed to further explore the perceptions of MSM to inform implementation of programmes should these HIV prevention methods become available.

Important considerations for feasibility studies in physical activity research involving persons with multiple sclerosis: a scoping systematic review and case study.

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Learmonth, Yvonne C; Motl, Robert W

2018-01-01

Much research has been undertaken to establish the important benefits of physical activity in persons with multiple sclerosis (MS). There is disagreement regarding the strength of this research, perhaps because the majority of studies on physical activity and its benefits have not undergone initial and systematic feasibility testing. We aim to address the feasibility processes that have been examined within the context of physical activity interventions in MS. A systematic scoping review was conducted based on a literature search of five databases to identify feasibility processes described in preliminary studies of physical activity in MS. We read and extracted methodology from each study based on the following feasibility metrics: process (e.g. recruitment), resource (e.g. monetary costs), management (e.g. personnel time requirements) and scientific outcomes (e.g. clinical/participant reported outcome measures). We illustrate the use of the four feasibility metrics within a randomised controlled trial of a home-based exercise intervention in persons with MS. Twenty-five studies were identified. Resource feasibility (e.g. time and resources) and scientific outcomes feasibility (e.g. clinical outcomes) methodologies were applied and described in many studies; however, these metrics have not been systematically addressed. Metrics related to process feasibility (e.g. recruitment) and management feasibility (e.g. human and data management) are not well described within the literature. Our case study successfully enabled us to address the four feasibility metrics, and we provide new information on management feasibility (i.e. estimate data completeness and estimate data entry) and scientific outcomes feasibility (i.e. determining data collection materials appropriateness). Our review highlights the existing research and provides a case study which assesses important metrics of study feasibility. This review serves as a clarion call for feasibility trials that will

A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study.

Directory of Open Access Journals (Sweden)

Ian Mcgowan

Full Text Available The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK, and pharmacodynamics (PD of three tenofovir (TFV gels for rectal application. The vaginal formulation (VF gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF gel was also evaluated in the CHARM-01 study.Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial.All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively. Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection.All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection.ClinicalTrials.gov NCT01575405.

The Feasibility of Real-Time Intraoperative Performance Assessment With SIMPL (System for Improving and Measuring Procedural Learning): Early Experience From a Multi-institutional Trial.

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Bohnen, Jordan D; George, Brian C; Williams, Reed G; Schuller, Mary C; DaRosa, Debra A; Torbeck, Laura; Mullen, John T; Meyerson, Shari L; Auyang, Edward D; Chipman, Jeffrey G; Choi, Jennifer N; Choti, Michael A; Endean, Eric D; Foley, Eugene F; Mandell, Samuel P; Meier, Andreas H; Smink, Douglas S; Terhune, Kyla P; Wise, Paul E; Soper, Nathaniel J; Zwischenberger, Joseph B; Lillemoe, Keith D; Dunnington, Gary L; Fryer, Jonathan P

Intraoperative performance assessment of residents is of growing interest to trainees, faculty, and accreditors. Current approaches to collect such assessments are limited by low participation rates and long delays between procedure and evaluation. We deployed an innovative, smartphone-based tool, SIMPL (System for Improving and Measuring Procedural Learning), to make real-time intraoperative performance assessment feasible for every case in which surgical trainees participate, and hypothesized that SIMPL could be feasibly integrated into surgical training programs. Between September 1, 2015 and February 29, 2016, 15 U.S. general surgery residency programs were enrolled in an institutional review board-approved trial. SIMPL was made available after 70% of faculty and residents completed a 1-hour training session. Descriptive and univariate statistics analyzed multiple dimensions of feasibility, including training rates, volume of assessments, response rates/times, and dictation rates. The 20 most active residents and attendings were evaluated in greater detail. A total of 90% of eligible users (1267/1412) completed training. Further, 13/15 programs began using SIMPL. Totally, 6024 assessments were completed by 254 categorical general surgery residents (n = 3555 assessments) and 259 attendings (n = 2469 assessments), and 3762 unique operations were assessed. There was significant heterogeneity in participation within and between programs. Mean percentage (range) of users who completed ≥1, 5, and 20 assessments were 62% (21%-96%), 34% (5%-75%), and 10% (0%-32%) across all programs, and 96%, 75%, and 32% in the most active program. Overall, response rate was 70%, dictation rate was 24%, and mean response time was 12 hours. Assessments increased from 357 (September 2015) to 1146 (February 2016). The 20 most active residents each received mean 46 assessments by 10 attendings for 20 different procedures. SIMPL can be feasibly integrated into surgical training programs

Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia

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Hajeer, Ali H.; Luke, Thomas; Raviprakash, Kanakatte; Balkhy, Hanan; Johani, Sameera; Al-Dawood, Abdulaziz; Al-Qahtani, Saad; Al-Omari, Awad; Al-Hameed, Fahad; Hayden, Frederick G.; Fowler, Robert; Bouchama, Abderrezak; Shindo, Nahoko; Al-Khairy, Khalid; Carson, Gail; Taha, Yusri; Sadat, Musharaf; Alahmadi, Mashail

2016-01-01

We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness. PMID:27532807

So you want to conduct a randomised trial? Learnings from a 'failed' feasibility study of a Crisis Resource Management prompt during simulated paediatric resuscitation.

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Teis, Rachel; Allen, Jyai; Lee, Nigel; Kildea, Sue

2017-02-01

No study has tested a Crisis Resource Management prompt on resuscitation performance. We conducted a feasibility, unblinded, parallel-group, randomised controlled trial at one Australian paediatric hospital (June-September 2014). Eligible participants were any doctor, nurse, or nurse manager who would normally be involved in a Medical Emergency Team simulation. The unit of block randomisation was one of six scenarios (3 control:3 intervention) with or without a verbal prompt. The primary outcomes tested the feasibility and utility of the intervention and data collection tools. The secondary outcomes measured resuscitation quality and team performance. Data were analysed from six resuscitation scenarios (n=49 participants); three control groups (n=25) and three intervention groups (n=24). The ability to measure all data items on the data collection tools was hindered by problems with the recording devices both in the mannequins and the video camera. For a pilot study, greater training for the prompt role and pre-briefing participants about assessment of their cardio-pulmonary resuscitation quality should be undertaken. Data could be analysed in real time with independent video analysis to validate findings. Two cameras would strengthen reliability of the methods. Copyright © 2016 College of Emergency Nursing Australasia. Published by Elsevier Ltd. All rights reserved.