WorldWideScience

Sample records for open randomized non-inferiority

  1. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa

    NARCIS (Netherlands)

    Olivennes, F.; Trew, G.; Borini, A.; Broekmans, F.; Arriagada, P.; Warne, D. W.; Howles, C. M.

    2015-01-01

    In this randomized, controlled, open-label, phase IV study, ovarian response after a follitropin alfa starting dose determined by the CONSORT calculator was compared with a standard dose (150 IU). Normo-ovulatory women (aged 18-34 years) eligible for assisted reproductive techniques were recruited (

  2. Simplification to abacavir/lamivudine + atazanavir maintains viral suppression and improves bone and renal biomarkers in ASSURE, a randomized, open label, non-inferiority trial.

    Directory of Open Access Journals (Sweden)

    David A Wohl

    Full Text Available OBJECTIVE: Simplification of antiretroviral therapy in patients with suppressed viremia may minimize long-term adverse effects. The study's primary objective was to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV was virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC+ATV/r over 24 weeks in a population of virologically suppressed, HIV-1 infected patients. DESIGN: This open-label, multicenter, non-inferiority study enrolled antiretroviral experienced, HIV-infected adults currently receiving a regimen of TDF/FTC+ATV/r for ≥ 6 months with no history of virologic failure and whose HIV-1 RNA had been ≤ 75 copies/mL on 2 consecutive measurements including screening. Patients were randomized 1 ∶ 2 to continue current treatment or simplify to ABC/3TC+ATV. METHODS: The primary endpoint was the proportion of patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic Response (TLOVR algorithm. Secondary endpoints included alternative measures of efficacy, adverse events (AEs, and fasting lipids. Exploratory endpoints included inflammatory, coagulation, bone, and renal biomarkers. RESULTS: After 24 weeks, ABC/3TC+ATV (n = 199 was non-inferior to TDF/FTC+ATV/r (n = 97 by both the primary analysis (87% in both groups and all secondary efficacy analyses. Rates of grade 2-4 AEs were similar between the two groups (40% vs 37%, respectively, but an excess of hyperbilirubinemia made the rate of grade 3-4 laboratory abnormalities higher in the TDF/FTC+ATV/r group (30% compared with the ABC/3TC+ATV group (13%. Lipid levels were stable except for HDL cholesterol, which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers improved significantly between baseline and Week 24 in patients taking ABC/3TC+ATV, and the difference between groups was significant at Week 24. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment

  3. Intravenous pamidronate versus oral and intravenous clodronate in bone metastatic breast cancer: a randomized, open-label, non-inferiority Phase III trial

    Directory of Open Access Journals (Sweden)

    von Au A

    2016-07-01

    Full Text Available Alexandra von Au,1 Eva Milloth,1 Ingo Diel,2 Stefan Stefanovic,1 Andre Hennigs,1 Markus Wallwiener,1 Joerg Heil,1 Michael Golatta,1 Joachim Rom,1 Christof Sohn,1 Andreas Schneeweiss,1 Florian Schuetz,1 Christoph Domschke1 1Breast Unit, Department of Gynecology and Obstetrics, Heidelberg University Hospital, Heidelberg, 2CGG Clinic – Centrum für ganzheitliche Gynäkologie Mannheim, Mannheim, Germany Purpose: Patients with metastasized breast cancer often suffer from discomfort caused by metastatic bone disease. Thus, osteoprotection is an important part of therapy in breast cancer metastasized to bone, and bisphosphonates (BPs are a major therapeutic option. In this study, our objectives were to compare the side effects of oral versus intravenous BP treatment and to assess their clinical effectiveness.  Patients and methods: In this prospective randomized, open-label, non-inferiority trial, we enrolled breast cancer patients with at least one bone metastasis and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were randomly assigned to one of the three treatment groups: A, 60 mg pamidronate intravenously q3w; B-iv, 900 mg clodronate intravenously q3w; and B-o, 2,400 mg oral clodronate daily. Assessments were performed at baseline and every 3 months thereafter.  Results: Between 1995 and 1999, 321 patients with confirmed bone metastases from breast cancer were included in the study. At first follow-up, gastrointestinal (GI tract side effects were most common, and adverse effects on the GI tract were more frequent in the oral treatment group (P=0.002 and P<0.001, respectively. There were no statistically significant differences among the treatment cohorts for other documented side effects (skin, serum electrolytes, urinary tract, immune system, and others. No significant differences in clinical effectiveness of BP treatment, as assessed by pain score, were detected among the groups; however, pathologic fractures

  4. A Randomized, Open-Label, Non-Inferiority Study of Intravenous Iron Isomaltoside 1,000 (Monofer) Compared With Oral Iron for Treatment of Anemia in IBD (PROCEED)

    DEFF Research Database (Denmark)

    Reinisch, Walter; Staun, Michael; Tandon, Rakesh K

    2013-01-01

    In the largest head-to-head comparison between an oral and an intravenous (IV) iron compound in patients with inflammatory bowel disease (IBD) so far, we strived to determine whether IV iron isomaltoside 1,000 is non-inferior to oral iron sulfate in the treatment of iron deficiency anemia (IDA)....

  5. Randomized Controlled Non-Inferiority Trial of a Telehealth Treatment for Chronic Stuttering: The Camperdown Program

    Science.gov (United States)

    Carey, Brenda; O'Brian, Sue; Onslow, Mark; Block, Susan; Jones, Mark; Packman, Ann

    2010-01-01

    Background: Although there are treatments that can alleviate stuttering in adults for clinically significant periods, in Australia there are barriers to the accessibility and availability of best-practice treatment. Aims: This parallel group, non-inferiority randomized controlled trial with multiple blinded outcome assessments investigated whether…

  6. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Roberto Hegg

    Full Text Available OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI for the rate of neutropenia between the two groups (12.61% was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa’s approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯.

  7. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    Science.gov (United States)

    Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie

    2016-01-01

    OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

  8. Psychotherapy for depression in older veterans via telemedicine: a randomised, open-label, non-inferiority trial.

    Science.gov (United States)

    Egede, Leonard E; Acierno, Ron; Knapp, Rebecca G; Lejuez, Carl; Hernandez-Tejada, Melba; Payne, Elizabeth H; Frueh, B Christopher

    2015-08-01

    Many older adults with major depression, particularly veterans, do not have access to evidence-based psychotherapy. Telemedicine could increase access to best-practice care for older adults facing barriers of mobility, stigma, and geographical isolation. We aimed to establish non-inferiority of behavioural activation therapy for major depression delivered via telemedicine to same-room care in largely male, older adult veterans. In this randomised, controlled, open-label, non-inferiority trial, we recruited veterans (aged ≥58 years) meeting DSM-IV criteria for major depressive disorder from the Ralph H Johnson Veterans Affairs Medical Center and four associated community outpatient-based clinics in the USA. We excluded actively psychotic or demented people, those with both suicidal ideation and clear intent, and those with substance dependence. The study coordinator randomly assigned participants (1:1; block size 2-6; stratified by race; computer-generated randomisation sequence by RGK) to eight sessions of behavioural activation for depression either via telemedicine or in the same room. The primary outcome was treatment response according to the Geriatric Depression Scale (GDS) and Beck Depression Inventory (BDI; defined as a 50% reduction in symptoms from baseline at 12 months), and Structured Clinical Interview for DSM-IV, clinician version (defined as no longer being diagnosed with major depressive disorder at 12 months follow-up), in the per-protocol population (those who completed at least four treatment sessions and for whom all outcome measurements were done). Those assessing outcomes were masked. The non-inferiority margin was 15%. This trial is registered with ClinicalTrials.gov, number NCT00324701. Between April 1, 2007, and July 31, 2011, we screened 780 patients, and the study coordinator randomly assigned participants to either telemedicine (120 [50%]) or same-room treatment (121 [50%]). We included 100 (83%) patients in the per-protocol analysis in

  9. Design of Phase II Non-inferiority Trials.

    Science.gov (United States)

    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.

  10. Homeopathic Individualized Q-Potencies versus Fluoxetine for Moderate to Severe Depression: Double-Blind, Randomized Non-Inferiority Trial

    Directory of Open Access Journals (Sweden)

    U. C. Adler

    2011-01-01

    Full Text Available Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day−1 (up to 40 mg day−1 in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654 and 8th weeks (P = .965 of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine were −3.04 (95% CI −6.95, 0.86 and −2.4 (95% CI −6.05, 0.77 at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of

  11. Telephone Cognitive-Behavioral Therapy for Adolescents With Obsessive-Compulsive Disorder: A Randomized Controlled Non-inferiority Trial

    Science.gov (United States)

    Turner, Cynthia M.; Mataix-Cols, David; Lovell, Karina; Krebs, Georgina; Lang, Katie; Byford, Sarah; Heyman, Isobel

    2014-01-01

    Objective Many adolescents with obsessive-compulsive disorder (OCD) do not have access to evidence-based treatment. A randomized controlled non-inferiority trial was conducted in a specialist OCD clinic to evaluate the effectiveness of telephone cognitive-behavioral therapy (TCBT) for adolescents with OCD compared to standard clinic-based, face-to-face CBT. Method Seventy-two adolescents, aged 11 through 18 years with primary OCD, and their parents were randomized to receive specialist TCBT or CBT. The intervention provided differed only in the method of treatment delivery. All participants received up to 14 sessions of CBT, incorporating exposure with response prevention (E/RP), provided by experienced therapists. The primary outcome measure was the Children’s Yale–Brown Obsessive-Compulsive Scale (CY-BOCS). Blind assessor ratings were obtained at midtreatment, posttreatment, 3-month, 6-month, and 12-month follow-up. Results Intent-to-treat analyses indicated that TCBT was not inferior to face-to-face CBT at posttreatment, 3-month, and 6-month follow-up. At 12-month follow-up, there were no significant between-group differences on the CY-BOCS, but the confidence intervals exceeded the non-inferiority threshold. All secondary measures confirmed non-inferiority at all assessment points. Improvements made during treatment were maintained through to 12-month follow-up. Participants in each condition reported high levels of satisfaction with the intervention received. Conclusion TCBT is an effective treatment and is not inferior to standard clinic-based CBT, at least in the midterm. This approach provides a means of making a specialized treatment more accessible to many adolescents with OCD. Clinical trial registration information–Evaluation of telephone-administered cognitive-behaviour therapy (CBT) for young people with obsessive-compulsive disorder (OCD); http://www.controlled-trials.com; ISRCTN27070832. PMID:25457928

  12. A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer

    NARCIS (Netherlands)

    Groenewoud, E. R.; Cohlen, B. J.; Al-Oraiby, A.; Brinkhuis, E. A.; Broekmans, F. J M; De Bruin, J. P.; Van Den Dool, G.; Fleisher, K.; Friederich, J.; Goddijn, M.; Hoek, A.; Hoozemans, D. A.; Kaaijk, E. M.; Koks, C. A M; Laven, J. S E; Van Der Linden, P. J Q; Manger, A. P.; Slappendel, E.; Spinder, T.; Kollen, B. J.; Macklon, N. S.

    2016-01-01

    studyquestion: Are live birth rates (LBRs) after artificial cycle frozen-thawed embryo transfer (AC-FET) non-inferior to LBRs after modified natural cycle frozen-thawed embryo transfer (mNC-FET)? summaryanswer: AC-FET is non-inferior to mNC-FET with regard to LBRs, clinical and ongoing pregnancy rat

  13. A non-inferiority, individually randomized trial of intermittent screening and treatment versus intermittent preventive treatment in the control of malaria in pregnancy

    DEFF Research Database (Denmark)

    Tagbor, Harry; Cairns, Matthew; Bojang, Kalifa

    2015-01-01

    BACKGROUND: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women...... (ISTp) is an alternative approach. METHODS AND FINDINGS: An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana......-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women...

  14. Azathioprine versus beta interferons for relapsing-remitting multiple sclerosis: a multicentre randomized non-inferiority trial.

    Directory of Open Access Journals (Sweden)

    Luca Massacesi

    Full Text Available For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of β interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct β interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available β interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ≥ 2 relapses in the last 2 years were randomly assigned to azathioprine or β interferons. The primary outcome was annualized relapse rate ratio (RR over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150 were randomized in 2 groups (77 azathioprine, 73 β interferons. At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 β interferons. Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19-0.37 in the azathioprine and 0.39 (95% CI 0.30-0.51 in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as β interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01. MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 β interferons. Annualized new T2 lesion rate was 0.76 (95% CI 0.61-0.95 in the azathioprine and 0.69 (95% CI 0.54-0.88 in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03 in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of β interferons for

  15. Azathioprine versus Beta Interferons for Relapsing-Remitting Multiple Sclerosis: A Multicentre Randomized Non-Inferiority Trial

    Science.gov (United States)

    Massacesi, Luca; Tramacere, Irene; Amoroso, Salvatore; Battaglia, Mario A.; Benedetti, Maria Donata; Filippini, Graziella; La Mantia, Loredana; Repice, Anna; Solari, Alessandra; Tedeschi, Gioacchino; Milanese, Clara

    2014-01-01

    For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of β interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct β interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available β interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ≥2 relapses in the last 2 years) were randomly assigned to azathioprine or β interferons. The primary outcome was annualized relapse rate ratio (RR) over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150) were randomized in 2 groups (77 azathioprine, 73 β interferons). At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 β interferons). Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19–0.37) in the azathioprine and 0.39 (95% CI 0.30–0.51) in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as β interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01). MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 β interferons). Annualized new T2 lesion rate was 0.76 (95% CI 0.61–0.95) in the azathioprine and 0.69 (95% CI 0.54–0.88) in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03) in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of

  16. Antibiotics in third molar extraction; are they really necessary: A non-inferiority randomized controlled trial

    Science.gov (United States)

    Arora, Ankit; Roychoudhury, Ajoy; Bhutia, Ongkila; Pandey, Sandeep; Singh, Surender; Das, Bimal K.

    2014-01-01

    Introduction: Antibiotic resistance is now a serious problem, although it was not so only a few years ago. The need of the hour is to give clear evidence of the efficacy of antibiotic use, or lack thereof, to the surgeon for a procedure as common as mandibular third molar surgery. Aim: This study aimed to evaluate whether postoperative combined amoxicillin and clavulanic acid in mandibular third molar extraction is effective in preventing inflammatory complications. Study and Design: The study was structured as a prospective randomized double-blind placebo-controlled clinical trial. Materials and Methods: A study was designed wherein the 96 units (two bilaterally similar impacted mandibular third molars per head in 48 patients) were randomly assigned to two treatment groups (Group I and Group II). Each patient served as his/her own control. Each patient received 625 mg of combined amoxicillin and clavulanic acid 1 h before surgery. In the case of third molars belonging to Group I, 625 mg of combined amoxicillin and clavulanic acid TDS was continued for 3 days; in Group II, placebo in similar-looking packs was continued for 3 days. The patients were evaluated on the third and seventh postoperative days for signs of clinical infection and for microbial load evaluation. Statistical Analysis: The data between the two groups were statistically analyzed by the two-tailed Fisher's exact test, with a 95% confidence interval. Results: The difference was not statistically significant between the test group and the control group with regard to erythema, dehiscence, swelling, pain, trismus, and infection based on microbial load. The data were statistically significant for alveolar osteitis, with the occurrence of alveolar osteitis (14.58%) in the placebo group. Conclusion: Postoperative antibiotics are recommended only for patients undergoing contaminated, long-duration surgery. PMID:25937728

  17. Microbiological Evaluation of the Efficacy of Soapy Water to Clean Hands: A Randomized, Non-Inferiority Field Trial

    Science.gov (United States)

    Amin, Nuhu; Pickering, Amy J.; Ram, Pavani K.; Unicomb, Leanne; Najnin, Nusrat; Homaira, Nusrat; Ashraf, Sania; Abedin, Jaynal; Islam, M. Sirajul; Luby, Stephen P.

    2014-01-01

    We conducted a randomized, non-inferiority field trial in urban Dhaka, Bangladesh among mothers to compare microbial efficacy of soapy water (30 g powdered detergent in 1.5 L water) with bar soap and water alone. Fieldworkers collected hand rinse samples before and after the following washing regimens: scrubbing with soapy water for 15 and 30 seconds; scrubbing with bar soap for 15 and 30 seconds; and scrubbing with water alone for 15 seconds. Soapy water and bar soap removed thermotolerant coliforms similarly after washing for 15 seconds (mean log10 reduction = 0.7 colony-forming units [CFU], P soap). Increasing scrubbing time to 30 seconds did not improve removal (P > 0.05). Scrubbing hands with water alone also reduced thermotolerant coliforms (mean log10 reduction = 0.3 CFU, P = 0.046) but was less efficacious than scrubbing hands with soapy water. Soapy water is an inexpensive and microbiologically effective cleansing agent to improve handwashing among households with vulnerable children. PMID:24914003

  18. Deficient reporting and interpretation of non-inferiority randomized clinical trials in HIV patients: a systematic review.

    Directory of Open Access Journals (Sweden)

    Adrian V Hernandez

    Full Text Available OBJECTIVES: Non-inferiority (NI randomized clinical trials (RCTs commonly evaluate efficacy of new antiretroviral (ARV drugs in human immunodeficiency virus (HIV patients. Their reporting and interpretation have not been systematically evaluated. We evaluated the reporting of NI RCTs in HIV patients according to the CONSORT statement and assessed the degree of misinterpretation of RCTs when NI was inconclusive or not established. DESIGN: Systematic review. METHODS: PubMed, Web of Science, and Scopus were reviewed until December 2011. Selection and extraction was performed independently by three reviewers. RESULTS: Of the 42 RCTs (n = 21,919; range 41-3,316 selected, 23 were in ARV-naïve and 19 in ARV-experienced patients. Twenty-seven (64% RCTs provided information about prior RCTs of the active comparator, and 37 (88% used 2-sided CIs. Two thirds of trials used a NI margin between 10 and 12%, although only 12 explained the method to determine it. Blinding was used in 9 studies only. The main conclusion was based on both intention-to-treat (ITT and per protocol (PP analyses in 5 trials, on PP analysis only in 4 studies, and on ITT only in 31 studies. Eleven of 16 studies with NI inconclusive or not established highlighted NI or equivalence, and distracted readers with positive secondary results. CONCLUSIONS: There is poor reporting and interpretation of NI RCTs performed in HIV patients. Maximizing the reporting of the method of NI margin determination, use of blinding and both ITT and PP analyses, and interpreting negative NI according to actual primary findings will improve the understanding of results and their translation into clinical practice.

  19. Rilonacept in the treatment of subacromial bursitis: A randomized, non-inferiority, unblinded study versus triamcinolone acetonide.

    Science.gov (United States)

    Carroll, Matthew B; Motley, Spencer A; Wohlford, Susanna; Ramsey, Bryan C

    2015-12-01

    Subacromial bursitis is caused by inflammation of the bursa that separates the superior surface of the supraspinatus tendon from the overlying coraco-acromial ligament and acromion. While multiple cytokines are implicated, interleukin-1 beta appears to play a prominent role. Rilonacept, an interleukin-1 trap, may be an alternative to corticosteroid injection for the management of this condition. This single center, randomized, non-inferiority, unblinded study recruited 33 subjects over 9 months. Twenty subjects received 160mg intrabursal injection of rilonacept and 13 received a 6mL mixture of lidocaine, bupivacaine, and 80mg triamcinolone acetonide. QuickDASH, subject reported pain, and adverse events were recorded at time of injection, 2 days later, 2 weeks later, and 4 weeks later. Primary outcome was improvement in QuickDASH 4 weeks post-injection. Secondary outcomes were improvement in subject reported pain and occurrence of adverse events at 4 weeks. Both study groups were equally matched for age, gender, ethnicity, and site of bursa injection. Both medications demonstrated a statistically significant improvement in QuickDASH 4 weeks post-injection, but triamcinolone acetonide injection offered greater improvement (P=0.004). Both medications demonstrated improvement in subject reported pain but between group comparison at 4 weeks showed that triamcinolone was superior (P=0.044). No statistically significant differences in adverse events were noted between groups, but subjects who received rilonacept experienced more episodes of diarrhea and headache. While improvement in QuickDASH and pain was noted with a single intrabursal injection of rilonacept at 4 weeks, injection with triamcinolone acetonide was more efficacious. This trial was registered with www.clinicaltrials.gov (NCT01830699). Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  20. Comparison of the neutral and retracted shoulder positions for infraclavicular subclavian venous catheterization: a randomized, non-inferiority trial.

    Science.gov (United States)

    Kim, H J; Jung, S H; Min, J; Hong, D M; Jeon, Y; Bahk, J-H

    2013-08-01

    There are controversies regarding the most efficient shoulder position during infraclavicular subclavian venous catheterization. We hypothesized that, regarding the success rate of subclavian venous catheterization, the neutral shoulder position would not be inferior to the retracted shoulder position. A total of 362 patients who underwent elective surgery were randomly assigned to two groups: those who underwent subclavian venous catheterizations in the neutral shoulder position (neutral group, n=181) or in the retracted shoulder position (retracted group, n=181). In the retracted group, a 1 litre saline bag was placed longitudinally beneath the spinal column between the scapulae to allow the shoulders to fall into a 'retracted' position. The incidence of failures to place the central venous catheters and complications such as arterial puncture, pneumothorax, or haemothorax were recorded. The success rates were 95.6% (173/181) in the neutral group and 96.1% (174/181) in the retracted group. The difference of 0.5% was within the prespecified non-inferiority margin of 5% with a P-value of 0.017 [two-sided 95% confidence interval (CI), -0.036 to 0.047; upper limit of the 95% CI, 0.040]. There were four catheterization failures (2.2%) in the neutral group and two failures (1.1%) in the retracted group. Complication rates were not significantly different between the neutral and retracted groups [3/181 (1.7%) vs 4/181 (2.2%) for arterial punctures and 1/181 (0.6%) vs 1/181 (0.6%) for pneumothorax]. The neutral shoulder position was as effective as the retracted shoulder position for infraclavicular subclavian venous catheterization. Shoulder retraction does not appear to be necessary for the infraclavicular subclavian venous catheterization. ClinicalTrials.gov, NCT01368692.

  1. Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial.

    Directory of Open Access Journals (Sweden)

    Christina S Polyak

    2016-01-01

    Full Text Available Cotrimoxazole (CTX prophylaxis is recommended by the World Health Organization (WHO for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART. The threshold for CTX discontinuation following ART is undefined in resource-limited settings.Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥ 18 mo with CD4 count > 350 cells/mm3 in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea and mortality. Incidence rate ratios (IRRs were estimated using Poisson regression. Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72% were women, and 442 (88% reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52-3.38; p < 0.001, driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52-241.02; p = 0.001. Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82-2.27, and IRR = 1.43, 95% CI 0.54-3.75, respectively. Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX

  2. Pyronaridine-Artesunate versus Chloroquine in Patients with Acute Plasmodium vivax Malaria: A Randomized, Double-Blind, Non-Inferiority Trial

    OpenAIRE

    Yi Poravuth; Duong Socheat; Ronnatrai Rueangweerayut; Chirapong Uthaisin; Aung Pyae Phyo; Neena Valecha; B. H. Krishnamoorthy Rao; Emiliana Tjitra; Asep Purnama; Isabelle Borghini-Fuhrer; Stephan Duparc; Chang-Sik Shin; Lawrence Fleckenstein

    2011-01-01

    BACKGROUND: New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria. METHODS AND FINDINGS: This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3-≤ 60 years) with microscopically confirmed P. vivax mono-infection ...

  3. Non-inferiority of short-term urethral catheterization following fistula repair surgery: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Barone Mark A

    2012-03-01

    Full Text Available Abstract Background A vaginal fistula is a devastating condition, affecting an estimated 2 million girls and women across Africa and Asia. There are numerous challenges associated with providing fistula repair services in developing countries, including limited availability of operating rooms, equipment, surgeons with specialized skills, and funding from local or international donors to support surgeries and subsequent post-operative care. Finding ways of providing services in a more efficient and cost-effective manner, without compromising surgical outcomes and the overall health of the patient, is paramount. Shortening the duration of urethral catheterization following fistula repair surgery would increase treatment capacity, lower costs of services, and potentially lower risk of healthcare-associated infections among fistula patients. There is a lack of empirical evidence supporting any particular length of time for urethral catheterization following fistula repair surgery. This study will examine whether short-term (7 day urethral catheterization is not worse by more than a minimal relevant difference to longer-term (14 day urethral catheterization in terms of incidence of fistula repair breakdown among women with simple fistula presenting at study sites for fistula repair service. Methods/Design This study is a facility-based, multicenter, non-inferiority randomized controlled trial (RCT comparing the new proposed short-term (7 day urethral catheterization to longer-term (14 day urethral catheterization in terms of predicting fistula repair breakdown. The primary outcome is fistula repair breakdown up to three months following fistula repair surgery as assessed by a urinary dye test. Secondary outcomes will include repair breakdown one week following catheter removal, intermittent catheterization due to urinary retention and the occurrence of septic or febrile episodes, prolonged hospitalization for medical reasons, catheter blockage, and

  4. A Non-Inferiority, Individually Randomized Trial of Intermittent Screening and Treatment versus Intermittent Preventive Treatment in the Control of Malaria in Pregnancy.

    Directory of Open Access Journals (Sweden)

    Harry Tagbor

    Full Text Available The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT and treatment of positive women (ISTp is an alternative approach.An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana. Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL. ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW, anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]. The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]. Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]. More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups.Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria

  5. Efficacy and safety of loxoprofen hydrogel patch versus loxoprofen tablet in patients with knee osteoarthritis: a randomized controlled non-inferiority trial.

    Science.gov (United States)

    Mu, Rong; Bao, Chun-de; Chen, Zhi-wei; Zheng, Yi; Wang, Guo-chun; Zhao, Dong-bao; Hu, Shao-xian; Li, Yu-jun; Shao, Zeng-wu; Zhang, Zhi-yi; Xiao, Wei-guo; Zhang, Weiya; Li, Zhan-guo

    2016-01-01

    This study is aimed at comparing the efficacy and safety of loxoprofen sodium hydrogel patch (LX-P) with loxoprofen sodium tablet (LX-T) in patients with knee osteoarthritis (OA). One hundred sixty-nine patients were enrolled in a randomized, controlled, double-blind, double-dummy, multicenter, non-inferiority trial of LX-P. Patients were randomly assigned to either LX-P or LX-T groups for a 4-week treatment. The primary efficacy endpoint was the proportion of patients with an overall improvement of ≥50%, and the secondary efficacy endpoint was the proportion of patients with an improvement of ≥25% from baseline in each of the seven main symptoms. The non-inferiority trial was based on a power of 80% and significance level of 2.5% with a non-inferiority margin of -10%. In both intention-to-treat (ITT) and per-protocol (PP) analyses, LX-P was as effective as LX-T in regard to the primary endpoint. In the ITT analysis, the difference between the two groups was 12.6% [95% confidence interval, -1.7 to 26.9%]. No significant differences were found between the two groups in any of the secondary efficacy outcomes. A lower incidence of adverse events was observed in LX-P group; however, the difference was not statistically significant. No serious adverse events were reported in the LX-P group, whereas one case was reported in LX-T group. Based on the present study, topical loxoprofen patch was non-inferior to oral loxoprofen in patients with knee osteoarthritis.

  6. Active management of the third stage of labour without controlled cord traction: a randomized non-inferiority controlled trial

    Directory of Open Access Journals (Sweden)

    Derman Richard

    2009-01-01

    Full Text Available Abstract Background The third stage of labour refers to the period between birth of the baby and complete expulsion of the placenta. Some degree of blood loss occurs after the birth of the baby due to separation of the placenta. This period is a risky period because uterus may not contract well after birth and heavy blood loss can endanger the life of the mother. Active management of the third stage of labour (AMTSL reduces the occurrence of severe postpartum haemorrhage by approximately 60–70%. Active management consists of several interventions packaged together and the relative contribution of each of the components is unknown. Controlled cord traction is one of those components that require training in manual skill for it to be performed appropriately. If it is possible to dispense with controlled cord traction without losing efficacy it would have major implications for effective management of the third stage of labour at peripheral levels of health care. Objective The primary objective is to determine whether the simplified package of oxytocin 10 IU IM/IV is not less effective than the full AMTSL package. Methods A hospital-based, multicentre, individually randomized controlled trial is proposed. The hypothesis tested will be a non-inferiority hypothesis. The aim will be to determine whether the simplified package without CCT, with the advantage of not requiring training to acquire the manual skill to perform this task, is not less effective than the full AMTSL package with regard to reducing blood loss in the third stage of labour. The simplified package will include uterotonic (oxytocin 10 IU IM injection after delivery of the baby and cord clamping and cutting at approximately 3 minutes after birth. The full package will include the uterotonic injection (oxytocin 10 IU IM, controlled cord traction following observation of uterine contraction and cord clamping and cutting at approximately 3 minutes after birth. The primary outcome

  7. Randomized single-blinded non-inferiority trial of 7 mg/kg pentamidine isethionate versus 4 mg/kg pentamidine isethionate for cutaneous leishmaniaisis in Suriname.

    Directory of Open Access Journals (Sweden)

    Ricardo V P F Hu

    2015-03-01

    Full Text Available Standard treatment of cutaneous leishmaniasis (CL in Suriname entails three injections of pentamidine isethionate (PI 4 mg/kg per injection in 7 days (7 day regimen. Compliance to treatment is low and may contribute to increasing therapy failure. A 3 day regimen, including 2 injections of 7 mg/kg in 3 days may increase compliance.In a randomized, single-blinded non-inferiority trial conducted in Suriname, 84 CL patients received the 7 day regimen and 79 CL patients received the 3 day regimen. Primary objective was the proportion of patients clinically cured at 6 weeks follow-up. Secondary objectives were clinical cure at 12 weeks follow-up; parasitological cure at 6 and 12 weeks; adverse and drug related toxicity events recorded one week after the end of treatment and health related quality of life. The non-inferiority margin was set at 15%, 1 sided test, α = 0.1.At 6 weeks follow-up 31 (39% patients in the 3 day regimen and 41 (49% patients in the 7 day regimen were clinically cured. Intention to treat (ITT analyses showed that the difference in proportion clinically cured was -9.6% (90% Confidence Interval (CI: -22.3% to 3.2%. Per protocol (PP analysis showed that the difference in proportion clinically cured was 0.2% (90% CI: -14.6% to 15.2%. ITT analysis showed that the difference in proportion parasitological cured at 6 weeks was -15.2% (90% CI:-28.0% to -2.5%. PP analyses showed similar results. Non-inferiority could not be concluded for all adverse and toxicological events.We cannot conclude that the 3 day regimen is non-inferior to the 7 day regimen regarding proportion clinically and parasitological cured. Therefore there is no evidence to change the current standard practice of the 7 day regimen for the treatment of CL in Suriname.

  8. Randomized prospective study showing the non-inferiority of tenofovir to entecavir in treatment-naïve chronic hepatitis B patients.

    Science.gov (United States)

    Koike, Kazuhiko; Suyama, Kazuaki; Ito, Hiroshi; Itoh, Hiroshi; Sugiura, Wataru

    2017-04-03

    The study aimed to evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) and entecavir hydrate (ETV) in nucleos(t)ide analog (NA)-naïve Japanese chronic hepatitis B (CHB) patients. This multicenter, randomized, double-blinded study assessing the efficacy and safety of TDF 300 mg and ETV 0.5 mg in NA-naïve CHB subjects was carried out from November 2011 to November 2014, and funded by GlaxoSmithKline. The subjects were assigned to the TDF arm or ETV arm in a 2:1 ratio. The primary efficacy endpoint was the non-inferiority of TDF to ETV at week 24. A total of 166 subjects (TDF arm, 110; ETV arm, 56) were enrolled. The change (mean ± SE) in serum hepatitis B virus (HBV)-DNA levels from baseline to week 24 was -4.63 ± 0.044 and -4.50 ± 0.063 log10 copies/mL in the TDF and ETV arms, respectively, indicating the non-inferiority of TDF to ETV (P < 0.0001). The proportion of subjects with undetectable HBV-DNA increased from 54 to 77% and 39 to 66% in the TDF and ETV arms with continuation of the treatment from week 24 to 48, respectively. Reduction in hepatitis B surface antigen level was greater in subjects with hepatitis B envelope antigen (+) and high alanine aminotransferase levels (≥80 IU/L). Prevalence of drug-related adverse events at week 48 was 20% and 18% in the TDF and ETV arms, respectively. The study is the first to report that TDF has non-inferiority to ETV in treatment effectiveness (lowering of serum HBV-DNA level) at week 24. ClinicalTrials.gov trial registration nos. NCT01480284 and GSK LOC115409. © 2017 The Japan Society of Hepatology.

  9. Immunogenicity and safety of a cell culture-based quadrivalent influenza vaccine in adults: A Phase III, double-blind, multicenter, randomized, non-inferiority study

    Science.gov (United States)

    Bart, Stephan; Cannon, Kevin; Herrington, Darrell; Mills, Richard; Forleo-Neto, Eduardo; Lindert, Kelly; Abdul Mateen, Ahmed

    2016-01-01

    ABSTRACT Quadrivalent influenza vaccines (QIVs), which include both B lineage strains, are expected to provide broader protection than trivalent influenza vaccines (TIVs). The non-inferiority, immunogenicity, and safety of a cell culture-based investigational QIVc and 2 TIVs (TIV1c, TIV2c), in adults (≥18 y), were evaluated in this Phase III, double-blind, multicenter study. A total of 2680 age-stratified subjects were randomized (2:1:1) to receive 1 dose of QIVc (n = 1335), TIV1c (n = 676), or TIV2c (n = 669). TIV1c (B/Yamagata) and TIV2c (B/Victoria) differed only in B strain lineage. The primary objective was to demonstrate non-inferiority of the hemagglutinin-inhibition antibody responses of QIVc against TIVc, 22 d post-vaccination. Secondary objectives included the evaluation of immunogenicity of QIVc and TIVc in younger (≥18 – <65 y) and older (≥65 y) adults. Hemagglutinin inhibition assays were performed at days 1 and 22. Solicited local and systemic adverse events (AEs) were monitored for 7 d post-vaccination, and unsolicited AEs and serious AEs until day 181. QIVc met the non-inferiority criteria for all 4 vaccine strains and demonstrated superiority for both influenza B strains over the unmatched B strain included in the TIV1c and TIV2c, when geometric mean titers and seroconversion rates with TIVc were compared at day 22. Between 48%–52% of subjects experienced ≥1 solicited AE, the most common being injection-site pain and headache. Serious AEs were reported by ≤1% of subjects, none were vaccine-related. The results indicate that QIVc is immunogenic and well tolerated in both younger and older adults. The immunogenicity and safety profiles of QIVc and TIVc were comparable at all ages evaluated. PMID:27322354

  10. Play distraction versus pharmacological treatment to reduce anxiety levels in children undergoing day surgery: a randomized controlled non-inferiority trial.

    Science.gov (United States)

    Al-Yateem, N; Brenner, M; Shorrab, A A; Docherty, C

    2016-07-01

    Perioperative experience can be one of the most distressful experiences in a child's life if not managed properly by healthcare professionals. Its consequences can extend well beyond surgery and recovery into the child's future life. Healthcare professionals have a responsibility to decrease the anxiety associated with this experience, improve the child's and the parent's experience and prevent negative consequences. This has traditionally been performed through pharmacological treatment which might have negative side effects. More developmentally appropriate distraction methods are currently being trialled globally to augment the evidence that supports their use as a similarly efficient alternative. The aim of this study was to explore the efficiency of storytelling, pictures and colouring activities as an anxiolytic intervention in comparison to the traditional pharmacological premedication technique in a non-inferiority study. A randomized non-inferiority controlled trial was carried out in 168 children scheduled for day surgery. Children's perioperative anxiety was assessed by a trained anaesthetist using the modified Yale Preoperative Assessment Scale and by parents using the State-Trait Anxiety Inventory for Children. Children's vital signs were also collected preoperatively during the induction period and during the recovery period. The primary endpoint, which is non-inferiority in terms of anxiety as per Yale Preoperative Assessment Scale survey between play distraction and preoperative medication, was met [average score 10.95 vs. 10.94, respectively, 95% confidence interval (-0.35; 0.37); P = 0.941]. Moreover, anxiety scores of both the intervention and the control group were quite comparable as per STAIC survey [20.90 vs. 20.73, respectively, 95% confidence interval (-0.52; 0.88); P = 0.708] and in terms of vital signs. The results indicate that the distraction technique employed can be considered as an efficient alternative to traditional

  11. Immunogenicity and safety of measles-mumps-rubella vaccine delivered by disposable-syringe jet injector in healthy Brazilian infants: a randomized non-inferiority study.

    Science.gov (United States)

    de Menezes Martins, Reinaldo; Curran, Birute; Maia, Maria de Lourdes Sousa; Ribeiro, Maria das Graças Tavares; Camacho, Luiz Antonio Bastos; da Silva Freire, Marcos; Yamamura, Anna Maya Yoshida; Siqueira, Marilda Mendonça; Lemos, Maria Cristina F; de Albuquerque, Elizabeth Maciel; von Doellinger, Vanessa dos Reis; Homma, Akira; Saganic, Laura; Jarrahian, Courtney; Royals, Michael; Zehrung, Darin

    2015-03-01

    This study aimed to determine if immunogenicity to measles-mumps-rubella vaccine delivered to infants via a disposable-syringe jet injector (DSJI) was non-inferior to that administered by needle and syringe (NS). Vaccination safety was evaluated, as were the use, performance, and acceptability of each delivery method. The DSJI was the PharmaJet 2009 generation-1 device (G1) and the vaccine was measles-mumps-rubella vaccine from Bio-Manguinhos. Five hundred eighty-two healthy Brazilian infants were randomized to receive vaccine via G1 or NS. Seroconversion rates against measles and mumps viruses in the G1 treatment group did not meet non-inferiority criteria when compared with the NS group; however, responses in the G1 group to rubella virus were non-inferior to those of NS vaccinees. Most adverse events were mild or moderate. Crying after injection was more frequent in the NS group, and local skin reactions were more common in the G1 group. Five serious adverse events were judged causally unrelated to treatment and all resolved. Parents/guardians expressed a strong preference for G1 over NS for their children. Vaccinators found the G1 easy to use but noted incomplete vaccine delivery in some cases. Although the G1 has been superseded by an updated device, our results are important for the continued improvement and evaluation of DSJIs, which have the potential to overcome many of the challenges and risks associated with needle-based injections worldwide. Recommendations for future DSJI clinical studies include rigorous training of vaccinators, quantitative measurement of wetness on the skin following injection, and regular monitoring of device and vaccinator performance.

  12. 5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study.

    Science.gov (United States)

    Baron, Ralf; Mayoral, Victor; Leijon, Göran; Binder, Andreas; Steigerwald, Ilona; Serpell, Michael

    2009-07-01

    To compare efficacy and safety of 5% lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN). This was a two-stage adaptive, randomized, open-label, multicentre, non-inferiority study. Data are reported from the initial 4-week comparative phase, in which adults with PHN or painful DPN received either topical 5% lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics. The primary endpoint was response rate at 4 weeks, defined as reduction averaged over the last three days from baseline of > or = 2 points or an absolute value of plaster and 61.5% receiving pregabalin were considered responders (corresponding numbers for the per protocol set, PPS: 65.3% vs. 62.0%). In PHN more patients responded to 5% lidocaine medicated plaster treatment than to pregabalin (PPS: 62.2% vs. 46.5%), while response was comparable for patients with painful DPN (PPS: 66.7% vs 69.1%). 30% and 50% reductions in NRS-3 scores were greater with 5% lidocaine medicated plaster than with pregabalin. Both treatments reduced allodynia severity. 5% lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN. PGIC and CGIC scores indicated greater improvement for 5% lidocaine medicated plaster treated patients with PHN. Improvements were comparable between treatments in painful DPN. Fewer patients administering 5% lidocaine medicated plaster experienced AEs (safety set, SAF: 18.7% vs. 46.4%), DRAEs (5.8% vs. 41.2%) and related discontinuations compared to patients taking pregabalin. 5% lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN. Within DPN, efficacy was comparable for both treatments. 5% lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and Qo

  13. Pyronaridine-artesunate versus chloroquine in patients with acute Plasmodium vivax malaria: a randomized, double-blind, non-inferiority trial.

    Directory of Open Access Journals (Sweden)

    Yi Poravuth

    Full Text Available BACKGROUND: New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria. METHODS AND FINDINGS: This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3-≤ 60 years with microscopically confirmed P. vivax mono-infection were randomized (1:1 to receive pyronaridine-artesunate (target dose 7.2:2.4 mg/kg to 13.8:4.6 mg/kg or chloroquine (standard dose once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100 with pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100 with chloroquine. Pyronaridine was non-inferior to chloroquine: treatment difference -0.5% (95%CI -2.6, 1.4, i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than -10%. Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with pyronaridine-artesunate (median 23.0 h versus chloroquine (32.0 h; p<0.0001, as was fever clearance time (median 15.9 h and 23.8 h, respectively; p = 0.0017. Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5% with pyronaridine-artesunate, 6.1% with chloroquine (p = 0.048, log-rank test. Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test. There were no deaths. Adverse events occurred in 92/228 (40.4% patients with pyronaridine-artesunate and 72/228 (31.6% with chloroquine. Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate. CONCLUSION: Pyronaridine-artesunate efficacy

  14. Pyronaridine-Artesunate versus Chloroquine in Patients with Acute Plasmodium vivax Malaria: A Randomized, Double-Blind, Non-Inferiority Trial

    Science.gov (United States)

    Poravuth, Yi; Socheat, Duong; Rueangweerayut, Ronnatrai; Uthaisin, Chirapong; Pyae Phyo, Aung; Valecha, Neena; Rao, B. H. Krishnamoorthy; Tjitra, Emiliana; Purnama, Asep; Borghini-Fuhrer, Isabelle; Duparc, Stephan; Shin, Chang-Sik; Fleckenstein, Lawrence

    2011-01-01

    Background New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria. Methods and Findings This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3–≤60 years) with microscopically confirmed P. vivax mono-infection were randomized (1∶1) to receive pyronaridine-artesunate (target dose 7.2∶2.4 mg/kg to 13.8∶4.6 mg/kg) or chloroquine (standard dose) once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100) with pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100) with chloroquine. Pyronaridine was non-inferior to chloroquine: treatment difference −0.5% (95%CI −2.6, 1.4), i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than −10%. Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with pyronaridine-artesunate (median 23.0 h) versus chloroquine (32.0 h; pestimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5% with pyronaridine-artesunate, 6.1% with chloroquine (p = 0.048, log-rank test). Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test). There were no deaths. Adverse events occurred in 92/228 (40.4%) patients with pyronaridine-artesunate and 72/228 (31.6%) with chloroquine. Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate. Conclusion Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine

  15. Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial.

    Science.gov (United States)

    Molenaar, Nina M; Brouwer, Marlies E; Bockting, Claudi L H; Bonsel, Gouke J; van der Veere, Christine N; Torij, Hanneke W; Hoogendijk, Witte J G; Duvekot, Johannes J; Burger, Huibert; Lambregtse-van den Berg, Mijke P

    2016-03-18

    Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist. 'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk. This study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority

  16. BASIC study: is intravaginal boric acid non-inferior to metronidazole in symptomatic bacterial vaginosis? Study protocol for a randomized controlled trial.

    Science.gov (United States)

    Zeron Mullins, Melinda; Trouton, Konia M

    2015-07-26

    Bacterial vaginosis is associated with increased transmission of sexually transmitted infections, preterm labor, post-surgical infections, and endometritis. Current treatment for symptomatic bacterial vaginosis includes antibiotics, such as metronidazole, which are 70-80 % effective at one month after treatment and result in high recurrence rates and secondary candida infections. Intravaginal boric acid has been used for over a hundred years to treat vaginal infections, such as bacterial vaginosis. Boric acid is inexpensive, accessible, and has shown to be an effective treatment for other infections, such as vaginal candidiasis. To date, there has been no clinical trial evaluation of boric acid effectiveness to treat bacterial vaginosis. The BASIC (Boric Acid, Alternate Solution for Intravaginal Colonization) trial is a randomized, double-blinded, multicenter study. The study will enroll a minimum of 240 women of 16-50 years of age who are symptomatic with bacterial vaginosis. Eligible participants will have Amsel and Nugent scores confirming bacterial vaginosis. Women who are pregnant or menopausal or have other active co-infections will be excluded. Consenting participants who meet exclusion and inclusion criteria will be randomly assigned to one of three treatment groups: boric acid, metronidazole, or an inert placebo. Self-administration of treatment intravaginally for 10 days will be followed by clinical assessment at 7 and 30 days (days 17 and 40, respectively) after the end of the treatment phase. Primary outcome is a non-inferiority, per-protocol comparison of the effectiveness of boric acid with that of metronidazole at day 17, as measured by the Nugent score in 16-50 year olds. Secondary outcomes include: non-inferiority, intention-to-treat comparison of effectiveness of boric acid with that of metronidazole at day 17, analysis for both per-protocol and intention-to-treat at day 40, and safety considerations, including adverse effects requiring patient

  17. A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

    Science.gov (United States)

    Youssef, M A; van Wely, M; Al-Inany, H; Madani, T; Jahangiri, N; Khodabakhshi, S; Alhalabi, M; Akhondi, M; Ansaripour, S; Tokhmechy, R; Zarandi, L; Rizk, A; El-Mohamedy, M; Shaeer, E; Khattab, M; Mochtar, M H; van der Veen, F

    2017-01-01

    In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Ongoing pregnancy rate was 12.8% (25/195) for mild

  18. Interchangeability of Quinvaxem during primary vaccination schedules: results from a phase IV, single-blind, randomized, controlled, single-center, non-inferiority study.

    Science.gov (United States)

    Capeding, Maria Rosario Z; Jica, Corina; Macura-Biegun, Anna; Rauscher, Martina; Alberto, Edison

    2014-02-07

    Combination vaccines against diphtheria, tetanus and pertussis (DTP) represent the core of childhood vaccination programs. Quinvaxem, a fully-liquid, pentavalent combination vaccine containing inactivated hepatitis B (HepB), Haemophilus influenzae type b (Hib) and whole-cell pertussis (wP) antigens, and tetanus and diphtheria toxoids, has been shown to be suitable for boosting children primed in infancy with another DTwP-HepB-Hib vaccine. This single-blind, randomized, controlled study was designed to demonstrate non-inferiority of a primary vaccination course (6-10-14 week schedule) of Tritanrix HB+Hib (first dose) and Quinvaxem (second/third doses) versus three doses of Quinvaxem with respect to the seroprotection/seroconversion rates for all antigens one month after vaccination course completion. Four hundred healthy subjects eligible for the local Expanded Program on Immunization were enrolled and equally randomized to the two treatment regimens. All subjects achieved seroprotection for tetanus and Hib, all except one for diphtheria, and all except two achieved seroconversion against Bordetella pertussis. Seroprotection against hepatitis B was achieved by 97.4% of Tritanrix HB+Hib followed by Quinvaxem and 94.9% of Quinvaxem subjects. Therefore, one month after vaccination course completion, seroprotection rates (seroconversion rate for B. pertussis) of Tritanrix HB+Hib followed by Quinvaxem were non-inferior to those elicited by Quinvaxem only, thus meeting the primary objective. Adverse events were comparable between the groups and were in line with the safety profile of the vaccines. The switch of vaccine had no apparent effect on safety endpoints. Our results support the use of Quinvaxem interchangeably with Tritanrix HB+Hib in a primary vaccination course and provides further evidence for the interchangeability of pentavalent vaccines (Clinical Trials.gov registry: NCT01357720). Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. The Impact of Covariate Adjustment at Randomization and Analysis For Binary Outcomes: Understanding Differences Between Superiority and Non-Inferiority Trials

    Science.gov (United States)

    Nicholas, Katherine; Yeatts, Sharon D; Zhao, Wenle; Ciolino, Jody; Borg, Keith; Durkalski, Valerie

    2015-01-01

    SUMMARY The question of when to adjust for important prognostic covariates often arises in the design of clinical trials, and there remain various opinions on whether to adjust during both randomization and analysis, at randomization alone, or at analysis alone. Furthermore, little is known about the impact of covariate adjustment in the context of non-inferiority (NI) designs. The current simulation-based research explores this issue in the NI setting, as compared to the typical superiority setting, by assessing the differential impact on power, type I error, and bias in the treatment estimate as well as its standard error, in the context of logistic regression under both simple and covariate adjusted permuted block randomization algorithms. In both the superiority and NI settings, failure to adjust for covariates that influence outcome in the analysis phase, regardless of prior adjustment at randomization, results in treatment estimates that are biased toward zero, with standard errors that are deflated. However, as no treatment difference is approached under the null hypothesis in superiority and under the alternative in NI, this results in decreased power and nominal or conservative (deflated) type I error in the context of superiority, but inflated power and type I error under NI. Results from the simulation study suggest that, regardless of the use of the covariate in randomization, it is appropriate to adjust for important prognostic covariates in analysis, as this yields nearly unbiased estimates of treatment as well as nominal type I error. PMID:25641057

  20. Self-refraction, ready-made glasses and quality of life among rural myopic Chinese children: a non-inferiority randomized trial.

    Science.gov (United States)

    Zhou, Zhongqiang; Chen, Tingting; Jin, Ling; Zheng, Dongxing; Chen, Shangji; He, Mingguang; Silver, Josh; Ellwein, Leon; Moore, Bruce; Congdon, Nathan G

    2017-09-01

    To study, for the first time, the effect of wearing ready-made glasses and glasses with power determined by self-refraction on children's quality of life. This is a randomized, double-masked non-inferiority trial. Children in grades 7 and 8 (age 12-15 years) in nine Chinese secondary schools, with presenting visual acuity (VA) ≤6/12 improved with refraction to ≥6/7.5 bilaterally, refractive error ≤-1.0 D and refraction (SR). Main study outcome was global score on the National Eye Institute Refractive Error Quality of Life-42 (NEI-RQL-42) after 2 months of wearing study glasses, comparing other groups with the U group, adjusting for baseline score. Only one child (0.18%) was excluded for anisometropia or astigmatism. A total of 426 eligible subjects (mean age 14.2 years, 84.5% without glasses at baseline) were allocated to U [103 (24.2%)], RM [113 (26.5%)], R [108 (25.4%)] and SR [102 (23.9%)] groups, respectively. Baseline and endline score data were available for 398 (93.4%) of subjects. In multiple regression models adjusting for baseline score, older age (p = 0.003) and baseline spectacle wear (p = 0.016), but not study group assignment, were significantly associated with lower final score. Quality of life wearing ready-mades or glasses based on self-refraction did not differ from that with cycloplegic refraction by an experienced optometrist in this non-inferiority trial. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  1. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial.

    Science.gov (United States)

    Goldstein, Joshua N; Refaai, Majed A; Milling, Truman J; Lewis, Brandon; Goldberg-Alberts, Robert; Hug, Bruce A; Sarode, Ravi

    2015-05-23

    Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures. The optimum means of VKA reversal has not been established in comparative clinical trials. We compared the efficacy and safety of four-factor prothrombin complex concentrate (4F-PCC) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures. In a multicentre, open-label, phase 3b randomised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure. We randomly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC (Beriplex/Kcentra/Confidex; CSL Behring, Marburg, Germany) or plasma, with dosing based on international normalised ratio (INR) and weight. The primary endpoint was effective haemostasis, and the co-primary endpoint was rapid INR reduction (≤1·3 at 0·5 h after infusion end). The analyses were intended to evaluate, in a hierarchical fashion, first non-inferiority (lower limit 95% CI greater than -10% for group difference) for both endpoints, then superiority (lower limit 95% CI >0%) if non-inferiority was achieved. Adverse events and serious adverse events were reported to days 10 and 45, respectively. This trial is registered at ClinicalTrials.gov, number NCT00803101. 181 patients were randomised (4F-PCC n=90; plasma n=91). The intention-to-treat efficacy population comprised 168 patients (4F-PCC, n=87; plasma, n=81). Effective haemostasis was achieved in 78 (90%) patients in the 4F-PCC group compared with 61 (75%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma (difference 14·3%, 95% CI 2·8-25·8). Rapid INR reduction was achieved in 48 (55%) patients in the 4F-PCC group compared with eight (10%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma

  2. Intradermally Administered Yellow Fever Vaccine at Reduced Dose Induces a Protective Immune Response: A Randomized Controlled Non-Inferiority Trial

    NARCIS (Netherlands)

    M.G. Roukens (Guy); A.C.Th.M. Vossen (Ann); P.J. Bredenbeek (Peter); J.T. van Dissel (Jaap); L.G. Visser

    2008-01-01

    textabstractBackground:Implementation of yellow fever vaccination is currently hampered by limited supply of vaccine. An alternative route of administration with reduced amounts of vaccine but without loss of vaccine efficacy would boost vaccination programmes.Methods and Findings:A randomized, cont

  3. Diabetes Care Protocol : effects on patient-important outcomes. A cluster randomized, non-inferiority trial in primary care

    NARCIS (Netherlands)

    Cleveringa, F. G. W.; Minkman, M. H.; Gorter, K. J.; van den Donk, M.; Rutten, G. E. H. M.

    2010-01-01

    P>Aims The Diabetes Care Protocol (DCP) combines task delegation, intensification of diabetes treatment and feedback. It reduces cardiovascular risk in Type 2 diabetes (T2DM) patients. This study determines the effects of DCP on patient-important outcomes. Methods A cluster randomized, non-inferiori

  4. Weekly azathioprine pulse versus daily azathioprine in the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study

    Directory of Open Access Journals (Sweden)

    Kaushal K Verma

    2015-01-01

    Full Text Available Background: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. Aims: To study the efficacy and safety of WAP and daily azathioprine in Parthenium dermatitis. Methods: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months. Patients were evaluated every month to assess the response to treatment and side effects. Results: The study included 32 patients in the weekly azathioprine group and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively completed the study. Twenty-three (92% patients on WAP and 21 (96% on daily azathioprine had a good or excellent response. The mean pretreatment clinical severity score decreased from 26.4 ± 14.5 to 4.7 ± 5.1 in the WAP group, and from 36.1 ± 18.1 to 5.7 ± 6.0 in the daily azathioprine group, which was statistically significant and comparable (P = 0.366. Patients on WAP had a higher incidence of adverse effects (P = 0.02. Limitations: The study had a small sample size and the amount of clobetasol propionate used in each patient was not determined, though it may not have affected the study outcome due to its comparable use in both groups. Conclusions: Azathioprine 300 mg weekly pulse and 100 mg daily dose are equally effective and safe in the treatment of Parthenium dermatitis.

  5. A randomized, non-inferiority trial comparing two bivalent killed, whole cell, oral cholera vaccines (Euvichol vs Shanchol) in the Philippines.

    Science.gov (United States)

    Baik, Yeong Ok; Choi, Seuk Keun; Olveda, Remigio M; Espos, Roberto A; Ligsay, Antonio D; Montellano, May B; Yeam, Jong Sun; Yang, Jae Seung; Park, Ju Yeon; Kim, Deok Ryun; Desai, Sachin N; Singh, Ajit Pal; Kim, Ick Young; Kim, Chan Wha; Park, Sue-nie

    2015-11-17

    Currently, there are two oral cholera vaccines (OCV) that are prequalified by the World Health Organization. Both (Dukoral and Shanchol) have been proven to be safe, immunogenic, and effective. As the global supply of OCV remains limited, we assessed the safety and immunogenicity of a new low cost, killed, bivalent OCV (Euvichol) in the Philippines. The randomized controlled trial was carried out in healthy Filipino adults and children. Two doses of either the current WHO prequalified OCV (Shanchol) or the same composition OCV being considered for WHO prequalification (Euvichol) were administered to participants. The pivotal study was conducted in total of 1263 healthy participants (777 adults and 486 children). No serious adverse reactions were elicited in either vaccine groups. Vibriocidal antibody responses to V. cholerae O1 Inaba following administration of two doses of Euvichol were non-inferior to those of Shanchol in adults (82% vs 76%) and children (87% vs 89%). Similar findings were observed for O1 Ogawa in adults (80% vs 74%) and children (91% vs 88%). A two dose schedule with Euvichol induces a strong vibriocidal response comparable to those elicited by the currently WHO prequalified OCV, Shanchol. Euvichol will be an oral cholera vaccine suitable for use in lower income countries, where cholera still has a significant economic and public health impact. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Single-session gamified virtual reality exposure therapy for spider phobia vs. traditional exposure therapy: study protocol for a randomized controlled non-inferiority trial.

    Science.gov (United States)

    Miloff, Alexander; Lindner, Philip; Hamilton, William; Reuterskiöld, Lena; Andersson, Gerhard; Carlbring, Per

    2016-02-02

    Traditional one-session exposure therapy (OST) in which a patient is gradually exposed to feared stimuli for up to 3 h in a one-session format has been found effective for the treatment of specific phobias. However, many individuals with specific phobia are reluctant to seek help, and access to care is lacking due to logistic challenges of accessing, collecting, storing, and/or maintaining stimuli. Virtual reality (VR) exposure therapy may improve upon existing techniques by facilitating access, decreasing cost, and increasing acceptability and effectiveness. The aim of this study is to compare traditional OST with in vivo spiders and a human therapist with a newly developed single-session gamified VR exposure therapy application with modern VR hardware, virtual spiders, and a virtual therapist. Participants with specific phobia to spiders (N = 100) will be recruited from the general public, screened, and randomized to either VR exposure therapy (n = 50) or traditional OST (n = 50). A behavioral approach test using in vivo spiders will serve as the primary outcome measure. Secondary outcome measures will include spider phobia questionnaires and self-reported anxiety, depression, and quality of life. Outcomes will be assessed using a non-inferiority design at baseline and at 1, 12, and 52 weeks after treatment. VR exposure therapy has previously been evaluated as a treatment for specific phobias, but there has been a lack of high-quality randomized controlled trials. A new generation of modern, consumer-ready VR devices is being released that are advancing existing technology and have the potential to improve clinical availability and treatment effectiveness. The VR medium is also particularly suitable for taking advantage of recent phobia treatment research emphasizing engagement and new learning, as opposed to physiological habituation. This study compares a market-ready, gamified VR spider phobia exposure application, delivered using consumer VR hardware, with

  7. Telemedicine-supported transition of stable coronary artery disease patients from tertiary to primary health care facilities: protocol for a randomized non-inferiority trial.

    Science.gov (United States)

    Batista, Joanna d'Arc Lyra; Furtado, Mariana Vargas; Katz, Natan; Agostinho, Milena Rodrigues; Neto, Brasil Silva; Harzheim, Erno; Polanczyk, Carisi Anne

    2016-07-07

    Many Brazilian patients with complex diseases who are treated in tertiary referral clinics have been stable for long periods. The main needs of these patients involve monitoring of risk factors and review of drug prescriptions, which could be satisfactorily done in primary care facilities. The goal of this protocol is to evaluate the safety and effectiveness of telemedicine services to support the transition of patients with stable chronic coronary artery disease from the tertiary to the primary level of care. We designed a randomized non-inferiority protocol that will include 280 patients with stable coronary artery disease (for at least 12 months). Patients will be selected from the Ischemic Heart Disease Clinic in a tertiary care hospital in southern Brazil. Enrolled participants will be randomized into one of two groups: 12 months of follow-up at the same clinic; or 12 months of follow-up at a primary care facility with clinical support from a telemedicine platform including a toll-free line for physicians (intervention group). In the intervention group, decisions to refer patients to tertiary care during follow-up will be made jointly by primary physicians and medical teleconsultants. The groups will be compared in terms of the primary outcome-maintenance of baseline functional class 1 or 2 after 12 months. Secondary outcomes include control of risk factors and instability of the disease. We intend to determine the effectiveness of using telemedicine to qualify the transition of patients with chronic coronary disease from the tertiary to the primary level of care. This should facilitate the access of patients to the healthcare system, since care will be provided closer to their homes, and provide more opportunities for treatment of severe cases at tertiary care hospitals that are often overcrowded. ClinicalTrials.gov # NCT02489565 - trial registration date May 13, 2015.

  8. Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

    Directory of Open Access Journals (Sweden)

    Gonzague Jourdain

    2013-08-01

    Full Text Available BACKGROUND: Viral load (VL is recommended for monitoring the response to highly active antiretroviral therapy (HAART but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand. METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3 non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4 monitoring versus viral-load (VL. Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3 initiating non-nucleotide reverse transcriptase inhibitor (NNRTI-based therapy. Randomization, stratified by site (21 public hospitals, was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 400 copies/ml at switch was 7.2 months (5.8-8.0 in VL versus 15.8 months (8.5-20.4 in CD4 (p=0.002. FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported. CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary.

  9. Dihydroartemisinin-piperaquine versus artesunate-amodiaquine for treatment of malaria infection in pregnancy in Ghana: an open-label, randomised, non-inferiority trial.

    Science.gov (United States)

    Osarfo, Joseph; Tagbor, Harry; Cairns, Matthew; Alifrangis, Michael; Magnussen, Pascal

    2017-08-01

    To determine whether dihydroartemisinin-piperaquine (DHA-PPQ) is non-inferior to artesunate-amodiaquine (ASAQ) for treating uncomplicated malaria infection in pregnancy. A total of 417 second/ third trimester pregnant women with confirmed asymptomatic Plasmodium falciparum parasitaemia were randomised to receive DHA-PPQ or ASAQ over 3 days. Women were followed up on days 1, 2, 3, 7, 14, 28 and 42 after treatment start and at delivery for parasitological, haematological, birth outcomes and at 6-week post-partum to ascertain the health status of the babies. Parasitological efficacy (PE) by days 28 and 42 were co-primary outcomes. Analysis was per-protocol (PP) and modified intention-to-treat (ITT). Non-inferiority was declared if the two-sided 95% confidence interval for PE at the endpoints excluded 5% lower efficacy for DHA-PPQ. Secondary outcomes were assessed for superiority. In PP analysis, PE was 91.6% for DHA-PPQ and 89.3% for ASAQ by day 28 and 89.0% and 86.5%, respectively, by day 42. DHA-PPQ was non-inferior to ASAQ with respect to uncorrected PE [adjusted difference by day 28 (DHA-PPQ-ASAQ); 3.5% (95%CI: -1.5, 8.5); and day 42: 3.9% (95%CI: -2.7, 10.4)]. ITT analysis gave similar results. PCR to distinguish recrudescence and reinfection was unsuccessful. DHA-PPQ recipients had fewer adverse events of vomiting, dizziness, and general weakness compared to ASAQ. Both drugs were well-tolerated, and there was no excess of adverse birth outcomes. DHA-PPQ was non-inferior to ASAQ for treatment of malaria infection during pregnancy. No safety concerns were identified. Our findings contribute to growing evidence that DHA-PPQ is useful for control of malaria in pregnancy. © 2017 John Wiley & Sons Ltd.

  10. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial.

    Science.gov (United States)

    Hegewisch-Becker, Susanna; Graeven, Ullrich; Lerchenmüller, Christian A; Killing, Birgitta; Depenbusch, Reinhard; Steffens, Claus-Christoph; Al-Batran, Salah-Eddin; Lange, Thoralf; Dietrich, Georg; Stoehlmacher, Jan; Tannapfel, Andrea; Reinacher-Schick, Anke; Quidde, Julia; Trarbach, Tanja; Hinke, Axel; Schmoll, Hans-Joachim; Arnold, Dirk

    2015-10-01

    The definition of a best maintenance strategy following combination chemotherapy plus bevacizumab in metastatic colorectal cancer is unclear. We investigated whether no continuation of therapy or bevacizumab alone are non-inferior to fluoropyrimidine plus bevacizumab, following induction treatment with a fluoropyrimidine plus oxaliplatin plus bevacizumab. In this open-label, non-inferiority, randomised phase 3 trial, we included patients aged 18 years or older with histologically confirmed, previously untreated metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, adequate bone marrow, liver, and renal function, no pre-existing neuropathy greater than grade 1, and measurable disease, from 55 hospitals and 51 private practices in Germany. After 24 weeks of induction therapy with either fluorouracil plus leucovorin plus oxaliplatin or capecitabine plus oxaliplatin, both with bevacizumab, patients without disease progression were randomly assigned centrally by fax (1:1:1) to standard maintenance treatment with a fluoropyrimidine plus bevacizumab, bevacizumab alone, or no treatment. Both patients and investigators were aware of treatment assignment. Stratification criteria were response status, termination of oxaliplatin, previous adjuvant treatment with oxaliplatin, and ECOG performance status. At first progression, re-induction with all drugs of the induction treatment was a planned part of the protocol. Time to failure of strategy was the primary endpoint, defined as time from randomisation to second progression after maintenance (and if applicable re-induction), death, or initiation of further treatment including a new drug. Time to failure of strategy was equivalent to time to first progression for patients who did not receive re-induction (for any reason). The boundary for assessment of non-inferiority was upper limit of the one-sided 98·8% CI 1·43. Analyses were done by intention to treat. The study has completed

  11. A Phase III, Randomized, Non-Inferiority Trial to Assess the Efficacy and Safety of Dihydroartemisinin-Piperaquine in Comparison with Artesunate-Mefloquine in Patients with Uncomplicated Plasmodium falciparum Malaria in Southern Laos

    Science.gov (United States)

    Mayxay, Mayfong; Keomany, Sommay; Khanthavong, Maniphone; Souvannasing, Phoutthalavanh; Stepniewska, Kasia; Khomthilath, Tiengthong; Keola, Siamphay; Pongvongsa, Tiengkham; Phompida, Samlane; Ubben, David; Valecha, Neena; White, Nicholas J.; Newton, Paul N.

    2010-01-01

    We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4–99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was −0.5% (−5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4–0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study. PMID:21118925

  12. Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

    Science.gov (United States)

    O'Ryan, Miguel; Bandyopadhyay, Ananda S; Villena, Rodolfo; Espinoza, Mónica; Novoa, José; Weldon, William C; Oberste, M Steven; Self, Steve; Borate, Bhavesh R; Asturias, Edwin J; Clemens, Ralf; Orenstein, Walter; Jimeno, José; Rüttimann, Ricardo; Costa Clemens, Sue Ann

    2015-11-01

    Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups

  13. A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain.

    Science.gov (United States)

    Juan-Giner, Aitana; Domicent, Camille; Langendorf, Céline; Roper, Martha H; Baoundoh, Paul; Fermon, Florence; Gakima, Primitive; Zipursky, Simona; Tamadji, Mbaihol; Grais, Rebecca F

    2014-10-29

    In resource-poor settings, cold chain requirements present barriers for vaccine delivery. We evaluated the immunogenicity and safety of tetanus toxoid (TT) vaccine in "Controlled Temperature Chain" (CTC; up to 40 °C for Tetanus antibody titers were measured using standard ELISA at inclusion and 4 weeks post-TT2. Primary outcome measures were post-vaccination seroconversion and fold-increase in geometric mean concentrations (GMC). Non-inferiority was by seroconversion difference (TTSCC-TTCTC) 95% of participants; upper 95%CI of the difference was 5.6%. Increases in GMC were over 4-fold; upper 95%CI of GMC ratio was 1.36 in the adjusted analysis. Few adverse events were recorded. This study demonstrates the immunogenicity and safety of TT in CTC at <40 °C for <30 days. The high proportion of participants protected at baseline results in a reduction of power to detect a 5% non-inferiority margin. However, results at a 10% non-inferiority margin, the comparable GMC increases and vaccine's stability demonstrated in the preliminary phase indicate that CTC can be an alternative strategy for TT delivery in situations where cold chain cannot be maintained. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Efficacy of fixed-dose combination artesunate-amodiaquine versus artemether-lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial

    Directory of Open Access Journals (Sweden)

    Espié Emmanuelle

    2012-05-01

    Full Text Available Abstract Background In 2005, the Democratic Republic of Congo (DRC adopted artesunate and amodiaquine (ASAQ as first-line anti-malarial treatment. In order to compare the efficacy of the fixed-dose formulation ASAQ versus artemether-lumefantrine (AL, a randomized, non-inferiority open-label trial was conducted in Katanga. Methods Children aged six and 59 months with uncomplicated Plasmodium falciparum malaria were enrolled and randomly allocated into one of the two regimens. The risk of recurrent parasitaemia by day 42, both unadjusted and adjusted by PCR genotyping to distinguish recrudescence from new infection, was analysed. Results Between April 2008 and March 2009, 301 children were included: 156 with ASAQ and 145 with AL. No early treatment failures were reported. Among the 256 patients followed-up at day 42, 32 patients developed late clinical or parasitological failure (9.9% (13/131 in the ASAQ group and 15.2% (19/125 in the AL group. After PCR correction, cure rates were 98.3% (95%CI, 94.1-99.8 in the ASAQ group and 99.1% (95%CI, 94.9-99.9 in the AL group (difference −0.7%, one sided 95% CI −3.1. Kaplan-Meier PCR-adjusted cure rates were similar. Both treatment regimens were generally well tolerated. Conclusion Both ASAQ and AL are highly effective and currently adequate as the first-line treatment of uncomplicated falciparum malaria in this area of Katanga, DRC. However, in a very large country, such as DRC, and because of possible emergence of resistance from other endemic regions, surveillance of efficacy of artemisinin-based combination treatments, including other evaluations of the resistance of ASAQ, need to be done in other provinces. Trial registration The protocol was registered with the clinicaltrials.gov, open clinical trial registry under the identifier number NCT01567423.

  15. Hysteropexy in the treatment of uterine prolapse stage 2 or higher: a multicenter randomized controlled non-inferiority trial comparing laparoscopic sacrohysteropexy with vaginal sacrospinous hysteropexy (LAVA-trial, study protocol).

    Science.gov (United States)

    van IJsselmuiden, Mèlanie N; Coolen, Anne-Lotte W M; Detollenaere, Renée J; den Boon, Jan; Bongers, Marlies; van de Pol, Geerte; Vollebregt, Astrid; Radder, Celine M; Deprest, Jan; van Eijndhoven, Hugo W F

    2014-09-17

    Pelvic organ prolapse is a common health problem: the lifetime risk of undergoing surgery for pelvic organ prolapse by the age of 85 years is 19%. Pelvic organ prolapse has significant negative effects on a woman's quality of life. Worldwide, vaginal hysterectomy is the leading treatment method for patients with symptomatic uterovaginal prolapse. Several studies have shown that vaginal sacrospinous hysteropexy and laparoscopic sacrohysteropexy are safe and effective alternatives in treating uterine descent. To date, it is unclear which of these techniques leads to the best operative result and the highest patient satisfaction. Therefore, we conducted the LAVA trial. The LAVA trial is a randomized controlled multicenter non-inferiority trial. The study compares laparoscopic sacrohysteropexy with vaginal sacrospinous hysteropexy in women with uterine prolapse stage 2 or higher. The primary outcome of this study is surgical success of the apical compartment at 1 and 5 years follow-up. Secondary outcomes are subjective improvement on urogenital symptoms and quality of life (assessed by disease-specific and general quality of life questionnaires), complications following surgery, hospital stay, post-operative recovery, sexual functioning and costs-effectiveness. Evaluation will take place pre-operatively, and 6 weeks, 6 months, 12 months and annually till 60 months after surgery. Validated questionnaires will be used.Analysis will be performed according to the intention to treat principle. Based on comparable recurrence rates of 3% and a non-inferiority margin of 10%, 62 patients are needed in each arm to prove the hypothesis with a 95% confidence interval. The LAVA trial is a randomized controlled multicenter non-inferiority trial that will provide evidence whether the efficacy of laparoscopic sacrohysteropexy is non-inferior to vaginal sacrospinous hysteropexy in women with symptomatic uterine prolapse stage 2 or higher. Netherlands Trial Register (NTR): NTR4029.

  16. Sublingual Misoprostol versus Intramuscular Oxytocin for Prevention of Postpartum Hemorrhage in Uganda: A Double-Blind Randomized Non-Inferiority Trial

    Science.gov (United States)

    Atukunda, Esther C.; Siedner, Mark J.; Obua, Celestino; Mugyenyi, Godfrey R.; Twagirumukiza, Marc; Agaba, Amon G.

    2014-01-01

    Background Postpartum hemorrhage (PPH) is a leading cause of maternal death in sub-Saharan Africa. Although the World Health Organization recommends use of oxytocin for prevention of PPH, misoprostol use is increasingly common owing to advantages in shelf life and potential for sublingual administration. There is a lack of data about the comparative efficacy of oxytocin and sublingual misoprostol, particularly at the recommended dose of 600 µg, for prevention of PPH during active management of labor. Methods and Findings We performed a double-blind, double-dummy randomized controlled non-inferiority trial between 23 September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in Uganda. We randomized 1,140 women to receive 600 µg of misoprostol sublingually or 10 IU of oxytocin intramuscularly, along with matching placebos for the treatment they did not receive. Our primary outcome of interest was PPH, defined as measured blood loss ≥500 ml within 24 h of delivery. Secondary outcomes included measured blood loss ≥1,000 ml; mean measured blood loss at 1, 2, and 24 h after delivery; death; requirement for blood transfusion; hemoglobin changes; and use of additional uterotonics. At 24 h postpartum, primary PPH occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%) participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05, poxytocin groups, respectively (RR 1.33, 95% CI 0.69 to 2.58, p = 0.391; absolute risk difference 0.9%, 95% CI −1.12 to 2.88). Mean measured blood loss was 341.5 ml (standard deviation [SD] 206.2) and 304.2 ml (SD 190.8, p = 0.002) at 2 h and 484.7 ml (SD 213.3) and 432.8 ml (SD 203.5, poxytocin groups, respectively. There were no significant differences between the two groups in any other secondary outcomes. Women in the misoprostol group more commonly experienced shivering (RR 1.91, 95% CI 1.65 to 2.21, poxytocin 10 IU for prevention of primary PPH in active management of

  17. Randomized, non-inferiority trial comparing a nitric oxide releasing solution with a macrolide antibiotic for control of bovine respiratory disease in beef feedlot calves at high-risk of developing respiratory tract disease.

    Science.gov (United States)

    Crepieux, T; Miller, C; Regev-Shoshani, G; Schaefer, A; Dorin, C; Alexander, T; Timsit, E

    2016-04-01

    Nitric oxide, a molecule produced in most mammalian cells, has bactericidal and virucidal properties. Nasal instillation of a nitric oxide releasing solution (NORS) on arrival at the feedlot was recently reported as non-inferior to a parenteral injection of a macrolide antibiotic, tilmicosin, for control of bovine respiratory disease (BRD) in cattle at low-to-moderate risk of developing BRD. The objective of this study was to evaluate whether NORS was non-inferior to tilmicosin for control of BRD in cattle at high-risk of developing BRD (the target population for many BRD control programs). High-risk Angus-cross heifers (n=840) were randomly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for BRD control. Non-inferiority was assessed by calculating the difference in prevalence of heifers diagnosed with BRD during the first 40 d after arrival between NORS and tilmicosin treatment groups. The non-inferiority margin (δ) was set at 8.5%. Thirty-six and 19% of heifers were diagnosed with BRD in the NORS and tilmicosin groups, respectively. Because the lower bound of the 2-sided 95% confidence interval (CI) of the difference in BRD prevalence between the 2 treatment groups (17%; 95% CI=11-23%) was higher than δ, an inferiority of NORS was concluded. Although on-arrival nasal administration of NORS can be viewed as a more rational control strategy than parental injection of antibiotics, further research is needed to improve NORS efficacy before it can be recommended to prevent BRD in high-risk cattle.

  18. A randomized, non-inferiority study comparing efficacy and safety of a single dose of pegfilgrastim versus daily filgrastim in pediatric patients after autologous peripheral blood stem cell transplant.

    Directory of Open Access Journals (Sweden)

    Simone Cesaro

    Full Text Available PURPOSE: To assess the non-inferiority of pegfilgrastim versus filgrastim in speeding the recovery of polymorphonuclear cells (PMN in pediatric patients who underwent autologous peripheral blood stem cell transplant (PBSCT. METHODS: The sample size of this randomized, multicenter, phase III study, was calculated assuming that a single dose of pegfilgrastim of 100 ug/kg was not inferior to 9 doses of filgrastim of 5 ug/kg/day. Randomization was performed by a computer-generated list and stored by sequentially numbered sealed envelopes. RESULTS: Sixty-one patients, with a median age of 11.5 years, were recruited: 29 in the filgrastim arm and 32 in the pegfilgrastim arm. Twenty percent were affected by lymphoma/leukaemia and eighty percent by solid tumors. The mean time to PMN engraftment was 10.48 days (standard deviation [SD] 1.57 and 10.44 days (SD 2.44 in the filgrastim and pegfilgrastim arms, respectively. Having fixed a non-inferiority margin Delta of 3, the primary endpoint of non-inferiority was reached. No differences were observed for other secondary endpoints: platelet engraftment, mean time to platelet recovery (28 days vs. 33 days, fever of unknown origin (79% vs. 78%, proven infection (34% vs. 28%, mucositis (76% vs. 59%. After a median follow-up of 2.3 years (95% C.I.: 1.5, 3.3, 20 deaths were observed due to disease progression. CONCLUSIONS: We conclude that pegfilgrastim was not inferior to daily filgrastim in pediatric patients who underwent PBSCT. EU CLINICAL TRIAL REGISTER NUMBER: 2007-001430-14.

  19. Comparison of Analgesic Efficacy of Laparoscope-Assisted and Ultrasound-Guided Transversus Abdominis Plane Block after Laparoscopic Colorectal Operation: A Randomized, Single-Blind, Non-Inferiority Trial.

    Science.gov (United States)

    Park, Soo Yeun; Park, Jun Seok; Choi, Gyu-Seog; Kim, Hye Jin; Moon, Suyoung; Yeo, Jinseok

    2017-09-01

    Transversus abdominis plane (TAP) block has been used as a component of multimodal analgesia after abdominal operation. We introduced a new laparoscope-assisted TAP (LTAP) block technique using intraperitoneal injection and compared its analgesic effect with that of an ultrasound-guided TAP (UTAP) block in terms of postoperative pain control. A prospective, randomized, single-blinded non-inferiority clinical trial was conducted with patients undergoing elective laparoscopic colectomy for colon cancer. Eighty patients were randomly assigned (1:1 ratio) to the UTAP and LTAP groups. At the end of the operation, opioid consumption and numeric rating scores (NRS; 0 [no pain] to 10 [worst pain]) of pain were recorded at 2, 6, 24, and 48 hours postoperatively and were compared between the groups. The primary end point was pain NRS during rest at 24 hours after operation. Thirty-eight patients in the LTAP group and 35 patients in the UTAP group completed the study protocol. We found no significant difference in mean ± SD pain NRS during rest at 24 hours between the LTAP group (3.90 ± 1.7) and the UTAP group (4.5 ± 1.9). The mean difference in pain NRS during rest at 24 hours was 0.57 (95% CI -0.26 to 1.41). Because the lower boundary of a 95% CI for the differences in pain NRS was > -1, non-inferiority was established. There was no significant difference between the groups in NRS pain during rest, NRS pain on movement, and postoperative morphine consumption during the 48 hours after operation. These results show our new LTAP block technique was non-inferior to the ultrasound-guided technique in providing a TAP block after laparoscopic colorectal operation. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  20. A non-inferiority, individually randomized trial of intermittent screening and treatment versus intermittent preventive treatment in the control of malaria in pregnancy

    DEFF Research Database (Denmark)

    Tagbor, Harry; Cairns, Matthew; Bojang, Kalifa;

    2015-01-01

    BACKGROUND: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women......). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia......-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women...

  1. Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial

    DEFF Research Database (Denmark)

    Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia;

    2016-01-01

    BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify...... an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria. METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days.......022. In a modified intention to treat analysis in which treatment failures day 0 and reinfections were also considered as treatment failures adequate clinical and parasitological responses were 94% and 97% (OR 0.42 [95% CI, 0.13-1.38], p = 0.15). Parasite clearance and symptom resolution were similar with both...

  2. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial

    DEFF Research Database (Denmark)

    Bousser, M.G.; Bouthier, J.; Buller, H.R.;

    2008-01-01

    BACKGROUND: Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim of this random...

  3. A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities

    Science.gov (United States)

    Dryden, Matthew; Zhang, Yingyuan; Wilson, David; Iaconis, Joseph P.; Gonzalez, Jesus

    2016-01-01

    Objectives Increasing the ceftaroline fosamil dose beyond 600 mg every 12 h may provide additional benefit for patients with complicated skin and soft tissue infections (cSSTIs) with severe inflammation and/or reduced pathogen susceptibility. A Phase III multicentre, randomized trial evaluated the safety and efficacy of ceftaroline fosamil 600 mg every 8 h in this setting. Methods Adult patients with cSSTI and systemic inflammation or comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g every 8 h) for 5–14 days. Clinical cure was assessed at the test of cure (TOC) visit (8–15 days after the final dose) in the modified ITT (MITT) and clinically evaluable (CE) populations. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference greater than –10%. An MRSA-focused expansion period was initiated after completion of the main study. Clinicaltrials.gov registration numbers NCT01499277 and NCT02202135. Results Clinical cure rates at TOC demonstrated non-inferiority of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in the MITT and CE populations: 396/506 (78.3%) versus 202/255 (79.2%) patients (difference −1.0%, 95% CI −6.9, 5.4) and 342/395 (86.6%) versus 180/211 (85.3%) patients (difference 1.3%, 95% CI −4.3, 7.5), respectively. In the expansion period, 3/4 (75%) patients treated with ceftaroline fosamil were cured at TOC. The frequency of adverse events was similar between groups. Conclusions Ceftaroline fosamil 600 mg every 8 h was effective for cSSTI patients with evidence of systemic inflammation and/or comorbidities. No new safety signals were identified. PMID:27585969

  4. Tai Chi-based exercise program provided via telerehabilitation compared to home visits in a post-stroke population who have returned home without intensive rehabilitation: study protocol for a randomized, non-inferiority clinical trial.

    Science.gov (United States)

    Tousignant, Michel; Corriveau, Hélène; Kairy, Dahlia; Berg, Katherine; Dubois, Marie-France; Gosselin, Sylvie; Swartz, Richard H; Boulanger, Jean-Martin; Danells, Cynthia

    2014-01-30

    The incidence of strokes in industrialized nations is on the rise, particularly in the older population. In Canada, a minority of individuals who have had a stroke actually receive intensive rehabilitation because most stroke patients do not have access to services or because their motor recovery was judged adequate to return home. Thus, there is a considerable need to organize home-based rehabilitation services for everyone who has had a stroke. To meet this demand, telerehabilitation, particularly from a service center to the patient's home, is a promising alternative approach that can help improve access to rehabilitation services once patients are discharged home. This non-inferiority study will include patients who have returned home post-stroke without requiring intensive rehabilitation. To be included in the study, participants will: 1) not be referred to an Intensive Functional Rehabilitation Unit, 2) have a Rankin score of 2 or 3, and 3) have a balance problem (Berg Balance Scale score between 46 and 54). Participants will be randomly assigned to either the teletreatment group or the home visits group. Except for the delivery mode, the intervention will be the same for both groups, that is, a personalized Tai Chi-based exercise program conducted by a trained physiotherapist (45-minute session twice a week for eight consecutive weeks). The main objective of this research is to test the non-inferiority of a Tai Chi-based exercise program provided via telerehabilitation compared to the same program provided in person at home in terms of effectiveness for retraining balance in individuals who have had a stroke but do not require intensive functional rehabilitation. The main outcome of this study is balance and mobility measured with the Community Balance and Mobility Scale. Secondary outcomes include physical and psychological capacities related to balance and mobility, participants' quality of life, satisfaction with services received, and cost

  5. Comparative study of the efficacy of transdermal buprenorphine patches and prolonged-release tramadol tablets for postoperative pain control after spinal fusion surgery: a prospective, randomized controlled non-inferiority trial.

    Science.gov (United States)

    Kim, Ho-Joong; Ahn, Hyo Sae; Nam, Yunjin; Chang, Bong-Soon; Lee, Choon-Ki; Yeom, Jin S

    2017-07-20

    To compare the efficacy of a transdermal buprenorphine patch (5, 10, 15, and 20 μg/h) with that of oral tramadol (150, 200, 250, and 300 mg) for postoperative pain control after single level spinal fusion surgery. The present study (ClinicalTrials.gov, number NCT02416804) was a prospective, randomized controlled non-inferiority trial designed to determine the efficacy of buprenorphine TDS for alleviating postoperative pain following patient controlled analgesia (PCA) in persons underwent a single level posterior lumbar interbody fusion surgery through 1:1 allocation. The primary outcome was the Visual Analog Pain Scale (VAS) score for postoperative back pain at 7 days after surgery. The non-inferior margin of the VAS was set at δ = 1.5 points. The VAS score (primary outcome) for postoperative back pain at 7 days after surgery in the Buprenorphine group was not inferior compared to the Tramadol group. The overall changes in VAS scores for postoperative pain during follow-up assessments over a 2-week period did not differ between both groups. However, the VAS scores for postoperative pain significantly improved with time after surgery in both groups. The patterns of changes in the VAS scores for postoperative pain during the follow-up period were not significantly different between the both groups. The efficacy of buprenorphine TDS was not inferior to that of oral tramadol medication for alleviating postoperative pain in the subacute period from 72 h after surgery, following PCA administration. In addition, adverse events were similar between both groups.

  6. Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on duration of antibiotic therapy in suspected neonatal early-onset sepsis: A multi-centre randomized superiority and non-inferiority Intervention Study.

    Science.gov (United States)

    Stocker, Martin; Hop, Wim C J; van Rossum, Annemarie M C

    2010-12-08

    Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications. Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation. Therefore, many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven. With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis. The study is designed as randomized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment. Term and near-term infants (gestational age ≥ 34 0/7 weeks) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included. The duration of antibiotic therapy in the standard group is based on the attending physician's assessment of the likelihood of infection (infection unlikely, possible, probable or proven). In the Procalcitonin group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range. Co-primary outcome measures are the duration of antibiotic therapy (superiority aspect of the trial) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and/or death in the first month of life (safety of study intervention, non-inferiority aspect of the trial). The number of infants to be included equals 800 per arm. With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety, i.e. excluding a disadvantage difference larger than 2% for the experimental arm, will both be greater than 80%. Benefit of the study is a possible limitation of unnecessary

  7. High concentration (400 mgI/mL) versus low concentration (320 mgI/mL) iodinated contrast media in multi detector computed tomography of the liver: A randomized, single centre, non-inferiority study

    Energy Technology Data Exchange (ETDEWEB)

    Rengo, Marco, E-mail: marco.rengo@gmail.com [Department of Radiological Sciences, Oncology and Pathology, University of Rome ' SAPIENZA' , Polo Pontino, I.C.O.T., Via Franco Faggiana 34, 04100 Latina (Italy); Caruso, Damiano, E-mail: dcaruso85@gmail.com [Department of Radiological Sciences, Oncology and Pathology, University of Rome ' SAPIENZA' , Polo Pontino, I.C.O.T., Via Franco Faggiana 34, 04100 Latina (Italy); De Cecco, Carlo N., E-mail: carlodececco@gmail.com [Department of Radiological Sciences, Oncology and Pathology, University of Rome ' SAPIENZA' , Polo Pontino, I.C.O.T., Via Franco Faggiana 34, 04100 Latina (Italy); Lucchesi, Paola, E-mail: paola.lucchesi@email.it [Department of Radiological Sciences, Oncology and Pathology, University of Rome ' SAPIENZA' , Polo Pontino, I.C.O.T., Via Franco Faggiana 34, 04100 Latina (Italy); Bellini, Davide, E-mail: bellinidavide29@gmail.com [Department of Radiological Sciences, Oncology and Pathology, University of Rome ' SAPIENZA' , Polo Pontino, I.C.O.T., Via Franco Faggiana 34, 04100 Latina (Italy); Maceroni, Marco Maria, E-mail: marcom.maceroni@gmail.com [Department of Radiological Sciences, Oncology and Pathology, University of Rome ' SAPIENZA' , Polo Pontino, I.C.O.T., Via Franco Faggiana 34, 04100 Latina (Italy); Ferrari, Riccardo, E-mail: ferraririccardo@gmail.com [Department of Radiological Sciences, San Giovanni Hospital, Via dell' Amba Aradam 9, 00184 Rome (Italy); Paolantonio, Pasquale, E-mail: paolantoniopasquale@hotmail.com [Department of Radiological Sciences, San Giovanni Hospital, Via dell' Amba Aradam 9, 00184 Rome (Italy); and others

    2012-11-15

    Objectives: To compare vascular and parenchymal contrast enhancement in multidetector computed tomography of the liver using two contrast media with different iodine concentration (Iodixanol 320 mgI/mL and Iomeprol 400 mgI/mL) and similar viscosity, using fixed total iodine volume (40 gI) and iodine delivery rate (1.6 gI/s). Methods: 110 patients were prospectively randomized into two groups. Group A received 125 mL of Iodixanol 320 and group B 100 mL of Iomeprol 400. Attenuation values were measured at the level of the aorta, portal vein and liver parenchyma on unenhanced, arterial, portal and equilibrium phases. A non inferiority test was performed on the differences between the two groups. An independent reader evaluated image quality. Results: The equivalence of the two CM was demonstrated in all measurements. Higher, but not statistically significant, attenuation values were obtained with Iomeprol 400 in the aorta during the arterial phase (305.3 HU versus 288.4 HU; P = 0.32) and with Iodixanol 320 in the liver parenchyma, during both portal (59.8 HU versus 65.5 HU; P = 0.78) and equilibrium (40.4 HU versus 41.8 HU; P = 0.55) phases. Conclusions: Iodixanol 320 and Iomeprol 400 injected at the same iodine delivery rate (1.6 gI/s) and total iodine load (40 gI) did not provide statistically significant differences in liver parenchymal and vascular contrast enhancement.

  8. Defining the non-inferiority margin and analyzing non-inferiority: An overview.

    Science.gov (United States)

    Althunian, Turki A; de Boer, Anthonius; Groenwold, Rolf H H; Klungel, Olaf H

    2017-03-02

    Non-inferiority trials are used to assess whether the effect of a new drug is not worse than an active comparator by more than a non-inferiority margin. If the difference between the new drug and the active comparator does not exceed this pre-specified margin, non-inferiority can be concluded. This margin must be specified based on clinical and statistical reasoning; however, it is considered as one the most challenging step in the design of non-inferiority trials. Regulators recommend that the margin should be defined based on the historical evidence of the active comparator (the latter is often the well-established standard treatment of the disease), which can be performed by different approaches. There are several factors and assumptions that need to be accounted for during the process of defining the margin and during the analysis of non-inferiority. Three methods are commonly used to analyze non-inferiority trials: the fixed-margin method, the point-estimate method, and the synthesis method. This article provides an overview of analyzing non-inferiority inferiority and choosing the non-inferiority margin.

  9. Cluster-randomized non-inferiority trial to compare supplement consumption and adherence to different dosing regimens for antenatal calcium and iron-folic acid supplementation to prevent preeclampsia and anaemia: rationale and design of the Micronutrient Initiative study

    Directory of Open Access Journals (Sweden)

    Moshood O. Omotayo

    2015-11-01

    Full Text Available Background: To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca intake, the World Health Organisation (WHO recommends routine Ca supplementation during antenatal care (ANC. WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients. Design and methods: This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill and IFA (60 mg Fe + 400 μg folic acid taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill with IFA taken as above. Measurements: Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Statistical analyses: Unit of randomization is the health-care facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering. Expected public health impact: If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources.

  10. Humidified High Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure as an Initial Respiratory Support in Preterm Infants with Respiratory Distress: a Randomized, Controlled Non-Inferiority Trial.

    Science.gov (United States)

    Shin, Jeonghee; Park, Kyuhee; Lee, Eun Hee; Choi, Byung Min

    2017-04-01

    Heated, humidified, high-flow nasal cannula (HHFNC) is frequently used as a noninvasive respiratory support for preterm infants with respiratory distress. But there are limited studies that compares HHFNC with nasal continuous positive airway pressure (nCPAP) only as the initial treatment of respiratory distress in preterm infants immediately after birth. The aim of this study is to assess the effectiveness and safety of HHFNC compared to nCPAP for the initial treatment of preterm infants with respiratory distress. Preterm infants at between 30 and 35 weeks of gestational age were randomized to HHFNC or nCPAP when they showed respiratory distress in less than 24 hours of age postnatally. Preterm infants who needed invasive respiratory supports were excluded. Primary outcome was the incidence of treatment failure (defined as need for the intubation or mechanical ventilation). Eighty-five infants were analyzed. Sixteen of 42 infants randomized to HHFNC showed treatment failure compared to 9 of 43 infants using nCPAP (Risk difference 17.17 [-1.90-36.23]; P = 0.099). In terms of the reason for treatment failure, the frequency of hypoxia was significantly higher in the HHFNC group than in the nCPAP group (P = 0.020). There was no difference between the 2 groups in terms of respiratory and clinical outcomes and complications. Although HHFNC is safe compared to nCPAP, it is not certain that HHFNC is effective compared to nCPAP non-inferiorly as an initial respiratory support in preterm infants with respiratory distress.

  11. Randomized Placebo-Controlled and Controlled Non-Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth Factor 2, and Enamel Matrix Derivative in Periodontal Regeneration in Intrabony Defects.

    Science.gov (United States)

    Kitamura, Masahiro; Akamatsu, Motoki; Kawanami, Masamitsu; Furuichi, Yasushi; Fujii, Takeo; Mori, Mari; Kunimatsu, Kazushi; Shimauchi, Hidetoshi; Ogata, Yorimasa; Yamamoto, Matsuo; Nakagawa, Taneaki; Sato, Shuichi; Ito, Koichi; Ogasawara, Takefumi; Izumi, Yuichi; Gomi, Kazuhiro; Yamazaki, Kazuhisa; Yoshie, Hiromasa; Fukuda, Mitsuo; Noguchi, Toshihide; Takashiba, Shogo; Kurihara, Hidemi; Nagata, Toshihiko; Hamachi, Takafumi; Maeda, Katsumasa; Yokota, Makoto; Sakagami, Ryuji; Hara, Yoshitaka; Noguchi, Kazuyuki; Furuuchi, Toshi; Sasano, Takashi; Imai, Enyu; Ohmae, Masatoshi; Koizumi, Hayuru; Watanuki, Mitsuru; Murakami, Shinya

    2016-04-01

    We investigated the efficacy, safety, and clinical significance of trafermin, a recombinant human fibroblast growth factor (rhFGF)-2, for periodontal regeneration in intrabony defects in Phase III trials. Study A, a multicenter, randomized, double-blind, placebo-controlled study, was conducted at 24 centers. Patients with periodontitis with 4-mm and 3-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 328 patients were randomly assigned (2:1) to receive 0.3% rhFGF-2 or placebo, and 323 patients received the assigned investigational drug during flap surgery. One of the co-primary endpoints, the percentage of bone fill at 36 weeks after drug administration, was significantly greater in the rhFGF-2 group at 37.131% (95% confidence interval [CI], 32.7502 to 41.5123; n = 208) than it was in the placebo group at 21.579% (95% CI, 16.3571 to 26.8011; n = 100; p < 0.001). The other endpoint, the clinical attachment level regained at 36 weeks, was not significantly different between groups. Study B, a multicenter, randomized, blinded (patients and evaluators of radiographs), and active-controlled study was conducted at 15 centers to clarify the clinical significance of rhFGF-2. Patients with 6-mm and 4-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 274 patients were randomly assigned (5:5:2) to receive rhFGF-2, enamel matrix derivative (EMD), or flap surgery alone. A total of 267 patients received the assigned treatment during flap surgery. The primary endpoint, the linear alveolar bone growth at 36 weeks, was 1.927 mm (95% CI, 1.6615 to 2.1920; n = 108) in the rhFGF-2 group and 1.359 mm (95% CI, 1.0683 to 1.6495; n = 109) in the EMD group, showing non-inferiority (a prespecified margin of 0.3 mm) and superiority of rhFGF-2 to EMD. Safety problems were not identified in either study. Therefore, trafermin is an effective and safe treatment for periodontal regeneration in intrabony

  12. Acceptability of Home-Assessment Post Medical Abortion and Medical Abortion in a Low-Resource Setting in Rajasthan, India. Secondary Outcome Analysis of a Non-Inferiority Randomized Controlled Trial

    Science.gov (United States)

    Paul, Mandira; Iyengar, Kirti; Essén, Birgitta; Gemzell-Danielsson, Kristina; Iyengar, Sharad D.; Bring, Johan; Soni, Sunita; Klingberg-Allvin, Marie

    2015-01-01

    Background Studies evaluating acceptability of simplified follow-up after medical abortion have focused on high-resource or urban settings where telephones, road connections, and modes of transport are available and where women have formal education. Objective To investigate women’s acceptability of home-assessment of abortion and whether acceptability of medical abortion differs by in-clinic or home-assessment of abortion outcome in a low-resource setting in India. Design Secondary outcome of a randomised, controlled, non-inferiority trial. Setting Outpatient primary health care clinics in rural and urban Rajasthan, India. Population Women were eligible if they sought abortion with a gestation up to 9 weeks, lived within defined study area and agreed to follow-up. Women were ineligible if they had known contraindications to medical abortion, haemoglobin Abortion outcome assessment through routine clinic follow-up by a doctor was compared with home-assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet. A computerized random number generator generated the randomisation sequence (1:1) in blocks of six. Research assistants randomly allocated eligible women who opted for medical abortion (mifepristone and misoprostol), using opaque sealed envelopes. Blinding during outcome assessment was not possible. Main Outcome Measures Women’s acceptability of home-assessment was measured as future preference of follow-up. Overall satisfaction, expectations, and comparison with previous abortion experiences were compared between study groups. Results 731 women were randomized to the clinic follow-up group (n = 353) or home-assessment group (n = 378). 623 (85%) women were successfully followed up, of those 597 (96%) were satisfied and 592 (95%) found the abortion better or as expected, with no difference between study groups. The majority, 355 (57%) women, preferred home-assessment in the event of a future abortion. Significantly more women, 284 (82

  13. Cluster-Randomized Non-Inferiority Trial to Compare Supplement Consumption and Adherence to Different Dosing Regimens for Antenatal Calcium and Iron-Folic Acid Supplementation to Prevent Preeclampsia and Anaemia: Rationale and Design of the Micronutrient Initiative Study.

    Science.gov (United States)

    Omotayo, Moshood O; Dickin, Katherine L; Chapleau, Gina M; Martin, Stephanie L; Chang, Christopher; Mwanga, Erick O; Kung'u, Jacqueline K; Stoltzfus, Rebecca J

    2015-11-17

    To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca) intake, the World Health Organisation (WHO) recommends routine Ca supplementation during antenatal care (ANC). WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA) supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose) regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients. This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill) and IFA (60 mg Fe + 400 µg folic acid) taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill) with IFA taken as above. Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Unit of randomization is the healthcare facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering. If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources. Significance for public healthPre-eclampsia is a leading cause of maternal mortality. Based on clinical evidence of significant reduction in risk of pre-eclampsia, the WHO recommends including calcium (Ca) supplementation in antenatal care services in settings with inadequate dietary Ca intakes. A

  14. Acceptability of Home-Assessment Post Medical Abortion and Medical Abortion in a Low-Resource Setting in Rajasthan, India. Secondary Outcome Analysis of a Non-Inferiority Randomized Controlled Trial.

    Science.gov (United States)

    Paul, Mandira; Iyengar, Kirti; Essén, Birgitta; Gemzell-Danielsson, Kristina; Iyengar, Sharad D; Bring, Johan; Soni, Sunita; Klingberg-Allvin, Marie

    2015-01-01

    Studies evaluating acceptability of simplified follow-up after medical abortion have focused on high-resource or urban settings where telephones, road connections, and modes of transport are available and where women have formal education. To investigate women's acceptability of home-assessment of abortion and whether acceptability of medical abortion differs by in-clinic or home-assessment of abortion outcome in a low-resource setting in India. Secondary outcome of a randomised, controlled, non-inferiority trial. Outpatient primary health care clinics in rural and urban Rajasthan, India. Women were eligible if they sought abortion with a gestation up to 9 weeks, lived within defined study area and agreed to follow-up. Women were ineligible if they had known contraindications to medical abortion, haemoglobin Abortion outcome assessment through routine clinic follow-up by a doctor was compared with home-assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet. A computerized random number generator generated the randomisation sequence (1:1) in blocks of six. Research assistants randomly allocated eligible women who opted for medical abortion (mifepristone and misoprostol), using opaque sealed envelopes. Blinding during outcome assessment was not possible. Women's acceptability of home-assessment was measured as future preference of follow-up. Overall satisfaction, expectations, and comparison with previous abortion experiences were compared between study groups. 731 women were randomized to the clinic follow-up group (n = 353) or home-assessment group (n = 378). 623 (85%) women were successfully followed up, of those 597 (96%) were satisfied and 592 (95%) found the abortion better or as expected, with no difference between study groups. The majority, 355 (57%) women, preferred home-assessment in the event of a future abortion. Significantly more women, 284 (82%), in the home-assessment group preferred home-assessment in the future, as

  15. Acceptability of Home-Assessment Post Medical Abortion and Medical Abortion in a Low-Resource Setting in Rajasthan, India. Secondary Outcome Analysis of a Non-Inferiority Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Mandira Paul

    Full Text Available Studies evaluating acceptability of simplified follow-up after medical abortion have focused on high-resource or urban settings where telephones, road connections, and modes of transport are available and where women have formal education.To investigate women's acceptability of home-assessment of abortion and whether acceptability of medical abortion differs by in-clinic or home-assessment of abortion outcome in a low-resource setting in India.Secondary outcome of a randomised, controlled, non-inferiority trial.Outpatient primary health care clinics in rural and urban Rajasthan, India.Women were eligible if they sought abortion with a gestation up to 9 weeks, lived within defined study area and agreed to follow-up. Women were ineligible if they had known contraindications to medical abortion, haemoglobin < 85 mg/l and were below 18 years.Abortion outcome assessment through routine clinic follow-up by a doctor was compared with home-assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet. A computerized random number generator generated the randomisation sequence (1:1 in blocks of six. Research assistants randomly allocated eligible women who opted for medical abortion (mifepristone and misoprostol, using opaque sealed envelopes. Blinding during outcome assessment was not possible.Women's acceptability of home-assessment was measured as future preference of follow-up. Overall satisfaction, expectations, and comparison with previous abortion experiences were compared between study groups.731 women were randomized to the clinic follow-up group (n = 353 or home-assessment group (n = 378. 623 (85% women were successfully followed up, of those 597 (96% were satisfied and 592 (95% found the abortion better or as expected, with no difference between study groups. The majority, 355 (57% women, preferred home-assessment in the event of a future abortion. Significantly more women, 284 (82%, in the home-assessment group preferred

  16. A mixed approach for proving non-inferiority in clinical trials with binary endpoints.

    Science.gov (United States)

    Rousson, Valentin; Seifert, Burkhardt

    2008-04-01

    When a new treatment is compared to an established one in a randomized clinical trial, it is standard practice to statistically test for non-inferiority rather than for superiority. When the endpoint is binary, one usually compares two treatments using either an odds-ratio or a difference of proportions. In this paper, we propose a mixed approach which uses both concepts. One first defines the non-inferiority margin using an odds-ratio and one ultimately proves non-inferiority statistically using a difference of proportions. The mixed approach is shown to be more powerful than the conventional odds-ratio approach when the efficacy of the established treatment is known (with good precision) and high (e.g. with more than 56% of success). The gain of power achieved may lead in turn to a substantial reduction in the sample size needed to prove non-inferiority. The mixed approach can be generalized to ordinal endpoints.

  17. Does mode of follow-up influence contraceptive use after medical abortion in a low-resource setting? Secondary outcome analysis of a non-inferiority randomized controlled trial.

    Science.gov (United States)

    Paul, Mandira; Iyengar, Sharad D; Essén, Birgitta; Gemzell-Danielsson, Kristina; Iyengar, Kirti; Bring, Johan; Klingberg-Allvin, Marie

    2016-10-17

    Post-abortion contraceptive use in India is low and the use of modern methods of contraception is rare, especially in rural areas. This study primarily compares contraceptive use among women whose abortion outcome was assessed in-clinic with women who assessed their abortion outcome at home, in a low-resource, primary health care setting. Moreover, it investigates how background characteristics and abortion service provision influences contraceptive use post-abortion. A randomized controlled, non-inferiority, trial (RCT) compared clinic follow-up with home-assessment of abortion outcome at 2 weeks post-abortion. Additionally, contraceptive-use at 3 months post-abortion was investigated through a cross-sectional follow-up interview with a largely urban sub-sample of women from the RCT. Women seeking abortion with a gestational age of up to 9 weeks and who agreed to a 2-week follow-up were included (n = 731). Women with known contraindications to medical abortions, Hb care clinics in Rajasthan. A computerised random number generator created the randomisation sequence (1:1) in blocks of six. Contraceptive use was measured at 2 weeks among women successfully followed-up (n = 623) and 3 months in the sub-set of women who were included if they were recruited at one of the urban study sites, owned a phone and agreed to a 3-month follow-up (n = 114). There were no differences between contraceptive use and continuation between study groups at 3 months (76 % clinic follow-up, 77 % home-assessment), however women in the clinic follow-up group were most likely to adopt a contraceptive method at 2 weeks (62 ± 12 %), while women in the home-assessment group were most likely to adopt a method after next menstruation (60 ± 13 %). Fifty-two per cent of women who initiated a method at 2 weeks chose the 3-month injection or the copper intrauterine device. Only 4 % of women preferred sterilization. Caste, educational attainment, or type of

  18. Through the looking glass: understanding non-inferiority

    Directory of Open Access Journals (Sweden)

    Wittes Janet T

    2011-05-01

    Full Text Available Abstract Non-inferiority trials test whether a new product is not unacceptably worse than a product already in use. This paper introduces concepts related to non-inferiority, and discusses the regulatory views of both the European Medicines Agency and the United States Food and Drug Administration.

  19. A randomized, open-label trial of iron isomaltoside 1000 (Monofer®) compared with iron sucrose (Venofer®) as maintenance therapy in haemodialysis patients

    OpenAIRE

    Bhandari, Sunil; Kalra, Philip A.; Kothari, Jatin; Ambühl, Patrice M.; Christensen, Jeppe H.; Essaian, Ashot M.; Thomsen, Lars L.; Macdougall, Iain C.; Coyne, Daniel W.

    2015-01-01

    Background Iron deficiency anaemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on haemodialysis. The aim of this trial was to compare the efficacy and safety of iron isomaltoside 1000 (Monofer®) with iron sucrose (Venofer®) in haemodialysis patients. Methods This was an open-label, randomized, multicentre, non-inferiority trial conducted in 351 haemodialysis subjects randomized 2 : 1 to either iron isomaltoside 1000 (Group A) or...

  20. Study duration for three-arm non-inferiority survival trials designed for accrual by cohorts.

    Science.gov (United States)

    Wu, Ying; Li, Yiqun; Hou, Yan; Li, Kang; Zhou, Xiaohua

    2016-03-17

    Study planning is particularly complex for survival trials because it usually involves an accrual period and a continued observation period after accrual closure. The three-arm clinical trial design, which includes a test treatment, an active reference, and a placebo control, is the gold standard design for the assessment of non-inferiority. The existing statistical methods of calculating minimal sample size for non-inferiority trials with three-arm design and survival-type endpoints cannot take into consideration the accrual rate of patients to the trial, the length of accrual period, the length of continued observation period after accrual closure, and unbalanced allocation of the total sample size. The purpose of this paper is to develop a statistical method, which allows for all these sources of variability for planning non-inferiority trials with the gold standard design for censored, exponentially distributed time-to-event data. The proposed method is based on the assumption of exponentially distributed failure times and a non-inferiority test formulated in terms of the retention of effect hypotheses. It can be used to calculate the duration of accrual required to assure a desired power for non-inferiority trials with active and placebo control. We illustrate the use of the method by considering a randomized, active- and placebo-controlled trial in depression associated with Parkinson's disease. We then explore the validity of the proposed method by simulation studies. An R-language program for the implementation of the proposed algorithm is provided as supplementary material. © The Author(s) 2016.

  1. BariSurg trial: Sleeve gastrectomy versus Roux-en-Y gastric bypass in obese patients with BMI 35–60 kg/m2 – a multi-centre randomized patient and observer blind non-inferiority trial

    OpenAIRE

    2015-01-01

    Background: Roux-en-Ygastric bypass (RYGB) and sleeve gastrectomy (SG) rank among the most frequently applied bariatric procedures worldwide due to their positive risk/benefit correlation. A systematic review revealed a similar excess weight loss (EWL) 2 years postoperatively between SG and RYGB. However, there is a lack of randomized controlled multi-centre trials comparing SG and RYGB, not only concerning EWL, but also in terms of remission of obesity-related co-morbidities, gastroesophagea...

  2. Comparing the effectiveness of copper intrauterine devices available in Canada. Is FlexiT non-inferior to NovaT when inserted immediately after first-trimester abortion? Study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Norman Wendy V

    2012-08-01

    Full Text Available Abstract Background We describe the rationale and protocol for a randomized noninferiority controlled trial (RCT to determine if the Flexi-T380(+ copper intrauterine contraceptive device (IUD is comparable in terms of effectiveness and expulsion rates to the most common Canadian IUD currently in use, NovaT-200, when placed immediately after a first-trimester abortion. Methods/Design Consenting women choosing to use an IUD after an abortion for a pregnancy of less than 12 weeks of gestation will be randomized to device-type groups to receive immediate post-abortion placement of either a Flexi-T380(+ IUD, a device for which no current evidence on expulsion or effectiveness rates is available, or the Nova-T200 IUD, the only other brand of copper IUD available in Canada at the time of study initiation. The primary outcome measure is IUD expulsion rate at 1 year. Secondary outcomes include: pregnancy rate, method continuation rate, complication rates (infection, perforation, and satisfaction with contraceptive method. A non-intervention group of consenting women choosing a range of other post-abortion contraception methods, including no contraception, will be included for comparison of secondary outcomes. Web-based contraception satisfaction questionnaires, clinical records, and government-linked health administrative databases will be used to assess primary and secondary outcomes. Discussion The RCT design, combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry, and hospital records, offers a unique opportunity to determine if a novel IUD has a comparable expulsion rate to that of the current standard IUD in Canada, in addition to the first opportunity to determine pregnancy rate and method satisfaction at 1 year post-abortion for women choosing a range of post-abortion contraceptive options. We highlight considerations of

  3. Non-inferiority study design: lessons to be learned from cardiovascular trials.

    Science.gov (United States)

    Head, Stuart J; Kaul, Sanjay; Bogers, Ad J J C; Kappetein, A Pieter

    2012-06-01

    The non-inferiority trial design has gained popularity within the last decades to compare a new treatment to the standard active control. In contrast to superiority trials, this design is complex and is based on assumptions that cannot be validated directly. Many readers and even investigators, therefore, have difficulty grasping the full methodological nature of non-inferiority trials. Non-inferiority margins are often arbitrarily chosen such that a favourable margin can bias a trial towards declaring non-inferiority. Pitfalls of non-inferiority trials are not fully appreciated, and without having identified these shortcomings, objective conclusions from non-inferiority trials cannot be made. This methodological review elaborates on what is a non-inferiority trial, why such a trial is performed, what the hazards are, and how conclusions from non-inferiority trials are derived, by providing examples of recent cardiovascular trials.

  4. Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.

    Science.gov (United States)

    Komatsu, Yoshito; Okita, Kenji; Yuki, Satoshi; Furuhata, Tomohisa; Fukushima, Hiraku; Masuko, Hiroyuki; Kawamoto, Yasuyuki; Isobe, Hiroshi; Miyagishima, Takuto; Sasaki, Kazuaki; Nakamura, Michio; Ohsaki, Yoshinobu; Nakajima, Junta; Tateyama, Miki; Eto, Kazunori; Minami, Shinya; Yokoyama, Ryoji; Iwanaga, Ichiro; Shibuya, Hitoshi; Kudo, Mineo; Oba, Koji; Takahashi, Yasuo

    2015-07-01

    The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.

  5. Excited random walks: results, methods, open problems

    CERN Document Server

    Kosygina, Elena

    2012-01-01

    We consider a class of self-interacting random walks in deterministic or random environments, known as excited random walks or cookie walks, on the d-dimensional integer lattice. The main purpose of this paper is two-fold: to give a survey of known results and some of the methods and to present several new results. The latter include functional limit theorems for transient one-dimensional excited random walks in bounded i.i.d. cookie environments as well as some zero-one laws. Several open problems are stated.

  6. Efficacy and safety of the single-capsule combination of fluticasone/formoterol in patients with persistent asthma: a non-inferiority trial

    Directory of Open Access Journals (Sweden)

    Marti Antilla

    2014-12-01

    Full Text Available OBJECTIVE: Fluticasone and formoterol are effective in the treatment of asthma. When a corticosteroid alone fails to control asthma, combination therapy is the treatment of choice. The objective of this study was to compare the efficacy and safety of formulations containing budesonide/formoterol (BUD/FOR, fluticasone alone (FLU, and the single-capsule combination of fluticasone/formoterol (FLU/FOR on lung function in patients with mild-to-moderate persistent asthma. METHODS: This was a randomized, multicenter, open phase III trial conducted in Brazil. The primary efficacy analysis was the assessment of non-inferiority between FLU/FOR and BUD/FOR combinations regarding FEV1 (in L at the final visit. The secondary analyses were PEF, level of asthma control, serum cortisol levels, frequency of adverse events, adherence to treatment, and appropriate inhaler use. RESULTS: We randomized 243 patients to three groups: FLU/FOR (n = 79, BUD/FOR (n = 83, and FLU (n = 81. In terms of the mean FEV1 after 12 weeks of treatment, the difference between the FLU/FOR and BUD/FOR groups was 0.22 L (95% CI: −0.06 to 0.49, whereas the difference between the FLU/FOR and FLU groups was 0.26 L (95% CI: −0.002 to 0.52. Non-inferiority was demonstrated by the difference between the lower limits of the two 95% CIs (−0.06 vs. −0.002. The level of asthma control and PEF were significantly greater in the FLU/FOR and BUD/FOR groups than in the FLU group. There were no significant differences among the groups regarding patient adherence, patient inhaler use, or safety profile of the formulations. CONCLUSIONS: The single-capsule combination of FLU/FOR showed non-inferiority to the BUD/FOR and FLU formulations regarding efficacy and safety, making it a new treatment option for persistent asthma.

  7. A multi-centre open-label randomised non-inferiority trial comparing watchful waiting to antibiotic treatment for acute otitis media without perforation in low-risk urban Aboriginal and Torres Strait Islander children (the WATCH trial): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Abbott, Penelope; Gunasekera, Hasantha; Leach, Amanda Jane; Askew, Deborah; Walsh, Robyn; Kong, Kelvin; Girosi, Federico; Bond, Chelsea; Morris, Peter; Lujic, Sanja; Hu, Wendy; Usherwood, Tim; Tyson, Sissy; Spurling, Geoffrey; Douglas, Markeeta; Schubert, Kira; Chapman, Shavaun; Siddiqui, Nadeem; Murray, Reeion; Rabbitt, Keitha; Porykali, Bobby; Woodall, Cheryl; Newman, Tina; Reath, Jennifer

    2016-03-03

    Treatment guidelines recommend watchful waiting for children older than 2 years with acute otitis media (AOM) without perforation, unless they are at high risk of complications. The high prevalence of chronic suppurative otitis media (CSOM) in remote Aboriginal and Torres Strait Islander communities leads these children to be classified as high risk. Urban Aboriginal and Torres Strait Islander children are at lower risk of complications, but evidence to support the subsequent recommendation for watchful waiting in this population is lacking. This non-inferiority multi-centre randomised controlled trial will determine whether watchful waiting is non-inferior to immediate antibiotics for urban Aboriginal and Torres Strait Islander children with AOM without perforation. Children aged 2 - 16 years with AOM who are considered at low risk for complications will be recruited from six participating urban primary health care services across Australia. We will obtain informed consent from each participant or their guardian. The primary outcome is clinical resolution on day 7 (no pain, no fever of at least 38 °C, no bulging eardrum and no complications of AOM such as perforation or mastoiditis) as assessed by general practitioners or nurse practitioners. Participants and outcome assessors will not be blinded to treatment. With a sample size of 198 children in each arm, we have 80 % power to detect a non-inferiority margin of up to 10 % at a significance level of 5 %, assuming clinical improvement of at least 80 % in both groups. Allowing for a 20 % dropout rate, we aim to recruit 495 children. We will analyse both by intention-to-treat and per protocol. We will assess the cost- effectiveness of watchful waiting compared to immediate antibiotic prescription. We will also report on the implementation of the trial from the perspectives of parents/carers, health professionals and researchers. The trial will provide evidence for the safety and effectiveness of watchful waiting

  8. Randomized control of open quantum systems

    CERN Document Server

    Viola, L

    2006-01-01

    The problem of open-loop dynamical control of generic open quantum systems is addressed. In particular, I focus on the task of effectively switching off environmental couplings responsible for unwanted decoherence and dissipation effects. After revisiting the standard framework for dynamical decoupling via deterministic controls, I describe a different approach whereby the controller intentionally acquires a random component. An explicit error bound on worst-case performance of stochastic decoupling is presented.

  9. STAR Study: single tablet regimen emtricitabine/rilpivirine/tenofovir DF is non-inferior to efavirenz/emtricitabine/tenofovir DF in ART-naïve adults

    Directory of Open Access Journals (Sweden)

    C Cohen

    2012-11-01

    Full Text Available Simplified antiretroviral treatment (ART regimens improve quality of life and long-term medication adherence. Emtricitabine/rilpivirine/tenofovir DF (FTC/RPV/TDF is a well-tolerated, once daily single tablet regimen (STR treatment option. This is the first study to directly compare the safety and efficacy of the two STRs FTC/RPV/TDF and efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF in treatment-naïve adults. STaR is a randomized, open-label, multi-center, international, 96-week study to evaluate the safety and efficacy of the STR FTC/RPV/TDF compared to the STR EFV/FTC/TDF in treatment-naïve HIV-1-infected subjects. Subjects were randomized 1:1 to FTC/RPV/TDF or EFV/FTC/TDF. Eligibility criteria included screening HIV-1 RNA ≥2,500 c/mL, genotypic sensitivity to EFV, FTC, TDF, and RPV, and no prior ARV therapy. Randomization was stratified by HIV-1 RNA level (≤100,000 c/mL or >100,000 c/mL at screening. The primary endpoint was the proportion of subjects with HIV-1 RNA <50 c/mL at Week 48 as determined by the FDA snapshot algorithm (12% pre-specified non-inferiority margin. A total of 784 subjects were randomized and received at least one dose of study drug (392 FTC/RPV/TDF; 392 EFV/FTC/TDF. Baseline characteristics were similar in both treatment arms, with a baseline mean CD4 count of 390 cells/mm3. and HIV-1 RNA of 4.8 log10 c/mL. FTC/RPV/TDF was non-inferior to EFV/FTC/TDF (86% vs 81% at Week 48 for HIV RNA <50 c/mL (difference 4.0%, 95% CI [-1.2%, 9.2%] per FDA snapshot analysis. Superior efficacy was demonstrated for baseline HIV-1 RNA ≤100,000 c/mL (n=508, 88% FTC/RPV/TDF vs 81% EFV/FTC/TDF (difference 7.2%, 95% CI [0.9%, 13.4%], and non-inferior for >100,000 c/mL (n=276, 80% FTC/RPV/TDF vs 82% EFV/FTC/TDF (difference −1.8%, 95% CI [−11.2%, 7.5%]. Overall, virologic failure, defined as HIV RNA ≥50 c/mL at Week 48, discontinuation due to lack of efficacy per investigator or discontinuation of study drug for reasons other

  10. Open quantum systems and Random Matrix Theory

    CERN Document Server

    Mulhall, Declan

    2014-01-01

    A simple model for open quantum systems is analyzed with Random Matrix Theory. The system is coupled to the continuum in a minimal way. In this paper we see the effect of opening the system on the level statistics, in particular the $\\Delta_3(L)$ statistic, width distribution and level spacing are examined as a function of the strength of this coupling. A super-radiant transition is observed, and it is seen that as it is formed, the level spacing and $\\Delta_3(L)$ statistic exhibit the signatures of missed levels.

  11. Open quantum systems and random matrix theory

    Science.gov (United States)

    Mulhall, Declan

    2015-01-01

    A simple model for open quantum systems is analyzed with random matrix theory. The system is coupled to the continuum in a minimal way. In this paper the effect on the level statistics of opening the system is seen. In particular the Δ3(L ) statistic, the width distribution and the level spacing are examined as a function of the strength of this coupling. The emergence of a super-radiant transition is observed. The level spacing and Δ3(L ) statistics exhibit the signatures of missed levels or intruder levels as the super-radiant state is formed.

  12. Cost and Outcome of Behavioural Activation versus Cognitive Behavioural Therapy for Depression (COBRA): a randomised, controlled, non-inferiority trial.

    Science.gov (United States)

    Richards, David A; Ekers, David; McMillan, Dean; Taylor, Rod S; Byford, Sarah; Warren, Fiona C; Barrett, Barbara; Farrand, Paul A; Gilbody, Simon; Kuyken, Willem; O'Mahen, Heather; Watkins, Ed R; Wright, Kim A; Hollon, Steven D; Reed, Nigel; Rhodes, Shelley; Fletcher, Emily; Finning, Katie

    2016-08-27

    Depression is a common, debilitating, and costly disorder. Many patients request psychological therapy, but the best-evidenced therapy-cognitive behavioural therapy (CBT)-is complex and costly. A simpler therapy-behavioural activation (BA)-might be as effective and cheaper than is CBT. We aimed to establish the clinical efficacy and cost-effectiveness of BA compared with CBT for adults with depression. In this randomised, controlled, non-inferiority trial, we recruited adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder from primary care and psychological therapy services in Devon, Durham, and Leeds (UK). We excluded people who were receiving psychological therapy, were alcohol or drug dependent, were acutely suicidal or had attempted suicide in the previous 2 months, or were cognitively impaired, or who had bipolar disorder or psychosis or psychotic symptoms. We randomly assigned participants (1:1) remotely using computer-generated allocation (minimisation used; stratified by depression severity [Patient Health Questionnaire 9 (PHQ-9) score of inferiority margin was 1·9 PHQ-9 points. This trial is registered with the ISCRTN registry, number ISRCTN27473954. Between Sept 26, 2012, and April 3, 2014, we randomly allocated 221 (50%) participants to BA and 219 (50%) to CBT. 175 (79%) participants were assessable for the primary outcome in the mITT population in the BA group compared with 189 (86%) in the CBT group, whereas 135 (61%) were assessable in the PP population in the BA group compared with 151 (69%) in the CBT group. BA was non-inferior to CBT (mITT: CBT 8·4 PHQ-9 points [SD 7·5], BA 8·4 PHQ-9 points [7·0], mean difference 0·1 PHQ-9 points [95% CI -1·3 to 1·5], p=0·89; PP: CBT 7·9 PHQ-9 points [7·3]; BA 7·8 [6·5], mean difference 0·0 PHQ-9 points [-1·5 to 1·6], p=0·99). Two (1%) non-trial-related deaths (one [1%] multidrug toxicity in the BA group and one [1

  13. Non-inferiority clinical trials: Practical issues and current regulatory perspective

    Directory of Open Access Journals (Sweden)

    Sandeep K Gupta

    2011-01-01

    Full Text Available Non-inferiority clinical trials are being performed with an increasing frequency now-a-days, because it helps in finding a new treatment that have approximately the same efficacy, but may offer other benefits such as better safety profile. Non-inferiority clinical trials aim to demonstrate that the test product is no worse than the comparator by more than a pre-specified small amount. There are several fundamental differences between non-inferiority and superiority trials. Some practical issues concerning the non-inferiority trials are assay sensitivity, choice of the non-inferiority margin, sample size estimation, choice of active-control, and analysis of non-inferiority clinical trials. For serious infections such as hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia, community-acquired bacterial pneumonia, and acute bacterial skin and skin structure infections, the United States Food and Drug Administration (US FDA has recently recommended that it is possible to define a reliable and consistent estimate of the efficacy of active treatment relative to placebo from available data, which can serve as the basis for defining a new inferiority margin for an active-controlled, non-inferiority trial. But for some indications with a high rate of resolution without antibacterial drug therapy such as acute bacterial sinusitis (ABS, acute bacterial exacerbation of chronic bronchitis (ABECB, and acute bacterial otitis media (ABOM, the US FDA has recommended that the available data will not support the use of a non-inferiority design and other trial designs (i.e., superiority designs should be used to provide the evidence of effectiveness in these three indications.

  14. Sample Size Estimation for Non-Inferiority Trials: Frequentist Approach versus Decision Theory Approach.

    Directory of Open Access Journals (Sweden)

    A C Bouman

    Full Text Available Non-inferiority trials are performed when the main therapeutic effect of the new therapy is expected to be not unacceptably worse than that of the standard therapy, and the new therapy is expected to have advantages over the standard therapy in costs or other (health consequences. These advantages however are not included in the classic frequentist approach of sample size calculation for non-inferiority trials. In contrast, the decision theory approach of sample size calculation does include these factors. The objective of this study is to compare the conceptual and practical aspects of the frequentist approach and decision theory approach of sample size calculation for non-inferiority trials, thereby demonstrating that the decision theory approach is more appropriate for sample size calculation of non-inferiority trials.The frequentist approach and decision theory approach of sample size calculation for non-inferiority trials are compared and applied to a case of a non-inferiority trial on individually tailored duration of elastic compression stocking therapy compared to two years elastic compression stocking therapy for the prevention of post thrombotic syndrome after deep vein thrombosis.The two approaches differ substantially in conceptual background, analytical approach, and input requirements. The sample size calculated according to the frequentist approach yielded 788 patients, using a power of 80% and a one-sided significance level of 5%. The decision theory approach indicated that the optimal sample size was 500 patients, with a net value of €92 million.This study demonstrates and explains the differences between the classic frequentist approach and the decision theory approach of sample size calculation for non-inferiority trials. We argue that the decision theory approach of sample size estimation is most suitable for sample size calculation of non-inferiority trials.

  15. Sample Size Estimation for Non-Inferiority Trials: Frequentist Approach versus Decision Theory Approach.

    Science.gov (United States)

    Bouman, A C; ten Cate-Hoek, A J; Ramaekers, B L T; Joore, M A

    2015-01-01

    Non-inferiority trials are performed when the main therapeutic effect of the new therapy is expected to be not unacceptably worse than that of the standard therapy, and the new therapy is expected to have advantages over the standard therapy in costs or other (health) consequences. These advantages however are not included in the classic frequentist approach of sample size calculation for non-inferiority trials. In contrast, the decision theory approach of sample size calculation does include these factors. The objective of this study is to compare the conceptual and practical aspects of the frequentist approach and decision theory approach of sample size calculation for non-inferiority trials, thereby demonstrating that the decision theory approach is more appropriate for sample size calculation of non-inferiority trials. The frequentist approach and decision theory approach of sample size calculation for non-inferiority trials are compared and applied to a case of a non-inferiority trial on individually tailored duration of elastic compression stocking therapy compared to two years elastic compression stocking therapy for the prevention of post thrombotic syndrome after deep vein thrombosis. The two approaches differ substantially in conceptual background, analytical approach, and input requirements. The sample size calculated according to the frequentist approach yielded 788 patients, using a power of 80% and a one-sided significance level of 5%. The decision theory approach indicated that the optimal sample size was 500 patients, with a net value of €92 million. This study demonstrates and explains the differences between the classic frequentist approach and the decision theory approach of sample size calculation for non-inferiority trials. We argue that the decision theory approach of sample size estimation is most suitable for sample size calculation of non-inferiority trials.

  16. Multicentre study evaluating the non-inferiority of the new paediatric formulation of artesunate/amodiaquine versus artemether/lumefantrine for the management of uncomplicated Plasmodium falciparum malaria in children in Cameroon, Ivory Coast and Senegal.

    Science.gov (United States)

    Faye, Babacar; Kuété, Thomas; Kiki-Barro, Christiane P; Tine, Roger C; Nkoa, Thérèse; Ndiaye, Jean Louis A; Kakpo, Claude A; Sylla, Khadime; El Menan, Hervé; Gaye, Oumar; Faye, Oumar; Same-Ekobo, Albert; Moussa, Koné

    2012-12-27

    This multicentre study was carried out in Cameroon, Ivory Coast and Senegal to evaluate the non-inferiority of the new paediatric formulation of artesunate/amodiaquine (AS+AQ)(Camoquin-Plus Paediatric®) in suspension form versus artemether/lumefantrine (AL)(Coartem®) in the management of African children with uncomplicated falciparum malaria. It was an open randomized trial including children aged between 7 months and 7 years. The endpoints were Adequate Clinical and Parasitological Response (ACPR) at day 28, the clinical and biological tolerability. Statistical analyses were done in Intention To Treat (ITT) and in Per protocol (PP). At the end of the study 481 patients were enrolled in the three countries (249 in the AS+AQ arm and 232 in the AL arm). ACRP in ITT after PCR correction did not show any statistical difference between the two groups with 97.6% for AS+AQ versus 94.8% for AL. In the PP analysis, the corrected ACRP were respectively 98.7% and 96.9% for the two regimens. The clinical tolerance was good without significant difference. Anaemia was significantly higher at D7 in the two groups compared to D0. This study demonstrates the non-inferiority of AS+AQ versus AL, its efficacy and tolerance in the management of uncomplicated Plasmodium falciparum malaria in African children.

  17. Likelihood ratio and score tests to test the non-inferiority (or equivalence) of the odds ratio in a crossover study with binary outcomes.

    Science.gov (United States)

    Li, Xiaochun; Li, Huilin; Jin, Man; D Goldberg, Judith

    2016-09-10

    We consider the non-inferiority (or equivalence) test of the odds ratio (OR) in a crossover study with binary outcomes to evaluate the treatment effects of two drugs. To solve this problem, Lui and Chang (2011) proposed both an asymptotic method and a conditional method based on a random effects logit model. Kenward and Jones (1987) proposed a likelihood ratio test (LRTM ) based on a log linear model. These existing methods are all subject to model misspecification. In this paper, we propose a likelihood ratio test (LRT) and a score test that are independent of model specification. Monte Carlo simulation studies show that, in scenarios considered in this paper, both the LRT and the score test have higher power than the asymptotic and conditional methods for the non-inferiority test; the LRT, score, and asymptotic methods have similar power, and they all have higher power than the conditional method for the equivalence test. When data can be well described by a log linear model, the LRTM has the highest power among all the five methods (LRTM , LRT, score, asymptotic, and conditional) for both non-inferiority and equivalence tests. However, in scenarios for which a log linear model does not describe the data well, the LRTM has the lowest power for the non-inferiority test and has inflated type I error rates for the equivalence test. We provide an example from a clinical trial that illustrates our methods. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Zotarolimus-eluting durable-polymer-coated stent versus a biolimus-eluting biodegradable-polymer-coated stent in unselected patients undergoing percutaneous coronary intervention (SORT OUT VI): a randomised non-inferiority trial.

    Science.gov (United States)

    Raungaard, Bent; Jensen, Lisette Okkels; Tilsted, Hans-Henrik; Christiansen, Evald Høj; Maeng, Michael; Terkelsen, Christian Juhl; Krusell, Lars Romer; Kaltoft, Anne; Kristensen, Steen Dalby; Bøtker, Hans Erik; Thuesen, Leif; Aarøe, Jens; Jensen, Svend Eggert; Villadsen, Anton Boel; Thayssen, Per; Veien, Karsten Tange; Hansen, Knud Nørregaard; Junker, Anders; Madsen, Morten; Ravkilde, Jan; Lassen, Jens Flensted

    2015-04-18

    New-generation drug-eluting coronary stents have reduced the risk of coronary events, especially in patients with complex disease or lesions. To what extent different stent platforms, polymers, and antiproliferative drugs affect outcomes, however, is unclear. We investigated the safety and efficacy of a third-generation stent by comparing a highly biocompatible durable-polymer-coated zotarolimus-eluting stent with a biodegradable-polymer-coated biolimus-eluting stent. This open-label, randomised, multicentre, non-inferiority trial was done at three sites across western Denmark. All patients who presented with stable coronary artery disease or acute coronary syndromes and at least one coronary artery lesion (more than 50% stenosis) from March, 2011, to August, 2012, were assessed for eligibility. Patients were randomly assigned in a 1:1 ratio to receive either the durable-polymer zotarolimus-eluting stent or the biodegradable-polymer biolimus-eluting stent. The primary endpoint was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target-lesion revascularisation) at 12 months, analysed by intention to treat. The trial was powered to assess non-inferiority of durable-polymer zotarolimus-eluting stent compared with the biodegradable-polymer biolimus-eluting stent with a predetermined non-inferiority margin of 0·025. This trial is registered with ClinicalTrials.gov, number NCT01956448. Of 7103 screened, 1502 patients with 1883 lesions were assigned to receive the durable-polymer zotarolimus-eluting stent and 1497 patients with 1791 lesions to receive the biodegradable-polymer biolimus-eluting stent. 79 (5·3%) and 75 (5·0%) patients, respectively, met the primary endpoint (absolute risk difference 0·0025, upper limit of one-sided 95% CI 0·016%; p=0·004). The individual components of the primary endpoint did not differ significantly between stent types at 12 months. The durable

  19. Issues on the selection of non-inferiority margin in clinical trials

    Institute of Scientific and Technical Information of China (English)

    HOU Yan; WU Xiao-yan; LI Kang

    2009-01-01

    Objective The determination of non-inferiority margin is an important and confusing issue which directly influences the acceptability of a new medication. We reviewed the published literature, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guidelines and Committee for Proprietary Medicinal Products (CPMP) papers on the selection of non-inferiority margin and the corresponding statistical tests in clinical trials, in order to provide practical recommendations and suggestions for establishing reference criteria for the non-inferiority margin in China.Data sources The literature on the selection of a non-inferiority margin and statistical tests was mainly extracted from relevant English articles on non-inferior clinical trials published from 1990 to 2007. The starting point (1990) was chosen due to lack of such papers published prior to 1990. This literature was searched via PubMed, Medline and Chinese Knowledge Information (CNKI). ICH guidelines and CPMP papers were downloaded from their official websites. The keywords "clinical trial", "non-inferiority" and "non-inferiority margin" were used.Study selection Forty-three original articles and critical reviews, ICH E10 guideline and CPMP papers were selected.Results The non-inferiority testing with treatment difference and ratio are commonly used, where the non-inferiority margin is determined with and without historical data. Traditionally, this margin is treated as a fixed value, while developed methods take the variation into account in the determination of this margin, on which the test depends is more convincing. The mixed margin consisting of a margin based on treatment difference and a margin based on treatment ratio can exactly control the type Ⅰ error at the desirable level and obtain a better power. In this review, we also provide some recommendations and suggestions for the selection of the non-inferiority margin in the western

  20. Treatment crossovers in time-to-event non-inferiority randomised trials of radiotherapy in patients with breast cancer

    Science.gov (United States)

    Parpia, Sameer; Julian, Jim A; Thabane, Lehana; Gu, Chushu; Whelan, Timothy J; Levine, Mark N

    2014-01-01

    Background In non-inferiority trials of radiotherapy in patients with early stage breast cancer, it is inevitable that some patients will cross over from the experimental arm to the standard arm prior to initiation of any treatment due to complexities in treatment planning or subject preference. Although the intention-to-treat (ITT) analysis is the preferred approach for superiority trials, its role in non-inferiority trials is still under debate. This has led to the use of alternative approaches such as the per-protocol (PP) analysis or the as-treated (AT) analysis, despite the inherent biases of such approaches. Methods Using simulations, we investigate the effect of 2%, 5% and 10% random and non-random crossovers prior to radiotherapy initiation on the ITT, PP, AT and the combination of ITT and PP analyses with respect to type I error in trials with time-to-event outcomes. We also evaluate bias and SE of the estimates from the ITT, PP and AT approaches. Results The AT approach had the best performance in terms of type I error, but was anticonservative as non-random crossover increased. The ITT and PP approaches were anticonservative under all percentages of random and non-random crossover. Similarly, lowest bias was seen with the AT approach; however, bias increased as the percentage of non-random crossover increased. The ITT and PP had poor performance in terms of bias as crossovers increased. Conclusions If minimal crossovers were to occur, we have shown that the AT approach has the lowest type I error rates and smallest opportunity for bias. Results of trials with a high number of crossovers should be interpreted with caution, especially when crossover is non-random. Attempts to prevent crossovers should be maximised. PMID:25344487

  1. Non-inferiority of minimally invasive oesophagectomy: an 8-year retrospective case series.

    Science.gov (United States)

    Findlay, L; Yao, C; Bennett, D H; Byrom, R; Davies, N

    2017-01-11

    The trend towards laparoscopic surgery seen in other specialties has not occurred at the same pace in oesophagectomy. This stems from concerns regarding compromised oncological clearance, and complications associated with gastric tube necrosis and anastomotic failure. We present our experience of minimally invasive oesophagectomy (MIO) compared to open and hybrid surgery. We aim to ascertain non-inferiority of MIO by evaluating impact on survival, oncological clearance by resection margin and lymph node harvest and post-operative complications. Data were sourced retrospectively 2008-2015. Three approaches were studied. MIO (3-stage Mckeown), hybrid (2-stage Ivor Lewis, laparoscopy, thoracotomy) and open (2-stage Ivor Lewis). Five-year survival was 54.2%. Surgical approach had no significant impact on survival at any stage of disease (Stage 0/I p = 0.98; stage II p = 0.2; stage III p = 0.76). There was no statistically significant difference in oncological clearance by resection margins between procedures when compared by disease stage (p = 0.49). A higher number of nodes were harvested in hybrid [median 27.5 (6-65)] and open surgeries [median 26 (4-54)] than in MIO [median 20 (7-44)] (p > 0.01). Numbers of nodes resected did not impact risk of recurrence [recurrence, median 25 (6-54), no recurrence, 26 (4-65)] (p = 0.25). Anastomotic strictures (22.4%) and potential leaks (17.9%) were more common in MIO (strictures p > 0.01, leaks p = 0.08), although associated morbidity was lower. Respiratory complications were less common in MIO (2.9%) versus hybrid (13.3%) (p = 0.02). Wound infection and chyle leak were also lower (wound 1.5% MIO 3.5% open, p = 0.6; chyle leak 1.5% MIO, 6.7% hybrid, p = 0.2). Our results show no negative impact of MIO on survival or oncological clearance. Respiratory and wound complications are lower in MIO, but rates of anastomotic strictures and potential anastomotic leaks are increased. This may be due to the longer

  2. 75 FR 9228 - Draft Guidance for Industry on Non-Inferiority Clinical Trials; Availability

    Science.gov (United States)

    2010-03-01

    ...The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Non- Inferiority Clinical Trials.'' This draft guidance provides sponsors and review staff in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) with the agency's interpretation of the underlying principles involved in the......

  3. Permutation test for non-inferiority of the linear to the optimal combination of multiple tests.

    Science.gov (United States)

    Jin, Hua; Lu, Ying

    2009-03-01

    We proposed a permutation test for non-inferiority of the linear discriminant function to the optimal combination of multiple tests based on Mann-Whitney statistic estimate of the area under the receiver operating characteristic curve. Monte Carlo simulations showed its good performance.

  4. Bronchodilator efficacy of 18 µg once-daily tiotropium inhalation via Discair® versus HandiHaler® in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial

    Directory of Open Access Journals (Sweden)

    Yildiz P

    2016-11-01

    Full Text Available Pinar Yildiz, Mesut Bayraktaroglu, Didem Gorgun, Funda Secik Clinics of Chest Diseases, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey Purpose: To compare the bronchodilator efficacy of 18 µg once-daily tiotropium inhalation administered via Discair® versus HandiHaler® in adults with moderate-to-severe chronic obstructive pulmonary disease (COPD.Patients and methods: Fifty-eight patients with moderate-to-severe COPD were enrolled in this randomized, active-controlled, parallel-group, open-label, Phase IV non-inferiority trial. Patients were randomly assigned to a test group (n=29, inhalation with Discair or a reference group (n=29, inhalation with HandiHaler. The primary efficacy parameter was the average maximum change in forced expiratory volume in 1 second (FEV1, in L. Change in forced vital capacity (FVC, in L, %FEV1 and %FVC, the standardized area under the response–time curve (AUC for the absolute change in FEV1 and FVC, time to onset and peak of response, and safety data were also evaluated.Results: The test inhaler was non-inferior to the reference inhaler in terms of maximum change in FEV1 at 24 h (unadjusted change: 0.0017 L [95% confidence interval [CI]: –0.0777, 0.0812]; change adjusted for time to reach maximum change in FEV1 and smoking in pack-years: 0.0116 L [95% CI: –0.0699, 0.0931], based on a non-inferiority margin of 0.100 L. There were also no significant differences between the two groups in maximum change in FVC value from baseline (0.3417 L vs 0.4438 L, P=0.113, percent change from baseline (22.235 vs 20.783 for FEV1, P=0.662; 16.719 vs 20.337 for FVC, P=0.257, and AUC0–24 h (2.949 vs 2.833 L for FEV1, P=0.891; 2.897 vs 4.729 L for FVC, P=0.178. There were no adverse events, serious adverse events, or deaths.Conclusion: Our findings show that the Discair was non-inferior to the HandiHaler. More specifically, these devices had similar clinical efficacy in terms of

  5. Quality of reporting of clinical non-inferiority and equivalence randomised trials - update and extension

    Directory of Open Access Journals (Sweden)

    Schiller Petra

    2012-11-01

    Full Text Available Abstract Background Non-inferiority and equivalence trials require tailored methodology and therefore adequate conduct and reporting is an ambitious task. The aim of our review was to assess whether the criteria recommended by the CONSORT extension were followed. Methods We searched the Medline database and the Cochrane Central Register for reports of randomised non-inferiority and equivalence trials published in English language. We excluded reports on bioequivalence studies, reports targeting on other than the main results of a trial, and articles of which the full-text version was not available. In total, we identified 209 reports (167 non-inferiority, 42 equivalence trials and assessed the reporting and methodological quality using abstracted items of the CONSORT extension. Results Half of the articles did not report on the method of randomisation and only a third of the trials were reported to use blinding. The non-inferiority or equivalence margin was defined in most reports (94%, but was justified only for a quarter of the trials. Sample size calculation was reported for a proportion of 90%, but the margin was taken into account in only 78% of the trials reported. Both intention-to-treat and per-protocol analysis were presented in less than half of the reports. When reporting the results, a confidence interval was given for 85% trials. A proportion of 21% of the reports presented a conclusion that was wrong or incomprehensible. Overall, we found a substantial lack of quality in reporting and conduct. The need to improve also applied to aspects generally recommended for randomised trials. The quality was partly better in high-impact journals as compared to others. Conclusions There are still important deficiencies in the reporting on the methodological approach as well as on results and interpretation even in high-impact journals. It seems to take more than guidelines to improve conduct and reporting of non-inferiority and equivalence

  6. A comparison of methods for sample size estimation for non-inferiority studies with binary outcomes.

    Science.gov (United States)

    Julious, Steven A; Owen, Roger J

    2011-12-01

    Non-inferiority trials are motivated in the context of clinical research where a proven active treatment exists and placebo-controlled trials are no longer acceptable for ethical reasons. Instead, active-controlled trials are conducted where a treatment is compared to an established treatment with the objective of demonstrating that it is non-inferior to this treatment. We review and compare the methodologies for calculating sample sizes and suggest appropriate methods to use. We demonstrate how the simplest method of using the anticipated response is predominantly consistent with simulations. In the context of trials with binary outcomes with expected high proportions of positive responses, we show how the sample size is quite sensitive to assumptions about the control response. We recommend when designing such a study that sensitivity analyses be performed with respect to the underlying assumptions and that the Bayesian methods described in this article be adopted to assess sample size.

  7. Re-formulating non-inferiority trials as superiority trials: The case of binary outcomes.

    Science.gov (United States)

    Durkalski, Valerie L; Berger, Vance W

    2009-02-01

    Non-inferiority trials are conducted for a variety of reasons including to show that a new treatment has a negligible reduction in efficacy or safety when compared to the current standard treatment, or a more complex setting of showing that a new treatment has a negligible reduction in efficacy when compared to the current standard yet is superior in terms of other treatment characteristics. The latter reason for conducting a non-inferiority trial presents the challenge of deciding on a balance between a suitable reduction in efficacy, known as the non-inferiority margin, in return for a gain in other important treatment characteristics/findings. It would be ideal to alleviate the dilemma on the choice of margin in this setting by reverting to a traditional superiority trial design where a single p -value for superiority of both the most important endpoint (efficacy) and the most important finding (treatment characteristic) is provided. We discuss how this can be done using the information-preserving composite endpoint (IPCE) approach and consider binary outcome cases in which the combination of efficacy and treatment characteristics, but not one itself, paints a clear picture that the novel treatment is superior to the active control. 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Open quantum systems and random matrix theory

    Science.gov (United States)

    Mulhall, Declan

    2014-10-01

    A simple model for open quantum systems is analyzed with RMT. The system is coupled to the continuum in a minimal way. In this paper we see the effect of opening the system on the level statistics, in particular the level spacing, width distribution and Δ3(L) statistic are examined as a function of the strength of this coupling. The usual super-radiant state is observed, and it is seen that as it is formed, the level spacing and Δ3(L) statistic exhibit the signatures of missed levels.

  9. Open quantum systems and random matrix theory

    Energy Technology Data Exchange (ETDEWEB)

    Mulhall, Declan [Department of Physics/Engineering, University of Scranton, Scranton, Pennsylvania 18510-4642 (United States)

    2014-10-15

    A simple model for open quantum systems is analyzed with RMT. The system is coupled to the continuum in a minimal way. In this paper we see the effect of opening the system on the level statistics, in particular the level spacing, width distribution and Δ{sub 3}(L) statistic are examined as a function of the strength of this coupling. The usual super-radiant state is observed, and it is seen that as it is formed, the level spacing and Δ{sub 3}(L) statistic exhibit the signatures of missed levels.

  10. Random walks of cytoskeletal motors in open and closed compartments

    NARCIS (Netherlands)

    Lipowsky, R.; Klumpp, S.

    2001-01-01

    Random walks of molecular motors, which bind to and unbind from cytoskeletal filaments, are studied theoretically. The bound and unbound motors undergo directed and nondirected motion, respectively. Motors in open compartments exhibit anomalous drift velocities. Motors in closed compartments generat

  11. Randomized clinical trial of laparoscopic versus open appendicectomy

    DEFF Research Database (Denmark)

    Pedersen, Allan Gorm; Petersen, O B; Wara, P;

    2001-01-01

    BACKGROUND: Laparoscopy in patients with a clinical suspicion of acute appendicitis has not gained wide acceptance, and its use remains controversial. METHODS: In a randomized controlled trial of laparoscopic versus open appendicectomy, 583 of 828 consecutive patients consented to participate...

  12. Random density matrices versus random evolution of open system

    Science.gov (United States)

    Pineda, Carlos; Seligman, Thomas H.

    2015-10-01

    We present and compare two families of ensembles of random density matrices. The first, static ensemble, is obtained foliating an unbiased ensemble of density matrices. As criterion we use fixed purity as the simplest example of a useful convex function. The second, dynamic ensemble, is inspired in random matrix models for decoherence where one evolves a separable pure state with a random Hamiltonian until a given value of purity in the central system is achieved. Several families of Hamiltonians, adequate for different physical situations, are studied. We focus on a two qubit central system, and obtain exact expressions for the static case. The ensemble displays a peak around Werner-like states, modulated by nodes on the degeneracies of the density matrices. For moderate and strong interactions good agreement between the static and the dynamic ensembles is found. Even in a model where one qubit does not interact with the environment excellent agreement is found, but only if there is maximal entanglement with the interacting one. The discussion is started recalling similar considerations for scattering theory. At the end, we comment on the reach of the results for other convex functions of the density matrix, and exemplify the situation with the von Neumann entropy.

  13. Sacrospinous hysteropexy versus vaginal hysterectomy with suspension of the uterosacral ligaments in women with uterine prolapse stage 2 or higher: multicentre randomised non-inferiority trial

    NARCIS (Netherlands)

    Detollenaere, R.J.; Boon, J. den; Stekelenburg, J.; IntHout, J.; Vierhout, M.E.; Kluivers, K.B.; Eijndhoven, H.W. van

    2015-01-01

    OBJECTIVE: To investigate whether uterus preserving vaginal sacrospinous hysteropexy is non-inferior to vaginal hysterectomy with suspension of the uterosacral ligaments in the surgical treatment of uterine prolapse. DESIGN: Multicentre randomised controlled non-blinded non-inferiority trial.

  14. COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer

    DEFF Research Database (Denmark)

    2009-01-01

    INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. Trial design: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized...... clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy...... analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal...

  15. A combined superiority and non-inferiority approach to multiple endpoints in clinical trials.

    Science.gov (United States)

    Bloch, Daniel A; Lai, Tze Leung; Su, Zheng; Tubert-Bitter, Pascale

    2007-03-15

    Treatment comparisons in clinical trials often involve multiple endpoints. By making use of bootstrap tests, we develop a new non-parametric approach to multiple-endpoint testing that can be used to demonstrate non-inferiority of a new treatment for all endpoints and superiority for some endpoint when it is compared to an active control. It is shown that this approach does not incur a large multiplicity cost in sample size to achieve reasonable power and that it can incorporate complex dependencies in the multivariate distributions of all outcome variables for the two treatments via bootstrap resampling. Copyright (c) 2006 John Wiley & Sons, Ltd.

  16. Testing non-inferiority of a new treatment in three-arm clinical trials with binary endpoints.

    Science.gov (United States)

    Tang, Nian-Sheng; Yu, Bin; Tang, Man-Lai

    2014-12-18

    A two-arm non-inferiority trial without a placebo is usually adopted to demonstrate that an experimental treatment is not worse than a reference treatment by a small pre-specified non-inferiority margin due to ethical concerns. Selection of the non-inferiority margin and establishment of assay sensitivity are two major issues in the design, analysis and interpretation for two-arm non-inferiority trials. Alternatively, a three-arm non-inferiority clinical trial including a placebo is usually conducted to assess the assay sensitivity and internal validity of a trial. Recently, some large-sample approaches have been developed to assess the non-inferiority of a new treatment based on the three-arm trial design. However, these methods behave badly with small sample sizes in the three arms. This manuscript aims to develop some reliable small-sample methods to test three-arm non-inferiority. Saddlepoint approximation, exact and approximate unconditional, and bootstrap-resampling methods are developed to calculate p-values of the Wald-type, score and likelihood ratio tests. Simulation studies are conducted to evaluate their performance in terms of type I error rate and power. Our empirical results show that the saddlepoint approximation method generally behaves better than the asymptotic method based on the Wald-type test statistic. For small sample sizes, approximate unconditional and bootstrap-resampling methods based on the score test statistic perform better in the sense that their corresponding type I error rates are generally closer to the prespecified nominal level than those of other test procedures. Both approximate unconditional and bootstrap-resampling test procedures based on the score test statistic are generally recommended for three-arm non-inferiority trials with binary outcomes.

  17. Half dose sugammadex combined with neostigmine is non-inferior to full dose sugammadex for reversal of rocuronium-induced deep neuromuscular blockade: a cost-saving strategy.

    Science.gov (United States)

    Aouad, Marie T; Alfahel, Waseem S; Kaddoum, Roland N; Siddik-Sayyid, Sahar M

    2017-04-11

    Sugammadex reverses the effect of rocuronium more rapidly and effectively than neostigmine, at all levels of neuromuscular blockade (NMB). However, its cost is prohibitive. The combination of half dose sugammadex with neostigmine would be non-inferior to full dose sugammadex for the reversal of deep NMB. This approach would reduce the cost of sugammadex while preserving its efficacy. Patients were randomly allocated to receive sugammadex 4 mg/kg (Group S) or sugammadex 2 mg/kg with neostigmine 50 μg/kg and glycopyrrolate 10 μg/kg (Group NS) for reversal of rocuronium deep NMB. The primary outcome was the percentage of patients who recovered to 90% Train of Four (TOF) ratio within 5 min. The non-inferiority margin was set at 10%. Twenty eight patients were enrolled in each group. The number of patients who reached 90% TOF ratio within 5 min was 27 out of 28 (96%) in group S versus 25 out of 28 (89%) in group NS by intention-to-treat (difference: 7%, 95% CI of the difference: -9% to 24%). The number of patients who reached 90% TOF ratio within 5 min was 26 out of 26 (100%) in group S versus 23 out of 25 (92%) in group NS by per-protocol (difference: 8%, 95% CI of the difference: -6% to 25%). Sugammadex 2 mg/kg with neostigmine 50 μg/kg was at worst 9% and 6% less effective than sugammadex 4 mg/kg by intention-to-treat and by per-protocol analysis respectively. Hence, the combination is non-inferior to the recommended dose of sugammadex. Clinicaltrials.gov NCT 02375217 , registered on February 11, 2015.

  18. Enteral Antibiotics are Non-inferior to Intravenous Antibiotics After Complicated Appendicitis in Adults

    DEFF Research Database (Denmark)

    Kleif, Jakob; Rasmussen, Louise; Fonnes, Siv

    2017-01-01

    BACKGROUND: Prolonging post-operative antibiotic treatment beyond 3 days does not seem to reduce the incidence of post-operative abscess formation or wound infection after surgery for complicated appendicitis. The route of administration seems to be based on an empirical basis. Using enteral...... antibiotics could reduce length of stay and reduce overall costs. We aimed to examine whether treatment with enteral antibiotics during the first three post-operative days is non-inferior to intravenous antibiotics regarding intra-abdominal abscess formation or wound infection after surgery for complicated...... of surgery. Route of antibiotic administration for the first three post-operative days was registered for all patients. RESULTS: A total of 1141 patients were included in the study. The overall risk of developing an intra-abdominal abscess was 6.7% (95% CI 5.2%; 8.1%), and the risk of wound infection was 1...

  19. A group sequential type design for three-arm non-inferiority trials with binary endpoints.

    Science.gov (United States)

    Li, Gang; Gao, Shan

    2010-08-01

    The three-arm design with a test treatment, an active control and a placebo group is the gold standard design for non-inferiority trials if it is ethically justifiable to expose patients to placebo. In this paper, we first use the closed testing principle to establish the hierarchical testing procedure for the multiple comparisons involved in the three-arm design. For the effect preservation test we derive the explicit formula for the optimal allocation ratios. We propose a group sequential type design, which naturally accommodates the hierarchical testing procedure. Under this proposed design, Monte Carlo simulations are conducted to evaluate the performance of the sequential effect preservation test when the variance of the test statistic is estimated based on the restricted maximum likelihood estimators of the response rates under the null hypothesis. When there are uncertainties for the placebo response rate, the proposed design demonstrates better operating characteristics than the fixed sample design.

  20. Blinded sample size reestimation in non-inferiority trials with binary endpoints.

    Science.gov (United States)

    Friede, Tim; Mitchell, Charles; Müller-Velten, Günther

    2007-12-01

    Sample size calculations in the planning of clinical trials depend on good estimates of the model parameters involved. When the estimates of these parameters have a high degree of uncertainty attached to them, it is advantageous to reestimate the sample size after an internal pilot study. For non-inferiority trials with binary outcome we compare the performance of Type I error rate and power between fixed-size designs and designs with sample size reestimation. The latter design shows itself to be effective in correcting sample size and power of the tests when misspecification of nuisance parameters occurs with the former design. (c) 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

  1. Stochastic perturbations in open chaotic systems: random versus noisy maps.

    Science.gov (United States)

    Bódai, Tamás; Altmann, Eduardo G; Endler, Antonio

    2013-04-01

    We investigate the effects of random perturbations on fully chaotic open systems. Perturbations can be applied to each trajectory independently (white noise) or simultaneously to all trajectories (random map). We compare these two scenarios by generalizing the theory of open chaotic systems and introducing a time-dependent conditionally-map-invariant measure. For the same perturbation strength we show that the escape rate of the random map is always larger than that of the noisy map. In random maps we show that the escape rate κ and dimensions D of the relevant fractal sets often depend nonmonotonically on the intensity of the random perturbation. We discuss the accuracy (bias) and precision (variance) of finite-size estimators of κ and D, and show that the improvement of the precision of the estimations with the number of trajectories N is extremely slow ([proportionality]1/lnN). We also argue that the finite-size D estimators are typically biased. General theoretical results are combined with analytical calculations and numerical simulations in area-preserving baker maps.

  2. Non-inferiority of retrospective data collection for assessing perioperative morbidity

    Science.gov (United States)

    Patel, Amour B.U.; Reyes, Anna

    2015-01-01

    Background. Postoperative morbidity has immediate and delayed consequences for surgical patients, including excess risk of premature death. Capturing these data objectively and routinely in large electronic databases using tools such as the Postoperative Morbidity Survey (POMS) would offer tremendous clinical and translational potential. However, POMS has thus far only utilised prospective data collection by research staff. We hypothesised that retrospective data collection from routinely collated hospital data from paper and electronic charts, medical and nursing notes was non-inferior to prospective data collection requiring research staff capturing POMS-defined morbidity in real-time. Methods. Morbidity was recorded by a trained investigator as defined by POMS prospectively on postoperative days 3 and 7. Separately, an independent investigator blinded to prospectively acquired data retrospectively assessed the same patients’ morbidity as defined by POMS criteria, using medical charts, nursing summaries and electronic data. Equivalence was accepted when the confidence limits for both modes of data collection fell completely inside the equivalence bounds, with the maximum equivalence difference (i.e., the largest value of the difference in sensitivities deemed to reach a conclusion of equivalence) set a priori at 0.2. Differences for confidence limits between retrospective and prospective data collection were based on Nam’s RMLE method. The relationship between morbidity on postoperative day 3 as recorded by each data collection method on time to become morbidity free and length of hospital stay was compared using the log-rank test. Results. POMS data from 85 patients undergoing elective or emergency surgery were analyzed. At postoperative day 3, POMS-defined morbidity was similar regardless of whether data were collected prospectively or retrospectively (95% CI [−0.13–0.013]; p < 0.001). Non-inferiority for sensitivity was observed for all other POMS

  3. Two new covariate adjustment methods for non-inferiority assessment of binary clinical trials data.

    Science.gov (United States)

    Hou, Yan; Ding, Victoria; Li, Kang; Zhou, Xiao-Hua

    2011-01-01

    In clinical trials, examining the adjusted treatment difference has become the preferred way to establish non-inferiority (NI) in cases involving a binary endpoint. However, current methods are inadequate in the area of covariate adjustment. In this paper, we introduce two new methods, nonparametric and parametric, of using the probability and probability (P-P) curve to address the issue of unadjusted categorical covariates in the traditional assessment of NI in clinical trials. We also show that the area under the P-P curve is a valid alternative for assessing NI using the adjusted treatment difference, and we compute this area using Mann-Whitney nonparametric statistics. Our simulation studies demonstrate that our proposed methods can not only control type I error at a predefined significance level but also achieve higher statistical power than those of traditional parametric and nonparametric methods that overlook covariate adjustment, especially when covariates are unbalanced in the two treatment groups. We illustrate the effectiveness of our methodology with data from clinical trials of a therapy for coronary heart disease.

  4. Sample size considerations in active-control non-inferiority trials with binary data based on the odds ratio.

    Science.gov (United States)

    Siqueira, Arminda Lucia; Todd, Susan; Whitehead, Anne

    2015-08-01

    This paper presents an approximate closed form sample size formula for determining non-inferiority in active-control trials with binary data. We use the odds-ratio as the measure of the relative treatment effect, derive the sample size formula based on the score test and compare it with a second, well-known formula based on the Wald test. Both closed form formulae are compared with simulations based on the likelihood ratio test. Within the range of parameter values investigated, the score test closed form formula is reasonably accurate when non-inferiority margins are based on odds-ratios of about 0.5 or above and when the magnitude of the odds ratio under the alternative hypothesis lies between about 1 and 2.5. The accuracy generally decreases as the odds ratio under the alternative hypothesis moves upwards from 1. As the non-inferiority margin odds ratio decreases from 0.5, the score test closed form formula increasingly overestimates the sample size irrespective of the magnitude of the odds ratio under the alternative hypothesis. The Wald test closed form formula is also reasonably accurate in the cases where the score test closed form formula works well. Outside these scenarios, the Wald test closed form formula can either underestimate or overestimate the sample size, depending on the magnitude of the non-inferiority margin odds ratio and the odds ratio under the alternative hypothesis. Although neither approximation is accurate for all cases, both approaches lead to satisfactory sample size calculation for non-inferiority trials with binary data where the odds ratio is the parameter of interest. © The Author(s) 2014.

  5. Efavirenz 400 mg daily remains non-inferior to 600 mg: 96 week data from the double-blind, placebo-controlled ENCORE1 study

    Directory of Open Access Journals (Sweden)

    Dianne Carey

    2014-11-01

    Full Text Available Introduction: ENCORE1 compared the efficacy and safety of reduced versus standard dose efavirenz (EFV with tenofovir/emtricitabine (TDF/FTC as first-line HIV therapy. The primary analysis at 48 weeks showed 400 mg EFV was safe and virologically non-inferior to 600 mg. This analysis explores over 96 weeks the durability of efficacy and safety. Materials and Methods: A multinational, double-blind, placebo-controlled, non-inferiority trial in treatment-naïve HIV-positive adults randomized to TDF/FTC plus reduced (400 mg, EFV400 or standard dose (600 mg, EFV600 EFV. The difference between proportions of participants with plasma HIV RNA (VL 200 copies/mL (p=0.47 or mean change from baseline VL (p=0.74. Mean change from baseline in CD4 T-cell counts at week 96 remained significantly higher for EFV400 than EFV600 (difference 25 cells/µL; 95% CI 2–48; p=0.03. There was no difference in the frequency or severity of AEs (EFV400 = 89.4%, EFV600 = 89.3%; difference 0.09; 95% CI −4.73 to 4.90; p=0.97. The proportions ever reporting an AE definitely or probably EFV-related were EFV400 (37.7% and EFV600 (47.9% (difference −10.2%; 95% CI −17.9 to −2.51; p=0.01. SAEs did not differ in frequency (EFV400 = 7.5%, EFV600 = 10.4%; difference −2.9%; 95% CI −7.3 to 1.6; p=0.20. Conclusions: Non-inferiority of EFV 400 mg to EFV 600 mg when combined with TDF/FTC as initial HIV therapy was confirmed at week 96. Both doses demonstrated similar safety profiles. These results support the use of a lower EFV dose as part of routine HIV management.

  6. Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study.

    Science.gov (United States)

    Held, Jana; Supan, Christian; Salazar, Carmen L O; Tinto, Halidou; Bonkian, Léa N; Nahum, Alain; Moulero, Bancole; Sié, Ali; Coulibaly, Boubacar; Sirima, Sodiomon B; Siribie, Mohamadou; Otsyula, Nekoye; Otieno, Lucas; Abdallah, Ahmed M; Kimutai, Robert; Bouyou-Akotet, Marielle; Kombila, Maryvonne; Koiwai, Kimiko; Cantalloube, Cathy; Din-Bell, Chantal; Djeriou, Elhadj; Waitumbi, John; Mordmüller, Benjamin; Ter-Minassian, Daniel; Lell, Bertrand; Kremsner, Peter G

    2015-12-01

    Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated Plasmodium falciparum malaria. Ferroquine is a new combination partner for fast-acting ACTs such as artesunate. We aimed to assess different doses of ferroquine in combination with artesunate against uncomplicated P falciparum malaria in a heterogeneous population in Africa. We did a phase 2, multicentre, parallel-group, double-blind, randomised, dose-ranging non-inferiority trial at eight African hospitals (two in Gabon, three in Burkina Faso, one in Benin, and two in Kenya). We recruited patients presenting with acute P falciparum monoinfection (1000-200,000 parasites per μL), and a central body temperature of at least 37·5°C or history of fever in the past 24 h. We assessed patients in two sequential cohorts: cohort 1 contained adults (bodyweight >50 kg) and adolescents (aged ≥14 years, >30 kg), and cohort 2 contained children (aged 2-13 years, 15-30 kg). We randomly assigned patients (1:1:1:1) to receive artesunate 4 mg/kg per day plus ferroquine 2 mg/kg, 4 mg/kg, or 6 mg/kg, given double-blind once per day for 3 days, or ferroquine monotherapy 4 mg/kg per day given single-blind (ie, allocation was only masked from the patient) once per day for 3 days. We did 14 patient visits (screening, 3 treatment days and 48 h post-treatment surveillance, a visit on day 7, then one follow-up visit per week until day 63). The primary endpoint was non-inferiority of treatment in terms of PCR-corrected cure rate against a reference value of 90%, with a 10% non-inferiority margin, assessed in patients treated without major protocol deviations for parasitologically confirmed malaria. We assessed safety in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00988507, and is closed. Between Oct 16, 2009, and Sept 22, 2010, we randomly assigned 326 eligible patients to treatment groups, with last follow-up visit on Dec 1, 2010. 284 patients

  7. FERRIC CARBOXYMALTOSE (FCM COMPLEX IN THE TREATMENT OF POSTPARTUM ANAEMIA- NON-INFERIORITY OF A 500 MG VERSUS 1000 MG SINGLE-DOSE ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    Hema Divakar

    2016-12-01

    Full Text Available BACKGROUND The aim of the study is to determine the non-inferiority of a single dose of 500 mg Ferric Carboxymaltose (FCM (Group 1 to a single dose of 1000 mg (Group 2 in treating women with postpartum anaemia. MATERIALS AND METHODS Women were recruited within 24 hours of delivery and randomised to one of the two study groups excluded were mothers with non-iron deficiency anaemia, iron intolerance and haematological disease. Haematological markers were measured at baseline and at 6 weeks after treatment. Main Outcome Measures- The primary outcome was an Hb increase ≥20 g/L. Secondary outcomes included the proportion of patients attaining Hb ≥120 g/L and the mean Hb change. Design- Open label, randomised, non-blinded, prospective study. Setting- Maternity units of four hospitals in Southern India. Population- Women ≥18 years old with haemoglobin of >60 - 20 g/L between Groups 1 and 2 (91.4% versus 96.7%. Similar proportions of women in both groups became non-anaemic achieving an Hb of >120 g/L (57% versus 45.7%. The mean Hb change was comparable between the groups and both doses were well tolerated. CONCLUSION A single dose of 500 mg FCM (cost INR 2000.00 is non-inferior to a 1000 mg dose (cost INR 5000.00 in the treatment of postpartum anaemia. This has major implications for the scaling up of the eradication of iron-deficiency anaemia in India, since double the number of women who would otherwise have been treated with the 1000 mg dose can be treated with half the dose at less than half the cost with similar outcomes. Tweetable Abstract- A single dose of 500 mg FCM is a safe, efficacious and cost-effective treatment for PPA in India.

  8. A Non-Inferiority Trial of an Evidence-Based Secondary HIV Prevention Behavioral Intervention Compared to an Adapted, Abbreviated Version: Rationale and Intervention Description

    Science.gov (United States)

    Shrestha, Roman; Krishnan, Archana; Altice, Frederick L.; Copenhaver, Michael

    2015-01-01

    Background Real-world clinical settings like addiction treatment programs are ill-equipped to deploy and sustain the existing-resource-demanding evidence-based interventions (EBIs) that target HIV-infected people who use drugs (PWUDs), and this has left a critical void in current HIV prevention efforts. In response to this unmet need, we have conducted formative research in addiction treatment settings that has resulted in Holistic Health for HIV (3H+) – an empirically adapted, substantially abbreviated version of Holistic Health Recovery Program (HHRP+), a CDC-recommended EBI targeting HIV-infected PWUDs. Methods Using a non-inferiority randomized controlled trial design, we will determine whether the abbreviated 3H+ intervention is comparable (i.e., within a 10% margin) and cost-effective relative to the original HHRP+ intervention in terms of reducing HIV risk behaviors and improving antiretroviral therapy (ART) adherence among HIV-infected PWUDs in addiction treatment who report drug- or sex-related HIV risk behaviors. Conclusions This article provides a description of the development and adaptation of the 3H+ intervention, the innovative non-inferiority comparative experimental design for testing the 3H+ to the HHRP+. Furthermore, it provides empirical evidence from a formal cost-effectiveness analysis justifying the cost-effectiveness of the 3H+ intervention when compared to the HHRP+ intervention. If confirmed to be comparable and more cost-effective, as hypothesized, the 3H+ intervention has the potential to be readily and immediately integrated within common clinical settings where large numbers of HIV-infected PWUDs receive clinical services. PMID:26253181

  9. In a subgroup of high-risk Asians, telmisartan was non-inferior to ramipril and better tolerated in the prevention of cardiovascular events.

    Directory of Open Access Journals (Sweden)

    Antonio L Dans

    Full Text Available BACKGROUND AND OBJECTIVES: Results of the recently published ONTARGET study (The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial showed that telmisartan (80 mg/day was non-inferior to ramipril (10 mg/day in reducing cardiovascular events. Clinicians in Asia doubt tolerability of these doses for their patients. We therefore analyzed data from this study and a parallel study TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease. Our objectives were to compare Asians and non-Asians with respect to the following: 1 Effectiveness of telmisartan vs. ramipril in reducing cardiovascular events;2 Proportions who reached the full dose of telmisartan, ramipril or placebo; and3 Proportions of overall discontinuations, and discontinuations due to adverse effects. METHOD: The ONTARGET study randomized 25,620 patients at risk of cardiovascular events to ramipril, telmisartan, or their combination. The primary composite endpoint was death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. TRANSCEND randomized 5926 high-risk patients with a history of intolerance to ACE-inhibitors to telmisartan or placebo. The primary outcome was the same. In this substudy, we compared Asians and non-Asians as to how well they tolerated telmisartan (given in both studies and ramipril (given in ONTARGET. RESULTS: 1 Telmisartan was non-inferior to ramipril in lowering the primary endpoint among Asians (RR = 0.92; 95% CI: 0.74, 1.13; 2 more Asians achieved the full dose of either drug; 3 less withdrew (overall; and 4 less withdrew for adverse effects. Furthermore, telmisartan was better tolerated than ramipril. This advantage was greater among Asians. CONCLUSION AND SIGNIFICANCE: Although Asians had lower BMI than non-Asians, Asians tolerated both drugs better. Regulatory agencies require reporting of safety and effectiveness data by

  10. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.

    NARCIS (Netherlands)

    Kullberg, B.J.; Sobel, J.D.; Ruhnke, M.; Pappas, P.; Viscoli, C.; Rex, J.H.; Cleary, J.D.; Rubinstein, E.; Church, L.W.; Brown, J.M.; Schlamm, H.T.; Oborska, I.T.; Hilton, F.; Hodges, M.R.

    2005-01-01

    BACKGROUND: Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients. ME

  11. Some open problems in random matrix theory and the theory of integrable systems

    OpenAIRE

    Deift, Percy

    2007-01-01

    We describe a list of open problems in random matrix theory and integrable systems which was presented at the conference ``Integrable Systems, Random Matrices, and Applications'' at the Courant Institute in May 2006.

  12. Some open problems in random matrix theory and the theory of integrable systems

    OpenAIRE

    Deift, Percy

    2007-01-01

    We describe a list of open problems in random matrix theory and integrable systems which was presented at the conference ``Integrable Systems, Random Matrices, and Applications'' at the Courant Institute in May 2006.

  13. Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged ≥50 years: a randomised non-inferiority clinical trial.

    Science.gov (United States)

    Diez-Domingo, Javier; Weinke, Thomas; Garcia de Lomas, Juan; Meyer, Claudius U; Bertrand, Isabelle; Eymin, Cécile; Thomas, Stéphane; Sadorge, Christine

    2015-02-04

    Zostavax(®) is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged ≥50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many healthcare professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged ≥50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mean fold-rise (GMFR) of antibody titres measured by glycoprotein enzyme-linked immunosorbent assay. Pre-specified non-inferiority was set as the lower bound of the 95% confidence interval (CI) of the GMT ratio (IM/SC) being >0.67. An acceptable GMFR for the IM route was pre-specified as the lower bound of its 95% CI being >1.4. Description of the VZV immune response using the interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay and of the safety were secondary objectives. Participants were randomised to IM or SC administration (1:1). The baseline demographics were comparable between groups; mean age: 62.6 years (range: 50.0-90.5). The primary immunogenicity objectives were met (per protocol analysis): GMT ratio (IM/SC): 1.05 (95% CI: 0.93-1.18); GMFR: 2.7 (2.4-3.0). VZV immune response using IFN-γ ELISPOT were comparable between groups. Frequencies of systemic adverse events were comparable between groups. Injection-site reactions were less frequent with IM than SC route: erythema (15.9% versus 52.5%), pain (25.6% versus 39.5%) and swelling (13.6% versus 37.3%), respectively. In adults aged ≥50 years, IM administration of Zostavax elicited similar immune responses to SC administration and was well tolerated, with fewer injection-site reactions than with SC

  14. Daily home fortification with iron as ferrous fumarate versus NaFeEDTA: a randomised, placebo-controlled, non-inferiority trial in Kenyan children.

    Science.gov (United States)

    Teshome, Emily M; Andang'o, Pauline E A; Osoti, Victor; Terwel, Sofie R; Otieno, Walter; Demir, Ayşe Y; Prentice, Andrew M; Verhoef, Hans

    2017-04-28

    We aimed to show the non-inferiority of home fortification with a daily dose of 3 mg iron in the form of iron as ferric sodium ethylenediaminetetraacetate (NaFeEDTA) compared with 12.5 mg iron as encapsulated ferrous fumarate in Kenyan children aged 12-36 months. In addition, we updated a recent meta-analysis to assess the efficacy of home fortification with iron-containing powders, with a view to examining diversity in trial results. We gave chemoprevention by dihydroartemisinin-piperaquine, albendazole and praziquantel to 338 afebrile children with haemoglobin concentration ≥70 g/L. We randomly allocated them to daily home fortification for 30 days with either placebo, 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate. We assessed haemoglobin concentration (primary outcome), plasma iron markers, plasma inflammation markers and Plasmodium infection in samples collected at baseline and after 30 days of intervention. We conducted a meta-analysis of randomised controlled trials in pre-school children to assess the effect of home fortification with iron-containing powders on anaemia and haemoglobin concentration at end of intervention. A total of 315 children completed the 30-day intervention period. At baseline, 66.9% of children had inflammation (plasma C-reactive protein concentration >5 mg/L or plasma α 1-acid glycoprotein concentration >1.0 g/L); in those without inflammation, 42.5% were iron deficient. There was no evidence, either in per protocol analysis or intention-to-treat analysis, that home fortification with either of the iron interventions improved haemoglobin concentration, plasma ferritin concentration, plasma transferrin receptor concentration or erythrocyte zinc protoporphyrin-haem ratio. We also found no evidence of effect modification by iron status, anaemia status and inflammation status at baseline. In the meta-analysis, the effect on haemoglobin concentration was highly heterogeneous between trials (I (2): 84

  15. Design and semiparametric analysis of non-inferiority trials with active and placebo control for censored time-to-event data.

    Science.gov (United States)

    Kombrink, Karola; Munk, Axel; Friede, Tim

    2013-08-15

    The clinical trial design including a test treatment, an active control and a placebo is called the gold standard design. In this paper, we develop a statistical method for planning and evaluating non-inferiority trials with gold standard design for right-censored time-to-event data. We consider both lost to follow-up and administrative censoring. We present a semiparametric approach that only assumes the proportionality of the hazard functions. In particular, we develop an algorithm for calculating the minimal total sample size and its optimal allocation to treatment groups such that a desired power can be attained for a specific parameter constellation under the alternative. For the purpose of sample size calculation, we assume the endpoints to be Weibull distributed. By means of simulations, we investigate the actual type I error rate, power and the accuracy of the calculated sample sizes. Finally, we compare our procedure with a previously proposed procedure assuming exponentially distributed event times. To illustrate our method, we consider a double-blinded, randomized, active and placebo controlled trial in major depression. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Necessity of 3D visualization for the removal of lower wisdom teeth: required sample size to prove non-inferiority of panoramic radiography compared to CBCT.

    Science.gov (United States)

    Roeder, Felix; Wachtlin, Daniel; Schulze, Ralf

    2012-06-01

    The availability of cone beam computed tomography (CBCT) and the numbers of CBCT scans rise constantly, increasing the radiation burden to the patient. A growing discussion is noticeable if a CBCT scan prior to the surgical removal of wisdom teeth may be indicated. We aimed to confirm non-inferiority with respect to damage of the inferior alveolar nerve in patients diagnosed by panoramic radiography compared to CBCT in a prospective randomized controlled multicentre trial. Sample size (number of required third molar removals) was calculated for the study and control groups as 183,474 comparing temporary and 649,036 comparing permanent neurosensory disturbances of the inferior alveolar nerve. Modifying parameter values resulted in sample sizes ranging from 39,584 to 245,724 respectively 140,024 to 869,250. To conduct a clinical study to prove a potential benefit from CBCT scans prior to surgical removal of lower wisdom teeth with respect to the most important parameter, i.e., nerval damage, is almost impossible due to the very large sample sizes required. This fact vice versa indicates that CBCT scans should only be performed in high risk wisdom tooth removals.

  17. Overcoming barriers to HPV vaccination: non-inferiority of antibody response to human papillomavirus 16/18 vaccine in adolescents vaccinated with a two-dose vs. a three-dose schedule at 21 months.

    Science.gov (United States)

    Lazcano-Ponce, Eduardo; Stanley, Margaret; Muñoz, Nubia; Torres, Leticia; Cruz-Valdez, Aurelio; Salmerón, Jorge; Rojas, Rosalba; Herrero, Rolando; Hernández-Ávila, Mauricio

    2014-02-01

    For middle and low-income countries, the cost of HPV vaccines remains challenging. We conducted an open-label nonrandomized clinical trial evaluating immune response to the HPV-16/18 AS04-adjuvanted vaccine administered on a standard (months (M) 0-1-6) versus extended schedule (M 0-6-60) at 7, 21, 60, 72 and 120 months post-vaccination. Participants were females recruited in Morelos, Mexico: 474 girls aged 9-10 years and 500 women aged 18-24 years receiving a standard schedule, and 1026 girls aged 9-10 years receiving an extended schedule (currently the girls in the extended schedule had received only the first 2 doses). This report presents the interim analysis results for non-inferiority between the regimes conducted with the current available data at 21 months after the first dose, with serum antibodies assessed by ELISA. A pre-stated margin of non-inferiority was defined by post-vaccination geometric mean titer (GMT) ratio (upper 95% confidence interval [CI]≤2.0) between the standard and the two-dose schedule in girls at month 21. Immune response to the vaccine was strongest in adolescent girls and in the 3-dose group. Statistical non-inferiority of the two-dose versus three-dose groups was demonstrated. At 21 months, comparing the adolescent 2-dose versus 3-dose groups, the GMT ratio and 95% CI were 1.66 (1.55-1.81) and 1.67 (1.51-1.86) for HPV16 and 18, respectively. The two-dose regimen was non-inferior when compared to the three-dose response in same-age girls and with women aged 18-24 years after 21 months of follow-up. The reduction in the number of doses from the current three-dose schedule may lower overall costs associated with the vaccination and increase accessibility and compliance with the recommended dosing of the HPV vaccine.

  18. Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study.

    Science.gov (United States)

    Van Damme, Pierre; Arnou, Robert; Kafeja, Froukje; Fiquet, Anne; Richard, Patrick; Thomas, Stéphane; Meghlaoui, Gilles; Samson, Sandrine Isabelle; Ledesma, Emilio

    2010-05-26

    Although seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly. Elderly volunteers (age > or = 65 years) were randomised to receive a single dose of trivalent seasonal influenza vaccine: either a split-virion vaccine containing 15 microg haemagglutinin [HA]/strain/0.1-ml dose administered intradermally, or a subunit vaccine (15 microg HA/strain/0.5-ml dose) adjuvanted with MF59C.1 and administered intramuscularly. Blood samples were taken before and 21 +/- 3 days post-vaccination. Anti-HA antibody titres were assessed using haemagglutination inhibition (HI) and single radial haemolysis (SRH) methods. We aimed to show that the intradermal vaccine was non-inferior to the adjuvanted vaccine. A total of 795 participants were enrolled (intradermal vaccine n = 398; adjuvanted vaccine n = 397). Non-inferiority of the intradermal vaccine was demonstrated for the A/H1N1 and B strains, but not for the A/H3N2 strain (upper bound of the 95% CI = 1.53) using the HI method, and for all three strains by the SRH method. A post-hoc analysis of covariance to adjust for baseline antibody titres demonstrated the non-inferiority of the intradermal vaccine by HI and SRH methods for all three strains. Both vaccines were, in general, well tolerated; the incidence of injection-site reactions was higher for the intradermal (70.1%) than the adjuvanted vaccine (33.8%) but these reactions were mild and of short duration. The immunogenicity and safety of the intradermal seasonal influenza vaccine in the elderly was comparable with that of the adjuvanted vaccine. Intradermal vaccination to target the immune properties of the skin appears to be an

  19. Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study

    Directory of Open Access Journals (Sweden)

    Thomas Stéphane

    2010-05-01

    Full Text Available Abstract Background Although seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly. Methods Elderly volunteers (age ≥ 65 years were randomised to receive a single dose of trivalent seasonal influenza vaccine: either a split-virion vaccine containing 15 μg haemagglutinin [HA]/strain/0.1-ml dose administered intradermally, or a subunit vaccine (15 μg HA/strain/0.5-ml dose adjuvanted with MF59C.1 and administered intramuscularly. Blood samples were taken before and 21 ± 3 days post-vaccination. Anti-HA antibody titres were assessed using haemagglutination inhibition (HI and single radial haemolysis (SRH methods. We aimed to show that the intradermal vaccine was non-inferior to the adjuvanted vaccine. Results A total of 795 participants were enrolled (intradermal vaccine n = 398; adjuvanted vaccine n = 397. Non-inferiority of the intradermal vaccine was demonstrated for the A/H1N1 and B strains, but not for the A/H3N2 strain (upper bound of the 95% CI = 1.53 using the HI method, and for all three strains by the SRH method. A post-hoc analysis of covariance to adjust for baseline antibody titres demonstrated the non-inferiority of the intradermal vaccine by HI and SRH methods for all three strains. Both vaccines were, in general, well tolerated; the incidence of injection-site reactions was higher for the intradermal (70.1% than the adjuvanted vaccine (33.8% but these reactions were mild and of short duration. Conclusions The immunogenicity and safety of the intradermal seasonal influenza vaccine in the elderly was comparable with that of the adjuvanted vaccine. Intradermal vaccination to target the

  20. OP-1 compared with iliac crest autograft in instrumented posterolateral fusion a randomized, multicenter non-inferiority trial

    NARCIS (Netherlands)

    Delawi, Diyar; Jacobs, Wilco; Van Susante, Job L C; Rillardon, Ludovic; Prestamburgo, Domenico; Specchia, Nicola; Gay, Emmanuel; Verschoor, Nico; Garcia-Fernandez, Carlos; Guerado, Enrique; Van Ufford, Henriette Quarles; Kruyt, Moyo C.; Dhert, Wouter J A; Cumhur Oner, F.

    2016-01-01

    Background: Spinal fusion with the use of autograft is a commonly performed procedure. However, harvesting of bone from the iliac crest is associated with complications. Bone morphogenetic proteins (BMPs) are extensively used as alternatives, often without sufficient evidence of safety and efficacy.

  1. OP-1 Compared with Iliac Crest Autograft in Instrumented Posterolateral Fusion : A Randomized, Multicenter Non-Inferiority Trial

    NARCIS (Netherlands)

    Delawi, Diyar; Jacobs, Wilco; van Susante, Job L C; Rillardon, Ludovic; Prestamburgo, Domenico; Specchia, Nicola; Gay, Emmanuel; Verschoor, Nico; Garcia-Fernandez, Carlos; Guerado, Enrique; Quarles van Ufford, Henriette; Kruyt, Moyo C; Dhert, Wouter J A; Oner, F Cumhur

    2016-01-01

    BACKGROUND: Spinal fusion with the use of autograft is a commonly performed procedure. However, harvesting of bone from the iliac crest is associated with complications. Bone morphogenetic proteins (BMPs) are extensively used as alternatives, often without sufficient evidence of safety and efficacy.

  2. Endoscopic Saphenous harvesting with an Open CO2 System (ESOS trial for coronary artery bypass grafting surgery: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Campanella Antonio

    2011-11-01

    and long-term outcomes and vein-graft patency after endoscopic open CO2 harvesting system versus conventional vein harvesting. The expected results are of high clinical relevance and will show the safety/efficacy or non-inferiority of one treatment approach in terms of vein harvesting for coronary artery bypass grafting surgery. Trial registration www.clinicalTrials.gov NCT01121341.

  3. Investigations on non-inferiority--the Food and Drug Administration draft guidance on treatments for nosocomial pneumonia as a case for exact tests for binomial proportions.

    Science.gov (United States)

    Röhmel, Joachim; Kieser, Meinhard

    2013-06-30

    This paper addresses statistical issues in non-inferiority trials where the primary outcome is a fatal event. The investigations are inspired by a recent Food and Drug Administration (FDA) draft guideline on treatments for nosocomial pneumonia. The non-inferiority margin suggested in this guideline for the endpoint all-cause mortality is defined on different distance measures (rate difference and odds ratio) and is discontinuous. Furthermore, the margin enables considerable power for the statistical proof of non-inferiority at alternatives that might be regarded as clinically unacceptable, that is, even if the experimental treatment is harmful as compared with the control. We investigated the appropriateness of the proposed non-inferiority margin as well as the performance of possible test statistics to be used for the analysis. A continuous variant of the margin proposed in the FDA guideline together with the unconditional exact test according to Barnard showed favorable characteristics with respect to type I error rate control and power. To prevent harmful new treatments from being declared as non-inferior, we propose to add a 'second hurdle'. We discuss examples and explore power characteristics when requiring both statistical significance and overcoming the second hurdle.

  4. Laparoscopic vs open incisional hernia repair a randomized clinical trial

    NARCIS (Netherlands)

    H.H. Eker (Hasan); B.M. Hansson; M. Buunen (Mark); I.M.C. Janssen (Ignace); R.E.G.J.M. Pierik (Robert); W.C.J. Hop (Wim); H.J. Bonjer (Jaap); J. Jeekel (Hans); J.F. Lange (Johan)

    2013-01-01

    textabstractImportance: Incisional hernia is the most frequent surgical complication after laparotomy. Up to 30% of all patients undergoing laparotomy develop an incisional hernia. Objective: To compare laparoscopic vs open ventral incisional hernia repairwith regard to postoperative pain and

  5. Efficacy and tolerability of a prolonged release ferrous sulphate formulation in iron deficiency anaemia: a non-inferiority controlled trial.

    Science.gov (United States)

    Zaim, Mohammed; Piselli, Leonardo; Fioravanti, Pino; Kanony-Truc, Claire

    2012-03-01

    Iron deficiency anaemia (IDA) is the last stage of iron deficiency, consecutive to an imbalance between iron supply through food intake and iron loss through physiological or pathological processes. As well as by haemoglobin levels, IDA is diagnosed by measuring biomarkers of iron stores. Women are most affected by IDA since their teenage years, as menstruation constitutes a chronic iron loss. Oral supplementation with ferrous sulphate is an effective therapy, but gastrointestinal side effects may impair treatment compliance. The present multicentric randomised controlled trial was designed to assess the non-inferiority of a ferrous sulphate prolonged release formulation called V0355 with the referential ferrous sulphate Ferrograd® in a population of Italian women aged 18-50 years diagnosed for IDA. Three hundred and ninety-nine patients were randomised to receive V0355 (80 mg Fe/day) or Ferrograd® (105 mg Fe/day). After 12 weeks of treatment, the difference in the mean haemoglobin level between the two groups was 0.081 g/dL ([-2.986;1.361], p = 0.54), which confirmed the hypothesis of non-inferiority. All the other biochemical parameters (serum iron, serum ferritin, transferrin, and soluble transferrin receptor) and haematological parameters (erythrocytes count, reticulocytes count, haematocrit, and mean corpuscular volume), as well as patient's anaemia-related symptoms, were not different between treatment groups throughout the study. Furthermore, the incidence of gastrointestinal adverse events of moderate and severe intensity was significantly lower (p = 0.007) in the V0355 group (5.6%) than in the Ferrograd® group (13.9%). V0355 was as efficient as Ferrograd® in the treatment of anaemia and exhibited a better gastrointestinal tolerance profile.

  6. Laparoscopic vs open incisional hernia repair a randomized clinical trial

    NARCIS (Netherlands)

    H.H. Eker (Hasan); B.M. Hansson; M. Buunen (Mark); I.M.C. Janssen (Ignace); R.E.G.J.M. Pierik (Robert); W.C.J. Hop (Wim); H.J. Bonjer (Jaap); J. Jeekel (Hans); J.F. Lange (Johan)

    2013-01-01

    textabstractImportance: Incisional hernia is the most frequent surgical complication after laparotomy. Up to 30% of all patients undergoing laparotomy develop an incisional hernia. Objective: To compare laparoscopic vs open ventral incisional hernia repairwith regard to postoperative pain and nausea

  7. Random Finite Set Based Bayesian Filtering with OpenCL in a Heterogeneous Platform

    National Research Council Canada - National Science Library

    Biao Hu; Uzair Sharif; Rajat Koner; Guang Chen; Kai Huang; Feihu Zhang; Walter Stechele; Alois Knoll

    2017-01-01

    ... applications such as pedestrian detection. Towards this goal, this paper investigates the use of OpenCL to accelerate the computation of random finite set-based Bayesian filtering in a heterogeneous system...

  8. Laparoscopic and open incisional hernia repair: A prospective randomized study

    Directory of Open Access Journals (Sweden)

    Mehmet Zafer Sabuncuoğlu

    2015-07-01

    Full Text Available As the number of major surgical procedures has increased in recent years, so there has been an increase in incisional hernias. With gained experience and new materials, laparoscopic repair of incisional hernia is now applied. This study was aimed to compare the results of incisional hernia repair with the open surgery or laparoscopic approach at the only centre in the region for laparoscopic incisional hernia repair. A total of 55 cases of incisional hernia at the General Surgery Clinic of SDU between November 2012 and 2014 were underwent laparoscopic ventral hernia repair (L-VHR and conventional incisional hernia repair (C-VHR. From the L-VHR group 6 cases and from the C-VHR 9 cases were excluded from the study, as they did not meet the inclusion criteria or did not wish to participate in the study. The two techniques were compared in respect of operative time, length of hospital stay, postoperative pain scores, complications and recurrence. A total of 40 cases of incisional hernia repair were evaluated. The mean follow-up period was found as 12.75±4.19 months. No difference was determined between the characteristics of the patients due to age, body mass index, American Society of Anesthesiologists (ASA score, comorbidities, hernia size, and follow-up. In the laparoscopic repair group, the postoperative pain scores, complication rates and duration of hospital stay were found significantly superior to those of the open technique group. While there was no mortality seen and wound complications as a morbidity were 0 % in the L-VHR (n = 0 and 20 % in C-VHR group (n = 4. In the comparison of mean operative time, the duration of surgery was significantly shorter in the laparoscopic repair group (67.25±19.23 min compared to the open technique group (91.50±24.87 min (p=0.001. Laparoscopic repair was associated with less postoperative pain (4.35±1.03 vs 5.60±1.31, p=0.002, lesser postoperative complications (5% vs. 35%, p=0.044, and shorter

  9. Sacrospinous hysteropexy versus vaginal hysterectomy with suspension of the uterosacral ligaments in women with uterine prolapse stage 2 or higher: multicentre randomised non-inferiority trial.

    Science.gov (United States)

    Detollenaere, Renée J; den Boon, Jan; Stekelenburg, Jelle; IntHout, Joanna; Vierhout, Mark E; Kluivers, Kirsten B; van Eijndhoven, Hugo W F

    2015-07-23

    To investigate whether uterus preserving vaginal sacrospinous hysteropexy is non-inferior to vaginal hysterectomy with suspension of the uterosacral ligaments in the surgical treatment of uterine prolapse. Multicentre randomised controlled non-blinded non-inferiority trial. 4 non-university teaching hospitals, the Netherlands. 208 healthy women with uterine prolapse stage 2 or higher requiring surgery and no history of pelvic floor surgery. Treatment with sacrospinous hysteropexy or vaginal hysterectomy with suspension of the uterosacral ligaments. The predefined non-inferiority margin was an increase in surgical failure rate of 7%. Primary outcome was recurrent prolapse stage 2 or higher of the uterus or vaginal vault (apical compartment) evaluated by the pelvic organ prolapse quantification system in combination with bothersome bulge symptoms or repeat surgery for recurrent apical prolapse at 12 months' follow-up. Secondary outcomes were overall anatomical recurrences, including recurrent anterior compartment (bladder) and/or posterior compartment (bowel) prolapse, functional outcome, complications, hospital stay, postoperative recovery, and sexual functioning. Sacrospinous hysteropexy was non-inferior for anatomical recurrence of the apical compartment with bothersome bulge symptoms or repeat surgery (n=0, 0%) compared with vaginal hysterectomy with suspension of the uterosacral ligaments (n=4, 4.0%, difference -3.9%, 95% confidence interval for difference -8.6% to 0.7%). At 12 months, overall anatomical recurrences, functional outcome, quality of life, complications, hospital stay, measures on postoperative recovery, and sexual functioning did not differ between the two groups. Five serious adverse events were reported during hospital stay. None was considered to be related to the type of surgery. Uterus preservation by sacrospinous hysteropexy was non-inferior to vaginal hysterectomy with suspension of the uterosacral ligaments for surgical failure of the

  10. The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS: rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    André Russowsky Brunoni

    Full Text Available CONTEXT AND OBJECTIVE: Major depressive disorder (MDD is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited due to refractoriness and adverse effects. We describe the study rationale and design of ELECT-TDCS (Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study, which is investigating a non-pharmacological treatment known as transcranial direct current stimulation (tDCS.DESIGN AND SETTING: Phase-III, randomized, non-inferiority, triple-arm, placebo-controlled study, ongoing in São Paulo, Brazil.METHODS: ELECT-TDCS compares the efficacy of active tDCS/placebo pill, sham tDCS/escitalopram 20 mg/day and sham tDCS/placebo pill, for ten weeks, randomizing 240 patients in a 3:3:2 ratio, respectively. Our primary aim is to show that tDCS is not inferior to escitalopram with a non-inferiority margin of at least 50% of the escitalopram effect, in relation to placebo. As secondary aims, we investigate several biomarkers such as genetic polymorphisms, neurotrophin serum markers, motor cortical excitability, heart rate variability and neuroimaging.RESULTS: Proving that tDCS is similarly effective to antidepressants would have a tremendous impact on clinical psychiatry, since tDCS is virtually devoid of adverse effects. Its ease of use, portability and low price are further compelling characteristics for its use in primary and secondary healthcare. Multimodal investigation of biomarkers will also contribute towards understanding the antidepressant mechanisms of action of tDCS.CONCLUSION: Our results have the potential to introduce a novel technique to the therapeutic arsenal of treatments for depression.

  11. Lot-to-lot consistency of live attenuated SA 14-14-2 Japanese encephalitis vaccine manufactured in a good manufacturing practice facility and non-inferiority with respect to an earlier product.

    Science.gov (United States)

    Zaman, K; Naser, Abu Mohd; Power, Maureen; Yaich, Mansour; Zhang, Lei; Ginsburg, Amy Sarah; Luby, Stephen P; Rahman, Mahmudur; Hills, Susan; Bhardwaj, Mukesh; Flores, Jorge

    2014-10-21

    We conducted a four-arm, double-blind, randomized controlled trial among 818 Bangladeshi infants between 10 and 12 months of age to establish equivalence among three lots of live attenuated SA 14-14-2 JE vaccine manufactured by the China National Biotec Group's Chengdu Institute of Biological Products (CDIBP) in a new Good Manufacturing Practice (GMP) facility and to evaluate non-inferiority of the product with a lot of the same vaccine manufactured in CDIBP's original facility. The study took place in two sites in Bangladesh, rural Matlab and Mirpur in urban Dhaka. We collected pre-vaccination (Day 0) and post-vaccination Day 28 (-4 to +14 days) blood samples to assess neutralizing anti-JE virus antibody titers in serum by plaque reduction neutralization tests (PRNT). Seroprotection following vaccination was defined as a PRNT titer ≥1:10 at Day 28 in participants non-immune at baseline. Follow-up for reactogenicity and safety was conducted through home visits at Day 7 and monitoring for serious adverse events through Day 28. Seroprotection rates ranged from 80.2% to 86.3% for all four lots of vaccine. Equivalence of the seroprotection rates between pairs of vaccine lots produced in the new GMP facility was satisfied at the pre-specified 10% margin of the 95% confidence interval (CI) for two of the three pairwise comparisons, but not for the third (-4.3% observed difference with 95% CI of -11.9 to 3.3%). Nevertheless, the aggregate seroprotection rate for all three vaccine lots manufactured in the GMP facility was calculated and found to be within the non-inferiority margin (within 10%) to the vaccine lot produced in the original facility. All four lots of vaccine were safe and well tolerated. These study results should facilitate the use of SA 14-14-2 JE vaccine as a routine component of immunization programs in Asian countries.

  12. Clinical Non-inferiority Trial on Treatment of Coronary Heart Disease Angina Pectoris of Xin-blood Stasis Syndrome Type with Lyophilized Salvia Salt of Lithospermic Acid Powder for Injection

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To evaluate the effectiveness and safety of lyophilized Salvia salt of lithospermic acid powder for injection (SSLA) in treating coronary heart diseases angina pectoris (CHD-AP) of Xin-blood positive control. Methods: An non-inferiority clinical layered, segmented, randomized, and blinded trial on three parallel and multiple centered groups was conducted in 480 patients with stable effort angina grade Ⅰ ,Ⅱ and Ⅲ, who had two or more times of attack every week. The 240 patients in test group A were treated with SSLA 200 mg added in 250 ml of 5% glucose solution for intravenous dripping every day; the 120 patients in test group B were treated with SSLA but the dosage doubled; and the 120 patients in the control group were treated with DSI 20 ml daily in the same method as SSLA was given. The clinical effectiveness and safety were evaluated after the patients were treated for 14 days. Results: The results showed that the markedly effective rate in test groups A, B and control group was 37.45 %, 36.75 % and 30.09 % respectively, while the total effective rate in them was 88.09%, 89.74% and 67.26% respectively. Statistical significance was shown in comparisons of the therapeutic effect between control group with test group A and test group B, with that in the two test groups superior to that in the control group, and non-inferiority trial showed eligibility (P<0.01). Adverse reaction appeared in 8 patients in the test groups and 2 in the control group.Conclusion: SSLA has definite therapeutic effect in treating patients with CHD-AP, with its effect not inferior to that of DSl, and no evident toxic-adverse reaction.

  13. A randomized trial of laparoscopic versus open surgery for rectal cancer

    DEFF Research Database (Denmark)

    Bonjer, H Jaap; Deijen, Charlotte L; Abis, Gabor A;

    2015-01-01

    (locoregional recurrence) and survival after laparoscopic and open resection of rectal cancer. METHODS: In this international trial conducted in 30 hospitals, we randomly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge, not invading adjacent tissues, and without...... of locoregional recurrence and disease-free and overall survival similar to those for open surgery. (Funded by Ethicon Endo-Surgery Europe and others; COLOR II ClinicalTrials.gov number, NCT00297791.)....

  14. Peri-articular local infiltration analgesia versus femoral nerve block for postoperative pain control following anterior cruciate ligament reconstruction: Prospective, comparative, non-inferiority study.

    Science.gov (United States)

    Lefevre, N; Klouche, S; de Pamphilis, O; Herman, S; Gerometta, A; Bohu, Y

    2016-11-01

    Femoral nerve block (FNB) is considered as a major advance in anterior cruciate ligament (ACL) reconstruction as it reduces the need for parenteral opioids. However, the incidence of transient or even permanent neurological deficits due to the FNB is estimated at 1.94% after knee surgery. The primary objective of this study was to compare local infiltration analgesia (LIA) to FNB during ACL reconstruction procedures. The study hypothesis was that LIA was not less effective than FNB on early postoperative pain. A retrospective analysis of data collected prospectively in the FAST cohort included a series of continuous patients who underwent primary repair for isolated ACL with a hamstring graft in 2013-2014. Changes in our anesthesia practices over time allowed us to form three successive groups: Group 1 - FNB, Group 2 - FNB+LIA, Group 3 - LIA only. Ultrasound-guided FNB was done pre-operatively. The LIA was done at the end of the procedure by the surgeon with systematic infiltration of all skin incisions and the hamstring donor site; no intra-articular injections were performed. The primary endpoint was the average early postoperative pain (Days 0-3) described by the patient on a visual analogue scale (0-10). Sample size calculation pointed to 36 subjects being needed per group for a non-inferiority study. The study involved 126 patients: G1=42, G2=38, G3=46. The patients were comparable at enrolment. The average early postoperative pain levels were 3.1±2.4, 2.8±2.0 and 2.5±2.2, respectively (P=0.66). A trend toward higher intake of tramadol was noted in the LIA group on D0 to D3, with a significant trend test on Day 1 (P=0.03) and Day 2 (P=0.02). After reconstruction of isolated ACL tears with a hamstring graft, FNB is not more effective than LIA on patients' early postoperative pain. Patients who received a FNB consumed significantly less opioid-like analgesics. III - Prospective, comparative, non-randomized study. Copyright © 2016 Elsevier Masson SAS. All

  15. Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus envenoming in Nigeria.

    Directory of Open Access Journals (Sweden)

    Isa S Abubakar

    Full Text Available BACKGROUND: In West Africa, envenoming by saw-scaled or carpet vipers (Echis ocellatus causes great morbidity and mortality, but there is a crisis in supply of effective and affordable antivenom (ISRCTN01257358. METHODS: In a randomised, double-blind, controlled, non-inferiority trial, "EchiTAb Plus-ICP" (ET-Plus equine antivenom made by Instituto Clodomiro Picado was compared to "EchiTAb G" (ET-G ovine antivenom made by MicroPharm, which is the standard of care in Nigeria and was developed from the original EchiTAb-Fab introduced in 1998. Both are caprylic acid purified whole IgG antivenoms. ET-G is monospecific for Echis ocellatus antivenom (initial dose 1 vial and ET-Plus is polyspecific for E. ocellatus, Naja nigricollis and Bitis arietans (initial dose 3 vials. Both had been screened by pre-clinical and preliminary clinical dose-finding and safety studies. Patients who presented with incoagulable blood, indicative of systemic envenoming by E. ocellatus, were recruited in Kaltungo, north-eastern Nigeria. Those eligible and consenting were randomly allocated with equal probability to receive ET-Plus or ET-G. The primary outcome was permanent restoration of blood coagulability 6 hours after the start of treatment, assessed by a simple whole blood clotting test repeated 6, 12, 18, 24 and 48 hr after treatment. Secondary (safety outcomes were the incidences of anaphylactic, pyrogenic and late serum sickness-type antivenom reactions. FINDINGS: Initial doses permanently restored blood coagulability at 6 hours in 161/194 (83.0% of ET-Plus and 156/206 (75.7% of ET-G treated patients (Relative Risk [RR] 1.10 one-sided 95% CI lower limit 1.01; P = 0.05. ET-Plus caused early reactions on more occasions than did ET-G [50/194 (25.8% and 39/206 (18.9% respectively RR (1.36 one-sided 95% CI 1.86 upper limit; P = 0.06. These reactions were classified as severe in 21 (10.8% and 11 (5.3% of patients, respectively. CONCLUSION: At these doses, ET-Plus was

  16. Active-control trials with binary data: a comparison of methods for testing superiority or non-inferiority using the odds ratio.

    Science.gov (United States)

    Siqueira, Arminda Lucia; Whitehead, Anne; Todd, Susan

    2008-02-10

    This paper considers methods for testing for superiority or non-inferiority in active-control trials with binary data, when the relative treatment effect is expressed as an odds ratio. Three asymptotic tests for the log-odds ratio based on the unconditional binary likelihood are presented, namely the likelihood ratio, Wald and score tests. All three tests can be implemented straightforwardly in standard statistical software packages, as can the corresponding confidence intervals. Simulations indicate that the three alternatives are similar in terms of the Type I error, with values close to the nominal level. However, when the non-inferiority margin becomes large, the score test slightly exceeds the nominal level. In general, the highest power is obtained from the score test, although all three tests are similar and the observed differences in power are not of practical importance.

  17. Laparoscopic versus open gastrectomy for gastric cancer, a multicenter prospectively randomized controlled trial (LOGICA-trial).

    Science.gov (United States)

    Haverkamp, Leonie; Brenkman, Hylke J F; Seesing, Maarten F J; Gisbertz, Suzanne S; van Berge Henegouwen, Mark I; Luyer, Misha D P; Nieuwenhuijzen, Grard A P; Wijnhoven, Bas P L; van Lanschot, Jan J B; de Steur, Wobbe O; Hartgrink, Henk H; Stoot, Jan H M B; Hulsewé, Karel W E; Spillenaar Bilgen, Ernst J; Rütter, Jeroen E; Kouwenhoven, Ewout A; van Det, Marc J; van der Peet, Donald L; Daams, Freek; Draaisma, Werner A; Broeders, Ivo A M J; van Stel, Henk F; Lacle, Miangela M; Ruurda, Jelle P; van Hillegersberg, Richard

    2015-07-29

    For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy. The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness. In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5

  18. Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial.

    Science.gov (United States)

    von Birgelen, Clemens; Sen, Hanim; Lam, Ming Kai; Danse, Peter W; Jessurun, Gillian A J; Hautvast, Raymond W M; van Houwelingen, Gert K; Schramm, Alexander R; Gin, R Melvyn Tjon Joe; Louwerenburg, Johannes W; de Man, Frits H A F; Stoel, Martin G; Löwik, Marije M; Linssen, Gerard C M; Saïd, Salah A M; Nienhuis, Mark B; Verhorst, Patrick M J; Basalus, Mounir W Z; Doggen, Carine J M; Tandjung, Kenneth

    2014-02-01

    Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial. In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov, number NCT01331707. Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned

  19. Return Probability of the Open Quantum Random Walk with Time-Dependence

    Institute of Scientific and Technical Information of China (English)

    Clement Ampadu

    2013-01-01

    We study the open quantum random walk (OQRW) with time-dependence on the one-dimensional lattice space and obtain the associated limit distribution.As an application we study the return probability of the OQRW.We also ask,"What is the average time for the return probability of the OQRW?"

  20. A randomized open-label comparison of the impact of olanzapine versus risperidone on sexual functioning

    NARCIS (Netherlands)

    Knegtering, H; Boks, M; Blijd, C; Castelein, S; Van den Bosch, RJ; Wiersma, D

    2006-01-01

    The objective of this study was to compare sexual functioning in patients treated with olanzapine or risperidone. This open-label trial included 46 patients randomized to olanzapine (5-15mg/d) or risperidone (1-6mg/d) for 6 weeks. We used sexual dysfunction was assessed by a semistructured interview

  1. OPEN, RANDOMIZED COMPARISON OF PEFLOXACIN AND CEFOTAXIME IN THE TREATMENT OF COMPLICATED URINARY-TRACT INFECTIONS

    NARCIS (Netherlands)

    TIMMERMAN, C; HOEPELMAN, [No Value; DEHOND, J; SCHREINEMACHERS, L; MENSINK, H; VERHOEF, J

    1992-01-01

    In an open, randomized study, the effect of pefloxacin (400 mg b.i.d.) was compared with that of cefotaxime (1 g t.i.d.) in the treatment of complicated urinary tract infections. In total 87 patients entered the study under the clinical diagnosis of complicated urinary tract infection, of whom 49 we

  2. Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial.

    Science.gov (United States)

    Rivera, Luis; Pedersen, Rasmus S; Peña, Lourdes; Olsen, Klaus J; Andreasen, Lars V; Kromann, Ingrid; Nielsen, Pernille I; Sørensen, Charlotte; Dietrich, Jes; Bandyopadhyay, Ananda S; Thierry-Carstensen, Birgit

    2017-07-01

    Cost and supply constraints are key challenges in the use of inactivated polio vaccine (IPV). Dose reduction through adsorption to aluminium hydroxide (Al) is a promising option, and establishing its effectiveness in the target population is a crucial milestone in developing IPV-Al. The aim of this clinical trial was to show the non-inferiority of three IPV-Al vaccines to standard IPV. In this phase 2, non-inferiority, observer-blinded, randomised, controlled, single-centre trial in the Dominican Republic, healthy infants aged 6 weeks, not previously polio vaccinated, were allocated after computer-generated randomisation by block-size of four, to receive one of four IPV formulations (three-times reduced dose [1/3 IPV-Al], five-times reduced dose [1/5 IPV-Al], ten-times reduced dose [1/10 IPV-Al], or IPV) intramuscularly in the thigh at 6, 10, and 14 weeks of age. The primary outcome was seroconversion for poliovirus types 1, 2, and 3 with titres more than or equal to four-fold higher than the estimated maternal antibody titre and more than or equal to 8 after three vaccinations. Non-inferiority was concluded if the lower two-sided 90% CI of the seroconversion rate difference between IPV-Al and IPV was greater than -10%. The safety analyses were based on the safety analysis set (randomly assigned participants who received at least one trial vaccination) and the immunogenicity analyses were based on the per-protocol population. This study is registered with ClinicalTrials.gov registration, number NCT02347423. Between Feb 2, 2015, and Sept 26, 2015, we recruited 824 infants. The per-protocol population included 820 infants; 205 were randomly assigned to receive 1/3 IPV-Al, 205 to receive 1/5 IPV-Al, 204 to receive 1/10 IPV-Al, and 206 to receive IPV. The proportion of individuals meeting the primary endpoint of seroconversion for poliovirus types 1, 2, and 3 was already high for the three IPV-Al vaccines after two vaccinations, but was higher after three vaccinations

  3. Are first-generation cephalosporins obsolete? A retrospective, non-inferiority, cohort study comparing empirical therapy with cefazolin versus ceftriaxone for acute pyelonephritis in hospitalized patients.

    Science.gov (United States)

    Hobbs, Athena L V; Shea, Katherine M; Daley, Mitchell J; Huth, R Gordon; Jaso, Theresa C; Bissett, Jack; Hemmige, Vagish

    2016-06-01

    Literature is lacking regarding the utilization of first-generation cephalosporins for the treatment of acute pyelonephritis. The aim of this study was to determine whether cefazolin is non-inferior to ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. The primary outcome included a composite of symptomatic resolution plus either defervescence at 72 h or normalization of serum white blood cell count at 72 h (non-inferiority margin 15%). Secondary outcomes included length of stay and 30 day readmission. A subgroup analysis of the composite outcome was also conducted for imaging-confirmed pyelonephritis. This was a retrospective, non-inferiority, multicentre, cohort study comparing cefazolin versus ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. Overall, 184 patients received one of the two treatments between July 2009 and March 2015. The composite outcome was achieved in 80/92 (87.0%) in the cefazolin group versus 79/92 (85.9%) in the ceftriaxone group (absolute difference 1.1%, 95% CI -11.1% to 8.9%, P = 0.83), meeting the pre-defined criteria for non-inferiority. The composite outcome for patients with imaging-confirmed pyelonephritis was achieved in 46/56 (82.1%) versus 42/50 (84.0%) for the cefazolin group and the ceftriaxone group, respectively (absolute difference 1.9%, 95% CI -12.8% to 16.5%, P = 0.80). Additionally, there were no statistically significant differences in length of stay or 30 day readmission for cystitis or pyelonephritis. Cefazolin was non-inferior to ceftriaxone with regard to clinical response for the treatment of hospitalized patients with acute pyelonephritis in this study. No difference was observed for length of stay or 30 day readmission. © The Author 2016. 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.

  4. Study protocol for a non-inferiority trial of cytisine versus nicotine replacement therapy in people motivated to stop smoking

    Directory of Open Access Journals (Sweden)

    Walker Natalie

    2011-11-01

    Full Text Available Abstract Background Smokers need effective support to maximise the chances of successful quit attempts. Current smoking cessation medications, such as nicotine replacement therapy (NRT, bupropion, nortriptyline or varenicline, have been shown to be effective in clinical trials but are underused by smokers attempting to quit due to adverse effects, contraindications, low acceptability and/or high cost. Cytisine is a low-cost, plant-based alkaloid that has been sold as a smoking cessation aid in Eastern Europe for 50 years. A systematic review of trial evidence suggests that cytisine has a positive impact on both short- and long-term abstinence rates compared to placebo. However, the quality of the evidence is poor and insufficient for licensing purposes in many Western countries. A large, well-conducted placebo-controlled trial (n = 740 of cytisine for smoking cessation has recently been published and confirms the findings of earlier studies, with 12-month continuous abstinence rates of 8.4% in the cytisine group compared to 2.4% in the placebo group (Relative risk = 3.4, 95% confidence intervals 1.7-7.1. No research has yet been undertaken to determine the effectiveness of cytisine relative to that of NRT. Methods/design A single-blind, randomised controlled, non-inferiority trial has been designed to determine whether cytisine is at least as effective as NRT in assisting smokers to remain abstinent for at least one month. Participants (n = 1,310 will be recruited through the national telephone-based Quitline service in New Zealand and randomised to receive a standard 25-day course of cytisine tablets (Tabex® or usual care (eight weeks of NRT patch and/or gum or lozenge. Participants in both study arms will also receive a behavioural support programme comprising an average of three follow-up telephone calls delivered over an eight-week period by Quitline. The primary outcome is continuous abstinence from smoking at one month, defined as not

  5. A Phase III, randomized, open-label trial of ferumoxytol compared with iron sucrose for the treatment of iron deficiency anemia in patients with a history of unsatisfactory oral iron therapy.

    Science.gov (United States)

    Hetzel, David; Strauss, William; Bernard, Kristine; Li, Zhu; Urboniene, Audrone; Allen, Lee F

    2014-06-01

    Iron deficiency anemia (IDA) is the most common form of anemia worldwide. Although oral iron is used as first-line treatment, many patients are unresponsive to or cannot take oral iron. This Phase III, open-label, non-inferiority study compared the efficacy and safety of ferumoxytol, a rapid, injectable intravenous (IV) iron product with low immunological reactivity and minimal detectable free iron, with IV iron sucrose in adults with IDA of any cause. Patients (N = 605) were randomized 2:1 to receive ferumoxytol (n = 406, two doses of 510 mg 5 ± 3 days apart) or iron sucrose (n = 199, five doses of 200 mg on five nonconsecutive days over 14 days) and followed for 5 weeks. Ferumoxytol demonstrated noninferiority to iron sucrose at the primary endpoint, the proportion of patients achieving a hemoglobin increase of ≥2 g dL(-1) at any time from Baseline to Week 5 (ferumoxytol, 84.0% [n = 406] vs. iron sucrose, 81.4% [n = 199]), with a noninferiority margin of 15%. Ferumoxytol was superior to iron sucrose (2.7 g dL(-1) vs. 2.4 g dL(-1) ) in the mean change in hemoglobin from Baseline to Week 5 (the alternative preplanned primary endpoint) with P = 0.0124. Transferrin saturation, quality-of-life measures, and safety outcomes were similar between the two treatment groups. Overall, ferumoxytol demonstrated comparable safety and efficacy to iron sucrose, suggesting that ferumoxytol may be a useful treatment option for patients with IDA in whom oral iron was unsatisfactory or could not be used.

  6. Task shifting in maternal and newborn care: a non-inferiority study examining delegation of antenatal counseling to lay nurse aides supported by job aids in Benin

    Directory of Open Access Journals (Sweden)

    Affo Jean

    2011-01-01

    Full Text Available Abstract Background Shifting the role of counseling to less skilled workers may improve efficiency and coverage of health services, but evidence is needed on the impact of substitution on quality of care. This research explored the influence of delegating maternal and newborn counseling responsibilities to clinic-based lay nurse aides on the quality of counseling provided as part of a task shifting initiative to expand their role. Methods Nurse-midwives and lay nurse aides in seven public maternities were trained to use job aids to improve counseling in maternal and newborn care. Quality of counseling and maternal knowledge were assessed using direct observation of antenatal consultations and patient exit interviews. Both provider types were interviewed to examine perceptions regarding the task shift. To compare provider performance levels, non-inferiority analyses were conducted where non-inferiority was demonstrated if the lower confidence limit of the performance difference did not exceed a margin of 10 percentage points. Results Mean percent of recommended messages provided by lay nurse aides was non-inferior to counseling by nurse-midwives in adjusted analyses for birth preparedness (β = -0.0, 95% CI: -9.0, 9.1, danger sign recognition (β = 4.7, 95% CI: -5.1, 14.6, and clean delivery (β = 1.4, 95% CI: -9.4, 12.3. Lay nurse aides demonstrated superior performance for communication on general prenatal care (β = 15.7, 95% CI: 7.0, 24.4, although non-inferiority was not achieved for newborn care counseling (β = -7.3, 95% CI: -23.1, 8.4. The proportion of women with correct knowledge was significantly higher among those counseled by lay nurse aides as compared to nurse-midwives in general prenatal care (β = 23.8, 95% CI: 15.7, 32.0, birth preparedness (β = 12.7, 95% CI: 5.2, 20.1, and danger sign recognition (β = 8.6, 95% CI: 3.3, 13.9. Both cadres had positive opinions regarding task shifting, although several preferred 'task sharing

  7. Open access, readership, citations: a randomized controlled trial of scientific journal publishing.

    Science.gov (United States)

    Davis, Philip M

    2011-07-01

    Does free access to journal articles result in greater diffusion of scientific knowledge? Using a randomized controlled trial of open access publishing, involving 36 participating journals in the sciences, social sciences, and humanities, we report on the effects of free access on article downloads and citations. Articles placed in the open access condition (n=712) received significantly more downloads and reached a broader audience within the first year, yet were cited no more frequently, nor earlier, than subscription-access control articles (n=2533) within 3 yr. These results may be explained by social stratification, a process that concentrates scientific authors at a small number of elite research universities with excellent access to the scientific literature. The real beneficiaries of open access publishing may not be the research community but communities of practice that consume, but rarely contribute to, the corpus of literature.

  8. Choice of non-inferiority (NI margins does not protect against degradation of treatment effects on an average--an observational study of registered and published NI trials.

    Directory of Open Access Journals (Sweden)

    Beryl Primrose Gladstone

    Full Text Available NI margins have to be chosen appropriately to control the risk of degradation of treatment effects in non-inferiority (NI trials. We aimed to study whether the current choice of NI margins protects sufficiently against a degradation of treatment effect on an average.NI trials reflecting current practice were assembled and for each trial, the NI margin was translated into a likelihood of degradation. The likelihood of degradation was calculated as the conditional probability of a treatment being harmful given that it is declared non-inferior in the trial, using simulation. Its distribution among the NI trials was then studied to assess the potential risk of degradation.The median (lower/upper quartile NI margin among 112 binary outcome NI trials corresponded to an odds ratio of 0.57(0.45, 0.66, while among 38 NI trials with continuous outcome, to a Cohen's d of -0.42(-0.54, -0.31 and a hazard ratio of 0.82(0.73, 0.86 among 24 survival outcome NI trials. Overall, the median likelihood of degradation was 56% (45%, 62%.Only two fifths of the current NI trials had a likelihood of degradation lower than 50%, suggesting that, in majority of the NI trials, there is no sufficient protection against degradation on an average. We suggest a third hurdle for the choice of NI margins, thus contributing a sufficient degree of protection.

  9. Chirp- and random-based coded ultrasonic excitation for localized blood-brain barrier opening

    Science.gov (United States)

    Kamimura, H. A. S.; Wang, S.; Wu, S.-Y.; Karakatsani, M. E.; Acosta, C.; Carneiro, A. A. O.; Konofagou, E. E.

    2015-10-01

    Chirp- and random-based coded excitation methods have been proposed to reduce standing wave formation and improve focusing of transcranial ultrasound. However, no clear evidence has been shown to support the benefits of these ultrasonic excitation sequences in vivo. This study evaluates the chirp and periodic selection of random frequency (PSRF) coded-excitation methods for opening the blood-brain barrier (BBB) in mice. Three groups of mice (n  =  15) were injected with polydisperse microbubbles and sonicated in the caudate putamen using the chirp/PSRF coded (bandwidth: 1.5-1.9 MHz, peak negative pressure: 0.52 MPa, duration: 30 s) or standard ultrasound (frequency: 1.5 MHz, pressure: 0.52 MPa, burst duration: 20 ms, duration: 5 min) sequences. T1-weighted contrast-enhanced MRI scans were performed to quantitatively analyze focused ultrasound induced BBB opening. The mean opening volumes evaluated from the MRI were 9.38+/- 5.71 mm3, 8.91+/- 3.91 mm3and 35.47+/- 5.10 mm3 for the chirp, random and regular sonications, respectively. The mean cavitation levels were 55.40+/- 28.43 V.s, 63.87+/- 29.97 V.s and 356.52+/- 257.15 V.s for the chirp, random and regular sonications, respectively. The chirp and PSRF coded pulsing sequences improved the BBB opening localization by inducing lower cavitation levels and smaller opening volumes compared to results of the regular sonication technique. Larger bandwidths were associated with more focused targeting but were limited by the frequency response of the transducer, the skull attenuation and the microbubbles optimal frequency range. The coded methods could therefore facilitate highly localized drug delivery as well as benefit other transcranial ultrasound techniques that use higher pressure levels and higher precision to induce the necessary bioeffects in a brain region while avoiding damage to the surrounding healthy tissue.

  10. Chirp- and random-based coded ultrasonic excitation for localized blood-brain barrier opening

    Science.gov (United States)

    Kamimura, HAS; Wang, S; Wu, S-Y; Karakatsani, ME; Acosta, C; Carneiro, AAO; Konofagou, EE

    2015-01-01

    Chirp- and random-based coded excitation methods have been proposed to reduce standing wave formation and improve focusing of transcranial ultrasound. However, no clear evidence has been shown to support the benefits of these ultrasonic excitation sequences in vivo. This study evaluates the chirp and periodic selection of random frequency (PSRF) coded-excitation methods for opening the blood-brain barrier (BBB) in mice. Three groups of mice (n=15) were injected with polydisperse microbubbles and sonicated in the caudate putamen using the chirp/PSRF coded (bandwidth: 1.5-1.9 MHz, peak negative pressure: 0.52 MPa, duration: 30 s) or standard ultrasound (frequency: 1.5 MHz, pressure: 0.52 MPa, burst duration: 20 ms, duration: 5 min) sequences. T1-weighted contrast-enhanced MRI scans were performed to quantitatively analyze focused ultrasound induced BBB opening. The mean opening volumes evaluated from the MRI were 9.38±5.71 mm3, 8.91±3.91 mm3 and 35.47 ± 5.10 mm3 for the chirp, random and regular sonications, respectively. The mean cavitation levels were 55.40±28.43 V.s, 63.87±29.97 V.s and 356.52±257.15 V.s for the chirp, random and regular sonications, respectively. The chirp and PSRF coded pulsing sequences improved the BBB opening localization by inducing lower cavitation levels and smaller opening volumes compared to results of the regular sonication technique. Larger bandwidths were associated with more focused targeting but were limited by the frequency response of the transducer, the skull attenuation and the microbubbles optimal frequency range. The coded methods could therefore facilitate highly localized drug delivery as well as benefit other transcranial ultrasound techniques that use higher pressure levels and higher precision to induce the necessary bioeffects in a brain region while avoiding damage to the surrounding healthy tissue. PMID:26394091

  11. Random Finite Set Based Bayesian Filtering with OpenCL in a Heterogeneous Platform

    Directory of Open Access Journals (Sweden)

    Biao Hu

    2017-04-01

    Full Text Available While most filtering approaches based on random finite sets have focused on improving performance, in this paper, we argue that computation times are very important in order to enable real-time applications such as pedestrian detection. Towards this goal, this paper investigates the use of OpenCL to accelerate the computation of random finite set-based Bayesian filtering in a heterogeneous system. In detail, we developed an efficient and fully-functional pedestrian-tracking system implementation, which can run under real-time constraints, meanwhile offering decent tracking accuracy. An extensive evaluation analysis was carried out to ensure the fulfillment of sufficient accuracy requirements. This was followed by extensive profiling analysis to spot the potential bottlenecks in terms of execution performance, which were then targeted to come up with an OpenCL accelerated application. Video-throughput improvements from roughly 15 fps to 100 fps (6× were observed on average while processing typical MOT benchmark videos. Moreover, the worst-case frame processing yielded an 18× advantage from nearly 2 fps to 36 fps, thereby comfortably meeting the real-time constraints. Our implementation is released as open-source code.

  12. Random Finite Set Based Bayesian Filtering with OpenCL in a Heterogeneous Platform.

    Science.gov (United States)

    Hu, Biao; Sharif, Uzair; Koner, Rajat; Chen, Guang; Huang, Kai; Zhang, Feihu; Stechele, Walter; Knoll, Alois

    2017-04-12

    While most filtering approaches based on random finite sets have focused on improving performance, in this paper, we argue that computation times are very important in order to enable real-time applications such as pedestrian detection. Towards this goal, this paper investigates the use of OpenCL to accelerate the computation of random finite set-based Bayesian filtering in a heterogeneous system. In detail, we developed an efficient and fully-functional pedestrian-tracking system implementation, which can run under real-time constraints, meanwhile offering decent tracking accuracy. An extensive evaluation analysis was carried out to ensure the fulfillment of sufficient accuracy requirements. This was followed by extensive profiling analysis to spot the potential bottlenecks in terms of execution performance, which were then targeted to come up with an OpenCL accelerated application. Video-throughput improvements from roughly 15 fps to 100 fps (6×) were observed on average while processing typical MOT benchmark videos. Moreover, the worst-case frame processing yielded an 18× advantage from nearly 2 fps to 36 fps, thereby comfortably meeting the real-time constraints. Our implementation is released as open-source code.

  13. Surface area and volume fraction of random open-pore systems

    Science.gov (United States)

    Hermann, H.; Elsner, A.; Stoyan, D.

    2013-12-01

    For the first time, explicit approximate formulas are presented for the volume fraction and specific surface area of random open-pore systems with poly-disperse pore size distributions. It is shown that the formulas are valid for broad classes of models for porous media characterized by tunable pore size distributions and a variable degree of inter-penetrability of pores. The formulas for the poly-disperse case are based on expressions derived previously for mono-disperse penetrable-sphere models. The results are obtained by analysis of a series of open-pore models, which are prepared by computer simulation of systems of randomly packed partially penetrable spheres with various poly-disperse size distributions such as gamma, lognormal, and Gaussian. The formulas are applied in a study of atomic layer deposition processes on open-pore systems, and the effective Young's modulus and the effective thermal conductivity of Al2O3 coated porous polypropylene electrodes for lithium ion batteries are predicted.

  14. Classification and valuation of postoperative complications in a randomized trial of open versus laparoscopic ventral herniorrhaphy.

    Science.gov (United States)

    Kaafarani, H M A; Hur, K; Campasano, M; Reda, D J; Itani, K M F

    2010-06-01

    Generic instruments used for the valuation of health states (e.g., EuroQol) often lack sensitivity to notable differences that are relevant to particular diseases or interventions. We developed a valuation methodology specifically for complications following ventral incisional herniorrhaphy (VIH). Between 2004 and 2006, 146 patients were prospectively randomized to undergo laparoscopic (n = 73) or open (n = 73) VIH. The primary outcome of the trial was complications at 8 weeks. A three-step methodology was used to assign severity weights to complications. First, each complication was graded using the Clavien classification. Second, five reviewers were asked to independently and directly rate their perception of the severity of each class using a non-categorized visual analog scale. Zero represented an uncomplicated postoperative course, while 100 represented postoperative death. Third, the median, lowest, and highest values assigned to each class of complications were used to derive weighted complication scores for open and laparoscopic VIH. Open VIH had more complications than laparoscopic VIH (47.9 vs. 31.5%, respectively; P = 0.026). However, complications of laparoscopic VIH were more severe than those of open VIH. Non-parametric analysis revealed a statistically higher weighted complication score for open VIH (interquartile range: 0-20 for open vs. 0-10 for laparoscopic; P = 0.049). In the sensitivity analysis, similar results were obtained using the median, highest, and lowest weights. We describe a new methodology for the valuation of complications following VIH that allows a direct outcome comparison of procedures with different complication profiles. Further testing of the validity, reliability, and generalizability of this method is warranted.

  15. Long-term follow-up of a randomized trial comparing laparoscopic and mini-incision open live donor nephrectomy.

    NARCIS (Netherlands)

    Dols, L.F.; Ijzermans, J.N.M.; Wentink, N.; Tran, T.C.K.; Zuidema, W.C.; Dooper, P.M.M.; Weimar, W.; Kok, N.F.

    2010-01-01

    Long-term physical and psychosocial effects of laparoscopic and open kidney donation are ill defined. We performed long-term follow-up of 100 live kidney donors, who had been randomly assigned to mini-incision open donor nephrectomy (MIDN) or laparoscopic donor nephrectomy (LDN). Data included blood

  16. Health-related quality of life after laparoscopic and open surgery for rectal cancer in a randomized trial

    DEFF Research Database (Denmark)

    Andersson, J; Angenete, E; Gellerstedt, M

    2013-01-01

    Previous studies comparing laparoscopic and open surgical techniques have reported improved health-related quality of life (HRQL). This analysis compared HRQL 12¿months after laparoscopic versus open surgery for rectal cancer in a subset of a randomized trial....

  17. Morphine versus Nalbuphine for Open Gynaecological Surgery: A Randomized Controlled Double Blinded Trial

    Directory of Open Access Journals (Sweden)

    Shiv Akshat

    2014-01-01

    Full Text Available Introduction. Pain is the commonest morbidity after open surgical procedures. The most effective treatment of postoperative pain is opioid therapy. Morphine, the commonly used opioid, is associated with many side effects including respiratory depression, sedation, postoperative nausea vomiting, and pruritus. Nalbuphine, on the other hand, is known to cause less respiratory depression. Thus this study was undertaken to compare the intraoperative and postoperative analgesic efficacy and side effect profile of the two drugs. Methodology. 60 patients undergoing open gynaecological surgery were randomized to receive either morphine (Group M or nalbuphine (Group N in the intraoperative and postoperative period. Intraoperative analgesic efficacy (measured by need for rescue analgesics, postoperative pain by visual analogue scale, and side effects like postoperative nausea, vomiting, sedation, respiratory depression, and pruritus were compared in both groups. Intraoperative and postoperative heart rate and blood pressure were also compared between the groups. Results. Need for intraoperative analgesia was significantly more in Group N (P=0.023. Postoperative VAS scores were significantly different between the groups at various time points; however, none of the patients required any rescue analgesia. The incidence of various side effects was not significantly different between the groups. The haemodynamic profile of patients was comparable between the groups in both intraoperative and postoperative period. Conclusion. Nalbuphine provides less effective intraoperative analgesia than morphine in patients undergoing open gynaecological surgery under general anaesthesia. Both drugs, however, provided similar postoperative analgesia and had similar haemodynamic and side effect profile.

  18. Combining video instruction followed by voice feedback in a self-learning station for acquisition of Basic Life Support skills: a randomised non-inferiority trial.

    Science.gov (United States)

    Mpotos, Nicolas; Lemoyne, Sabine; Calle, Paul A; Deschepper, Ellen; Valcke, Martin; Monsieurs, Koenraad G

    2011-07-01

    Current computerised self-learning (SL) stations for Basic Life Support (BLS) are an alternative to instructor-led (IL) refresher training but are not intended for initial skill acquisition. We developed a SL station for initial skill acquisition and evaluated its efficacy. In a non-inferiority trial, 120 pharmacy students were randomised to IL small group training or individual training in a SL station. In the IL group, instructors demonstrated the skills and provided feedback. In the SL group a shortened Mini Anne™ video, to acquire the skills, was followed by Resusci Anne Skills Station™ software (both Laerdal, Norway) with voice feedback for further refinement. Testing was performed individually, respecting a seven week interval after training for every student. One hundred and seventeen participants were assessed (three drop-outs). The proportion of students achieving a mean compression depth 40-50mm was 24/56 (43%) IL vs. 31/61 (51%) SL and 39/56 (70%) IL vs. 48/61 (79%) SL for a mean compression depth ≥ 40 mm. Compression rate 80-120/min was achieved in 49/56 (88%) IL vs. 57/61 (93%) SL and any incomplete release (≥ 5 mm) was observed in 31/56 (55%) IL and 35/61 (57%) SL. Adequate mean ventilation volume (400-1000 ml) was achieved in 29/56 (52%) IL vs. 36/61 (59%) SL. Non-inferiority was confirmed for depth and although inconclusive, other areas came close to demonstrate it. Compression skills acquired in a SL station combining video-instruction with training using voice feedback were not inferior to IL training. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. A randomised, double-blind, parallel design, multi-institutional, non-inferiority phase IV trial of imidafenacin versus fesoterodine for overactive bladder.

    Science.gov (United States)

    Lee, K-S; Park, B; Kim, J H; Kim, H G; Seo, J T; Lee, J G; Jang, Y; Choo, M-S

    2013-12-01

    Our objective was to compare the efficacy and safety of imidafenacin over fesoterodine in patients with overactive bladder (OAB). This study is a randomised, double-blind, parallel-group, fesoterodine-controlled study in patients with continuous OAB symptoms for ≥ 3 months, daily mean voiding frequency (DMVF) ≥ 8, and daily mean urgency or urgency incontinence frequency ≥ 2. A twice-daily 0.1 mg imidafenacin with placebo, or once-daily 4 mg fesoterodine with placebo were administered for 12 weeks. The primary efficacy end-point was the difference in DMVF at 12 weeks. The secondary efficacy end-points were differences in daily mean: (i) voiding frequency at 4 and 8 weeks; (ii) urgency frequency; (iii) urgency incontinence frequency; (iv) incontinence frequency; (v) nocturia frequency; and (vi) quality of life score. The variables for safety analysis were adverse events, vital signs, residual urine volume and clinical laboratory tests. An efficacy analysis was conducted in per-protocol patients and the safety analysis was conducted in all randomised patients. The differences in DMVF at 12 weeks were -3.38 ± 3.63 and -2.45 ± 3.73 in the imidafenacin and fesoterodine groups, respectively, and the difference was not significant between the two groups. Imidafenacin was non-inferior to fesoterodine, and the lower limit of 95% two-sided confidence intervals was -0.53. The other six secondary end-points and variables for safety analysis showed no difference between the two groups. Imidafenacin was non-inferior to fesoterodine in terms of efficacy, and showed no significant difference in terms of safety. © 2013 John Wiley & Sons Ltd.

  20. Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

    Science.gov (United States)

    Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

    2016-01-01

    Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

  1. Mothers screening for malnutrition by mid-upper arm circumference is non-inferior to community health workers

    DEFF Research Database (Denmark)

    Alé, Franck G B; Phelan, Kevin P Q; Issa, Hassan

    2016-01-01

    Background: Community health workers (CHWs) are recommended to screen for acute malnutrition in the community by assessing mid-upper arm circumference (MUAC) on children between 6 and 59 months of age. MUAC is a simple screening tool that has been shown to be a better predictor of mortality...... in acutely malnourished children than other practicable anthropometric indicators. This study compared, under program conditions, mothers and CHWs in screening for severe acute malnutrition (SAM) by color-banded MUAC tapes. Methods: This pragmatic interventional, non-randomized efficacy study took place...... in two health zones of Niger's Mirriah District from May 2013 to April 2014. Mothers in Dogo (Mothers Zone) and CHWs in Takieta (CHWs Zone) were trained to screen for malnutrition by MUAC color-coded class and check for edema. Exhaustive coverage surveys were conducted quarterly, and relevant data...

  2. Albendazole versus metronidazole treatment of adult giardiasis:An open randomized clinical study

    Institute of Scientific and Technical Information of China (English)

    Oguz Karabay; Ali Tamer; Huseyin Gunduz; Derya Kayas; Huseyin Arinc; Harika Celebi

    2004-01-01

    AIM: To investigate the efficacy and tolerability of albendazole and metranidazole treatment in giardiasis.METHODS: The open comparative randomized trial was carried out prospectively from_December 1999 to July 2001in Duzce City of Turkey. The diagnosis was based on the presence of signs and symptoms compatible with giardiasis including a positive stool examination of giardia cysts or trophozoite. Metranidazole group consisted of 29 patients and was given metranidazole 500 mg, three times a day for 5 d and albendazole group was consisted of 28 patients and was given albendazole 400 mg/d for 5 d.RESULTS: There were no significant differences in demographical and therapeutical effects and patient′s compliance between both groups. But side effects were seen more in metranidazole group than in albendazole group.CONCLUSION: Albendazole is as effective as metranidazole in adults′ giardiasis. Albendazole has less side effect potentials than metranidazole in the treatment of giardiasis.

  3. A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation.

    Science.gov (United States)

    White, William D; Crockford, David; Patten, Scott; El-Guebaly, Nady

    2005-10-01

    This 6-week, randomized, open-label pilot study estimated the treatment effect size of gabapentin (n = 17) compared with bupropion SR (n = 19) for smoking cessation, thereby allowing sample size calculations for a definitive comparison study. The primary outcome measure was smoking cessation. Secondary outcome measures included smoking reduction and withdrawal severity. Gabapentin was less efficacious than bupropion for smoking cessation but was associated with fewer dropouts from adverse effects. Withdrawal severity was less with bupropion. Bupropion remains the first-line non-nicotine pharmacotherapy for smoking cessation. Further study is required to determine if gabapentin has any useful role in smoking cessation. Based on our primary outcome measure, 79 subjects would be required in each treatment group of a two-armed study to achieve 90% power for detecting a difference in efficacy between gabapentin and bupropion.

  4. Open-label placebo treatment in chronic low back pain: a randomized controlled trial

    Science.gov (United States)

    Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J.; Kirsch, Irving

    2016-01-01

    Abstract This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland–Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P < 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (−0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P < 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (−1.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain. PMID:27755279

  5. Reduction of claustrophobia with short-bore versus open magnetic resonance imaging: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Judith Enders

    Full Text Available BACKGROUND: Claustrophobia is a common problem precluding MR imaging. The purpose of the present study was to assess whether a short-bore or an open magnetic resonance (MR scanner is superior in alleviating claustrophobia. METHODS: Institutional review board approval and patient informed consent were obtained to compare short-bore versus open MR. From June 2008 to August 2009, 174 patients (139 women; mean age = 53.1 [SD 12.8] with an overall mean score of 2.4 (SD 0.7, range 0 to 4 on the Claustrophobia Questionnaire (CLQ and a clinical indication for imaging, were randomly assigned to receive evaluation by open or by short-bore MR. The primary outcomes were incomplete MR examinations due to a claustrophobic event. Follow-up was conducted 7 months after MR imaging. The primary analysis was performed according to the intention-to-treat strategy. RESULTS: With 33 claustrophobic events in the short-bore group (39% [95% confidence interval [CI] 28% to 50% versus 23 in the open scanner group (26% [95% CI 18% to 37%]; P = 0.08 the difference was not significant. Patients with an event were in the examination room for 3.8 min (SD 4.4 in the short-bore and for 8.5 min (SD 7 in the open group (P = 0.004. This was due to an earlier occurrence of events in the short-bore group. The CLQ suffocation subscale was significantly associated with the occurrence of claustrophobic events (P = 0.003. New findings that explained symptoms were found in 69% of MR examinations and led to changes in medical treatment in 47% and surgery in 10% of patients. After 7 months, perceived claustrophobia increased in 32% of patients with events versus in only 11% of patients without events (P = 0.004. CONCLUSIONS: Even recent MR cannot prevent claustrophobia suggesting that further developments to create a more patient-centered MR scanner environment are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT00715806.

  6. Reduction of claustrophobia with short-bore versus open magnetic resonance imaging: a randomized controlled trial.

    Science.gov (United States)

    Enders, Judith; Zimmermann, Elke; Rief, Matthias; Martus, Peter; Klingebiel, Randolf; Asbach, Patrick; Klessen, Christian; Diederichs, Gerd; Wagner, Moritz; Teichgräber, Ulf; Bengner, Thomas; Hamm, Bernd; Dewey, Marc

    2011-01-01

    Claustrophobia is a common problem precluding MR imaging. The purpose of the present study was to assess whether a short-bore or an open magnetic resonance (MR) scanner is superior in alleviating claustrophobia. Institutional review board approval and patient informed consent were obtained to compare short-bore versus open MR. From June 2008 to August 2009, 174 patients (139 women; mean age = 53.1 [SD 12.8]) with an overall mean score of 2.4 (SD 0.7, range 0 to 4) on the Claustrophobia Questionnaire (CLQ) and a clinical indication for imaging, were randomly assigned to receive evaluation by open or by short-bore MR. The primary outcomes were incomplete MR examinations due to a claustrophobic event. Follow-up was conducted 7 months after MR imaging. The primary analysis was performed according to the intention-to-treat strategy. With 33 claustrophobic events in the short-bore group (39% [95% confidence interval [CI] 28% to 50%) versus 23 in the open scanner group (26% [95% CI 18% to 37%]; P = 0.08) the difference was not significant. Patients with an event were in the examination room for 3.8 min (SD 4.4) in the short-bore and for 8.5 min (SD 7) in the open group (P = 0.004). This was due to an earlier occurrence of events in the short-bore group. The CLQ suffocation subscale was significantly associated with the occurrence of claustrophobic events (P = 0.003). New findings that explained symptoms were found in 69% of MR examinations and led to changes in medical treatment in 47% and surgery in 10% of patients. After 7 months, perceived claustrophobia increased in 32% of patients with events versus in only 11% of patients without events (P = 0.004). Even recent MR cannot prevent claustrophobia suggesting that further developments to create a more patient-centered MR scanner environment are needed. ClinicalTrials.gov NCT00715806.

  7. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome.

    Science.gov (United States)

    Vermeulen, Ruud C W; Scholte, Hans R

    2004-01-01

    We compared the effects of acetylcarnitine, propionylcarnitine and both compounds on the symptoms of chronic fatigue syndrome (CFS). In an open, randomized fashion we compared 2 g/d acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 CFS patients during 24 weeks. Effects were rated by clinical global impression of change. Secondary endpoints were the Multidimensional Fatigue Inventory, McGill Pain Questionnaire, and the Stroop attention concentration test. Scores were assessed 8 weeks before treatment; at randomization; after 8, 16, and 24 weeks of treatment; and 2 weeks later. Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine group (37%). Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not decrease in any group. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37% in the acetylcarnitine, propionylcarnitine, and combined group, respectively. In the acetylcarnitine group, but not in the other groups, the changes in plasma carnitine levels correlated with clinical improvement. Acetylcarnitine and propionylcarnitine showed beneficial effect on fatigue and attention concentration. Less improvement was found by the combined treatment. Acetylcarnitine had main effect on mental fatigue and propionylcarnitine on general fatigue.

  8. Laparoscopic versus open cholecystectomy in cirrhotic patients: a prospective randomized study.

    Science.gov (United States)

    El-Awadi, Saleh; El-Nakeeb, Ayman; Youssef, Tamer; Fikry, Amir; Abd El-Hamed, Tito M; Ghazy, Hosam; Foda, Elyamany; Farid, Mohamed

    2009-02-01

    Improved laparoscopic experience and techniques have made laparoscopic cholecystectomy (LC) feasible options in cirrhotic patients. This study was designed to compare the risk and benefits of open cholecystectomy (OC) versus LC in compensated cirrhosis. A randomized prospective study, in the period from October 2002 till December 2006, where 110 cirrhotic patients with symptomatic gallstone were randomly divided into OC group (55 patients) and LC group (55 patients). There was no operative mortality. In LC group 4 (7.33%) patients were converted to OC. Mean surgical time was significantly longer in OC group than LC group (96.13+17.35 min versus 76.13+15.12) P<0.05, associated with significantly higher intraoperative bleeding in OC group (P<0.01), necessitating blood transfusions to 7 (12.72%) patients in OC group. The time to resume diet was 18.36+8.18 h in LC group which is significantly earlier than in OC group 47.84+14.6h P<0.005. Hospital stay was significantly longer in OC group than LC group (6+1.74 days versus 1.87+1.11 days) P<0.01 with low postoperative morbidity. LC in cirrhotics is still complicated and highly difficult which associates with significant morbidity compared with that of patients without cirrhosis. However, it offers lower morbidity, shorter operative time; early resume dieting with less need for blood transfusion and reducing hospital stay than OC.

  9. Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy : study protocol of a pragmatic multicentre non-inferiority randomized controlled trial

    NARCIS (Netherlands)

    Molenaar, Nina M; Brouwer, Marlies E; Bockting, Claudi L H; Bonsel, Gouke J; van der Veere, Christine N; Torij, Hanneke W; Hoogendijk, Witte J G; Duvekot, Johannes J; Burger, Huibert; Lambregtse-van den Berg, Mijke P

    2016-01-01

    Background: Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still

  10. Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy : study protocol of a pragmatic multicentre non-inferiority randomized controlled trial

    NARCIS (Netherlands)

    Molenaar, Nina; Brouwer, M. E.; Bockting, C. L. H.; Bonsel, G. J.; Van der Veere, C. N.; Torij, H. W.; Hoogendijk, W.; Duvekot, J. J.; Burger, H. N.; Lambregtse-van den Berg, M. P.

    2016-01-01

    Background Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still contr

  11. Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: Study protocol of a pragmatic multicentre non-inferiority randomized controlled trial

    NARCIS (Netherlands)

    N.M. Molenaar (Nina M.); M. Brouwer (Marije); C.L.H. Bockting (Claudi ); G.J. Bonsel (Gouke); C.N. van der Veere (Christine N.); H.W. Torij (H. W.); W.J.G. Hoogendijk (Witte); J.J. Duvekot (Hans); H. Burger (Huibert); M.P. Lambregtse-van den Berg (Mijke)

    2016-01-01

    textabstractBackground: Approximately 6.2% of women in the USA and 3.7% of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2%. Nonetheless, SSRI use during pregnancy is s

  12. Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy : study protocol of a pragmatic multicentre non-inferiority randomized controlled trial

    NARCIS (Netherlands)

    Molenaar, Nina M; Brouwer, Marlies E; Bockting, Claudi L H; Bonsel, Gouke J; van der Veere, Christine N; Torij, Hanneke W; Hoogendijk, Witte J G; Duvekot, Johannes J; Burger, Huibert; Lambregtse-van den Berg, Mijke P

    2016-01-01

    Background: Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still cont

  13. Single-session gamified virtual reality exposure therapy for spider phobia vs. traditional exposure therapy: study protocol for a randomized controlled non-inferiority trial

    OpenAIRE

    2016-01-01

    Background Traditional one-session exposure therapy (OST) in which a patient is gradually exposed to feared stimuli for up to 3 h in a one-session format has been found effective for the treatment of specific phobias. However, many individuals with specific phobia are reluctant to seek help, and access to care is lacking due to logistic challenges of accessing, collecting, storing, and/or maintaining stimuli. Virtual reality (VR) exposure therapy may improve upon existing techniques by facili...

  14. Electromagnetic-Guided Bedside Placement of Nasoenteral Feeding Tubes by Nurses Is Non-Inferior to Endoscopic Placement by Gastroenterologists: A Multicenter Randomized Controlled Trial

    NARCIS (Netherlands)

    Gerritsen, A.; Rooij, T. de; Dijkgraaf, M.G.; Busch, O.R.; Bergman, J.J.; Ubbink, D.T.; Duijvendijk, P. van; Erkelens, G.W.; Klos, M.; Kruyt, P.M.; Bac, D.J.; Rosman, C.; Tan, A.C.; Molenaar, I.Q.; Monkelbaan, J.F.; Mathus-Vliegent, E.M.; Besselink, M.G.

    2016-01-01

    OBJECTIVES: Electromagnetic (EM)-guided bedside placement of nasoenteral feeding tubes by nurses may improve efficiency and reduce patient discomfort and costs compared with endoscopic placement by gastroenterologists. However, evidence supporting this task shift from gastroenterologists to nurses i

  15. Cost effectiveness of intermittent screening followed by treatment versus intermittent preventive treatment during pregnancy in West Africa: analysis and modelling of results from a non-inferiority trial.

    Science.gov (United States)

    Fernandes, Silke; Sicuri, Elisa; Halimatou, Diawara; Akazili, James; Boiang, Kalifa; Chandramohan, Daniel; Coulibaly, Sheikh; Diawara, Sory Ibrahim; Kayentao, Kassoum; Ter Kuile, Feiko; Magnussen, Pascal; Tagbor, Harry; Williams, John; Woukeu, Arouna; Cairns, Matthew; Greenwood, Brian; Hanson, Kara

    2016-09-23

    Emergence of high-grade sulfadoxine-pyrimethamine (SP) resistance in parts of Africa has led to growing concerns about the efficacy of intermittent preventive treatment of malaria during pregnancy (IPTp) with SP. The incremental cost-effectiveness of intermittent screening and treatment (ISTp) with artemether-lumefantrine (AL) as an alternative strategy to IPTp-SP was estimated followed by a simulation of the effects on cost-effectiveness of decreasing efficacy of IPTp-SP due to SP resistance. The analysis was based on results from a multi-centre, non-inferiority trial conducted in West Africa. A decision tree model was analysed from a health provider perspective. Model parameters for all trial countries with appropriate ranges and distributions were used in a probabilistic sensitivity analysis. Simulations were performed in hypothetical cohorts of 1000 pregnant women who received either ISTp-AL or IPTp-SP. In addition a cost-consequences analysis was conducted. Trial estimates were used to calculate disability-adjusted-life-years (DALYs) for low birth weight and severe/moderate anaemia (both shown to be non-inferior for ISTp-AL) and clinical malaria (inferior for ISTp-AL). Cost estimates were obtained from observational studies, health facility costings and public procurement databases. Results were calculated as incremental cost per DALY averted. Finally, the cost-effectiveness changes with decreasing SP efficacy were explored by simulation. Relative to IPTp-SP, delivering ISTp-AL to 1000 pregnant women cost US$ 4966.25 more (95 % CI US$ 3703.53; 6376.83) and led to a small excess of 28.36 DALYs (95 % CI -75.78; 134.18), with LBW contributing 81.3 % of this difference. The incremental cost-effectiveness ratio was -175.12 (95 % CI -1166.29; 1267.71) US$/DALY averted. Simulations show that cost-effectiveness of ISTp-AL increases as the efficacy of IPTp-SP decreases, though the specific threshold at which ISTp-AL becomes cost-effective depends on assumptions

  16. Comparing Effectiveness of Active and Passive Client Follow-Up Approaches in Sustaining the Continued Use of Long Acting Reversible Contraceptives (LARC) in Rural Punjab: A Multicentre, Non-Inferiority Trial

    Science.gov (United States)

    Hameed, Waqas; Azmat, Syed Khurram; Ali, Moazzam; Ishaque, Muhammad; Abbas, Ghazunfer; Munroe, Erik; Harrison, Rebecca; Shamsi, Wajahat Hussain; Mustafa, Ghulam; Khan, Omar Farooq; Ali, Safdar; Ahmed, Aftab

    2016-01-01

    Background The use of long-acting reversible contraceptive (LARC) methods is very low in Pakistan with high discontinuation rates mainly attributed to method-related side effects. Mixed evidence is available on the effectiveness of different client follow-up approaches used to ensure method continuation. We compared the effectiveness of active and passive follow-up approaches in sustaining the use of LARC—and within ‘active’ follow-up, we further compared a telephone versus home-based approach in rural Punjab, Pakistan. Methods This was a 12-month multicentre non-inferiority trial conducted in twenty-two (16 rural- and 6 urban-based) franchised reproductive healthcare facilities in district Chakwal of Punjab province, between November 2013 and December 2014. The study comprised of three groups of LARC clients: a) home-based follow-up, b) telephone-based follow-up, and c) passive or needs-based follow-up. Participants in the first two study groups received counselling on scheduled follow-up from the field workers at 1, 3, 6, 9, and 12 month post-insertion whereas participants in the third group were asked to contact the health facility if in need of medical assistance relating to LARC method use. Study participants were recruited with equal allocation to each study group, but participants were not randomized. The analyses are based on 1,246 LARC (intra-uterine contraceptive device and implant) users that completed approximately 12-months of follow-up. The non-inferiority margin was kept at five percentage points for the comparison of active and passive follow-up and six percentage points for telephone and home-based approach. The primary outcome was cumulative probability of method continuation at 12-month among LARC users. Results Women recruited in home-based, telephone-based, and passive groups were 400, 419 and 427, respectively. The cumulative probability of LARC continuation at 12 month was 87.6% (95% CI 83.8 to 90.6) among women who received home

  17. OxMaR: open source free software for online minimization and randomization for clinical trials.

    Science.gov (United States)

    O'Callaghan, Christopher A

    2014-01-01

    Minimization is a valuable method for allocating participants between the control and experimental arms of clinical studies. The use of minimization reduces differences that might arise by chance between the study arms in the distribution of patient characteristics such as gender, ethnicity and age. However, unlike randomization, minimization requires real time assessment of each new participant with respect to the preceding distribution of relevant participant characteristics within the different arms of the study. For multi-site studies, this necessitates centralized computational analysis that is shared between all study locations. Unfortunately, there is no suitable freely available open source or free software that can be used for this purpose. OxMaR was developed to enable researchers in any location to use minimization for patient allocation and to access the minimization algorithm using any device that can connect to the internet such as a desktop computer, tablet or mobile phone. The software is complete in itself and requires no special packages or libraries to be installed. It is simple to set up and run over the internet using online facilities which are very low cost or even free to the user. Importantly, it provides real time information on allocation to the study lead or administrator and generates real time distributed backups with each allocation. OxMaR can readily be modified and customised and can also be used for standard randomization. It has been extensively tested and has been used successfully in a low budget multi-centre study. Hitherto, the logistical difficulties involved in minimization have precluded its use in many small studies and this software should allow more widespread use of minimization which should lead to studies with better matched control and experimental arms. OxMaR should be particularly valuable in low resource settings.

  18. [Laparoscopic inguinal hernia repair "IPOM" vs "open tension free". Preliminary results of a prospective randomized study].

    Science.gov (United States)

    Catani, M; De Milito, R; Spaziani, E; Chiaretti, M; Manili, G; Capitano, S; Di Filippo, A; Simi, M

    2003-12-01

    The authors report the preliminary results of a prospective comparison of IPOM (group A) and "open tension free" (group B) hernioplasty in 50 patients having a mono or bilateral primitive hernia. In group A (26 patients) hernia repair was performed using "Gore-Tex DualMesh Plus biomaterial with holes Corduroy" and in group B (24 patients) using the patch and plug technique with Marlex prosthesis. No intraoperative complications occurred and, in group A, no conversion was necessary. Four minor complications were obser-ved in group A (10.8%): 3 seromas and 1 transient paresthesia; 5 in group B (16%): 4 hematomas and 1 wound infection (p=n.s.). In group A only 2 patients (7.6%) needed analgesics after the first 24 hours and 12 patients (50%) in group B (p<0.001). Mean resumption of normal activity was 8 days in group A and 17 days in group B (p<0.001). At a 12-month-follow-up, no recurrence was reported in both groups. The results of this prospective randomized study show that IPOM may be not only a feasible and effective procedure in the treatment of recurrent and bilateral hernia or when hernia repair is performed during other laparoscopic procedures, but also in particular cases of primitive hernia such as in very active young males or heavy duty workers. However it is necessary to definitely ascertain the true incidence of recurrence in non limited series and in longer follow-up and the preliminary results of this study encourage the authors to complete the randomized study.

  19. OxMaR: open source free software for online minimization and randomization for clinical trials.

    Directory of Open Access Journals (Sweden)

    Christopher A O'Callaghan

    Full Text Available Minimization is a valuable method for allocating participants between the control and experimental arms of clinical studies. The use of minimization reduces differences that might arise by chance between the study arms in the distribution of patient characteristics such as gender, ethnicity and age. However, unlike randomization, minimization requires real time assessment of each new participant with respect to the preceding distribution of relevant participant characteristics within the different arms of the study. For multi-site studies, this necessitates centralized computational analysis that is shared between all study locations. Unfortunately, there is no suitable freely available open source or free software that can be used for this purpose. OxMaR was developed to enable researchers in any location to use minimization for patient allocation and to access the minimization algorithm using any device that can connect to the internet such as a desktop computer, tablet or mobile phone. The software is complete in itself and requires no special packages or libraries to be installed. It is simple to set up and run over the internet using online facilities which are very low cost or even free to the user. Importantly, it provides real time information on allocation to the study lead or administrator and generates real time distributed backups with each allocation. OxMaR can readily be modified and customised and can also be used for standard randomization. It has been extensively tested and has been used successfully in a low budget multi-centre study. Hitherto, the logistical difficulties involved in minimization have precluded its use in many small studies and this software should allow more widespread use of minimization which should lead to studies with better matched control and experimental arms. OxMaR should be particularly valuable in low resource settings.

  20. Continuous-time random walk for open systems: fluctuation theorems and counting statistics.

    Science.gov (United States)

    Esposito, Massimiliano; Lindenberg, Katja

    2008-05-01

    We consider continuous-time random walks (CTRW) for open systems that exchange energy and matter with multiple reservoirs. Each waiting time distribution (WTD) for times between steps is characterized by a positive parameter alpha , which is set to alpha=1 if it decays at least as fast as t{-2} at long times and therefore has a finite first moment. A WTD with alpha<1 decays as t{-alpha-1} . A fluctuation theorem for the trajectory quantity R , defined as the logarithm of the ratio of the probability of a trajectory and the probability of the time reversed trajectory, holds for any CTRW. However, R can be identified as a trajectory entropy change only if the WTDs have alpha=1 and satisfy separability (also called "direction time independence"). For nonseparable WTDs with alpha=1 , R can only be identified as a trajectory entropy change at long times, and a fluctuation theorem for the entropy change then only holds at long times. For WTDs with 0

  1. Proposal for a Modified Jaw Opening Exercise for Dysphagia: A Randomized, Controlled Trial.

    Science.gov (United States)

    Koyama, Yuji; Sugimoto, Ayaka; Hamano, Takahide; Kasahara, Takashi; Toyokura, Minoru; Masakado, Yoshihisa

    2017-07-20

    To verify the feasibility and effectiveness of a newly developed modified jaw opening exercise (MJOE) in post-stroke patients with pharyngeal residue who completed a sixweek exercise regimen. Double-blind, randomized, controlled trial. 16 patients with stroke-related dysphagia. Participants were allocated to an intervention group (MJOE: one set of five repetitions at 80% maximum voluntary contraction (MVC) for 6 seconds) or a control group (isometric jaw closing exercise: one set of five repetitions at 20% MVC for 6 seconds). Each group performed four sets a day, five times a week, for a total of six weeks. A videofluorographic swallowing study was performed before and after exercise. The distance between the mental spine and the hyoid bone (DMH) and hyoid displacement (HD) were measured. Twelve participants completed the study. No pain in the temporomandibular joint and/or anterior region of the neck occurred during the exercise period. In the intervention group (N=6), a decrease in DMH where anterior HD ended and an increase in anterior HD were seen. In the control group (N=6), no changes were seen. MJOE is feasible without any adverse events in poststroke patients, and it promotes anterior HD during swallowing.

  2. Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study.

    Science.gov (United States)

    Yari, Zahra; Rahimlou, Mehran; Eslamparast, Tannaz; Ebrahimi-Daryani, Naser; Poustchi, Hossein; Hekmatdoost, Azita

    2016-06-01

    A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (p< 0.05); however, this reduction was significantly greater in those who took flaxseed supplementation (p < 0.05). The significant mean differences were reached in hepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; P< 0.001], AST [-8.29 compared with -4 U/L; p < 0.001], GGT [-15.7 compared with -2.62 U/L; p < 0.001], fibrosis score [-1.26 compared with -0.77 kPa; p = 0.013] and steatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

  3. Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Peter G Kremsner

    2016-01-01

    Full Text Available Current artesunate (ARS regimens for severe malaria are complex. Once daily intramuscular (i.m. injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v. or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%.This randomized controlled trial included children (0.5-10 y with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h (n = 348 or three injections of 4 mg/kg (at 0, 24, and 48 h either i.m. (n = 348 or i.v. (n = 351, both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333; 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78% children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79% receiving the five-dose i

  4. Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial.

    Science.gov (United States)

    Kremsner, Peter G; Adegnika, Akim A; Hounkpatin, Aurore B; Zinsou, Jeannot F; Taylor, Terrie E; Chimalizeni, Yamikani; Liomba, Alice; Kombila, Maryvonne; Bouyou-Akotet, Marielle K; Mawili Mboumba, Denise P; Agbenyega, Tsiri; Ansong, Daniel; Sylverken, Justice; Ogutu, Bernhards R; Otieno, Godfrey A; Wangwe, Anne; Bojang, Kalifa A; Okomo, Uduak; Sanya-Isijola, Frank; Newton, Charles R; Njuguna, Patricia; Kazungu, Michael; Kerb, Reinhold; Geditz, Mirjam; Schwab, Matthias; Velavan, Thirumalaisamy P; Nguetse, Christian; Köhler, Carsten; Issifou, Saadou; Bolte, Stefanie; Engleitner, Thomas; Mordmüller, Benjamin; Krishna, Sanjeev

    2016-01-01

    Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i

  5. Non-inferiority of nitric oxide releasing intranasal spray compared to sub-therapeutic antibiotics to reduce incidence of undifferentiated fever and bovine respiratory disease complex in low to moderate risk beef cattle arriving at a commercial feedlot.

    Science.gov (United States)

    Regev-Shoshani, G; McMullin, B; Nation, N; Church, J S; Dorin, C; Miller, C

    2017-03-01

    Undifferentiated fever, or bovine respiratory disease complex (BRDc), is a challenging multi-factorial health issue caused by viral/bacterial pathogens and stressors linked to the transport and mixing of cattle, negatively impacting the cattle feedlot industry. Common practice during processing at feedlots is administration of antibiotic metaphylaxis to reduce the incidence of BRDc. Nitric oxide (NO) is a naturally occurring nano-molecule with a wide range of physiological attributes. This study evaluated the metaphylactic use of intranasal NO releasing spray (NORS) to control BRDc incidence in calves at low-moderate risk of developing BRDc, arriving at a commercial feedlot as compared to conventional antibiotic metaphylaxis. One thousand and eighty crossbred, multiple-sourced, commingled, commercial, weaned beef calves were screened, enrolled, randomized and treated upon arrival. Animals appearing sick were pulled (from their pen) by blinded pen keepers then assessed for BRDc symptoms; blood samples were taken for haptoglobin quantification and the animals were rescued with an antibiotic. After 35 days both groups showed no significant difference in BRDc incidence (5.2% of animals from NORS group and 3.2% from antibiotic group). Average daily weight gain of animals at day 150 for the NORS cohort was 1.17kg compared to 1.18kg for the antibiotic group (p>0.05). There was no significant difference in mortality in the first 35 days (p=0.7552), however, general mortality over 150 days trended higher in the antibiotic cohort. NORS treatment was shown to be safe, causing neither distress nor adverse effects on the animals. This large randomized controlled study in low-moderate BRDc incidence risk calves demonstrates that NORS treatment, as compared to conventional metaphylactic antibiotics, is non-inferior based on BRDc incidence and other metrics like weight and mortality. These data justify further studies in higher BRDc incidence risk populations to evaluate NORS as

  6. Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12

    Directory of Open Access Journals (Sweden)

    Sanz-Cuesta Teresa

    2012-05-01

    Full Text Available Abstract Background The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency. Methods/design The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain, and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm. Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3–8,and 1 mg/month in weeks 9–52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml, adherence to treatment, quality of life (EuroQoL-5D questionnaire, patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses. Discussion The results of this study should help establish

  7. Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial – The NeuroMorfeo trial

    Directory of Open Access Journals (Sweden)

    Guzzetti Stefano

    2009-04-01

    Full Text Available Abstract Background Many studies have attempted to determine the "best" anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA with volatile-based neuroanaesthesia (VA has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaestesiological strategy depends only on the anaesthetists' preferences or institutional policies. This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures. Methods/Design NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III and Glasgow Coma Scale (GCS equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil. The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score ≥ 9 (primary end-point. Two statistical comparisons have been planned: 1 sevoflurane + fentanyl vs. propofol + remifentanil; 2 sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a measurement of urinary catecholamines and plasma and urinary cortisol and (b estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded

  8. Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial – The NeuroMorfeo trial

    Science.gov (United States)

    Citerio, Giuseppe; Franzosi, Maria Grazia; Latini, Roberto; Masson, Serge; Barlera, Simona; Guzzetti, Stefano; Pesenti, Antonio

    2009-01-01

    Background Many studies have attempted to determine the "best" anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA) with volatile-based neuroanaesthesia (VA) has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaestesiological strategy depends only on the anaesthetists' preferences or institutional policies. This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures. Methods/Design NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III) and Glasgow Coma Scale (GCS) equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score ≥ 9 (primary end-point). Two statistical comparisons have been planned: 1) sevoflurane + fentanyl vs. propofol + remifentanil; 2) sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement of urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anaesthesia

  9. An open randomized comparison of gatifloxacin versus cefixime for the treatment of uncomplicated enteric fever.

    Directory of Open Access Journals (Sweden)

    Anil Pandit

    Full Text Available OBJECTIVE: To assess the efficacy of gatifloxacin versus cefixime in the treatment of uncomplicated culture positive enteric fever. DESIGN: A randomized, open-label, active control trial with two parallel arms. SETTING: Emergency Room and Outpatient Clinics in Patan Hospital, Lagankhel, Lalitpur, Nepal. PARTICIPANTS: Patients with clinically diagnosed uncomplicated enteric fever meeting the inclusion criteria. INTERVENTIONS: Patients were allocated to receive one of two drugs, Gatifloxacin or Cefixime. The dosages used were Gatifloxacin 10 mg/kg, given once daily for 7 days, or Cefixime 20 mg/kg/day given in two divided doses for 7 days. OUTCOME MEASURES: The primary outcome measure was fever clearance time. The secondary outcome measure was overall treatment failure (acute treatment failure and relapse. RESULTS: Randomization was carried out in 390 patients before enrollment was suspended on the advice of the independent data safety monitoring board due to significant differences in both primary and secondary outcome measures in the two arms and the attainment of a priori defined endpoints. Median (95% confidence interval fever clearance times were 92 hours (84-114 hours for gatifloxacin recipients and 138 hours (105-164 hours for cefixime-treated patients (Hazard Ratio[95%CI] = 2.171 [1.545-3.051], p<0.0001. 19 out of 70 (27% patients who completed the 7 day trial had acute clinical failure in the cefixime group as compared to 1 out of 88 patients (1% in gatifloxacin group(Odds Ratio [95%CI] = 0.031 [0.004 - 0.237], p<0.001. Overall treatment failure patients (relapsed patients plus acute treatment failure patients plus death numbered 29. They were determined to be (95% confidence interval 37.6 % (27.14%-50.2% in the cefixime group and 3.5% (2.2%-11.5% in the gatifloxacin group (HR[95%CI] = 0.084 [0.025-0.280], p<0.0001. There was one death in the cefixime group. CONCLUSIONS: Based on this study, gatifloxacin is a better treatment for

  10. An open-label,randomized,cross-over bioequivalence study of lafutidine 10 mg under fasting condition

    Institute of Scientific and Technical Information of China (English)

    Bhupesh; Dewan; Raghuram; Chimata

    2010-01-01

    AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-treatment,single dose cross-over bioequivalence study,under non-fed condition to compare the pharmacokinetic prof iles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd.,India using an indigenously developed active pharmaceutical ingredient(API) and the commercially available Stogra formulation,of UCB Japan Co.,Ltd.,Japan.The two treatments were separated by a washout period of 5 d.After an overnight fasting period of 10 h,the subjects were administered either the test or the reference medication as per the randomization schedule.Blood samples were collected at intervals up to 24 h,as per the approved protocol.Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry(LC/MS/MS) method,and a non-compartmental model was used for pharmacokinetic analysis.The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence,subjects,period and treatment.Statistical significance was evaluated at 95% conf idence level(P ≥ 0.05).RESULTS:The mean(±SD) values of the pharmacokinetic parameters(test vs reference) were Cmax(265.15±49.84 ng/mL vs 246.79±29.30 ng/mL,P<0.05),Area under the curve(AUC)(0-t)(1033.13±298.74 ng.h/mL vs 952.93±244.07 ng.h/mL,P < 0.05),AUC(0-∞)(1047.61±301.22 ng.h/mL vs 964.21±246.45 ng.h/mL,P<0.05),and tv2(1.92±0.94 h vs 2.05±1.01 h,P<0.05).The 90% conf idence intervals(CI) for the test/reference ratio of mean Cmax,AUC(0-t),and AUC(0-∞) were within the acceptable range of 80.00 to 125.00.The mean times(± SD) to attain maximal plasma concentration(tmax) of lafutidine were 0.95±0.24 h vs 1.01±0.29 h(P<0.05) for the test and the reference formulations respectively.Both the formulations were well tolerated.

  11. Randomized controlled trial comparing ciprofloxacin and cefepime in febrile neutropenic patients with hematological malignancies.

    Science.gov (United States)

    Yasuda, Takahiko; Suzuki, Ritsuro; Ishikawa, Yuichi; Terakura, Seitaro; Inamoto, Yoshihiro; Yanada, Masamitsu; Nagai, Hirokazu; Ozawa, Yukiyasu; Ozeki, Kazutaka; Atsuta, Yoshiko; Emi, Nobuhiko; Naoe, Tomoki

    2013-06-01

    Ciprofloxacin (CPFX) is a potential alternative in patients with febrile neutropenia (FN) because of its activity against Gram-negative organisms. We conducted a non-inferiority, open-label, randomized controlled trial comparing intravenous CPFX and cefepime (CFPM) for FN patients with hematological malignancies. Patients aged from 15 to 79 years with an absolute neutrophil count of response, and early toxicity were evaluated. Fifty-one episodes were included in this trial, and 49 episodes (CPFX vs. CFPM: 24 vs. 25) were evaluated. Treatment efficacy at day 7 was significantly higher in the CFPM group (successful clinical response: nine with CPFX and 19 with CFPM; p=0.007). The response was better in high-risk patients with neutrophil counts of ≤ 0.100 × 10(9/)l (p=0.003). The overall response during the study period was similar between the CPFX and CFPM groups (p=0.64). Adverse events were minimal, and all patients could continue the treatment. We could not prove the non-inferiority of CPFX in comparison with CFPM for the initial treatment of FN. CFPM remains the standard treatment of choice for FN. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Open and Closed Endotracheal Suctioning and Arterial Blood Gas Values: A Single-Blind Crossover Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Azam Faraji

    2015-01-01

    Full Text Available Aim. This study was aimed at comparing the effects of the open and closed suctioning techniques on the arterial blood gas values in patients undergoing open-heart surgery. Methods. In a clinical trial, we recruited 42 patients after open-heart surgery in an educational hospital. Each patient randomly underwent both open and closed suctioning. ABGs, PaO2, SaO2, PaCO2, were analyzed before and one, five, and fifteen minutes after each suctioning episode. Results. At first the pressure of oxygen in arterial blood increased; however, this increase in the open technique was greater than that of the closed system (P<0.001. The pressure of oxygen decreased five and fifteen minutes after both suctioning techniques (P<0.05. The trends of carbon dioxide variations after the open and closed techniques were upward and downward, respectively. Moreover, the decrease in the level of oxygen saturation five and fifteen minutes after the open suctioning was greater than that of the closed suctioning technique (P<0.05.  Conclusion. Arterial blood gas disturbances in the closed suctioning technique were less than those of the open technique. Therefore, to eliminate the unwanted effects of endotracheal suctioning on the arterial blood gases, the closed suctioning technique is recommended.

  13. Efficacy and tolerability of a new formulation of artesunate-mefloquine for the treatment of uncomplicated malaria in adult in Senegal: open randomized trial

    Directory of Open Access Journals (Sweden)

    CK Tine Roger

    2012-12-01

    Full Text Available Abstract Background Prompt treatment of malaria attacks with arteminisin-based combination therapy (ACT is an essential tool for malaria control. A new co-blister tablet of artesunate-mefloquine (AM with 25 mg/kg mefloquine has been developed for the management of uncomplicated malaria attacks. This non-inferiority randomized trial, was conducted to evaluate the efficacy and safety of the new formulation of AM in comparison to artemether-lumefantrine (AL for the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in Senegal. Methods The study was carried out from September to December 2010 in two health centres in Senegal. The study end points included (i PCR corrected adequate clinical and parasitological response (ACPR at day 28, (ii ACPR at days 42 and 63, (iii parasites and fever clearance time, (iv incidence of adverse events and patients biological profile at day 7 using the WHO 2003 protocol for anti-malarial drug evaluation. Results Overall, 310 patients were randomized to receive either AM (n = 157 or AL (n = 153. PCR corrected ACPR at day 28 was at 95.5% in the AM arm while that in the AL arm was at 96.7% (p = 0.83. Therapeutic efficacy was at 98.5% in the AM arm versus 98.2% in the AL group at day 42 (p = 1. At day 63, ACPR in the AM and AL arms was at 98.2% and 97.7%, respectively (p = 0.32. The two treatments were well tolerated with similar biological profile at day 7. However, dizziness was more frequent in the AM arm. Conclusion Artesunate-mefloquine (25 mg/Kg mefloquine is efficacious and well-tolerated for the treatment of uncomplicated P. falciparum malaria in adult patients.

  14. Randomised clinical trial: sodium alginate oral suspension is non-inferior to omeprazole in the treatment of patients with non-erosive gastroesophageal disease.

    Science.gov (United States)

    Chiu, C-T; Hsu, C-M; Wang, C-C; Chang, J-J; Sung, C-M; Lin, C-J; Chen, L-W; Su, M-Y; Chen, T-H

    2013-11-01

    The burden of gastroesophageal reflux disease (GERD) is increasing in the Asia area and the majority of GERD patients have non-erosive reflux disease (NERD). To evaluate the efficacy and safety of sodium alginate suspension compared to omeprazole in adult subjects with NERD. In this 4-week, double-blind, parallel study, 195 NERD subjects were randomised to one of two treatment groups: sodium alginate suspension 20 mL three times a day and omeprazole 20 mg once daily. The primary efficacy endpoint was the percentage of patients achieving adequate heartburn or regurgitation relief at day 28 assessed by patient diary. The secondary efficacy endpoints included percentage of patients achieving adequate heartburn or regurgitation relief, change from baseline of the Reflux Disease Questionnaire total score at day 14 and 28 from baseline, and patients' overall satisfaction. In this study, 183 subjects were included in the intent-to-treat population, and 172 subjects were included in the per-protocol population. Non-inferiority of sodium alginate to omeprazole was demonstrated in the intent-to-treat population [difference, 2.7% (53.3% vs. 50.5%, P = 0.175), 95% lower confidence interval -11.9%, above the preset margin of -19%]. All of the secondary efficacy endpoints were comparable between two groups. The incidence of adverse event was relatively low and there was no difference between the two groups (5.4% vs. 5.5% for sodium alginate vs. omeprazole). No severe adverse event was noted in this study. The study showed that sodium alginate was as effective as omeprazole for symptomatic relief in patients with non-erosive reflux disease (Clinicaltrials.gov NCT01338077). © 2013 John Wiley & Sons Ltd.

  15. Dexmedetomidine versus propofol in dilatation and curettage: An open-label pilot randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Priyanka Sethi

    2015-01-01

    Full Text Available Background: Traditionally propofol has been used for providing sedation in dilatation and curettage (D and C. Recently, dexmedetomidine has been tried, but very little evidence exists to support its use. Aims: The aim was to compare hemodynamic and recovery profile of both the drugs along with a degree of comfort experienced by patients and the usefulness of the drug to surgeons. Settings and Design: Tertiary care center and open-label randomized controlled trial. Materials and Methods: Patients posted for D and C were enrolled in two groups (25 each. Both groups received fentanyl 1 μg/kg intravenous (IV at the beginning of the procedure. Group P received IV propofol in dose of 1.5 mg/kg over 10-15 min and Group D received dexmedetomidine at a loading dose of 1 μg/kg over 10 min, followed by 0.5 μg/kg/h infusion until Ramsay sedation score reached 3-4. Hemodynamic vitals were compared during and after the procedure. In the recovery room time to reach modified Aldrete score (MAS of 9-10 and patient′s and surgeon′s satisfaction scores were also recorded and compared. Results: In Group D, patients had statistically significant lower heart rate at 2, 5, 10 and 15 min as compared to Group P. Hypotension was present in 52% in Group P and 4% in Group D (P < 0.05. MAS of 9-10 was achieved in 4.4 min in subjects in Group D in contrast to 16.2 min in Group P (P < 0.05. Group D showed higher patient and surgeon satisfaction scores (P < 0.05. Conclusion: Dexmedetomidine provide better hemodynamic and recovery profile than propofol. It can be a superior alternative for short surgical day care procedures.

  16. Topical olive oil is not inferior to hyperoxygenated fatty aids to prevent pressure ulcers in high-risk immobilised patients in home care. Results of a multicentre randomised triple-blind controlled non-inferiority trial.

    Directory of Open Access Journals (Sweden)

    Inmaculada Lupiañez-Perez

    Full Text Available Pressure ulcers represent a major current health problem and produce an important economic impact on the healthcare system. Most of studies to prevent pressure ulcers have been carried out in hospital contexts, with respect to the use of hyperoxygenated fatty acids and to date, no studies have specifically examined the use of olive oil-based substances.Main objective: To assess the effectiveness of the use of olive oil, comparing it with hyperoxygenated fatty acids, for immobilised home-care patients at risk of suffering pressure ulcers. Design: Non-inferiority, triple-blind, parallel, multicentre, randomised clinical trial. Scope: Population attending Primary Healthcare Centres in Andalusia (Spain. Sample: 831 immobilised patients at risk of suffering pressure ulcers.The follow-up period was 16 weeks. Groups were similar after randomization. In the per protocol analysis, none of the body areas evaluated presented risk differences for pressure ulcers incidence that exceeded the 10% delta value established. Sacrum: Olive Oil 8 (2.55% vs HOFA 8 (3.08%, ARR 0.53 (-2.2 to 3.26 Right heel: Olive Oil 4 (1.27% vs HOFA 5 (1.92%, ARR0.65 (-1.43 to 2.73. Left heel: Olive Oil 3 (0.96% vs HOFA 3 (1.15%, ARR0.2 (-1.49 to 1.88. Right trochanter: Olive Oil 0 (0% vs HOFA 4 (1.54%, ARR1.54 (0.04 to 3.03. Left trochanter: Olive Oil 1 (0.32% vs HOFA 1 (0.38%, ARR0.07 (-0.91 to 1.04. In the intention to treat analysis the lower limit of the established confidence interval was never exceeded.The results obtained confirmed that the use of topical extra-virgin olive oil to prevent PU in the home environment, for immobilised patients at high risk, is not inferior to the use of HOFA. Further studies are needed to investigate the mechanism by which olive oil achieves this outcome.Clinicaltrials.gov NCT01595347.

  17. A randomized controlled trial of laparoscopic versus open cholecystectomy in patients with cirrhotic portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Wu Ji; Ling-Tang Li; Zhi-Ming Wang; Zhu-Fu Quan; Xun-Ru Chen; Jie-Shou Li

    2005-01-01

    AIM: To evaluate the characters, risks and benefits of laparoscopic cholecystectomy (LC) in cirrhotic portal hypertension (CPH) patients.METHODS: Altogether 80 patients with symptomatic gallbladder disease and CPH, including 41 Child class A,32 Child class B and 7 Child class C, were randomly divided into open cholecystectomy (OC) group (38 patients) and LC group (42 patients). The cohorts were well-matched for number, age, sex, Child classification and types of disease.Data of the two groups were collected and analyzed.RESULTS: In LC group, LC was successfully performed in 36 cases, and 2 patients were converted to OC for difficulty in managing bleeding under laparoscope and dense adhesion of Calot's triangle. The rate of conversion was 5.3%. The surgical duration was 62.6±15.2 min. The operative blood loss was 75.5±15.5 mL. The time to resume diet was 18.3±6.5 h. Seven postoperative complications occurred in five patients (13.2%). All patients were dismissed after an average of 4.6±2.4 d. In OC group, the operation time was 60.5±17.5 min. The operative blood loss was 112.5±23.5 mL. The time to resume diet was 44.2±10.5 h.Fifteen postoperative complications occurred in 12patients (30.0%). All patients were dismissed after an average of 7.5±3.5 d. There was no significant difference in operation time between OC and LC group. But LC offered several advantages over OC, including fewer blood loss and lower postoperative complication rate, shorter time to resume diet and shorter length of hospitalization in patients with CPH.CONCLUSION: Though LC for patients with CPH is difficult, it is feasible, relatively safe, and superior to OC.It is important to know the technical characters of the operation, and pay more attention to the meticulous perioperative managements.

  18. Patient-reported genitourinary dysfunction after laparoscopic and open rectal cancer surgery in a randomized trial (COLOR II)

    DEFF Research Database (Denmark)

    Andersson, J; Abis, G; Gellerstedt, M

    2014-01-01

    BACKGROUND: This article reports on patient-reported sexual dysfunction and micturition symptoms following a randomized trial of laparoscopic and open surgery for rectal cancer. METHODS: Patients in the COLOR II randomized trial, comparing laparoscopic and open surgery for rectal cancer, completed...... the European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR38 questionnaire before surgery, and after 4 weeks, 6, 12 and 24 months. Adjusted mean differences on a 100-point scale were calculated using changes from baseline value at the various time points in the domains of sexual functioning...... radiotherapy, did not change these results. CONCLUSION: Sexual dysfunction is common in patients with rectal cancer, and treatment (including surgery) increases the proportion of patients affected. A laparoscopic approach does not change this. REGISTRATION NUMBER: NCT0029779 (http://www.clinicaltrials.gov)....

  19. Minimally invasive lumbar interbody fusion via MAST Quadrant retractor versus open surgery: a prospective randomized clinical trial

    Institute of Scientific and Technical Information of China (English)

    WANG Hong-li; L(U) Fei-zhou; JIANG Jian-yuan; MA Xin; XIA Xin-lei; WANG Li-xun

    2011-01-01

    Background In recent years,a variety of minimally invasive lumbar surgery techniques have achieved desirable efficacy,but some dispute remains regarding the advantages over open surgery.This study aimed to compare minimally invasive lumbar interbody fusion via MAST Quadrant retractor with open surgery in terms of perioperative factors,postoperative back muscle function,and 24-month postoperative follow-up results.Methods From September 2006 to June 2008,patients with single-level degenerative lumbar spine disease who were not responsive to conservative treatment were enrolled in this study.Patients were randomized to undergo either minimally invasive surgery (MIS,transforaminal lumbar interbody fusion via MAST Quadrant retractor,41 cases) or open surgery (improved transforaminal lumbar interbody fusion,38 cases).Results The MIS group had longer intraoperative fluoroscopy time than the open surgery group,and the open surgery group had significantly increased postoperative drainage volume and significantly prolonged postoperative recovery time compared with the MIS group (P <0.05 for all).MRI scanning showed that the T2 relaxation time in the multifidus muscle was significantly shorter in the MIS group than in the open surgery group at 3 months after surgery (P <0.01).Surface electromyography of the sacrospinalis muscle showed that the average discharge amplitude and frequency were significantly higher in the MIS group than in the open surgery group (P <0.01).The Oswestry disability index and visual analog scale scores were better at 3,6,12 and 24 months postoperatively than preoperatively in both groups.Both groups of patients met the imaging convergence criteria at the last follow-up.Conclusions MIS can effectively reduce sacrospinalis muscle injury compared with open surgery,which is conducive to early functional recovery.In the short term,MIS is superior to open surgery,but in the long term there is no significant difference between the two procedures.

  20. Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis

    Science.gov (United States)

    Xu, Jane; Liu, Yingrui Cyril; Adams, Susan; Karpelowsky, Jonathan

    2016-01-01

    Introduction This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention. Design A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals. Participants Children who meet the inclusion criteria of an age between 5 and 15 years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients. Interventions Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30 days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost. Analysis Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson χ2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an α level of 0.05. Ethics and dissemination The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations. Trial

  1. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib

    Science.gov (United States)

    Hochberg, Marc C; Martel-Pelletier, Johanne; Monfort, Jordi; Möller, Ingrid; Castillo, Juan Ramón; Arden, Nigel; Berenbaum, Francis; Blanco, Francisco J; Conaghan, Philip G; Doménech, Gema; Henrotin, Yves; Pap, Thomas; Richette, Pascal; Sawitzke, Allen; du Souich, Patrick; Pelletier, Jean-Pierre

    2016-01-01

    Objectives To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain. Methods Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2–3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0–500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D. Results The adjusted mean change (95% CI) in WOMAC pain was −185.7 (−200.3 to −171.1) (50.1% decrease) with CS+GH and −186.8 (−201.7 to −171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of −40: −1.11 (−22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups. Conclusions CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile. Trial

  2. Randomized clinical trial of laparoscopic versus open repair of the perforated peptic ulcer: The LAMA trial

    NARCIS (Netherlands)

    M.J.O.E. Bertleff (Marietta); J.A. Halm (Jens); W.A. Bemelman (Willem); A.C. van der Ham (Arie); E. van der Harst (Erwin); H.I. Oei (Hok); J.F. Smulders; E.W. Steyerberg (Ewout); J.F. Lange (Johan)

    2009-01-01

    textabstractBackground: Laparoscopic surgery has become popular during the last decade, mainly because it is associated with fewer postoperative complications than the conventional open approach. It remains unclear, however, if this benefit is observed after laparoscopic correction of perforated

  3. Using Random Parameter Logit in Open and Distance Learning (ODL) Institutions in Malaysia

    Science.gov (United States)

    Chiam, Chooi Chea; Loo, SzeWei

    2015-01-01

    Attention has been drawn to Open Distance Learning (ODL) as a mode for teaching and learning with the advancement in communication via the Internet. Education today has expanded the role of ICT in learning and knowledge generation, leveraging on Internet technology to transmit education across the country. Due to the advancement of technology and…

  4. Randomized Clinical Trial of Laparoscopic Versus Open Repair of the Perforated Peptic Ulcer: The LAMA Trial

    NARCIS (Netherlands)

    M.J.O.E. Bertleff; J.A. Halm; W.A. Bemelman; A.C. van der Ham; E. van der Harst; H.I. Oei; J.F. Smulders; E.W. Steyerberg; J.F. Lange

    2009-01-01

    Laparoscopic surgery has become popular during the last decade, mainly because it is associated with fewer postoperative complications than the conventional open approach. It remains unclear, however, if this benefit is observed after laparoscopic correction of perforated peptic ulcer (PPU). The goa

  5. Randomized clinical trial of laparoscopic versus open repair of the perforated peptic ulcer: The LAMA trial

    NARCIS (Netherlands)

    M.J.O.E. Bertleff (Marietta); J.A. Halm (Jens); W.A. Bemelman (Willem); A.C. van der Ham (Arie); E. van der Harst (Erwin); H.I. Oei (Hok); J.F. Smulders; E.W. Steyerberg (Ewout); J.F. Lange (Johan)

    2009-01-01

    textabstractBackground: Laparoscopic surgery has become popular during the last decade, mainly because it is associated with fewer postoperative complications than the conventional open approach. It remains unclear, however, if this benefit is observed after laparoscopic correction of perforated pep

  6. Randomized Clinical Trial of Laparoscopic Versus Open Repair of the Perforated Peptic Ulcer: The LAMA Trial

    NARCIS (Netherlands)

    Bertleff, M.J.O.E.; Halm, J.A.; Bemelman, W.A.; van der Ham, A.C.; van der Harst, E.; Oei, H.I.; Smulders, J.F.; Steyerberg, E.W.; Lange, J.F.

    2009-01-01

    Laparoscopic surgery has become popular during the last decade, mainly because it is associated with fewer postoperative complications than the conventional open approach. It remains unclear, however, if this benefit is observed after laparoscopic correction of perforated peptic ulcer (PPU). The

  7. Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study

    DEFF Research Database (Denmark)

    Nielsen, T L; Eeftinck Schattenkerk, J K; Jensen, B N

    1992-01-01

    Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a...

  8. Open Problems in Applying Random-Matrix Theory to Nuclear Reactions

    CERN Document Server

    Weidenmueller, H A

    2014-01-01

    Problems in applying random-matrix theory (RMT) to nuclear reactions arise in two domains. To justify the approach, statistical properties of isolated resonances observed experimentally must agree with RMT predictions. That agreement is less striking than would be desirable. In the implementation of the approach, the range of theoretically predicted observables is too narrow.

  9. Open problems in applying random-matrix theory to nuclear reactions

    Science.gov (United States)

    Weidenmüller, H. A.

    2014-09-01

    Problems in applying random-matrix theory (RMT) to nuclear reactions arise in two domains. To justify the approach, statistical properties of isolated resonances observed experimentally must agree with RMT predictions. That agreement is less striking than would be desirable. In the implementation of the approach, the range of theoretically predicted observables is too narrow.

  10. Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12)

    Science.gov (United States)

    2012-01-01

    Background The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency. Methods/design The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain), and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm). Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3–8,and 1 mg/month in weeks 9–52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml), adherence to treatment, quality of life (EuroQoL-5D questionnaire), patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses. Discussion The

  11. Norfloxacin as prophylaxis against urethral strictures following transurethral resection of the prostate: an open, prospective, randomized study.

    Science.gov (United States)

    Hammarsten, J; Lindqvist, K

    1993-11-01

    An open, prospective, randomized study was performed to investigate the effect of norfloxacin prophylaxis on stricture formation and operative outcome after transurethral resection of the prostate. After resection, the 359 patients studied were randomly divided into 2 groups: 1) those given norfloxacin as prophylaxis for 15 days following removal of the catheter (norfloxacin group) and 2) those given no antimicrobial prophylaxis during the same period (control group). Of the patients 94 were excluded. At followup 6 to 12 months postoperatively, the number of strictures in the anterior urethra was 2 of 135 in the norfloxacin group and 22 of 130 in the control group (p norfloxacin group, fewer patients in that group were dissatisfied with the operative outcome. The results suggest that norfloxacin provides effective prophylaxis against stricture formation after transurethral resection of the prostate.

  12. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal.

    Science.gov (United States)

    Mariani, John J; Rosenthal, Richard N; Tross, Susan; Singh, Prameet; Anand, Om P

    2006-01-01

    Gabapentin was compared with phenobarbital for the treatment of alcohol withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There were no significant differences in the proportion of treatment completers between treatment groups or the proportion of patients in each group requiring rescue medication for breakthrough signs and symptoms of alcohol withdrawal. There were no significant treatment differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study of its effectiveness in treating alcohol withdrawal is warranted.

  13. Treatment of asymptomatic vaginal candidiasis in pregnancy to prevent preterm birth: an open-label pilot randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Rickard Kristen

    2011-03-01

    Full Text Available Abstract Background Although the connection between ascending infection and preterm birth is undisputed, research focused on finding effective treatments has been disappointing. However evidence that eradication of Candida in pregnancy may reduce the risk of preterm birth is emerging. We conducted a pilot study to assess the feasibility of conducting a large randomized controlled trial to determine whether treatment of asymptomatic candidiasis in early pregnancy reduces the incidence of preterm birth. Methods We used a prospective, randomized, open-label, blinded-endpoint (PROBE study design. Pregnant women presenting at Candida were randomized to 6-days of clotrimazole vaginal pessaries (100mg or usual care (screening result is not revealed, no treatment. The primary outcomes were the rate of asymptomatic vaginal candidiasis, participation and follow-up. The proposed primary trial outcome of spontaneous preterm birth Results Of 779 women approached, 500 (64% participated in candidiasis screening, and 98 (19.6% had asymptomatic vaginal candidiasis and were randomized to clotrimazole or usual care. Women were not inconvenienced by participation in the study, laboratory testing and medication dispensing were problem-free, and the follow-up rate was 99%. There was a tendency towards a reduction in spontaneous preterm birth among women with asymptomatic candidiasis who were treated with clotrimazole RR = 0.33, 95%CI 0.04-3.03. Conclusions A large, adequately powered, randomized trial of clotrimazole to prevent preterm birth in women with asymptomatic candidiasis is both feasible and warranted. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12609001052224

  14. Quality evaluation of randomized controlled trials reports of laparoscopy compared with open colorectal resection for colorectal cancer.

    Science.gov (United States)

    Huang, Dandan; Jin, Xin; Gao, Jie; Li, Yuying; Lu, Liming; Sun, Feng; Chen, Dan; Zhao, Wentao; Luo, Weimin; Li, Hongjie; Hu, Yunyun; Hu, Fengliang

    2015-06-01

    Previously, there were no data looking at the quality evaluation of randomized controlled trials (RCTs) on effect comparison of laparoscopic surgery and open surgery for colorectal cancer in China. Here, we evaluate the completeness and transparency of RCT reports in this field. The following databases were searched: Medline, EMbase, SCI Expanded, China National Knowledge Infrastructure, the Chinese Biological Medicine Database, VIP database and Wan Fang databases) to search RCT reports on the effect comparison of laparoscopic surgery and open surgery for colorectal cancer in China. Our study evaluated the reporting quality of RCTs based on 22 standards of Consolidated Standards for Reporting Trials (CONSORT) 2010 Statement. Two reviewers responded with 'yes' or 'no' to each standard to judge whether the authors had reported or had recorded concrete details of the reports accomplished in accordance with the requirement of each standard. A total of 40 relevant RCTs were included in the final analysis. For the 'Title and abstract', only three articles (7.5%) could be identified directly from its title as the report of RCTs. For the 'Methods', only three articles (7.5%) applied the method of random allocation of sequences; only two articles (5%) mentioned the type of randomization or gave the description of the mechanism of allocation concealment; no article referred the concrete implementation of random method. Only one article (2.5%) applied the method of blinding or sample size calculation; no article had analysis about the metaphase of an experiment or an explanation of its interruption. For 'results', only one article (2.5%) described participant flow, primary and secondary outcomes with estimated effect size or ancillary analyses. Only 13 articles (32.5%) showed baseline demographic and clinical characteristics, 10 (25%) referred to intention-to-treat analysis, and 12 (30%) mentioned important harms or unintended effects. For the 'discussion', only eight

  15. Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    Science.gov (United States)

    Helmy, Sally A; El-Bedaiwy, Heba M

    2014-11-01

    Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated.

  16. Effect of Gum Chewing on Bowel Motility in Patients with Colorectal Cancer after Open Colectomy: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Cherdsak Duangchan

    2016-05-01

    Full Text Available Background: Postoperative ileus (POI usually delays the postoperative recovery after open colectomy. Gum chewing may facilitate bowel motility through cephalic-vagal stimulation. Bowel sounds, the time to first postoperative flatus and defecation, the common nursing outcomes of bowel motility, has not been investigated in Thai patients. This study examines the effect of gum chewing on bowel motility in colorectal cancer patients after open colectomy. Methods: A single blind randomized controlled trial was conducted with 32 patients in experimental and 32 patients in control groups. The experimental group chewed a piece of sugar-free gum with a fruity flavor for 20 minutes each time, three times a day starting from the first postoperative day till the date of first oral liquid received, while the control group receive routine care. Results: The bowel sounds of the experimental group after chewing gum significantly increased more than those of the control group (p = 0.00. The time to the first postoperative flatus in the experimental group was significantly shorter than that in the control group; likewise the first postoperative defecation was also shorter (p = 0.04, p = 0.02, respectively. Conclusion: Gum chewing is helpful in stimulating bowel motility measured by an increase in bowel sounds and in reduced times to first postoperative flatus and defecation. This nursing intervention may be used for stimulating bowel motility in patients with colorectal cancer after an open colectomy.

  17. Treatment of Bankart lesions in traumatic anterior instability of the shoulder: a randomized controlled trial comparing arthroscopy and open techniques.

    Science.gov (United States)

    Archetti Netto, Nicola; Tamaoki, Marcel Jun Sugawara; Lenza, Mario; dos Santos, João Baptista Gomes; Matsumoto, Marcelo Hide; Faloppa, Flavio; Belloti, João Carlos

    2012-07-01

    The objective of this study was to compare the functional assessments of arthroscopy and open repair for treating Bankart lesion in traumatic anterior shoulder instability. Fifty adult patients, aged less than 40 years, with traumatic anterior shoulder instability and the presence of an isolated Bankart lesion confirmed by diagnostic arthroscopy were included in the study. They were randomly assigned to receive open or arthroscopic treatment of an isolated Bankart lesion. In all cases of both groups, the lesion was repaired with metallic suture anchors. The primary outcomes included the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. After a mean follow-up period of 37.5 months, 42 patients were evaluated. On the DASH scale, there was a statistically significant difference favorable to the patients treated with the arthroscopic technique, but without clinical relevance. There was no difference in the assessments by University of California, Los Angeles and Rowe scales. There was no statistically significant difference regarding complications and failures, as well as range of motion, for the 2 techniques. On the basis of this study, the open and arthroscopic techniques were effective in the treatment of traumatic anterior shoulder instability. The arthroscopic technique showed a lower index of functional limitation of the upper limb, as assessed by the DASH questionnaire; this, however, was not clinically relevant. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  18. The effect of laser and botulinum toxin in the treatment of myofascial pain and mouth opening: A randomized clinical trial.

    Science.gov (United States)

    De Carli, Bethânia Molin Giaretta; Magro, Alessandra Kuhn Dall; Souza-Silva, Bianca Núbia; Matos, Felipe de Souza; De Carli, João Paulo; Paranhos, Luiz Renato; Magro, Eduardo Dall

    2016-06-01

    This study conducted a randomized clinical trial in 15 patients, who sought care at the Dental Clinic of the University of Passo Fundo, in order to compare the use of low-level laser and botulinum toxin in the treatment of myofascial pain and whether they alter the mouth opening of patients with temporomandibular disorder. The patients were divided into two groups: the Laser group received low-level GaAlAs laser, 100mW of power at a wavelength of 830nm in continuous light emission; and the Toxin group received 30U of botulinum toxin type A (BTX-A) in the first session, and 15U after fifteen days. The assessments were performed by measuring pain with Visual Analogue Scale (VAS), and mouth opening with a digital caliper. Data were submitted to Student's t test at 5% significance level. Regarding pain symptoms, the results indicate that groups treated with laser and toxin registered 7U in VAS, at day 5 the scores were 4.75 and 4.86U, respectively. The laser worked faster (day 12) at 2.75U, and the group treated with BTX-A registered 2.86U at day 30. Both therapies investigated were effective in reducing pain, but the effect of low-level laser was faster than the use of BTX-A. Both treatments showed no statistically significant improvement in mouth opening.

  19. Multimedia educational tools for cognitive surgical skill acquisition in open and laparoscopic colorectal surgery: a randomized controlled trial.

    Science.gov (United States)

    Shariff, U; Kullar, N; Haray, P N; Dorudi, S; Balasubramanian, S P

    2015-05-01

    Conventional teaching in surgical training programmes is constrained by time and cost, and has room for improvement. This study aimed to determine the effectiveness of a multimedia educational tool developed for an index colorectal surgical procedure (anterior resection) in teaching and assessment of cognitive skills and to evaluate its acceptability amongst general surgical trainees. Multimedia educational tools in open and laparoscopic anterior resection were developed by filming multiple operations which were edited into procedural steps and substeps and then integrated onto interactive navigational platforms using Adobe® Flash® Professional CS5 10.1. A randomized controlled trial was conducted on general surgical trainees to evaluate the effectiveness of online multimedia in comparison with conventional 'study day' teaching for the acquisition of cognitive skills. All trainees were assessed before and after the study period. Trainees in the multimedia group evaluated the tools by completing a survey. Fifty-nine trainees were randomized but 27% dropped out, leaving 43 trainees randomized to the multimedia group (n = 25) and study day group (n = 18) who were available for analysis. Posttest scores improved significantly in both groups (P educational resource. Multimedia tools are effective for the acquisition of cognitive skills in colorectal surgery and are well accepted as an educational resource. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  20. Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

    Science.gov (United States)

    Kaeley, Gurjit S; Evangelisto, Amy M; Nishio, Midori J; Goss, Sandra L; Liu, Shufang; Kalabic, Jasmina; Kupper, Hartmut

    2016-08-01

    To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

  1. Effect of a new insulin treatment regimen on glycaemic control and quality of life of Muslim patients with type 2 diabetes mellitus during Ramadan fast - an open label, controlled, multicentre, cluster randomised study.

    Science.gov (United States)

    Shehadeh, N; Maor, Y

    2015-11-01

    We performed a non-inferiority trial comparing insulin detemir (Levemir) and biphasic insulin (NovoMix70) to standard care during Ramadan fast in insulin treated type 2 diabetes mellitus (T2DM) patients. This was an open label, controlled, multicentre, cluster randomised non-inferiority study. Insulin treated T2DM patients from 12 randomly selected primary clinics received Levemir and NovoMix 70 (intervention, n = 127) or standard care according to the American Diabetes Association recommendations (control, n = 118). Insulin dose (intervention) was 60% of the usual, of this 40% was dosed as Levemir at sunrise and 60% as NovoMix 70 before dinner. Insulin was titrated according to daily 4 point self-measured blood glucose (4P-SMBG) levels. The primary outcome was the difference in mean daily 4P-SMBG during days 23-30 of treatment. Mean age was 60.1 (SD 8.9) and 59.4 (SD 10.1) years in the intervention and control respectively. Mean HbA1c was 8.38% (68 mmol/mol) (SD 0.96) and 8.45% (69 mmol/mol) (SD 1.08). Mean BMI was 32.99 (SD 7.05) and 33.08 (SD 7.24), respectively. The intervention was non-inferior to standard care as assessed by mean 4P-SMBG during days 23-30 of treatment [155 (SD 30.76) mg% and 159 (SD 33.24) mg% respectively, p = 0.269]. Adverse event rate was significantly lower in the intervention group [0.04 (SD 0.06) vs. 0.07 (SD 0.11), p = 0.010]. In particular, hypoglycaemia event rate was lower in the intervention group [0.00 (SD 0.01) vs. 0.01 (SD 0.03), p ≤ 0.001]. To conclude, treatment with Levemir and NovoMix 70 was non-inferior to standard care in this heterogeneous group of patients and was associated with less adverse events.

  2. Respiratory Muscle Training in Patients Recovering Recent Open Cardiothoracic Surgery: A Randomized-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Ernesto Crisafulli

    2013-01-01

    Full Text Available Objectives. To evaluate the clinical efficacy and feasibility of an expiratory muscle training (EMT device (Respilift applied to patients recovering from recent open cardiothoracic surgery (CTS. Design. Prospective, double-blind, 14-day randomised-controlled trial. Participants and Setting. A total of 60 inpatients recovering from recent CTS and early admitted to a pulmonary rehabilitation program. Interventions. Chest physiotherapy plus EMT with a resistive load of 30 cm H2O for active group and chest physiotherapy plus EMT with a sham load for control group. Measures. Changes in maximal expiratory pressure (MEP were considered as primary outcome, while maximal inspiratory pressures (MIP, dynamic and static lung volumes, oxygenation, perceived symptoms of dyspnoea, thoracic pain, and well being (evaluated by visual analogic scale—VAS and general health status were considered secondary outcomes. Results. All outcomes recorded showed significant improvements in both groups; however, the change of MEP (+34.2 mmHg, and +26.1%, for absolute and % of predicted, resp. was significantly higher in active group. Also VAS dyspnoea improved faster and more significantly ( at day 12, and 14 in active group when compared with control. The drop-out rate was 6%, without differences between groups. Conclusions. In patients recovering from recent CTS, specific EMT by Respilift is feasible and effective. This trial is registered with ClinicalTrials.gov NCT01510275.

  3. Using Random Parameter Logit In Open And Distance Learning (ODL Institutions In Malaysia

    Directory of Open Access Journals (Sweden)

    Chooi Chea Chiam

    2015-10-01

    Full Text Available Attention has been drawn to Open Distance Learning (ODL as a mode for teaching and learning with the advancement in communication via the Internet. Education today has expanded the role of ICT in learning and knowledge generation, leveraging on Internet technology to transmit education across the country. Technology advancement and the introduction of ODL in educationhas created heated competition among these private higher education providers in Malaysia. ODL mode offers a flexible form of learning. Learners of ODL tend to be more challenging to fulfill their needs as they have other commitments in life, therefore, these learners will have certain criteria when choosing their learning education institution. The aim of this study is to investigate the vital attributes contributing in choosing an ODL higher education institution in Malaysia and to explore the consumers’ socioeconomic characteristicswith their willingness-to-pay fees. Although studies on the attributes that influence student choice of a university exist, these have failed to use the choice experiment method to examine the attributes influencing choice of ODL education provider. The sample population was 320 using face-to-face interview. The results would be able to provide ODL education providers in Malaysia with knowledge on making the right marketing strategy.

  4. Alemtuzumab in lung transplantation: an open-label, randomized, prospective single center study.

    Science.gov (United States)

    Jaksch, P; Ankersmit, J; Scheed, A; Kocher, A; Muraközy, G; Klepetko, W; Lang, G

    2014-08-01

    Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil. Group B received thymoglobulin in association with standard dose IS. Patient and graft survival, freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, kidney function, infectious complications and posttransplant lymphoproliferative disorder were analyzed. Alemtuzumab induction therapy resulted in complete the absence of ACR episodes ≥ A2 within the first year post-TX. The difference to thymoglobulin was significant (alemtuzumab 0 vs. ATG 0.33; p = 0.019). All other factors studied did not show any differences between the two groups. Alemtuzumab induction therapy after LUTX in combination with reduced maintenance IS significantly reduces higher-grade rejection rates. This novel therapeutic agent had no impact on survival, infections rates, kidney function and incidence of malignancies.

  5. Coagulation, inflammatory, and stress responses in a randomized comparison of open and laparoscopic repair of recurrent inguinal hernia

    DEFF Research Database (Denmark)

    Rahr, H B; Bendix, J; Ahlburg, P;

    2006-01-01

    with recurrent inguinal hernia were randomized to OR under local anesthesia (n = 30) or LR under general anesthesia (n = 31). The magnitude of the surgical trauma was assessed by measuring markers of coagulation (prothrombin fragment 1 + 2), endothelial activation (von Willebrand factor), inflammation......BACKGROUND: In previous comparisons of inflammatory and stress responses to open (OR) and laparoscopic (LR) hernia repair, all operations were performed under general anesthesia. Since local anesthesia is widely used for OR, a comparison of this approach with LR seemed relevant. METHODS: Patients...... in both groups, with the CRP increase being significantly greater in the OR group. The other markers did not increase significantly. CONCLUSION: The acute phase response was more pronounced after OR, even when this was done under local anesthesia. Both techniques seemed rather atraumatic....

  6. A Randomized Open Label Comparison of the Effects ofRisperidone and Haloperidol on Sexual Function

    Directory of Open Access Journals (Sweden)

    S. Jaber Mousavi

    2009-12-01

    Full Text Available "n Objective: "nSexual dysfunction in patients who take antipsychotics causes adecline in their quality of life and medication acceptance. Considering the restrictions in cross sectional design of many earlier researches, we used a clinical trial aimed at assessing sexual dysfunction by substituting Risperidone, an atypical antipsychotic drug, with Haloperidol, a typical one . "n "n "nMethod: This clinical trial was conducted on 51 patients who had been using Risperidone with a minimum dose of 2 mg/daily for at least 2 months. The patients were randomly divided into 2 groups. The first group continued taking Risperidone, whereas the second group was given Haloperidol. Sexual function prior to and after the drug substitution was assessed using a sexual questionnaire designed to assess four stages of sexual function . "nResults: Compared to those who changed their medication to Haloperidol, the patients who remained on Risperidone therapy suffered from more sexual dysfunction, especially in their tendency towards having sexual activities (P= 0.01, post menstrual sexual activity (P= 0.002, and reaching orgasm in their sexual activities (P= 0.04; however in the Haloperidol group, no significant difference was observed before and after the change in medication . "nConclusion: Although Risperidone and Haloperidol can both disturb patients'sexual function, the side effects of Risperidone are stronger. Hence toprevent the decline of medication acceptance or irregular consumption by patients which may lead to possible relapse, substitution of Risperidone withanother drug with fewer side effects on sexual activities is definitely to the advantage of the patients .

  7. [Efficacy of combined 5-nitroimidazole and probiotic therapy of bacterial vaginosis: randomized open trial].

    Science.gov (United States)

    Kovachev, S; Vatcheva-Dobrevski, R

    2013-01-01

    The aim of the current research is to identify the clinical and microbiological effect of 5-nitroimidazol therapy for the treatment of bacterial vaginosis and in combination with probiotics and the influence of such therapy upon vaginal flora. Women (n = 539) with bacterial vaginosis who meet the criteria were included in the study. They were randomized into two groups with the following therapeutic regimes: in the first group (n = 242 women) the treatment included applications of 2g BID tinidazole for two days and vaginal suppositories of 1000 mg metronidazol at day 1 and 3 (T+M). In the second group (n = 297) the women were cured with the same treatment as those in the first group. In addition to it from the fifth day of the treatment was added a topical administration of vaginal probiotic which contains species of alive lactobacilli: Lactobacillus acidophilus, Lactobacillus rhamnosus (T+M+P). The efficacy from the therapy was evaluated using the clinical compliances of the women, the data from the clinical examination and the microbiological tests results. The results showed expected increase of clinical therapy efficacy (Amsel - criteria) from 42.8% (T+M; n = 211/242) to 84.06% (T+M+P; n = 274/297) in groups and of microbiological efficacy (Nugent) from 44.7% (T+M; n = 211/242) to 83.3% (T+M+P; n = 274/297), in follow up 35-40 days from the beginning of treatment. The percentage of women with normal vaginal flora on 35-40 day after the therapy increase with 57% in the (T+M) first group while in the second group (T+M+P) with 94%. Combining the therapies of 5-nitroimidazoles and vaginal probiotic reduce bacterial vaginosis recurrence and restores permanently normal vaginal flora.

  8. Randomized single-blind clinical trial of intradermal methylene blue on pain reduction after open diathermy haemorrhoidectomy.

    Science.gov (United States)

    Sim, H-L; Tan, K-Y

    2014-08-01

    Open haemorrhoidectomy has been associated with considerable postoperative pain and discomfort. Perianal intradermal injection of methylene blue has been shown to ablate perianal nerve endings and may bring about temporary pain relief after haemorrhoidectomy. We hypothesized that the administration of intradermal methylene blue would reduce postoperative pain during the initial period after surgery. A randomized, prospective, single-blind placebo-controlled trial was conducted. Patients were randomized to intradermal injection at haemorrhoidectomy of either 4 ml 1% methylene blue and 16 ml 0.5% marcaine or of 16 ml 0.5% marcaine and 4 ml saline prior to surgical dissection. Patients were asked to fill in a pain diary with a visual analogue scale. The primary outcome measure was pain score and analgesic use. Secondary outcomes were complications. There were 37 patients in the methylene blue arm and 30 patients in the placebo arm. There were no statistically significant differences in the sex, type of haemorrhoid, number of haemorrhoids excised, duration of surgery or hospital stay. The mean pain scores were significantly lower and the use of paracetamol was also significantly less in the methylene blue group during the first three postoperative days. The risk ratio of acute urinary retention occurring when methylene blue was not used was 2.320 (95% CI 1.754-3.067). Other complication rates were not significantly different. Perianal intradermal injection of methylene blue was useful in reducing the initial postoperative pain of open haemorrhoidectomy. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  9. Single-center open-label randomized study of anemia management improvement in ESRD patients with secondary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Bellasi Antonio

    2016-04-01

    Full Text Available Whether anemia and mineral bone abnormalities (chronic kidney disease–mineral bone disorder [CKD-MBD] are associated still remains to be elucidated. Both anemia and CKD-MBD have been associated with adverse cardiovascular outcome and poor quality of life. However, recent evidence suggests that use of large doses of erythropoietin-stimulating agents (ESAs to correct hemoglobin (Hb may be detrimental in CKD. The Optimal Anemia Treatment in End Stage Renal Disease (ESRD (Optimal ESRD Treatment study will assess whether lowering of parathyroid hormone (PTH is associated with a reduction in ESA consumption. The Optimal ESRD Treatment study is a pilot single-center open-label study with blinded end point (a prospective randomized open blinded end-point [PROBE] design enrolling 50 patients on maintenance dialysis. Eligible patients with intact PTH (iPTH 300-540 pg/mL and Hb 10-11.5 g/dL will be randomized 1:1 to strict PTH control (150-300 pg/mL versus standard care (PTH range 300-540 pg/mL. Available drugs for CKD-MBD and anemia treatment will be managed by the attending physician to maintain the desired levels of PTH (according to study arm allocation and Hb (10-11.5 g/dL. Echocardiographic data for cardiac structure and function as well as arterial stiffness will be assessed at study inception and completion. The Optimal ESRD Treatment study should shed light on the complicated interplay of anemia and CKD-MBD and on the feasibility of clinical trials in this domain. The study results are expected in the spring of 2017.

  10. Oxidative stress markers in laparoscopic vs. open appendectomy for acute appendicitis: A double-blind randomized study

    Directory of Open Access Journals (Sweden)

    Recep Aktimur

    2016-01-01

    Full Text Available Background: Oxidative stress is a complicated process, which was defined as an increase in prooxidants and decrease in antioxidants caused by various mechanisms, including inflammation and surgical trauma. The association between acute appendicitis and oxidative stress has been showed in previous studies. However, comparison of oxidative stress in laparoscopic or open appendectomy (OA has not been established. Patients and Methods: Patients who were diagnosed as acute appendicitis between October 2012 and January 2013 were randomized to open (OA, n = 50 and laparoscopic appendectomy (LA, n = 50. Blood samples for oxidative stress markers (total oxidant status [TOS] and total antioxidant status [TAS], C-reactive protein (CRP and white blood cells (WBC's were collected just before the surgery and 24 h after surgery. Results: There were no differences in preoperative values of WBC and CRP between LA and OA groups (P = 0.523 and 0.424, however, in postoperative 24th h, CRP was reduced in LA group (P = 0.031. There were no differences in preoperative levels of TOS, TAS, and oxidative stress index (OSI between LA and OA groups. In the postoperative 24th h, TOS and OSI were found to be significantly higher in OA group when compared to LA group (P = 0.017 and 0.002 whereas no difference was detected in TAS level in the postoperative 24th h (P = 0.172. Conclusions: This double-blind, randomized clinical trial provides evidence that LA for uncomplicated appendicitis is associated with significantly lower oxidative stress compared with OA. Some of the advantages of LA may be attributed to the significant reduction of oxidative stress in these patients.

  11. A Randomized Experiment Testing the Efficacy of a Scheduling Nudge in a Massive Open Online Course (MOOC

    Directory of Open Access Journals (Sweden)

    Rachel Baker

    2016-10-01

    Full Text Available An increasing number of students are taking classes offered online through open-access platforms; however, the vast majority of students who start these classes do not finish. The incongruence of student intentions and subsequent engagement suggests that self-control is a major contributor to this stark lack of persistence. This study presents the results of a large-scale field experiment (N = 18,043 that examines the effects of a self-directed scheduling nudge designed to promote student persistence in a massive open online course. We find that random assignment to treatment had no effects on near-term engagement and weakly significant negative effects on longer-term course engagement, persistence, and performance. Interestingly, these negative effects are highly concentrated in two groups of students: those who registered close to the first day of class and those with .edu e-mail addresses. We consider several explanations for these findings and conclude that theoretically motivated interventions may interact with the diverse motivations of individual students in possibly unintended ways.

  12. Effect of Repeated Anthelminthic Treatment on Malaria in School Children in Kenya: A Randomized, Open-Label, Equivalence Trial.

    Science.gov (United States)

    Kepha, Stella; Nuwaha, Fred; Nikolay, Birgit; Gichuki, Paul; Mwandawiro, Charles S; Mwinzi, Pauline N; Odiere, Maurice R; Edwards, Tansy; Allen, Elizabeth; Brooker, Simon J

    2016-01-15

    School children living in the tropics are often concurrently infected with plasmodium and helminth parasites. It has been hypothesized that immune responses evoked by helminths may modify malaria-specific immune responses and increase the risk of malaria. We performed a randomized, open-label, equivalence trial among 2436 school children in western Kenya. Eligible children were randomized to receive either 4 repeated doses or a single dose of albendazole and were followed up during 13 months to assess the incidence of clinical malaria. Secondary outcomes were Plasmodium prevalence and density, assessed by repeat cross-sectional surveys over 15 months. Analysis was conducted on an intention-to-treat basis with a prespecified equivalence range of 20%. During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, -.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys. Our findings suggest that repeated deworming does not alter risks of clinical malaria or malaria parasitemia among school children and that school-based deworming in Africa may have no adverse consequences for malaria. NCT01658774. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  13. Antidepressant monotherapy compared with combinations of antidepressants in the treatment of resistant depressive patients: a randomized, open-label study.

    Science.gov (United States)

    Bares, Martin; Novak, Tomas; Kopecek, Miloslav; Stopkova, Pavla; Cermak, Jan; Kozeny, Jiri; Höschl, Cyril

    2013-02-01

    This randomized, 6-week, open-label study compared efficacy of CAD and antidepressant monotherapies (ADM) that had been chosen according to clinical judgment of the attending psychiatrist. A total of 60 inpatients (intent-to-treat analysis) with depressive disorder (≥ 1 unsuccessful antidepressant treatment) were randomly assigned to the interventions. The responders who completed the acute phase of study, were evaluated for relapse within 2 months of follow-up treatment. The primary outcome measure was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) and response was defined as a ≥ 50% reduction of MADRS score. Mean changes in total MADRS score from baseline to week 6 for patients in both treatment modalities were not different (ADM = 13.2 ± 8.6 points; CAD = 14.5 ± 9.5 points; P = 0.58). The analysis of covariance performed for significantly higher value of imipramine equivalent dose in CAD group showed only a non-significant between-group difference for total MADRS change (P = 0.17). There were also no differences between groups in response rate (ADM = 48%; CAD = 58%) and number of drop-outs in acute treatment as well as proportion of responders' relapses in the follow-up. Both treatment modalities produced clinically relevant reduction of depressive symptomatology in acute treatment of patients with resistant depression and their effect was comparable.

  14. Effect of high-dose phenobarbital on oxidative stress in perinatal asphyxia: an open label randomized controlled trial.

    Science.gov (United States)

    Gathwala, Geeta; Marwah, Ashish; Gahlaut, Veena; Marwah, Poonam

    2011-08-01

    To evaluate the effect of high dose phenobarbital on lipid peroxidation and antioxidant enzymes in perinatal asphyxia. Open label, Randomized controlled trial. Neonatal intensive care unit of a tertiary care teaching hospital. 72 full term inborn neonates with severe birth asphyxia. Neonates were randomized to Study (phenobarbital) group and Control group. The infants in the study group received phenobarbital infusion (40 mg/kg) within first two hours of life while babies in the control group did not receive any phenobarbital. Rest of the management in both the groups was as per the unit protocol for the management of hypoxic ischemic encephalopathy. A cerebrospinal fluid examination was done at 12 ± 2 hours of life to determine the levels of superoxide dismutase, glutathione peroxidise and malonyldialdehyde. 60 neonates were followed up at 1 month of age when a detailed neurological examination was done. Four neonates in the study group and six neonates in the control group died during the study. Two neonates in the study group were lost to follow up. The cerebrospinal fluid lipid peroxides and antioxidant enzymes were significantly lower in the phenobarbital group as compared to the control group. The neurological outcome at one month follow up was found to be comparable between the two groups. Phenobarbital (40 mg/kg) given in the first two hours of life in term neonates with perinatal asphyxia led to a decrease in CSF levels of lipid peroxides and antioxidant enzymes at 12 ± 2 hours of life.

  15. Cloning of open reading frames and promoters from the Saccharomyces cerevisiae genome: construction of genomic libraries of random small fragments.

    Science.gov (United States)

    Santangelo, G M; Tornow, J; Moldave, K

    1986-01-01

    We have developed a novel efficient method, carrier-facilitated insertion, to insert small (150-600 bp) DNA fragments into plasmid vectors. This method employs a carrier segment of vector DNA to circumvent the difficulties in ligating two fragments together to generate a recombinant circle efficiently. We have used carrier-facilitated insertion to construct three genomic libraries of random (DNase I-generated) fragments from the Saccharomyces cerevisiae genome. One of these was an expression library, and the other two were promoter-cloning libraries. 87-90% of the Escherichia coli colonies in each library contained recombinant plasmids, and less than 3% of the recombinants contained more than one insert. Detection of open reading frames among the inserts in the expression library was accomplished by testing for beta-galactosidase activity. This methodology, unencumbered by the intrinsic disproportionality of cDNA libraries, can be used to identify and clone DNA that codes for a specific antigenic determinant. When used in combination with a method to detect and isolate random constitutive, repressible and inducible yeast promoters, these libraries should permit a comprehensive analysis of the yeast genome and its expression.

  16. Pharmacokinetics, pharmacodynamics, and safety of pasireotide LAR in patients with acromegaly: a randomized, multicenter, open-label, phase I study.

    Science.gov (United States)

    Petersenn, Stephan; Bollerslev, Jens; Arafat, Ayman M; Schopohl, Jochen; Serri, Omar; Katznelson, Laurence; Lasher, Janet; Hughes, Gareth; Hu, Ke; Shen, George; Reséndiz, Karina Hermosillo; Giannone, Vanessa; Beckers, Albert

    2014-11-01

    Pasireotide (SOM230), a multireceptor-targeted somatostatin analogue, has exhibited favorable safety/tolerability in several clinical studies. A long-acting-release (LAR) formulation of pasireotide may offer advantages over the subcutaneous formulation. This randomized, open-label, Phase I study evaluated the safety, PK, and PD of pasireotide LAR 20, 40, or 60 mg/month in patients with acromegaly. Safety assessments and blood samples for PK and PD were taken at designated time points. Thirty-five patients were randomized and completed the study. Steady-state pasireotide concentrations were achieved following three monthly injections. Trough pasireotide concentrations (ng/mL) 28 days after each injection were: 2.48, 4.16, and 3.10 (20 mg group); 6.42, 6.62, and 7.12 (40 mg group); and 9.51, 11.7, and 13.0 (60 mg group). At study end, 51% and 57% of patients achieved GH levels ≤2.5 μg/L and IGF-1 levels below ULN, respectively. Compared with baseline, fasting blood glucose and HbA1c levels increased, whereas fasting blood insulin levels decreased. Acromegaly symptoms were generally improved. Adverse events were mostly gastrointestinal and mild/moderate. Pasireotide LAR was generally well tolerated. Steady-state PK was achieved after three monthly doses; exposures were approximately dose proportional. Control of GH, IGF-1, and symptoms improved, suggesting that pasireotide LAR may be an effective treatment for acromegaly.

  17. Topical adapalene in the treatment of plantar warts; Randomized comparative open trial in comparison with cryo-therapy

    Directory of Open Access Journals (Sweden)

    Ramji Gupta

    2015-01-01

    Full Text Available Background: Various therapeutic modalities, which are available for treating plantar wart, have not been successful every time. Aims: To evaluate topical adapalene under occlusion in the treatment of plantar warts and compare it with cryo-therapy. Materials and Methods: 50 patients with 424 plantar warts were included in this single center, two arm, prospective, randomized, control, open study. Patients were allocated randomly into two groups consisting of 25 patients each. Group A patients having 299 plantar warts were treated using adapalene gel 0.1% under occlusion while Group B patients having 125 warts were treated using cryo-therapy. All the patients were evaluated weekly till the clearance of all the warts and the results compared. Result: All the warts of 25 patients of Group A that were treated using adapalene gel 0.1% cleared in 36.71 ± 19.24 (55.95-17.47 days except those in one patient. In Group B, warts in all except one treated by cryo-therapy cleared in 52.17 ± 30.06 (82.23-22.11 days. There were no side effects like scar formation, irritation, erythema, or infections with adapalene group while in the cryo group scar was seen in 2 patients, pain in 24, erythema in 10, and infection in 3 patients. Conclusion: Adapalene gel 0.1% under occlusion is an effective, safe and easy to use treatment for plantar warts and may help clear lesions faster than cryo-therapy.

  18. COMBINED THERAPY OF VIRAL DIARRHEA IN CHILDREN: FIRST RESULTS OF AN OPEN COMPARATIVE RANDOMIZED CLINICAL TRIAL OF INTERFERON EFFICIENCY

    Directory of Open Access Journals (Sweden)

    A.V. Gorelov

    2011-01-01

    Full Text Available The article presents an interim statistical analysis of the open multicenter randomized clinical trial, whose goal was to evaluate the efficiency and safety of immunomodulatory therapy of acute intestinal infections of viral etiology in children. Patients and methods: at this stage 28 children aged 6 months to 6 years with a clinically diagnosed viral diarrhea were included in the study. Children were randomly assigned to two groups: basic, where for the treatment was used the suppository preparation of recombinant human interferon alpha-2b in combination with taurine, and a control group, where the patients admitted the drug as the recombinant human interferon alpha-2b in combination with a complex immunoglobulin preparation. The dynamics of the relief of individual viral diarrhea symptoms was assessed within 5 days after the patient was included in the study. Results: the analysis of the data revealed no significant differences in the efficiency of the investigated drugs, this fact suggests the equivalence of the produced therapeutic effect. The use of the preparation containing recombinant human interferon alpha-2b in combination with taurine, reduces the level of a drug load on the child’s organism without loss of the treatment efficiency.Key words: recombinant human interferon alpha-2b, taurine, an acute intestinal infection of viral etiology, treatment, children.

  19. Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial.

    Science.gov (United States)

    Kim, Min Jung; Park, Sung Chan; Park, Ji Won; Chang, Hee Jin; Kim, Dae Yong; Nam, Byung-Ho; Sohn, Dae Kyung; Oh, Jae Hwan

    2017-05-25

    The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer. The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet. Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life. A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03). Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

  20. Tinospora cordifolia stem supplementation in diabetic dyslipidemia: an open labelled randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kuhu Roy

    2015-08-01

    Full Text Available Background: Medicinal plants are powerful health promoting nutritional agents. Among the vast library of medicinal plants Tinospora cordifolia (Willd. has been meagrely explored. It belongs to the family Menispermaceae and is a rich source of alkaloid and terpenes. It has hepatoprotective, antioxidant, immunostimulatory, hyperlipidemic, anticancer and antidiabetic properties. The stem contains berberine, palmatine, tembetarine, magnoflorine, tinosporin, tinocordifolin. The stem starch is highly nutritive and digestive. In modern medicine it is called the magical rejuvenating herb owing to its properties to cure many diseases. The stem contains higher alkaloid content than the leaves because of which it is approved for medicinal usage. With a host of phytochemical properties present in the stem, it may hold potential to manage dyslipidemia and dysglycemia, which otherwise has been proven only in pre-clinical studies. Objective: To study the impact of tinospora cordifolia stem supplementation on the glycemic and lipemic profile of subjects with diabetic dyslipidemia. Methods: Type 2 diabetics with dyslipidemia on oral hypoglycemic agents were enrolled. Baseline data on medical history, family history of lifestyle diseases, duration of diabetes diagnosis, drug profile, anthropometric data, dietary data and physical activity data was obtained along with a fasting blood sample for estimating high sensitivity C reactive protein (hs-CRP, hepatic, renal, lipid profile and glycated hemoglobin. The participants were randomized into either of the two groups; intervention group (n=29 received 250mg of encapsulated mature stem of tinospora cordifolia pre meal twice a day along with prescribed dyslipidemic agent and control group (n=30 only on dyslipidemic agents for a period of 60 days. After 60 days all the parameters were re-assessed to analyse the impact of the intervention. Results: Majority of the subjects in both the arms were in the 50-60 years age

  1. Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial.

    Science.gov (United States)

    Brinkmann, Saskia J H; Buijs, Nikki; Vermeulen, Mechteld A R; Oosterink, Efraim; Schierbeek, Henk; Beishuizen, Albertus; de Vries, Jean-Paul P M; Wisselink, Willem; van Leeuwen, Paul A M

    2016-09-01

    Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis. This open-label clinical trial randomized patients who underwent clamping of the aorta during open abdominal aortic surgery to receive a perioperative supplement of intravenous alanyl-glutamine (0.5 g·kg(-1)·day(-1); group A, n = 5) or no supplement (group B, n = 5). One day after surgery, stable isotopes and tracer methods were used to analyze the metabolism and conversion of glutamine, citrulline, and arginine. Whole body plasma flux of glutamine, citrulline, and arginine was significantly higher in group A than in group B (glutamine: 391 ± 34 vs. 258 ± 19 μmol·kg(-1)·h(-1), citrulline: 5.7 ± 0.4 vs. 2.8 ± 0.4 μmol·kg(-1)·h(-1), and arginine: 50 ± 4 vs. 26 ± 2 μmol·kg(-1)·h(-1), P glutamine (4.8 ± 0.7 vs. 1.6 ± 0.3 μmol·kg(-1)·h(-1)), citrulline from arginine (2.3 ± 0.3 vs. 0.96 ± 0.1 μmol·kg(-1)·h(-1)), and arginine from glutamine (7.7 ± 0.4 vs. 2.8 ± 0.2 μmol·kg(-1)·h(-1)), respectively (P arginine is severely reduced after clamping during aortic surgery. This study shows that an intravenous supplement of glutamine increases the production of citrulline and arginine and compensates for the inhibitory effect of ischemia-reperfusion injury.

  2. Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial.

    Directory of Open Access Journals (Sweden)

    Samir Koirala

    Full Text Available BACKGROUND: Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A. METHODOLOGY AND PRINCIPAL FINDINGS: Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day in a single dose or ofloxacin (20 mg/kg/day in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9-23 years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73. The median time to fever clearance was 4.70 days (IQR 2.98-5.90 in the ofloxacin group versus 3.31 days (IQR 2.29-4.75 in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004. The results in all blood culture-confirmed patients and all randomized patients were comparable. CONCLUSION: Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. TRIAL REGISTRATION: ISRCTN 63006567 (www.controlled-trials.com.

  3. Combined gemcitabine and S-1 chemotherapy for treating unresectable hilar cholangiocarcinoma: a randomized open-label clinical trial.

    Science.gov (United States)

    Li, Hao; Zhang, Zheng-Yun; Zhou, Zun-Qiang; Guan, Jiao; Tong, Da-Nian; Zhou, Guang-Wen

    2016-05-03

    Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50-0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27-0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733).

  4. Eldecalcitol improves muscle strength and dynamic balance in postmenopausal women with osteoporosis: an open-label randomized controlled study.

    Science.gov (United States)

    Saito, Kimio; Miyakoshi, Naohisa; Matsunaga, Toshiki; Hongo, Michio; Kasukawa, Yuji; Shimada, Yoichi

    2016-09-01

    The antifracture efficacy of vitamin D in osteoporosis is due to its direct action on bones and indirect extraskeletal effects to prevent falls. Eldecalcitol is an analog of active vitamin D3 that improves bone mineral density and reduces the risk of osteoporotic fractures. However, the effects of eldecalcitol on muscle strength and static and dynamic postural balance are unclear. In this open-label randomized controlled study, we assessed the effects of eldecalcitol on muscle strength and static and dynamic postural balance in 50 postmenopausal women (mean age 74 years) with osteoporosis treated with bisphosphonate. Participants were randomly divided into a bisphosphonate group (alendronate at 35 mg/week; n = 25) or an eldecalcitol group (eldecalcitol at 0.75 μg/day and alendronate at 35 mg/week; n = 25) and were followed up for 6 months. Trunk muscle strength, including back extensor strength and iliopsoas muscle strength, was measured. Static standing balance was evaluated and the one leg standing test was performed to assess static postural balance. Dynamic sitting balance was evaluated and the 10-m walk test, functional reach test, and timed up and go test were performed to assess dynamic postural balance. At 6 months, there were no significant changes in any measure of muscle strength or balance in the bisphosphonate group, whereas eldecalcitol significantly increased back extensor strength (p = 0.012) and iliopsoas muscle strength (p = 0.035). Eldecalcitol also significantly improved findings on the timed up and go test (p = 0.001) and dynamic sitting balance (p = 0.015) at 6 months. These results with eldecalcitol may have an impact on prevention of falls.

  5. Chest closure without drainage after open patent ductus arteriosus ligation in Ugandan children: A non blinded randomized controlled trial.

    Science.gov (United States)

    Kebba, Naomi; Mwambu, Tom; Oketcho, Michael; Izudi, Jonathan; Obuku, Ekwaro A

    2016-09-29

    There is clinical equipoise regarding post-operative management of patients with patent ductus arteriosus (PDA) without insertion of a chest drain. This study evaluated post operative outcomes of chest closure with or without a drain following Patent Ductus Arteriosus ligation among childen at Uganda Heart Instritute (UHI). This was an open label randomized controlled trial of 62 children 12 years of age and below diagnosed with patent ductus arteriosus at Mulago National Teaching and Referral Hospital, Uganda. Participants were randomized in the ratio of 1:1 with surgical ligation of patent ductus arteriosus to either thoracotomy closure with a chest tube or without a chest tube. All participants received standard care and were monitored hourly for 24 hours then until hospital discharge. The combined primary endpoint consisted of significant pleural space accumulation of fluid or air, higher oxygen need or infection of the surgical site. Analysis was conducted by multivariable logistic regression analysis at 5 % significance level. We enrolled 62 participants, 46 (74 %) of whom were females. Their median age was 12 months (IQR: 8-36). Participants in the no-drain arm significantly had less post-operative complications compared to the drain arm (Unadjusted odds ratio [uOR]: 0.21, 95 % CI: 0.06-0.73, p = 0.015). This "protective effect" remained without statistical significance in the multivariable regression model (Adjusted odds ratio [aOR]: 0.07, 95 % CI: 0.00-2.50, p = 0.144). Children aged below 6 years with patent ductus arterious can safely and effectively have thoracotomy closure without using a drain in uncomplicated surgical ligation of the PDA. Chest drain was associated with post-operative complications. The trial was registered in the Pan African Clinical Trials registry on 1st/July/2012, retrospectively registered. Identifier number PACTR201207000395469 .

  6. A randomized, open-label study of sirolimus versus cyclosporine in primary de novo renal allograft recipients.

    Science.gov (United States)

    Flechner, Stuart M; Gurkan, Alihan; Hartmann, Anders; Legendre, Christophe M; Russ, Graeme R; Campistol, Josep M; Schena, Francesco P; Hahn, Carolyn M; Li, Huihua; Korth-Bradley, Joan M; Tai, Sandi See; Schulman, Seth L

    2013-05-27

    Despite a decreased incidence of acute rejection and early renal allograft loss due to calcineurin inhibitors (CNIs) in transplant recipients, nephrotoxicity associated with long-term CNI use remains an important issue. This study evaluated whether a CNI-free regimen, including sirolimus, mycophenolate mofetil, corticosteroids, and anti-interleukin-2 receptor antibody induction, results in improved long-term renal function. This open-label, randomized, parallel group, comparative study in primary de novo renal transplant recipients was planned for 48 months but terminated early because of high acute rejection rates in the sirolimus arm. Enrollment was stopped after ≈12 months, with 475 transplanted patients randomized (2:1) to sirolimus (n=314) or cyclosporine A (CsA) treatment (n=161). Mean length of follow-up after transplantation was 190 days; this article focuses on available data through 6 months. Mean±SD on-therapy Nankivell-calculated glomerular filtration rate was not significantly different between the sirolimus (69.1±18.7 mL/min) and CsA (66.0±15.2 mL/min) treatment groups. Occurrence and length of delayed graft function was not significantly different between groups. Patients in the sirolimus group experienced numerically lower survival rates (96.9% vs. 99.4%; P=0.14), with nine deaths reported with sirolimus and one with CsA; higher rates of biopsy-confirmed acute rejection (21.4% vs. 6.1%; P<0.001); and higher rates of discontinuations due to adverse events (17.4% vs. 6.8%; P=0.001). A sirolimus-based, CNI-free immunosuppressive regimen, when used with mycophenolate mofetil, corticosteroids, and anti-interleukin-2 receptor antibody induction, was associated with high rates of biopsy-confirmed acute rejection compared with CsA-based immunosuppression and is not recommended.

  7. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  8. A Deterministic and Random Propagation Study with the Design of an Open Path 320 GHz to 340 GHz Transmissometer

    Science.gov (United States)

    Scally, Lawrence J.

    This program was implemented by Lawrence J. Scally for a Ph.D. under the EECE department at the University of Colorado at Boulder with most funding provided by the U.S. Army. Professor Gasiewski is the advisor and guider for the entire program; he has a strong history decades ago in this type of program. This program is developing a more advanced than previous years transmissometer, called Terahertz Atmospheric and Ionospheric Propagation, Absorption and Scattering System (TAIPAS), on an open path between the University of Colorado EE building roof and the mesa on owned by National Institute of Standards and Technology (NIST); NIST has invested money, location and support for the program. Besides designing and building the transmissometer, that has never be accomplished at this level, the system also analyzes the atmospheric propagation of frequencies by scanning between 320 GHz and 340 GHz, which includes the peak absorption frequency at 325.1529 GHz due to water absorption. The processing and characterization of the deterministic and random propagation characteristics of the atmosphere in the real world was significantly started; this will be executed with varies aerosols for decades on the permanently mounted system that is accessible 24/7 via a network over the CU Virtual Private Network (VPN).

  9. 4-WEEK OPEN-LABEL CONTROLLED RANDOMIZED COMPARATIVE STUDY OF THE INJECTABLE AND TABLETTED FORMULATIONS OF METHOTREXATE IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Yu. V. Muravyev

    2011-01-01

    Full Text Available Objective: to estimate the advantages and disadvantages of using the injectable formulation of methotrexate (MT (Methoject (MTJ in rheumatoid arthritis (RA in clinical practice. Subjects and methods. A 24-week open-label controlled randomized comparative study evaluated the therapeutic and side effects of MTJ and methotrexate tablets in RA and clarified whether MTJ treatment might be continued if its tabletted formulation was discontinued because of adverse reactions. Results and discussion. MTJ was found to be more effective than the tabletted formulation of MT and as a whole; and following 3-month therapy, more patients receiving MTJ achieved an ACR20 response. The advantage of MTJ was also retained 6 months after therapy. Higher transaminase levels were noted in 2 patients, one in each group. Switching from MT to MTJ noticeably reduced the number of adverse reactions in the majority of patients from an additional group. Conclusion. As compared to MT, MTJ used in RA patients is more effective when given in an equivalent dose, exerts a therapeutic effect more rapidly, and induces adverse gastrointestinal reactions less frequently. 

  10. Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Raquel Pei Chen Chan

    2009-01-01

    Full Text Available BACKGROUND: The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days. A p-value of 0.05. CONCLUSIONS: In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes.

  11. [An open randomized comparative trial of efficacy and safety of selective alpha-adrenoblocker setegis (terazosin) in therapy of patients with chronic bacterial prostatitis].

    Science.gov (United States)

    Trapeznikova, M F; Morozov, A P; Dutov, V V; Urenkov, S B; Pozdniakov, K V; Bychkova, N V

    2007-01-01

    An open randomized comparative trial of setegis (terazosine) has shown good subjective and objective results in patients with chronic bacterial prostatitis. The drug is well tolerated and produces insignificant side effects. It is also demonstrated that combined therapy with alpha-adrenoblockers is more effective that monotherapy with antibacterial drugs in patients with bacterial prostatitis.

  12. A randomized clinical trial of living donor nephrectomy : a plea for a differentiated appraisal of mini-open muscle splitting incision and hand-assisted laparoscopic donor nephrectomy

    NARCIS (Netherlands)

    Hofker, H.S.; Nijboer, W.N.; Niesing, J.; Krikke, C.; Seelen, M.A.; van Son, W.J.; van Wijhe, M.; Groen, H.; Van der Heide, J.J.; Ploeg, R.J.

    A randomized controlled trial was designed to compare various outcome variables of the retroperitoneal mini-open muscle splitting incision (MSI) technique and the transperitoneal hand-assisted laparoscopic technique (HAL) in performing living donor nephrectomies. Fifty living kidney donors were

  13. Locking intramedullary nailing with and without reaming for open fractures of the tibial shaft. A prospective, randomized study.

    Science.gov (United States)

    Keating, J F; O'Brien, P J; Blachut, P A; Meek, R N; Broekhuyse, H M

    1997-03-01

    Ninety-one patients who had ninety-four open fractures of the tibial shaft were randomized into two treatment groups. Fifty fractures (nine type-I, eighteen type-II, sixteen type-IIIA, and seven type-IIIB fractures, according to the classification of Gustilo et al.) were treated with nailing after reaming, and forty-four fractures (five type-I, sixteen type-II, nineteen type-IIIA, and four type-IIIB fractures) were treated with nailing without reaming. The average diameter of the nail was 11.5 millimeters (range, nine to fourteen millimeters) in the group treated with reaming and 9.2 millimeters (range, eight to ten millimeters) in the group treated without reaming. Follow-up information was adequate for forty-five patients (forty-seven fractures) who had been managed with reaming and forty patients (forty-one fractures) who had been managed without reaming. No clinically important differences were found between the two groups with regard to the technical aspects of the procedure or the rate of early postoperative complications. The average time to union was thirty weeks (range, thirteen to seventy-two weeks) in the group treated with reaming and twenty-nine weeks (range, thirteen to fifty weeks) in the group treated without reaming. Four (9 per cent) of the fractures treated with reaming and five (12 per cent) of the fractures treated without reaming did not unite (p = 0.73). There were two infections in the group treated with reaming and one in the group treated without reaming. Significantly more screws broke in the group treated without reaming (twelve; 29 per cent) than in the group treated with reaming (four; 9 per cent) (p = 0.014). There was no difference between the two groups with regard to the frequency of broken nails (two nails that had been inserted after reaming broke, compared with one that had been inserted without reaming). The functional outcome, in terms of pain in the knee, range of motion, return to work, and recreational activity, did not

  14. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial

    Science.gov (United States)

    Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery; de Almeida, Roque Pacheco; de Melo, Enaldo Viera; de Carvalho, Sílvio Fernando Guimarães; Rabello, Ana; de Carvalho, Andréa Lucchesi; Sousa, Anastácio de Queiroz; Leite, Robério Dias; Lima, Simone Soares; Amaral, Thais Alves; Alves, Fabiana Piovesan; Rode, Joelle

    2017-01-01

    Background There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. Methods A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. Results 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). Conclusions Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. Trial registration

  15. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.

    Science.gov (United States)

    Bolaman, Zahit; Kadikoylu, Gurhan; Yukselen, Vahit; Yavasoglu, Irfan; Barutca, Sabri; Senturk, Taskin

    2003-12-01

    Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p

  16. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial.

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Sierra Romero

    2017-06-01

    Full Text Available There is insufficient evidence to support visceral leishmaniasis (VL treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option.A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i amphotericin B deoxycholate (AmphoB (1 mg/kg/day for 14 days, (ii liposomal amphotericin B (LAMB (3 mg/kg/day for 7 days and (iii a combination of LAMB (10 mg/kg single dose plus meglumine antimoniate (MA (20 mg Sb+5/kg/day for 10 days, compared to (iv standard treatment with MA (20 mg Sb+5/kg/day for 20 days. Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption.378 patients were randomized to the four treatment arms: MA (n = 112, AmphoB (n = 45, LAMB (n = 109, or LAMB plus MA (n = 112. A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222. LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE (p = 0.045, proportion of patients presenting at least one severe AE (p = 0.029, and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003.Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738.ClinicalTrials.gov NCT01310738.

  17. EFFICACY AND SAFETY OF IVABRADINE AND BISOPROLOL IN PATIENTS WITH ISCHEMIC HEART DISEASE: RESULTS OF COMPARATIVE RANDOMIZED OPEN STUDY

    Directory of Open Access Journals (Sweden)

    R. D. Kurbanov

    2011-01-01

    Full Text Available Aim. To study influence of ivabradine as compared with bisoprolol on clinical and hemodynamic indices, exercise tolerance, endothelial function, quality of life (QL and erectile function in patients with ischemic heart disease. Material and methods. 60 males with stable angina pectoris were enrolled into comparative randomized crossover open study. One half of patients randomly received ivabradine during 14 days with replace it with bisoprolol for the next 3 months, another half of patients received compared drugs in the reverse order . Treadmill-test and flow-mediated dilatation (FMD test were performed initially and after 14 days of treatment with each drug. QL and erectile function were evaluated after 3 months with Seattle Angina Questionnaire (SAQ and International Index of Erectile Function (IIEF-5, respectively. Results. Heart rate reduced by 16.7±4.6 (p<0.005 and 16.4±4.8 bpm (p<0.005 after 2 weeks of treatment with bisoprolol and ivabradine, respectively. 30 (50.0% and 31 (51.7% patients treated with bisoprolol and ivabradine, respectively , increased exercise tolerance ≥1 min in the treadmill-test. Ivabradine treatment, in comparison with bisoprolol one, was associated by more expressed increase in chronotropic reserve in treadmill-test (p<0.05 and significant improvement of sensitivity coefficient of brachial artery to tension shift in FMD (p<0.005. In patients with endothelial dysfunction bisoprolol (69.4 % and ivabradine (52.8% efficacy did not differ significantly. At the same time in patients with normal endothelial functions increase in exercise tolerance ≥1 min in treadmill-test was observed in 50% (p<0.05 and 20.8% of patients treated with ivabradine and bisoprolol, respectively. Both drugs significantly increased QL, and ivabradine improved erectile function (p<0.005 in comparison with bisoprolol. Conclusion. The If-channel inhibitor ivabradine and beta-blocker bisoprolol have a similar antianginal efficacy in patients

  18. Effects of quetiapine and olanzapine in patients with psychosis and violent behavior: a pilot randomized, open-label, comparative study

    Directory of Open Access Journals (Sweden)

    Gobbi G

    2014-05-01

    Full Text Available Gabriella Gobbi,1,2 Stefano Comai,1 Guy Debonnel1,2,† 1Neurobiological Psychiatric Unit, Department of Psychiatry, McGill University and McGill University Health Center, 2Institut Philippe Pinel, Department of Psychiatry, Université de Montréal, Montréal, QC, Canada †Guy Debonnel passed away on November 4, 2006 Objective: Patients suffering from psychosis are more likely than the general population to commit aggressive acts, but the therapeutics of aggressive behavior are still a matter of debate. Methods: This pilot randomized, open-label study compared the efficacy of quetiapine versus olanzapine in reducing impulsive and aggressive behaviors (primary endpoints and psychotic symptoms (secondary endpoints from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent schizophrenic patients hospitalized in a maximum-security psychiatric hospital. Results: Quetiapine (525±45 mg and olanzapine (18.5±4.8 mg were both efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day 70 compared to baseline, and no differences were observed between treatments. Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive symptoms in the items “depression” in Brief Psychiatric Rating Scale and “blunted affect” in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale scores were also decreased from baseline to the endpoint, but due to the limited number of patients, it was not possible to detect a significant difference. Conclusion: In this pilot study, quetiapine and olanzapine equally decreased impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large studies are needed to confirm the validity of these two treatments in highly aggressive and violent schizophrenic patients. Keywords: schizophrenia, aggression

  19. Comparative study of amrutbhallataka and glucosamine sulphate in osteoarthritis: Six months open label randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Ashwinikumar Raut

    2013-01-01

    Full Text Available Background: AmrutBhallatak (ABFN02, a ′rasayana′ drug from Ayurveda is indicated in degenerative diseases and arthritis. Objective: To evaluate safety and efficacy of ABFN02 in osteoarthritis (OA and compare it with Glucosamine sulphate (GS Materials and Methods: This was a r andomized open comparative study. Ambulant OPD patients of OA knees (n = 112 were enrolled for 24 weeks. Tablets (750mg each of GS and ABFN02 were matched. Three groups of patients: (A GS, one tablet × twice/day × 24 weeks. (B ABFN02, incremental pulse dosage (one tablet x twice/day × two weeks, two tablets × twice/day × two weeks, three tablets × twice/day × two weeks, two such cycles of drug and non-drug phases alternately for six weeks each (C ABFN02 continuous dosage akin to GS. Pain visual analogue score (Pain-VAS and Western Ontario and Mc-Master University Osteoarthritis Index (WOMAC were the primary outcome measures. Secondary outcome measures were Health assessment questionnaire (HAQ, paracetamol consumption, 50 feet walking, physician and patient global assessment, knee stiffness, knee status, urinary CTX II, serum TNFa-SRI, SRII and MRI knee in randomly selected patients. Results: ABFNO2 and GS demonstrated, adherence to treatment 87.75% and 74.3%, reduction in Pain-VAS at rest 61.05% and 57.1%, reduction in pain-VAS on activity 57.4% and 59.8%, WOMAC score drop 62.8% and 59.1% respectively. Secondary outcome measures were comparable in all groups. Safety measures were also comparable. No serious adverse events reported. However, asymptomatic reversible rise in liver enzymes was noted in the ABFNO2 group. Conclusions: ABFN02 has significant activity in OA; the formulation needs further investigation.

  20. A systematic review and meta-analysis of randomized and non-randomized studies comparing laparoscopic and open abdominoperineal resection for rectal cancer.

    LENUS (Irish Health Repository)

    Ahmad, N Z

    2013-03-01

    Evidence supporting the role of laparoscopy in abdominoperineal resection (APR) is limited. This study compared the short-term and long-term outcomes and complications associated with open and laparoscopic APR.

  1. Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial

    DEFF Research Database (Denmark)

    Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia

    2016-01-01

    BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify an al...... treatments. CONCLUSIONS: Both treatments achieved the WHO recommended efficacy for antimalarials about to be adopted as policy. DP was not inferior to AL for treatment of uncomplicated P. falciparum malaria in Guinea-Bissau. TRIAL REGISTRATION: ClinicalTrials.gov NTC01704508....

  2. Improvement of functional constipation with kiwifruit intake in a Mediterranean patient population: An open, non-randomized pilot study

    Directory of Open Access Journals (Sweden)

    Oriol Cunillera

    2015-07-01

    Full Text Available Introduction: Kiwifruit consumption has shown to improve functional constipation in healthy elderly population, according to studies in New Zealand and China. The aim of this study was to evaluate the effect of kiwifruit intake on functional constipation in a Mediterranean patient population characterized by its distinctive nutritional habits.Material and Methods: An open, non-controlled and non-randomized longitudinal study was conducted in 46 patients with constipation (Rome III criteria. Patients monitored for five weeks: weeks 1 and 2 no kiwifruit and weeks 3-5 three kiwifruit per day (Green kiwifruit, Actinidia deliciosa var Hayward. Bristol Scale, volume of stools, and ease of defecation was self- reported daily. The evolution of the categorical variables was tested using the Bhapkar test; functional data methodology was used for continuous variables, and Generalized Estimating Equation (GEE models were adjusted.Results: The percentage of patients with ≥3 stools per week increased from 82.61% (95% CI: 69–91.2 at week 1 to 97.78% (95% CI: 87.4–99.9 at week 2 of kiwifruit intake, with 76.09% (95% CI: 61.9–86.2 responding during the first week. The reporting of stable ideal stools increased from 17.39% (95% CI: 8.8–31 at week 2 to 33.33% (95% CI: 21.3–48 at week 5. According to GEE models, the number of depositions increased significantly (p-values<0.001 in 0.398 daily units at week 1 the first week of intake, up to 0.593 daily units at week 5; significant improvements on facility in evacuation and volume of evacuation were found from the firstweek of intake (all p-values<0.001.Conclusions: The intake of three kiwifruits per day significantly improves the quality of evacuation (number of depositions, volume, consistency and ease in a Mediterranean patient population suffering from functional constipation.

  3. An Open-Label, Randomized Trial of Methylphenidate and Atomoxetine Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Shang, Chi-Yung; Pan, Yi-Lei; Lin, Hsiang-Yuan; Huang, Lin-Wan; Gau, Susan Shur-Fen

    2015-09-01

    The efficacy of both methylphenidate and atomoxetine has been established in placebo-controlled trials. The present study aimed to directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms among children with attention-deficit/hyperactivity disorder (ADHD). The study sample included 160 drug-naïve children and adolescents 7-16 years of age, with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24 week, open-label, head-to-head clinical trial. The primary efficacy measure was the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents, teachers, and subjects. At week 24, mean changes in ADHD-RS-IV Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate and 12.65 points (Cohen's d, -3.05) for atomoxetine; and mean changes in ADHD-RS-IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS-methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of parent-, teacher-, and self-ratings on behavioral symptoms, both of the two treatment groups significantly decreased on the SNAP-IV scores at the end-point, with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from 0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate; and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant differences between treatment groups were observed on the outcome measures. Vomiting, somnolence, and dizziness were reported more often for atomoxetine than for OROS-methylphenidate, whereas insomnia was reported

  4. Effectiveness of percutaneous laser disc decompression versus conventional open discectomy in the treatment of lumbar disc herniation; design of a prospective randomized controlled trial

    OpenAIRE

    Koes Bart W; Arts Mark P; Brand Ronald; Peul Wilco C; Brouwer Patrick A; Berg Annette; van Buchem Mark A

    2009-01-01

    Abstract Background The usual surgical treatment of refractory sciatica caused by lumbar disc herniation, is open discectomy. Minimally invasive procedures, including percutaneous therapies under local anesthesia, are increasingly gaining attention. One of these treatments is Percutaneous Laser Disc Decompression (PLDD). This treatment can be carried out in an outpatient setting and swift recovery and return to daily routine are suggested. Thus far, no randomized trial into cost-effectiveness...

  5. Diabetes-specific enteral nutrition formula in hyperglycemic, mechanically ventilated, critically ill patients: a prospective, open-label, blind-randomized, multicenter study

    OpenAIRE

    Mesejo, Alfonso; Montejo-González, Juan Carlos; Vaquerizo-Alonso, Clara; Lobo-Tamer, Gabriela; Zabarte-Martinez, Mercedes; Herrero-Meseguer, Jose Ignacio; Acosta-Escribano, Jose; Blesa-Malpica, Antonio; Martinez-Lozano, Fátima

    2015-01-01

    Introduction Although standard enteral nutrition is universally accepted, the use of disease-specific formulas for hyperglycemic patients is still controversial. This study examines whether a high-protein diabetes-specific formula reduces insulin needs, improves glycemic control and reduces ICU-acquired infection in critically ill, hyperglycemic patients on mechanical ventilation (MV). Methods This was a prospective, open-label, randomized (web-based, blinded) study conducted at nine Spanish ...

  6. Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy

    OpenAIRE

    2015-01-01

    Aims. To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. Methods. In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycem...

  7. Evaluation of efficacy and tolerability of eperisone and thiocolchicoside in treatment of low back pain associated with muscle spasm: An open label, prospective, randomized controlled trial

    OpenAIRE

    Syed H. Maaz; Prakash N. Khandelwal; Shiraz M. Baig; Sudhakar M. Doifode; Ulhas M. Ghotkar

    2016-01-01

    Background: Low back pain has a high prevalence in adult population. Because of reflex muscle spasm, muscle relaxants are frequently used either alone or in combination with analgesics. Eperisone inhibits voltage gated sodium channels in brain stem and Thiocolchicoside acts via GABA-mediated mechanism to relax muscle spasm and relieves pain. Methods: This was a prospective; open labeled, randomized, two-arm, parallel group, controlled, clinical trial. 113 patients were randomised to two gr...

  8. Effectiveness of percutaneous laser disc decompression versus conventional open discectomy in the treatment of lumbar disc herniation; design of a prospective randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Koes Bart W

    2009-05-01

    Full Text Available Abstract Background The usual surgical treatment of refractory sciatica caused by lumbar disc herniation, is open discectomy. Minimally invasive procedures, including percutaneous therapies under local anesthesia, are increasingly gaining attention. One of these treatments is Percutaneous Laser Disc Decompression (PLDD. This treatment can be carried out in an outpatient setting and swift recovery and return to daily routine are suggested. Thus far, no randomized trial into cost-effectiveness of PLDD versus standard surgical procedure has been performed. We present the design of a randomized controlled trial, studying the cost-effectiveness of PLDD versus conventional open discectomy in patients with sciatica from lumbar disc herniation. Methods/design The study is a randomized prospective multi-center trial, in which two treatment strategies are compared in a parallel group design. Patients (age 18–70 years visiting the neurosurgery department of the participating hospitals, are considered for inclusion in the trial when sciatica due to lumbar disc herniation has lasted more than 8 weeks. Patients with disc herniation smaller than 1/3 of the spinal canal diameter, without concomitant lateral recess stenosis or sequestration, are eligible for participation, and are randomized into one of two treatment arms; either Percutaneous Laser Disc Decompression or conventional discectomy. The functional outcome of the patient, as assessed by the Roland Disability Questionnaire for Sciatica at 8 weeks and 1 year after treatment, is the primary outcome measure. The secondary outcome parameters are recovery as perceived by the patient, leg and back pain, incidence of re-intervention, complications, quality of life, medical consumption, absence of work and secondary costs. Discussion Open discectomy is still considered to be the golden standard in the surgical treatment of lumbar disc herniation. Whether Percutaneous Laser Disc Decompression has at least as

  9. A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB project

    Directory of Open Access Journals (Sweden)

    Merle Corinne SC

    2012-05-01

    Full Text Available Abstract Background There have been no major advances in tuberculosis (TB drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385. Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically

  10. Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery

    Directory of Open Access Journals (Sweden)

    Hedenstierna Göran

    2011-05-01

    Full Text Available Abstract Background Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery. Methods The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO" trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH2O with recruitment maneuvers (the lung-protective strategy or mechanical ventilation with the level of PEEP at maximum 2 cmH2O without recruitment maneuvers (the conventional strategy. The primary endpoint is any post-operative pulmonary complication. Discussion The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications. Trial registration ISRCTN: ISRCTN70332574

  11. Comparison of the effectiveness and safety of cefpodoxime and ciprofloxacin in acute exacerbation of chronic suppurative otitis media: A randomized, open-labeled, phase IV clinical trial

    Directory of Open Access Journals (Sweden)

    Arijit Ghosh

    2012-01-01

    Full Text Available Objective : To compare the effectiveness and safety of cefpodoxime and ciprofloxacin for the treatment of mild to moderate cases of acute exacerbation of chronic suppurative otitis media (AECSOM. Materials and Methods : Adult patients diagnosed with AECSOM were screened and patients fulfilling the inclusion criteria were randomized to receive either cefpodoxime 200 mg twice daily or ciprofloxacin 500 mg twice daily orally for 7 days. The primary outcome of this randomized, open-labeled, phase IV clinical trial (Registration Number - CTRI/2011/10/002079 was clinical success rate at day 14 visit and the secondary outcome was incidence of adverse events (AEs. Forty-six patients were enrolled: 23 in the cefpodoxime group and 23 in the ciprofloxacin group. Results : The clinical success rates were 95.6% in the cefpodoxime group versus 90.9% in the ciprofloxacin group. These rates are comparable, but no statistically significant difference was observed between the groups. Few mild and self-limiting AEs were observed and the tolerability of both the drugs was also good. Conclusion : The results of this randomized, open-labeled phase IV clinical trial showed that a 7-day course of cefpodoxime is therapeutically comparable to ciprofloxacin in terms of both clinical effectiveness and safety for the treatment of patients with AECSOM.

  12. Randomized trial comparing the Prolene Hernia System, mesh plug repair and Lichtenstein method for open inguinal hernia repair.

    NARCIS (Netherlands)

    Nienhuijs, S.W.; Oort, I.M. van; Keemers-Gels, M.E.; Strobbe, L.J.; Rosman, C.

    2005-01-01

    BACKGROUND: Most surgeons favour the use of a mesh for open inguinal hernia repair as it has a low recurrence rate. Procedures used most frequently are the Lichtenstein method, mesh plug repair and the Prolene Hernia System. The choice of technique may be influenced by the effects on postoperative p

  13. A prospective randomized trial of open surgery versus endourological stone removal in patients of staghorn stones with chronic renal failure

    Directory of Open Access Journals (Sweden)

    Anant Kumar

    2001-01-01

    Conclusion: In view of the better clearance rate and lesser cost of treatment, open surgery still has a place in the management of staghorn stones with chronic renal failure even in a tertiary urological center. However postoperative pain and a larger scar cannot be ignored.

  14. Opening the Black Box: Intervention Fidelity in a Randomized Trial of a Preschool Teacher Professional Development Program

    Science.gov (United States)

    Mendive, Susana; Weiland, Christina; Yoshikawa, Hirokazu; Snow, Catherine

    2016-01-01

    "Un Buen Comienzo" [A Good Start] was a professional development program implemented with prekindergarten and kindergarten teachers in Chilean public schools serving low-income families. In a randomized trial, the program showed moderate to large impacts on classroom quality but no impacts on targeted child outcomes. To unpack these…

  15. Lithium augmentation compared with phenelzine in treatment-resistant depression in the elderly : An open, randomized, controlled trial

    NARCIS (Netherlands)

    Kok, Rob M.; Vink, Dagmar; Heeren, Thea J.; Nolen, Willem A.

    2007-01-01

    Background: Up to a third of elderly patients with major depressive disorder do not respond to a first course of treatment with an antidepressant. There is a lack of controlled studies evaluating therapies for treatment-resistant depression in latelife depression, and no randomized controlled studie

  16. A Prospective Randomized Trial to Assess Fixation Strategies for Severe Open Tibia Fractures: Modern Ring External Fixators Versus Internal Fixation (FIXIT Study).

    Science.gov (United States)

    OʼToole, Robert V; Gary, Joshua L; Reider, Lisa; Bosse, Michael J; Gordon, Wade T; Hutson, James; Quinnan, Stephen M; Castillo, Renan C; Scharfstein, Daniel O; MacKenzie, Ellen J

    2017-04-01

    The treatment of high-energy open tibia fractures is challenging in both the military and civilian environments. Treatment with modern ring external fixation may reduce complications common in these patients. However, no study has rigorously compared outcomes of modern ring external fixation with commonly used internal fixation approaches. The FIXIT study is a prospective, multicenter randomized trial comparing 1-year outcomes after treatment of severe open tibial shaft fractures with modern external ring fixation versus internal fixation among men and women of ages 18-64. The primary outcome is rehospitalization for major limb complications. Secondary outcomes include infection, fracture healing, limb function, and patient-reported outcomes including physical function and pain. One-year treatment costs and patient satisfaction will be compared between the 2 groups, and the percentage of Gustilo IIIB fractures that can be salvaged without soft tissue flap among patients receiving external fixation will be estimated.

  17. Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

    Science.gov (United States)

    Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

    2017-07-28

    A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levelsacromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GHacromegaly or pituitary gigantism.

  18. Comparison of the acute-phase response after laparoscopic versus open aortobifemoral bypass surgery: a substudy of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Krog AH

    2016-09-01

    Full Text Available Anne H Krog,1,2 Mehdi Sahba,3 Erik M Pettersen,4 Irene Sandven,5 Per M Thorsby,1,6 Jørgen J Jørgensen,1,2 Jon O Sundhagen,2 Syed SS Kazmi2 1Institute of Clinical Medicine, University of Oslo, 2Department of Vascular Surgery, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, Oslo, 3Department of Vascular Surgery, Østfold Central Hospital, Fredrikstad, 4Department of Vascular Surgery, Sørlandet Hospital HF, Kristiansand, 5Oslo Center for Biostatistics and Epidemiology (OCBE, 6Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway Purpose: Minimally invasive surgical techniques have been shown to reduce the inflammatory response related to a surgical procedure. The main objective of our study was to measure the inflammatory response in patients undergoing a totally laparoscopic versus open aortobifemoral bypass surgery. This is the first randomized trial on subjects in this population.Patients and methods: This is a substudy of a larger randomized controlled multicenter trial (Norwegian Laparoscopic Aortic Surgery Trial. Thirty consecutive patients with severe aortoiliac occlusive disease eligible for aortobifemoral bypass surgery were randomized to either a totally laparoscopic (n=14 or an open surgical procedure (n=16. The inflammatory response was measured by perioperative monitoring of serum interleukin-6 (IL-6, IL-8, and C-reactive protein (CRP at six different time points.Results: The inflammatory reaction caused by the laparoscopic procedure was reduced compared with open surgery. IL-6 was significantly lower after the laparoscopic procedure, measured by comparing area under the curve (AUC, and after adjusting for the confounding effect of coronary heart disease (P=0.010. The differences in serum levels of IL-8 and CRP did not reach statistical significance.Conclusion: In this substudy of a randomized controlled trial comparing laparoscopic and open aortobifemoral bypass

  19. Clinical Efficacy Comparison of Saccharomyces boulardii and Yogurt Fluid in Acute Non-Bloody Diarrhea in Children: A Randomized, Controlled, Open Label Study

    OpenAIRE

    Makbule EREN; Dinleyici, Ener C; Vandenplas,Yvan

    2010-01-01

    The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 ± 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, a...

  20. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin;

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer.......This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  1. Early Open-Lung Ventilation Improves Clinical Outcomes in Patients with Left Cardiac Dysfunction Undergoing Off-Pump Coronary Artery Bypass: a Randomized Controlled Trial

    Science.gov (United States)

    Bolzan, Douglas W.; Gomes, Walter José; Rocco, Isadora S.; Viceconte, Marcela; Nasrala, Mara L. S.; Pauletti, Hayanne O.; Moreira, Rita Simone L.; Hossne Jr, Nelson A.; Arena, Ross; Guizilini, Solange

    2016-01-01

    Objective To compare pulmonary function, functional capacity and clinical outcomes amongst three groups of patients with left ventricular dysfunction following off-pump coronary artery bypass, namely: 1) conventional mechanical ventilation (CMV); 2) late open lung strategy (L-OLS); and 3) early open lung strategy (E-OLS). Methods Sixty-one patients were randomized into 3 groups: 1) CMV (n=21); 2) L-OLS (n=20) initiated after intensive care unit arrival; and 3) E-OLS (n=20) initiated after intubation. Spirometry was performed at bedside on preoperative and postoperative days (PODs) 1, 3, and 5. Partial pressure of arterial oxygen (PaO2) and pulmonary shunt fraction were evaluated preoperatively and on POD1. The 6-minute walk test was applied on the day before the operation and on POD5. Results Both the open lung groups demonstrated higher forced vital capacity and forced expiratory volume in 1 second on PODs 1, 3 and 5 when compared to the CMV group (P<0.05). The 6-minute walk test distance was more preserved, shunt fraction was lower, and PaO2 was higher in both open-lung groups (P<0.05). Open-lung groups had shorter intubation time and hospital stay and also fewer respiratory events (P<0.05). Key measures were significantly more favorable in the E-OLS group compared to the L-OLS group. Conclusion Both OLSs (L-OLS and E-OLS) were able to promote higher preservation of pulmonary function, greater recovery of functional capacity and better clinical outcomes following off-pump coronary artery bypass when compared to conventional mechanical ventilation. However, in this group of patients with reduced left ventricular function, initiation of the OLS intra-operatively was found to be more beneficial and optimal when compared to OLS initiation after intensive care unit arrival. PMID:27982344

  2. An Open-Label, Randomized Study of a 9-Valent Human Papillomavirus Vaccine Given Concomitantly with Diphtheria, Tetanus, Pertussis, and Poliomyelitis Vaccines to Healthy Adolescents 11 to 15 Years of Age

    DEFF Research Database (Denmark)

    Kosalaraksa, Pope; Mehlsen, Jesper; Vesikari, Timo

    2015-01-01

    (diphtheria, tetanus, acellular pertussis, and inactivated poliomyelitis vaccine). METHODS: This open-label, randomized, multicenter study enrolled 1054 males and females ages 11-15 years. Subjects were randomly assigned to each group in a 1:1 ratio. Subjects received a 0.5mL dose of 9vHPV vaccine...

  3. The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

    Science.gov (United States)

    Deuse, Tobias; Bara, Christoph; Barten, Markus J; Hirt, Stephan W; Doesch, Andreas O; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Garbade, Jens; Wimmer, Peter; May, Christoph; Porstner, Martina; Schulz, Uwe

    2015-11-01

    In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein.

  4. Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Henzen Christoph

    2007-07-01

    Full Text Available Abstract Background: Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. The goal of this trial is to compare medical outcomes, use of antibiotics and hospital resources in a strategy based on enforced evidence-based guidelines versus procalcitonin guided antibiotic therapy in patients with lower respiratory tract infections. Methods and design: We describe a prospective randomized controlled non-inferiority trial with an open intervention. We aim to randomize over a fixed recruitment period of 18 months a minimal number of 1002 patients from 6 hospitals in Switzerland. Patients must be >18 years of age with a lower respiratory tract infections Discussion: Use of and prolonged exposure to antibiotics in lower respiratory tract infections is high. The proposed trial investigates whether procalcitonin-guidance may safely reduce antibiotic consumption along with reductions in hospitalization costs and antibiotic resistance. It will additionally generate insights for improved prognostic assessment of patients with lower respiratory tract infections. Trial registration: ISRCTN95122877

  5. Open-label randomized trial of titrated disease management for patients with hypertension: Study design and baseline sample characteristics.

    Science.gov (United States)

    Jackson, George L; Weinberger, Morris; Kirshner, Miriam A; Stechuchak, Karen M; Melnyk, Stephanie D; Bosworth, Hayden B; Coffman, Cynthia J; Neelon, Brian; Van Houtven, Courtney; Gentry, Pamela W; Morris, Isis J; Rose, Cynthia M; Taylor, Jennifer P; May, Carrie L; Han, Byungjoo; Wainwright, Christi; Alkon, Aviel; Powell, Lesa; Edelman, David

    2016-09-01

    Despite the availability of efficacious treatments, only half of patients with hypertension achieve adequate blood pressure (BP) control. This paper describes the protocol and baseline subject characteristics of a 2-arm, 18-month randomized clinical trial of titrated disease management (TDM) for patients with pharmaceutically-treated hypertension for whom systolic blood pressure (SBP) is not controlled (≥140mmHg for non-diabetic or ≥130mmHg for diabetic patients). The trial is being conducted among patients of four clinic locations associated with a Veterans Affairs Medical Center. An intervention arm has a TDM strategy in which patients' hypertension control at baseline, 6, and 12months determines the resource intensity of disease management. Intensity levels include: a low-intensity strategy utilizing a licensed practical nurse to provide bi-monthly, non-tailored behavioral support calls to patients whose SBP comes under control; medium-intensity strategy utilizing a registered nurse to provide monthly tailored behavioral support telephone calls plus home BP monitoring; and high-intensity strategy utilizing a pharmacist to provide monthly tailored behavioral support telephone calls, home BP monitoring, and pharmacist-directed medication management. Control arm patients receive the low-intensity strategy regardless of BP control. The primary outcome is SBP. There are 385 randomized (192 intervention; 193 control) veterans that are predominately older (mean age 63.5years) men (92.5%). 61.8% are African American, and the mean baseline SBP for all subjects is 143.6mmHg. This trial will determine if a disease management program that is titrated by matching the intensity of resources to patients' BP control leads to superior outcomes compared to a low-intensity management strategy.

  6. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.

    Science.gov (United States)

    Pujade-Lauraine, Eric; Hilpert, Felix; Weber, Béatrice; Reuss, Alexander; Poveda, Andres; Kristensen, Gunnar; Sorio, Roberto; Vergote, Ignace; Witteveen, Petronella; Bamias, Aristotelis; Pereira, Deolinda; Wimberger, Pauline; Oaknin, Ana; Mirza, Mansoor Raza; Follana, Philippe; Bollag, David; Ray-Coquard, Isabelle

    2014-05-01

    In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. Eligible patients had measurable/assessable OC that had progressed two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.

  7. Renal access in PNL under sonographic guidance: Do we really need to insert an open end ureteral catheter in dilated renal systems? A prospective randomized study.

    Science.gov (United States)

    Eryildirim, Bilal; Tuncer, Murat; Camur, Emre; Ustun, Fatih; Tarhan, Fatih; Sarica, Kemal

    2017-10-03

    To evaluate the true necessity of open end ureteral catheter insertion in patients with moderate to severe pelvicalyceal system dilation treated with percutaneous nephrolithotomy (PNL) under sonographic guidance. 50 cases treated with PNL under sonographic guidance in prone position for solitary obstructing renal stones were evaluated. Patients were randomly divided into two groups; Group 1: Patients in whom a open end ureteral catheter was inserted prior to the procedure; Group 2: Patients receiving no catheter before PNL. In addition to the duration of the procedure as a whole and also all relevant stages as well, radiation exposure time, hospitalization period, mean nephrostomy tube duration, mean drop in Hb levels and all intra and postoperative complications have been evaluated. Mean size of the stones was 308.5 ± 133.2 mm2. Mean total duration of the PNL procedure in cases with open end ureteral catheter was significantly longer than the other cases (p < 0.001). Evaluation of the outcomes of the PNL procedures revealed no statistically significant difference between two groups regarding the stone-free rates (86% vs 84%). Additionally, there was no significant difference with respect to the duration of nephrostomy tube, hospitalization period and secondary procedures needed, complication rates as well as the post-operative Hb drop levels in both groups (p = 0.6830). Our results indicate that the placement of an open end ureteral catheter prior to a PNL procedure performed under sonographic access may not be indicated in selected cases presenting with solitary obstructing renal pelvic and/or calyceal stones.

  8. Expert opinion on laparoscopic surgery for colorectal cancer parallels evidence from a cumulative meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Guillaume Martel

    Full Text Available BACKGROUND: This study sought to synthesize survival outcomes from trials of laparoscopic and open colorectal cancer surgery, and to determine whether expert acceptance of this technology in the literature has parallel cumulative survival evidence. STUDY DESIGN: A systematic review of randomized trials was conducted. The primary outcome was survival, and meta-analysis of time-to-event data was conducted. Expert opinion in the literature (published reviews, guidelines, and textbook chapters on the acceptability of laparoscopic colorectal cancer was graded using a 7-point scale. Pooled survival data were correlated in time with accumulating expert opinion scores. RESULTS: A total of 5,800 citations were screened. Of these, 39 publications pertaining to 23 individual trials were retained. As well, 414 reviews were included (28 guidelines, 30 textbook chapters, 20 systematic reviews, 336 narrative reviews. In total, 5,782 patients were randomized to laparoscopic (n = 3,031 and open (n = 2,751 colorectal surgery. Survival data were presented in 16 publications. Laparoscopic surgery was not inferior to open surgery in terms of overall survival (HR = 0.94, 95% CI 0.80, 1.09. Expert opinion in the literature pertaining to the oncologic acceptability of laparoscopic surgery for colon cancer correlated most closely with the publication of large RCTs in 2002-2004. Although increasingly accepted since 2006, laparoscopic surgery for rectal cancer remained controversial. CONCLUSIONS: Laparoscopic surgery for colon cancer is non-inferior to open surgery in terms of overall survival, and has been so since 2004. The majority expert opinion in the literature has considered these two techniques to be equivalent since 2002-2004. Laparoscopic surgery for rectal cancer has been increasingly accepted since 2006, but remains controversial. Knowledge translation efforts in this field appear to have paralleled the accumulation of clinical trial evidence.

  9. Efficacy of Gum Chewing on Bowel Movement After Open Colectomy for Left-Sided Colorectal Cancer: A Randomized Clinical Trial.

    Science.gov (United States)

    Kobayashi, Takaaki; Masaki, Tadahiko; Kogawa, Koji; Matsuoka, Hiroyoshi; Sugiyama, Masanori

    2015-11-01

    Prolonged intestinal paralysis can be a problem after gastrointestinal surgery. Several systematic reviews and meta-analyses have suggested the efficacy of gum chewing for the prevention of postoperative ileus. The purpose of this study was to examine the efficacy of gum chewing for the recovery of bowel function after surgery for left-sided colorectal cancer and to determine the physiological mechanism underlying the effect of gum chewing on bowel function. This was a single-center, placebo-controlled, parallel-group, prospective randomized trial. The study was conducted at a general hospital in Japan. Forty-eight patients with left-sided colorectal cancer were included. The patients were randomly assigned to a gum group (N = 25) and a control group (N = 23). Four patients in the gum group and 1 in the control group were subsequently excluded because of difficulties in continuing the trial, resulting in the analysis of 21 and 22 patients in the respective groups. Patients in the gum group chewed commercial gum 3 times a day for ≥5 minutes each time from postoperative day 1 to the first day of food intake. The time to first flatus and first bowel movement after the operation were recorded, and the colonic transit time was measured. Gut hormones (gastrin, des-acyl ghrelin, motilin, and serotonin) were measured preoperatively, perioperatively, and on postoperative days 1, 3, 5, 7, and 10. Gum chewing did not significantly shorten the time to the first flatus (53 ± 2 vs. 49 ± 26 hours; p = 0.481; gum vs. control group), time to first bowel movement (94 ± 44 vs. 109 ± 34 hours; p = 0.234), or the colonic transit time (88 ± 28 vs. 88 ± 21 hours; p = 0.968). However, gum chewing significantly increased the serum levels of des-acyl ghrelin and gastrin. The main limitation was a greater rate of complications than anticipated, which limited the significance of the findings. Gum chewing changed the serum levels of des-acyl ghrelin and gastrin, but we were unable to

  10. Open suprapubic versus retropubic prostatectomy in the treatment of benign prostatic hyperplasia during resident's learning curve: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Arie Carneiro

    2016-04-01

    Full Text Available ABSTRACT Purpose: This study compared the suprapubic (SP versus retropubic (RP prostatectomy for the treatment of large prostates and evaluated perioperative surgical morbidity and improvement of urinary symptoms. Materials and Methods: In this single centre, prospective, randomised study, 65 consecutive patients with LUTS and surgical indication with prostate volume greater than 75g underwent open prostatectomy to compare the RP (32 patients versus SP (33 patients technique. Results: The SP group exhibited a higher incidence of complications (p=0.002. Regarding voiding pattern analysis (IPSS and flowmetry, both were significantly effective compared to pre-treatment baseline. The RP group parameters were significantly better, with higher peak urinary flow (SP: 16.77 versus RP: 23.03mL/s, p=0.008 and a trend of lower IPSS score (SP: 6.67 versus RP 4.14, p=0.06. In a subgroup evaluation of patients with prostate volumes larger than 100g, blood loss was lower in those undergoing SP prostatectomy (p=0.003. Patients with prostates smaller than 100g in the SP group exhibited a higher incidence of low grade late complications (p=0.004. Conclusions: The SP technique was related to a higher incidence of minor complications in the late postoperative period. High volume prostates were associated with increased bleeding when the RP technique was utilized. The RP prostatectomy was associated with higher peak urinary flow and a trend of a lower IPSS Score.

  11. AUGMENTATION VS NONAUGMENTATION TECHNIQUES FOR OPEN REPAIRS OF ACHILLES TENDON RUPTURES WITH EARLY FUNCTIONAL TREATMENT: A PROSPECTIVE RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    Gündüz Tezeren

    2006-12-01

    Full Text Available A prospective randomized study was conducted in order to compare augmentation technique versus nonaugmentation technique, followed by early functional postoperative treatment, for operative repair of Achilles tendon ruptures. Twenty-four consecutive patients were assigned to two groups. Group I included 12 patients treated with Lindholm augmentation technique, whereas group II included 12 patients treated with modified Kessler end-to-end repair. Thereafter, these patients had postoperative management with a below-knee-cast for three weeks. The physioteraphy was initiated immediately after the cast was removed. Full weight bearing was allowed after five weeks postoperatively in the both groups. Two patients had reruptures in group II, whereas group I had prolonged operative time significantly. The patients with reruptures underwent reoperations and at the most final follow-up, it was observed that they could not resume to sporting activities. The other objective and subjective results were similar between two groups. Because of quite high rerupture rate in the group of patients treated with nonaugmentation technique, we favor functional postoperative treatment with early ankle movement in the patients treated with augmentation technique for the management of acute rupture of the Achilles tendon

  12. Long-Term Effects of Goshajinkigan in Prevention of Diabetic Complications: A Randomized Open-Labeled Clinical Trial

    Directory of Open Access Journals (Sweden)

    K. Watanabe

    2014-01-01

    Full Text Available Objective. This clinical trial was designed to investigate whether goshajinkigan reduces the onset of diabetic complications or not. Materials and Methods. A total of 332 type 2 diabetic mellitus patients were registered from 9 clinical centers from March 2000 to August 2007. Patients were randomly assigned to take goshajinkigan extract powder, 2.5 grams for 3 times a day or no kampo therapy, additionally to the regular treatment. The primary endpoints were the onset of macrovascular diseases or progression of nephropathy or retinopathy. Statistical analysis was performed by the intention-to-treat method. Results. After 5 years of observation, 116 patients were submitted to analysis. Among them, no macrovascular events were observed in both groups. Although 43 participants had upstaging of retinopathy or nephropathy in total, there was no significant difference between goshajinkigan group and control group. Deterioration of ankle reflex was suppressed in goshajinkigan group. Also glycated hemoglobin, and fasting plasma glucose were decreased in the goshajinkigan group. Conclusion. Although the power of analysis was too low to demonstrate any effects of goshajinkigan on the progression of macrovascular diseases, retinopathy or nephropathy, goshajinkigan may be beneficial for diabetic neuropathy and glycemic control.

  13. Adverse drug reaction monitoring with angiotensin converting enzyme inhibitors: A prospective, randomized, open-label, comparative study.

    Science.gov (United States)

    Sangole, Nishant V; Dadkar, Vaishali N

    2010-02-01

    Angiotensin converting enzyme inhibitors (ACEIs) are known to possess different chemical structures, and change in structure of a drug can bring about change in its adverse drug reaction (ADR) profile. The study aims to observe the incidence and severity of ADRs between the di-carboxyl group containing ACEIs (d-ACEIs) versus phosphonate group containing ACEIs (p-ACEIs), in patients suffering from essential hypertension. One hundred and twenty patients with essential hypertension were randomized into four groups receiving enalapril, lisinopril, ramipril, and fosinopril. They were followed up for four months, to observe the clinical efficacy along with the associated ADRs. Mild, dry brassy cough (% incidence; 95% CI) was observed with d-ACEIs (6.6%; 0 to 15.6) versus p-ACEI (20%; 5.7 to 34.3), in which the cough observed was moderate-to-severe in intensity and two patients required treatment discontinuation (P ACEIs, whereas, two patients on p-ACEI (6.6%; 0 to15.6) had hypotension (P ACEIs had nausea, which was not observed with p-ACEI treatment (0%) (P ACEIs may have a probable relationship with increase in the incidence and severity of ADRs such as dry brassy cough and hypotension. The di-carboxyl group in d-ACEIs may have a probable relationship with increase in the incidence of ADRs like nausea.

  14. Differential Effects of Acetylcholinesterase Inhibitors on Clinical Responses and Cerebral Blood Flow Changes in Patients with Alzheimer's Disease: A 12-Month, Randomized, and Open-Label Trial

    Directory of Open Access Journals (Sweden)

    Soichiro Shimizu

    2015-04-01

    Full Text Available Background/Aims: The present study evaluated the differences in treatment outcomes and brain perfusion changes among 3 types of acetylcholinesterase inhibitors (AchEIs, i.e. donepezil, rivastigmine, and galantamine. Methods: This was a prospective, longitudinal, randomized, open-label, 3-arm (donepezil, rivastigmine, or galantamine, parallel-group, 12-month clinical trial carried out in 55 patients with AD. Results: At 6 months, the results of the Mini-Mental State Examination (MMSE and the Trail Making Test (TMT-Part A showed an improvement versus baseline in the donepezil treatment group. All groups showed a significant increase in regional cerebral blood flow (rCBF, mainly in the frontal lobe. Significant rCBF reduction was observed in the temporal lobe and cingulate gyrus in all 3 groups. Conclusion: AchEI treatment prevents the progression of cognitive impairment and increases the relative rCBF in the frontal lobe.

  15. An open-label, randomized clinical trial to assess the immunomodulatory activity of a novel oligosaccharide compound in healthy adults

    Directory of Open Access Journals (Sweden)

    Karriem H. Ali

    2012-07-01

    Full Text Available Background: Rice Bran Arabinoxylan Compound (RBAC is a nutritional supplement produced by enzymatic hydrolysis of hemicellulose B derived from rice bran. Several in vitro studies and clinical reports have shown RBAC to possess promising immunomodulating effects, specifically with respect to natural killer cell and cytokine activity. The concept of a true immunomodulator is an agent possessing a broad range of activity dependent upon the existing state of health and immunity in the individual host. The present study investigated the immunomodulatory effect of RBAC in a healthy adult human population over 60 days by assessing changes in natural killer cell cytotoxicity (NKCC and cytokines and growth factors. Subjects participated in a two-group, randomized intervention, where one group (n=10 consumed 1 gram/day and the other (n=10 consumed 3 gram/day. Safety and tolerability of RBAC were assessed with total bilirubin, total protein, creatinine, and liver function tests.Results: We found that both groups had similar responses for NKCC, cytokines, and growth factors. The NKCC peaked at 1 week, whereas interferon-γ, tumor necrosis factor-α, interleukins-1α, -1β, -8, and -10, and epidermal growth factor peaked at 30 days. All subjects tolerated the supplement without any adverse reactions.Conclusions: Our results showed transient, bi-directional, immune marker effects consistent with true, multifactorial immunomodulation rather than simply immunostimulation or immunosuppression. Given our findings, the immunomodulatory activity of RBAC merits studyFunctional Foods in Health and Disease 2012, 2(7:265-279 in conditions where the immune system is functionally compromised (e.g., otherwise-healthy smokers and HIV/AIDS or cancer patients. RBAC may not only help to destroy tumor cells and viruses directly, but also increase the activity of immune cells, thereby optimizing the immune system, especially NKCC, which can increase the chance and speed of host

  16. Effects of Lactobacillus salivarius-containing tablets on caries risk factors: a randomized open-label clinical trial.

    Science.gov (United States)

    Nishihara, Tetsuyo; Suzuki, Nao; Yoneda, Masahiro; Hirofuji, Takao

    2014-09-02

    To evaluate the effects of the lactic acid bacterium Lactobacillus salivarius on caries risk factors. The study was performed in 64 healthy volunteers to evaluate the effects of L. salivarius-containing tablets on caries risk factors. The participants were divided randomly into four groups, and took tablets containing L. salivarius WB21, L. salivarius TI 2711, Ovalgen® DC (antibody against glucosyltransferase from Streptococcus mutans), or xylitol. Levels of mutans streptococci and lactobacilli, amount of salivary flow, salivary pH, and salivary buffering capacity were assessed before and after taking the tablets. Subsequently, a short-term administration trial using L. salivarius WB21-containing tablets was performed in eight healthy volunteers. The participants took L. salivarius WB21-containing tablets (2.0 × 10(9) colony forming units/day) for 2 weeks, and the numbers of mutans streptococci in saliva were counted. The levels of mutans streptococci seemed to decrease in the L. salivarius WB21, TI 2711, and Ovalgen® DC groups compared to the xylitol group, with no significant differences between the groups. Lactobacilli levels significantly increased in the L. salivarius WB21 and TI 2711 groups compared to the other groups. Concerning salivary flow and salivary pH, no significant differences were observed between the groups. The salivary buffering capacity significantly increased in the L. salivarius TI 2711 group (P = 0.003) and Ovalgen® DC group (P = 0.002) compared to the xylitol group. The short-term administration trial showed that the L. salivarius WB21-containing tablets significantly decreased the number of mutans streptococci (P = 0.039). L. salivarius-containing tablets were suggested to increase resistance to caries risk factors. UMIN000013160 (registration date: February 14, 2014).

  17. STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

    Science.gov (United States)

    Chibaudel, Benoist; Bonnetain, Franck; Tournigand, Christophe; de Larauze, Marine Hug; de Gramont, Armand; Laurent-Puig, Pierre; Paget, Jérôme; Hadengue, Alexandra; Notelet, Dominique; Benetkiewicz, Magdalena; André, Thierry; de Gramont, Aimery

    2015-07-04

    The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013

  18. A comparison between intravenous lidocaine and ketamine on acute and chronic pain after open nephrectomy: A prospective, double-blind, randomized, placebo-controlled study

    Science.gov (United States)

    Jendoubi, Ali; Naceur, Imed Ben; Bouzouita, Abderrazak; Trifa, Mehdi; Ghedira, Salma; Chebil, Mohamed; Houissa, Mohamed

    2017-01-01

    Background: Recently, there has been increasing interest in the use of analgesic adjuncts such as intravenous (IV) ketamine and lidocaine. Objectives: To compare the effects of perioperative IV lidocaine and ketamine on morphine requirements, pain scores, quality of recovery, and chronic pain after open nephrectomy. Study Design: A prospective, randomized, placebo-controlled, double-blind trial. Settings: The study was conducted in Charles Nicolle University Hospital of Tunis. Methods: Sixty patients were randomly allocated to receive IV lidocaine: bolus of 1.5 mg/kg at the induction of anesthesia followed by infusion of 1 mg/kg/h intraoperatively and for 24 h postoperatively or ketamine: bolus of 0.15 mg/kg followed by infusion of 0.1 mg/kg/h intraoperatively and for 24 h postoperatively or an equal volume of saline (control group [CG]). Measurements: Morphine consumption, visual analog scale pain scores, time to the first passage of flatus and feces, postoperative nausea and vomiting (PONV), 6-min walk distance (6MWD) at discharge, and the incidence of chronic neuropathic pain using the “Neuropathic Pain Questionnaire” at 3 months. Results: Ketamine and lidocaine reduced significantly morphine consumption (by about 33% and 42%, respectively) and pain scores compared with the CG (P Lidocaine and ketamine also significantly improved bowel function in comparison to the CG (P lidocaine group (P Lidocaine, but not ketamine, reduced significantly the development of neuropathic pain at 3 months (P lidocaine are safe and effective adjuvants to decrease opioid consumption and control early pain. We also suggest that lidocaine infusion serves as an interesting alternative to improve the functional walking capacity and prevent chronic neuropathic pain at 3 months after open nephrectomy. PMID:28442956

  19. Open- and Closed-Skill Exercise Interventions Produce Different Neurocognitive Effects on Executive Functions in the Elderly: A 6-Month Randomized, Controlled Trial

    Directory of Open Access Journals (Sweden)

    Chia-Liang Tsai

    2017-09-01

    Full Text Available This study aimed to explore the effects of open- and closed-skill exercise interventions on the neurocognitive performance of executive functions in the elderly. Sixty-four healthy elderly males were randomly assigned to either a closed-skill (bike riding or brisk walking/jogging, n = 22, open-skill (table tennis, n = 21, or control (n = 21 group. Various neuropsychological [e.g., accuracy rates (AR and reaction time (RT] and electrophysiological [e.g., event-related potential (ERP P3 component] measures were assessed during a variant of the task-switching paradigm, as well as an N-back task at baseline and after either a 6-month exercise intervention or control period. The results showed that, when performing the task-switching paradigm, the two exercise groups relative to control group showed significantly faster RTs in the switch trials after the exercise intervention. However, the RT facilitation in the non-switch and switch trials post-exercise relative to pre-exercise only emerged in the open-skill group. In terms of the N-back task, the two exercise groups significantly increased ARs in the 1-back condition after the exercise intervention, and the beneficial AR effect on the 2-back condition only emerged in the closed-skill group. In addition, the two exercise groups exhibited significantly larger P3 amplitudes on the frontal-to-parietal cortex areas after the exercise intervention relative to the baseline when performing the two cognitive tasks. These neurocognitive results still remained unchanged even when the confounding factors (e.g., cardiorespiratory fitness, social participation, and BMI were controlled for. The present study concluded that, although 6-month open- and closed-skill exercise interventions facilitate overall electrophysiological effects (i.e., increased ERP P3 amplitudes on the frontal-to-parietal cortices in the elderly, the two exercise modes produced different levels of neuropsychologically beneficial effects on

  20. Perioperative and long-term results after left pancreatectomy: a single-institution, non-randomized, comparative study between open and laparoscopic approach.

    Science.gov (United States)

    Butturini, Giovanni; Partelli, Stefano; Crippa, Stefano; Malleo, Giuseppe; Rossini, Roberto; Casetti, Luca; Melotti, Gian Luigi; Piccoli, Micaela; Pederzoli, Paolo; Bassi, Claudio

    2011-09-01

    Laparoscopic left pancreatic resections are being increasingly performed. In this study, we provide a nonrandomized comparison between laparoscopic and open left pancreatectomy (OLP) for benign and borderline tumors, focusing on both perioperative and long-term results. Demographic, pathologic, and perioperative details from patients who underwent laparoscopic and OLP between 1999 and 2006 were retrieved from our database and analyzed. Long-term results, including resume to full-time work, occurrence of incisional hernias, and incidence of exocrine and endocrine insufficiency also were evaluated. A total of 116 patients were included in the analysis; 43 (37.1%) were managed laparoscopically and 73 (62.9%) underwent the open procedure. There were no significant differences regarding clinical and pathological data. All of the resections attempted laparoscopically were completed. The rate of splenic preservation was significantly higher in the laparoscopic group (P = 0.0001). Postoperative outcomes were similar between the two groups. Longitudinal comparison between two time periods (1999-June 2004 vs. July 2004-2006) showed that pancreatic fistula and hospital stay significantly diminished over time in the laparoscopic group (P = 0.04 and P = 0.004, respectively). Median follow-up was 53 months. The incidence of exocrine insufficiency and incisional hernias was significantly higher after open resections (both P = 0.05). After hospital discharge, median time to resume full-time work was 6 weeks in the open group and 3 weeks after laparoscopic resections (P < 0.0001). Laparoscopy also resulted as an independent factor for an early resume to full-time activities in the multivariate analysis (P < 0.0001). Laparoscopic left pancreatectomy is a safe procedure for benign and borderline tumors, with similar perioperative outcomes compared with the open procedure. In the long term, the laparoscopic approach is likely to be superior thanks to a more rapid resume

  1. Pharmacokinetic interaction between udenafil and dapoxetine: a randomized, open-labeled crossover study in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-02-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Hyeong-Seok Lim,1 Mi Young Bahng,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, 2Clinical Development Department, Dong-A ST Co, Ltd, Seoul, Republic of Korea Background: “Udenafil” is a phosphodiesterase-5 inhibitor indicated for erectile dysfunction. “Dapoxetine” is a serotonin transport inhibitor indicated for premature ejaculation. The aim of the study reported here was to investigate the pharmacokinetic drug interaction between udenafil and dapoxetine in healthy male subjects. Methods: An open-label, three-treatment, six-sequence, three-period crossover study was performed in healthy male subjects. In varying sequences, each subjects received single oral doses of udenafil 200 mg, dapoxetine 60 mg, and both treatments. The periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 hours after dosing. The plasma concentrations of udenafil and dapoxetine were determined using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by non-compartmental analysis. Tolerability was assessed throughout the study. Results: Twenty-three healthy subjects completed the study. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for udenafil were 0.923 (90% confidence interval [CI]: 0.863–0.987 and 0.864 (90% CI: 0.789–0.947, respectively. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for dapoxetine were 1.125 (90% CI: 1.044–1.213 and 0.837 (90% CI: 0.758–0.925, respectively. There were no serious adverse events reported, and none of the subjects dropped out due to adverse events

  2. Random Poly(Amino Acids Synthesized by Ring Opening Polymerization as Additives in the Biomimetic Mineralization of CaCO3

    Directory of Open Access Journals (Sweden)

    Vladimir Dmitrovic

    2012-05-01

    Full Text Available Biominerals such as bones, teeth and seashells, very often have advanced material properties and are a source of inspiration for material chemists. As in biological systems acidic proteins play an important role in regulating the formation of CaCO3 biominerals, we employ poly(amino acids to mimic the processes involved in the laboratory. Here we report on the synthesis of random aminoacid copolymers of glutamic acid (Glu, lysine (Lys and alanine (Ala using the ring opening polymerization (ROP of their respective N-carboxy anhydrides (NCA. The synthetic approach yields a series of polymers with different monomer composition but with similar degrees of polymerization (DP 45–56 and comparable polydispersities (PDI 1.2–1.6. Using random copolymers we can investigate the influence of composition on the activity of the polymers without having to take into account the effects of secondary structure or specific sequences. We show that variation of the Glu content of the polymer chains affects the nucleation and thereby also the particle size. Moreover, it is shown that the polymers with the highest Glu content affect the kinetics of mineral formation such that the first precipitate is more soluble than in the case of the control.

  3. Effects of Qianlie'an(前列安) Suppository in Patients with Chronic Prostatitis Syndrome: A Randomized Open-Labelled Prospective and Controlled Trial

    Institute of Scientific and Technical Information of China (English)

    邢俊平; 陈兴发; 杨志尚; 王明珠; 贺大林

    2003-01-01

    Objective: To evaluate the clinical efficacy of Qianlie'an(前列安,QLA) suppository via anal route administration in treating chronic prostatitis syndrome. Methods: A randomized open-labelled prospective controlled trial was carried out. The total of 120 patients with chronic prostatitis syndrome were randomly divided into 2 groups: 60 patients in the treated group who were treated with QLA suppository combined with ofloxacin, and the other 60 patients in the control group who were given ofloxacin alone. The efficacy was evaluated by WBC count in the expressed prostatic secretion (EPS) and the Chronic Prostatitis Symptom Index (CPSI) made by the National Institute of Health (NIH). The clinical effects were also observed in a 4-week follow-up. Results: All but six cases completed the trial and the follow-up.It showed that in the treated group recovery rate was 17. 2%, markedly effective rate 34. 5%, effective rate 32.8%, total markedly effective rate 51.7%, and total effective rate 84. 5%, all of which were superior to those in the control group (total markedly effective rate 32.1% and total effective rate 66.1%, respectively), P<0.01. Conclusion: Administration of QLA suppository via anal route combined with oral antibiotics is an effective therapy for chronic prostatitis syndrome. It can relieve the symptoms of chronic prostatitis syndrome markedly and rapidly. It is a new choice for treatment of the disease.

  4. Comparison of Low-Dose Rosuvastatin with Atorvastatin in Lipid-Lowering Efficacy and Safety in a High-Risk Pakistani Cohort: An Open-Label Randomized Trial

    Directory of Open Access Journals (Sweden)

    Abdul Rehman Arshad

    2014-01-01

    Full Text Available Background. Treatment of hyperlipidemia is helpful in both primary and secondary prevention of coronary heart disease and stroke. Aim. To compare lipid-lowering efficacy of rosuvastatin with atorvastatin. Methodology. This open-label randomized controlled trial was carried out at 1 Mountain Medical Battalion from September 2012 to August 2013 on patients with type 2 diabetes, hypertension, myocardial infarction, or stroke, meriting treatment with a statin. Those with secondary causes of dyslipidemia were excluded. Blood samples for estimation of serum total cholesterol, triglycerides, HDL-C, and LDL-C were collected after a 12-hour fast. Patients were randomly allocated to receive either atorvastatin 10 mg HS or rosuvastatin 5 mg HS daily. Lipid levels were rechecked after six weeks. Results. Atorvastatin was used in 63 patients and rosuvastatin in 66. There was a greater absolute and percent reduction in serum LDL-C levels with rosuvastatin as compared to atorvastatin (0.96 versus 0.54 mg/dL; P=0.011 and 24.34 versus 13.66%; P=0.045, whereas reduction in all other fractions was equal. Myalgias were seen in 5 (7.94% patients treated with atorvastatin and 8 (12.12% patients treated with rosuvastatin (P: 0.432. Conclusion. Rosuvastatin produces a greater reduction in serum LDL-C levels and should therefore be preferred over atorvastatin.

  5. The effects of orally administered Beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study.

    Directory of Open Access Journals (Sweden)

    Jenneke Leentjens

    Full Text Available RATIONALE: To prevent or combat infection, increasing the effectiveness of the immune response is highly desirable, especially in case of compromised immune system function. However, immunostimulatory therapies are scarce, expensive, and often have unwanted side-effects. β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models. Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use. METHODS: We performed a randomized open-label intervention pilot-study in 15 healthy male volunteers. Subjects were randomized to either the β -glucan (n = 10 or the control group (n = 5. Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days. Blood was sampled at various time-points to determine β-glucan serum levels, perform ex vivo stimulation of leukocytes, and analyze microbicidal activity. RESULTS: β-glucan was barely detectable in serum of volunteers at all time-points. Furthermore, neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered β-glucan. CONCLUSION: The present study does not support the use of oral β-glucan to enhance innate immune responses in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT01727895.

  6. HEAD - TO - HEAD COMPARISON OF TOLERABILITY AND ACCEPTABILITY OF SINGLE DOSE OF FOUR TOPICAL NSAIDS IN PATIENTS UNDERGOING CATARACT SURGERY : A RANDOMIZED OPEN LABEL PARALLEL GROUP STUDY

    Directory of Open Access Journals (Sweden)

    Chandra Sekhar

    2015-07-01

    Full Text Available INTRODUCTION : Ophthalmic NSAIDs are used to control pain , discomfort and inflammation associated with ocular conditions and also , following ophthalmic cataract surgeries. These drugs can cause ocular discomfort following administration which lasts for a short duration. However , there exist differences in the intensity and duration of burning sensation among the c ommonly used ophthalmic NSAIDs. Hence , we evaluated the tolerability and acceptability of four topical NSAIDS i.e. , 0.3% nepafenac (N , 0.5% ketorolac (K , 0.4% ketorolac (K LS and 0.09% bromfenac (B after instilling a single drop. METHODS: This randomized , open label , parallel group study was conducted in the department of Ophthalmology in Narayana Medical College , Nellore. A total number of 80 patients participated in the study. Randomization list was computer generated in a ratio of 1:1:1:1 of N , K , K L Sand B. Each patient received one drop of the study drug either in right or left eye which was also decidedat random.Patients of either gender above21 years of age , having no ocular surface pathology and eligible for cataract surgery were include d in the study. Outcome variables included ocular burning intensity on VAS (0 - 100 mm at 0 min (immediately , 2 min and 6 min after administration of medications , time to complete pain relief and global medication performance rated by patient as 0 (bad , 1 (fair , 2(good or 3 (severe . RESULTS: The mean age of patients was 52.85±17.46 years. All groups were age matched , however there were more females than males (pN>K LS >K on global medication performance. CONCLUSION: Bromfenac had better tolerability and acceptability as compared to other tested topical NSAIDs , which was in the order of B>N> K LS >K.

  7. Clarithromycin Plus Intravenous Immunoglobulin Therapy Can Reduce the Relapse Rate of Kawasaki Disease: A Phase 2, Open-Label, Randomized Control Study.

    Science.gov (United States)

    Nanishi, Etsuro; Nishio, Hisanori; Takada, Hidetoshi; Yamamura, Kenichiro; Fukazawa, Mitsuharu; Furuno, Kenji; Mizuno, Yumi; Saigo, Kenjiro; Kadoya, Ryo; Ohbuchi, Noriko; Onoe, Yasuhiro; Yamashita, Hironori; Nakayama, Hideki; Hara, Takuya; Ohno, Takuro; Takahashi, Yasuhiko; Hatae, Ken; Harada, Tatsuo; Shimose, Takayuki; Kishimoto, Junji; Ohga, Shouichi; Hara, Toshiro

    2017-07-06

    We previously reported that biofilms and innate immunity contribute to the pathogenesis of Kawasaki disease. Therefore, we aimed to assess the efficacy of clarithromycin, an antibiofilm agent, in patients with Kawasaki disease. We conducted an open-label, multicenter, randomized, phase 2 trial at 8 hospitals in Japan. Eligible patients included children aged between 4 months and 5 years who were enrolled between days 4 and 8 of illness. Participants were randomly allocated to receive either intravenous immunoglobulin (IVIG) or IVIG plus clarithromycin. The primary end point was the duration of fever after the initiation of IVIG treatment. Eighty-one eligible patients were randomized. The duration of the fever did not differ between the 2 groups (mean±SD, 34.3±32.4 and 31.1±31.1 hours in the IVIG plus clarithromycin group and the IVIG group, respectively [P=0.66]). The relapse rate of patients in the IVIG plus clarithromycin group was significantly lower than that in the IVIG group (12.5% versus 30.8%, P=0.046). No serious adverse events occurred during the study period. In a post hoc analysis, the patients in the IVIG plus clarithromycin group required significantly shorter mean lengths of hospital stays than those in the IVIG group (8.9 days versus 10.3 days, P=0.049). Although IVIG plus clarithromycin therapy failed to shorten the duration of fever, it reduced the relapse rate and shortened the duration of hospitalization in patients with Kawasaki disease. URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000015437. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  8. All-arthroscopic versus mini-open repair of small or moderate-sized rotator cuff tears: A protocol for a randomized trial [NCT00128076

    Directory of Open Access Journals (Sweden)

    Razmjou Helen

    2006-03-01

    Full Text Available Abstract Background Rotator cuff tears are the most common source of shoulder pain and disability. Only poor quality studies have compared mini-open to arthroscopic repair, leaving surgeons with inadequate evidence to support optimal, minimally-invasive repair. Methods/Design This randomized, multi-centre, national trial will determine whether an arthroscopic or mini-open repair provides better quality of life for patients with small or moderate-sized rotator cuff tears. A national consensus meeting of investigators in the Joint Orthopaedic Initiative for National Trials of the Shoulder (JOINTS Canada identified this question as the top priority for shoulder surgeons across Canada. The primary outcome measure is a valid quality-of-life scale (Western Ontario Rotator Cuff (WORC that addresses 5 domains of health affected by rotator cuff disease. Secondary outcomes will assess rotator cuff functionality (ROM, strength, Constant score, secondary dimensions of health (general health status (SF-12 and work limitations, and repair integrity (MRI. Outcomes are measured at baseline, at 6 weeks, 3, 6, 12, and 24 months post-operatively by blinded research assistants and musculoskeletal radiologists. Patients (n = 250 with small or medium-sized cuff tears identified by clinical examination and MRI who meet eligibility criteria will be recruited. This sample size will provide 80% power to statistically detect a clinically important difference of 20% in WORC scores between procedures after controlling for baseline WORC score (α = 0.05. A central methods centre will manage randomization, data management, and monitoring under supervision of experienced epidemiologists. Surgeons will participate in either conventional or expertise-based designs according to defined criteria to avoid biases from differential surgeon expertise. Mini-open or all-arthroscopic repair procedures will be performed according to a standardized protocol. Central Adjudication (of cases

  9. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study

    Science.gov (United States)

    Canaud, Bernard; Mingardi, Giulio; Braun, Johann; Aljama, Pedro; Kerr, Peter G.; Locatelli, Francesco; Villa, Giuseppe; Van Vlem, Bruno; McMahon, Alan W.; Kerloëguen, Cécile; Beyer, Ulrich

    2008-01-01

    Background. Extending the administration interval of erythropoiesis-stimulating agents (ESAs) represents an opportunity to improve the efficiency of anaemia management in patients with chronic kidney disease (CKD). However, effective haemoglobin (Hb) maintenance can be challenging with epoetin alfa and epoetin beta administered at extended intervals. C.E.R.A., a continuous erythropoietin receptor activator, has a unique pharmacologic profile and long half-life (∼130 h), allowing administration at extended intervals. Phase III results have demonstrated that C.E.R.A. administered once every 4 weeks effectively maintains stable Hb levels in patients with CKD on dialysis. Methods. STRIATA (Stabilizing haemoglobin TaRgets in dialysis following IV C.E.R.A. Treatment for Anaemia) was a multicentre, open-label randomized phase III study to evaluate the efficacy and safety of intravenous C.E.R.A. administered once every 2 weeks (Q2W) for Hb maintenance following direct conversion from darbepoetin alfa (DA). Adult patients on dialysis receiving stable intravenous DA once weekly (QW) or Q2W were randomized (1:1) to continue their current DA regimen (n = 156) or receive intravenous C.E.R.A. Q2W (n = 157) for 52 weeks. Doses were adjusted to maintain Hb levels within ± 1.0 g/dl of baseline and between 10.0 and 13.5 g/dl. The primary endpoint was the mean Hb change between baseline and the evaluation period (weeks 29–36). Results. Most patients (>80%) received DA QW before randomization. The mean (95% CI) difference between C.E.R.A. and DA in the primary endpoint was 0.18 g/dl (−0.05, 0.41), within a pre-defined non-inferiority limit. C.E.R.A. was clinically non-inferior to DA (P < 0.0001) in maintaining Hb levels. Both treatments were well tolerated. Conclusions. Stable Hb levels were successfully maintained in patients on haemodialysis directly converted to Q2W intravenous C.E.R.A. from DA. PMID:18586762

  10. Pharmacokinetics of multiple doses of Co-Crystal of Tramadol-Celecoxib: findings from a 4-way randomized open-label Phase I clinical trial.

    Science.gov (United States)

    Videla, Sebastián; Lahjou, Mounia; Vaqué, Anna; Sust, Mariano; Escriche, Marisol; Soler, Lluis; Sans, Artur; Sicard, Eric; Gascón, Neus; Encina, Gregorio; Plata-Salamán, Carlos

    2017-09-09

    We compared the pharmacokinetic (PK) profiles of Co-Crystal of Tramadol-Celecoxib (CTC) versus each reference product (alone and in open combination) after single (first dose) and multiple dosing. Healthy adults aged 18-50 years received, under fasted conditions, 15 twice-daily doses of the following treatments (separated by ≥14-day wash-out): 200 mg immediate-release (IR) CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment-1); 100 mg IR tramadol (Treatment-2), 100 mg celecoxib (Treatment-3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment-4). Treatment sequence was assigned by computer-generated randomization. PK parameters were calculated using non-compartmental analysis. Parameters for CTC were adjusted according to reference product dose. Thirty subjects (20 males, mean age 35 years) were included. Multiple-dose tramadol PK parameters for Treatments-1, -2 and -4, respectively, were 551, 632 and 661 ng ml(-1) (mean maximum plasma concentration [Cmax ]); 4796, 4990 and 5284 ng h ml(-1) (area under the plasma concentration-time curve over the dosing interval at steady state); and 3.0, 2.0 and 2.0 h (median time to Cmax at steady state). For Treatments-1, -3 and -4, multiple-dose celecoxib PK parameters were 445, 536 and 396 ng ml(-1) ; 2803, 3366 and 2897 ng h ml(-1) ; and 2.0, 2.0 and 3.0 h. Single-dose findings were consistent with multiple-dose data. Types of adverse events were consistent with known reference product safety profiles. After single (first dose) and multiple dosing, PK parameters of each active pharmaceutical ingredient in CTC were modified by co-crystallization compared with reference products alone or in open combination. This article is protected by copyright. All rights reserved.

  11. A randomized trial in a massive online open course shows people don’t know what a statistically significant relationship looks like, but they can learn

    Directory of Open Access Journals (Sweden)

    Aaron Fisher

    2014-10-01

    Full Text Available Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online course (MOOC. Each subject was shown a random set of scatterplots and asked to visually determine if the underlying relationships were statistically significant at the P < 0.05 level. Subjects correctly classified only 47.4% (95% CI [45.1%–49.7%] of statistically significant relationships, and 74.6% (95% CI [72.5%–76.6%] of non-significant relationships. Adding visual aids such as a best fit line or scatterplot smooth increased the probability a relationship was called significant, regardless of whether the relationship was actually significant. Classification of statistically significant relationships improved on repeat attempts of the survey, although classification of non-significant relationships did not. Our results suggest: (1 that evidence-based data analysis can be used to identify weaknesses in theoretical procedures in the hands of average users, (2 data analysts can be trained to improve detection of statistically significant results with practice, but (3 data analysts have incorrect intuition about what statistically significant relationships look like, particularly for small effects. We have built a web tool for people to compare scatterplots with their corresponding p-values which is available here: http://glimmer.rstudio.com/afisher/EDA/.

  12. A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

    Science.gov (United States)

    Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

    2005-08-01

    Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

  13. Hand washing with soap and water together with behavioural recommendations prevents infections in common work environment: an open cluster-randomized trial.

    Science.gov (United States)

    Savolainen-Kopra, Carita; Haapakoski, Jaason; Peltola, Piia A; Ziegler, Thedi; Korpela, Terttu; Anttila, Pirjo; Amiryousefi, Ali; Huovinen, Pentti; Huvinen, Markku; Noronen, Heikki; Riikkala, Pia; Roivainen, Merja; Ruutu, Petri; Teirilä, Juha; Vartiainen, Erkki; Hovi, Tapani

    2012-01-16

    Hand hygiene is considered as an important means of infection control. We explored whether guided hand hygiene together with transmission-limiting behaviour reduces infection episodes and lost days of work in a common work environment in an open cluster-randomized 3-arm intervention trial. A total of 21 clusters (683 persons) were randomized to implement hand hygiene with soap and water (257 persons), with alcohol-based hand rub (202 persons), or to serve as a control (224 persons). Participants in both intervention arms also received standardized instructions on how to limit the transmission of infections. The intervention period (16 months) included the emergence of the 2009 influenza pandemic and the subsequent national hand hygiene campaign influencing also the control arm. In the total follow-up period there was a 6.7% reduction of infection episodes in the soap-and water arm (p = 0.04). Before the onset of the anti-pandemic campaign, a statistically significant (p = 0.002) difference in the mean occurrence of infection episodes was observed between the control (6.0 per year) and the soap-and-water arm (5.0 per year) but not between the control and the alcohol-rub arm (5.6 per year). Neither intervention had a decreasing effect on absence from work. We conclude that intensified hand hygiene using water and soap together with behavioural recommendations can reduce the occurrence of self-reported acute illnesses in common work environment. Surprisingly, the occurrence of reported sick leaves also increased in the soap-and water-arm. ClinicalTrials.gov: NCT00981877 The Finnish Work Environment Fund and the National Institute for Health and Welfare.

  14. Hand washing with soap and water together with behavioural recommendations prevents infections in common work environment: an open cluster-randomized trial

    Directory of Open Access Journals (Sweden)

    Savolainen-Kopra Carita

    2012-01-01

    Full Text Available Abstract Background Hand hygiene is considered as an important means of infection control. We explored whether guided hand hygiene together with transmission-limiting behaviour reduces infection episodes and lost days of work in a common work environment in an open cluster-randomized 3-arm intervention trial. Methods A total of 21 clusters (683 persons were randomized to implement hand hygiene with soap and water (257 persons, with alcohol-based hand rub (202 persons, or to serve as a control (224 persons. Participants in both intervention arms also received standardized instructions on how to limit the transmission of infections. The intervention period (16 months included the emergence of the 2009 influenza pandemic and the subsequent national hand hygiene campaign influencing also the control arm. Results In the total follow-up period there was a 6.7% reduction of infection episodes in the soap-and water arm (p = 0.04. Before the onset of the anti-pandemic campaign, a statistically significant (p = 0.002 difference in the mean occurrence of infection episodes was observed between the control (6.0 per year and the soap-and-water arm (5.0 per year but not between the control and the alcohol-rub arm (5.6 per year. Neither intervention had a decreasing effect on absence from work. Conclusions We conclude that intensified hand hygiene using water and soap together with behavioural recommendations can reduce the occurrence of self-reported acute illnesses in common work environment. Surprisingly, the occurrence of reported sick leaves also increased in the soap-and water-arm. Trial Registration ClinicalTrials.gov: NCT00981877 Source of funding The Finnish Work Environment Fund and the National Institute for Health and Welfare.

  15. Hand washing with soap and water together with behavioural recommendations prevents infections in common work environment: an open cluster-randomized trial

    Science.gov (United States)

    2012-01-01

    Background Hand hygiene is considered as an important means of infection control. We explored whether guided hand hygiene together with transmission-limiting behaviour reduces infection episodes and lost days of work in a common work environment in an open cluster-randomized 3-arm intervention trial. Methods A total of 21 clusters (683 persons) were randomized to implement hand hygiene with soap and water (257 persons), with alcohol-based hand rub (202 persons), or to serve as a control (224 persons). Participants in both intervention arms also received standardized instructions on how to limit the transmission of infections. The intervention period (16 months) included the emergence of the 2009 influenza pandemic and the subsequent national hand hygiene campaign influencing also the control arm. Results In the total follow-up period there was a 6.7% reduction of infection episodes in the soap-and water arm (p = 0.04). Before the onset of the anti-pandemic campaign, a statistically significant (p = 0.002) difference in the mean occurrence of infection episodes was observed between the control (6.0 per year) and the soap-and-water arm (5.0 per year) but not between the control and the alcohol-rub arm (5.6 per year). Neither intervention had a decreasing effect on absence from work. Conclusions We conclude that intensified hand hygiene using water and soap together with behavioural recommendations can reduce the occurrence of self-reported acute illnesses in common work environment. Surprisingly, the occurrence of reported sick leaves also increased in the soap-and water-arm. Trial Registration ClinicalTrials.gov: NCT00981877 Source of funding The Finnish Work Environment Fund and the National Institute for Health and Welfare. PMID:22243622

  16. Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Yu Chih-Chieh

    2012-05-01

    Full Text Available Abstract Background Reducing low-density lipoprotein cholesterol (LDL-C is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83 to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026 and total cholesterol (20.8% vs 12.2%, p = 0.0003. Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6% vs doubling statin (41.2%, but the difference was not statistically significant (p = 0.1675. The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327

  17. Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects.

    Science.gov (United States)

    Valentino, L A; Rusen, L; Elezovic, I; Smith, L M; Korth-Bradley, J M; Rendo, P

    2014-05-01

    Few randomized studies have reported on the use of factor IX (FIX) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX, nonacog alfa, compared with on-demand therapy. Male subjects aged 6-65 years with severe or moderately severe haemophilia B (FIX:C ≤ 2, n = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open-label, four-period crossover trial. The primary measure was the annualized bleeding rate (ABR) of two prophylactic regimens vs. on-demand therapy. In the intent-to-treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on-demand period, the 50 IU kg(-1) twice-weekly period, and the 100 IU kg(-1) once-weekly period respectively. Differences in ABR between the first on-demand period and both prophylaxis regimens were significant (P < 0.0001); no significant differences were observed between prophylaxis regimens (P = 0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50 IU kg(-1) twice weekly or 100 IU kg(-1) once weekly reduced ABR by 89.4% relative to on-demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B.

  18. Efficacy of a standardized herbal preparation (Roidosanal® in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

    Directory of Open Access Journals (Sweden)

    Kapil Aggrawal

    2014-01-01

    Full Text Available Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal® , in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III were randomly assigned to receive either Roidosanal® (Gr R; n = 37 or Daflon® 500 mg (Gr D; n = 36, for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended.

  19. Effect of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes: A 1-year, open-label randomized study

    Directory of Open Access Journals (Sweden)

    Mohammad Shafi Kuchay

    2015-01-01

    Full Text Available Background: Whether Vitamin D supplementation in prediabetes subjects prevents the development of diabetes is a matter of debate, and the results are inconsistent. This open-label, randomized study in subjects with prediabetes evaluated the effect of 12 months of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes in an ethnically homogeneous Kashmiri population. Materials and Methods: A total of 147 subjects were diagnosed as prediabetes out of which 137 subjects were randomized to receive in addition to standard lifestyle measures, either Vitamin D 60,000 IU weekly for 4 weeks and then 60,000 IU monthly (n = 69 or no Vitamin D (n = 68. Fasting plasma glucose (FPG, 2-h plasma glucose and A1C levels were estimated at 0, 6 and 12 months. Changes in FPG, 2-h plasma glucose, A1C level and the proportion of subjects developing diabetes were assessed among 129 subjects. Results: At 12 months, A1C levels were significantly lesser (5.7% ± 0.4% in the Vitamin D supplemented group when compared with non-Vitamin D supplemented (6.0% ± 0.3%. Similarly, FPG (97 ± 7 and 2-h plasma glucose (132 ± 16 were significantly less in Vitamin D supplemented group as compared with non-Vitamin D supplemented group (FPG = 116 ± 6 and 2-h plasma glucose = 157 ± 25 at 12 months. Nine out of 65 in non-Vitamin D supplemented and seven out of 64 in the Vitamin D supplemented group developed diabetes. Conclusions: Vitamin D supplementation in prediabetes subjects significantly lowered FPG, 2-h plasma glucose and A1C levels.

  20. Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in northern Cambodia: an open-label randomized trial.

    Directory of Open Access Journals (Sweden)

    Chanthap Lon

    Full Text Available Emerging antimalarial drug resistance in mobile populations remains a significant public health concern. We compared two regimens of dihydroartemisinin-piperaquine in military and civilians on the Thai-Cambodian border to evaluate national treatment policy.Efficacy and safety of two and three-day regimens of dihydroartemisinin-piperaquine were compared as a nested open-label evaluation within a malaria cohort study in 222 otherwise healthy volunteers (18% malaria-infected at baseline. The first 80 volunteers with slide-confirmed Plasmodium falciparum or vivax malaria were randomized 1:1 to receive either regimen (total dose 360 mg dihydroartemisinin and 2880 mg piperaquine and followed weekly for up to 6 months. The primary endpoint was malaria recurrence by day 42. Volunteers with vivax infection received primaquine at study discharge with six months follow-up.Eighty patients (60 vivax, 15 falciparum, and 5 mixed were randomized to dihydroartemisinin-piperaquine. Intention-to-treat all-species efficacy at Day 42 was 85% for the two-day regimen (95% CI 69-94 and 90% for the three-day regimen (95% CI 75-97. PCR-adjusted falciparum efficacy was 75% in both groups with nearly half (45% still parasitemic at Day 3. Plasma piperaquine levels were comparable to prior published reports, but on the day of recrudescence were below measurable in vitro piperaquine IC50 levels in all falciparum treatment failures.In the brief period since introduction of dihydroartemisinin-piperaquine, there is early evidence suggesting declining efficacy relative to previous reports. Parasite IC50 levels in excess of plasma piperaquine levels seen only in treatment failures raises concern for clinically significant piperaquine resistance in Cambodia. These findings warrant improved monitoring of clinical outcomes and follow-up, given few available alternative drugs.ClinicalTrials.gov NCT01280162.

  1. Comparative efficacy trial of cupping and serkangabin versus conventional therapy of migraine headaches: A randomized, open-label, comparative efficacy trial

    Directory of Open Access Journals (Sweden)

    Mohammad Dehghani Firoozabadi

    2014-01-01

    Full Text Available Background: Migraine headaches are the most common acute and recurrent headaches. Current treatment of a migraine headache consists of multiple medications for control and prevention of recurrent attacks. Global emergence of alternative medicine led us to examine the efficacy of cupping therapy plus serkangabin syrup in the treatment of migraine headaches. Materials and Methods: This study was a randomized, controlled, open-label, comparative efficacy trial. We randomly assigned patients with migraine into cupping therapy plus serkangabin group (30 patients and conventional treatment group (30 patients. An investigator assessed the severity of headache, frequency of attacks in a week and duration of attacks per hour in 5 visits (at the end of 2 weeks, 1, 3 and 6 months. Generalized estimating equations approach was used to analyze repeated measures data to compare outcomes in both groups. Results: Average age for cupping therapy group and conventional treatment group were 31.7 (±7.6 and 32.6 (±12.7 years, respectively (P = 0.45. After treatment for 2 weeks; and 1, 3 and 6 months, severity of headache (P = 0.80, frequency of migraine attacks (P = 0.63 and duration of attacks per hours (P = 0.48 were similar in conventional and cupping groups but these symptoms were decreased in each group during the study (P < 0.001. Conclusion: There was no significant difference between cupping plus serkangabin therapy and conventional treatment in the treatment and prophylaxis of migraine. The alternative therapy may be used in cases of drug intolerance, no medication response, and in primary care.

  2. A randomized trial in a massive online open course shows people don't know what a statistically significant relationship looks like, but they can learn.

    Science.gov (United States)

    Fisher, Aaron; Anderson, G Brooke; Peng, Roger; Leek, Jeff

    2014-01-01

    Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online course (MOOC). Each subject was shown a random set of scatterplots and asked to visually determine if the underlying relationships were statistically significant at the P < 0.05 level. Subjects correctly classified only 47.4% (95% CI [45.1%-49.7%]) of statistically significant relationships, and 74.6% (95% CI [72.5%-76.6%]) of non-significant relationships. Adding visual aids such as a best fit line or scatterplot smooth increased the probability a relationship was called significant, regardless of whether the relationship was actually significant. Classification of statistically significant relationships improved on repeat attempts of the survey, although classification of non-significant relationships did not. Our results suggest: (1) that evidence-based data analysis can be used to identify weaknesses in theoretical procedures in the hands of average users, (2) data analysts can be trained to improve detection of statistically significant results with practice, but (3) data analysts have incorrect intuition about what statistically significant relationships look like, particularly for small effects. We have built a web tool for people to compare scatterplots with their corresponding p-values which is available here: http://glimmer.rstudio.com/afisher/EDA/.

  3. A randomized trial in a massive online open course shows people don’t know what a statistically significant relationship looks like, but they can learn

    Science.gov (United States)

    Fisher, Aaron; Anderson, G. Brooke; Peng, Roger

    2014-01-01

    Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online course (MOOC). Each subject was shown a random set of scatterplots and asked to visually determine if the underlying relationships were statistically significant at the P < 0.05 level. Subjects correctly classified only 47.4% (95% CI [45.1%–49.7%]) of statistically significant relationships, and 74.6% (95% CI [72.5%–76.6%]) of non-significant relationships. Adding visual aids such as a best fit line or scatterplot smooth increased the probability a relationship was called significant, regardless of whether the relationship was actually significant. Classification of statistically significant relationships improved on repeat attempts of the survey, although classification of non-significant relationships did not. Our results suggest: (1) that evidence-based data analysis can be used to identify weaknesses in theoretical procedures in the hands of average users, (2) data analysts can be trained to improve detection of statistically significant results with practice, but (3) data analysts have incorrect intuition about what statistically significant relationships look like, particularly for small effects. We have built a web tool for people to compare scatterplots with their corresponding p-values which is available here: http://glimmer.rstudio.com/afisher/EDA/. PMID:25337457

  4. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Ito Mikako

    2011-10-01

    Full Text Available Abstract Background Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Hydrogen effects are ascribed to specific radical-scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also to signal-modulating activities, but the detailed molecular mechanisms still remain elusive. Hydrogen is a safe molecule that is largely produced by intestinal bacteria in rodents and humans, and no adverse effects have been documented. Methods We performed open-label trial of drinking 1.0 liter per day of hydrogen-enriched water for 12 weeks in five patients with progressive muscular dystrophy (PMD, four patients with polymyositis/dermatomyositis (PM/DM, and five patients with mitochondrial myopathies (MM, and measured 18 serum parameters as well as urinary 8-isoprostane every 4 weeks. We next conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10 patients with DM and 12 patients with MM, and measured 18 serum parameters every 4 weeks. Results In the open-label trial, no objective improvement or worsening of clinical symptoms was observed. We, however, observed significant effects in lactate-to-pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum matrix metalloproteinase-3 (MMP3 in PM/DM, and serum triglycerides in PM/DM. In the double-blind trial, no objective clinical effects were observed, but a significant improvement was detected in lactate in MM. Lactate-to-pyruvate ratios in MM and MMP3 in DM also exhibited favorable responses but without statistical significance. No adverse effect was observed in either trial except for hypoglycemic episodes in an insulin

  5. Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial

    Science.gov (United States)

    Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim

    2017-01-01

    The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4–6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Trial

  6. Early versus Late Enteral Feeding in Preterm Intrauterine Growth Restricted Neonates with Antenatal Doppler Abnormalities: An Open-Label Randomized Trial.

    Science.gov (United States)

    Tewari, Vishal Vishnu; Dubey, Sachin Kumar; Kumar, Reema; Vardhan, Shakti; Sreedhar, C M; Gupta, Girish

    2017-03-24

    Enteral feeding in preterm neonates with intrauterine growth restriction (IUGR) and absent or reversed end diastolic flow (AREDF) on umbilical artery (UA) Doppler is delayed owing to an increased risk of necrotizing enterocolitis (NEC). Delaying enteral feeding with longer duration of parenteral nutrition (PN) carries an increased risk of sepsis. To study early versus late feeding in preterm IUGR neonates for time required to attain sufficient feed volume to discontinue PN and increased risk of NEC or feed intolerance (FI). Open-label randomized controlled trial. Tertiary care neonatal unit and fetal-maternal medicine unit in India. Preterm intrauterine growth restricted neonates' ≤32 weeks with AREDF on UA Doppler enrolled from 1 January 2014 to 31 July 2015. Randomized to receive early or late feeding using mothers own or donor breast milk as per a feed initiation and advancement protocol. Time in days required to attain sufficient feed volume allowing discontinuation of PN and incidence of NEC in neonates fed early versus late. There were 77 eligible neonates. Sixty-two neonates were included and stratified as extreme preterm (27-29 weeks) ( n  = 20) and very preterm (30-32 weeks) ( n  = 42). Ten extreme preterm and 21 very preterm neonates were randomized to each early feeding and late feeding arm. There was a significantly faster attainment of sufficient feeds in the early feeding arm of both the stratified groups [extreme preterm: median 14 days (Interquartile range IQR: 12-15) compared with 18 days (IQR: 18-20), hazard ratio (HR): 1.59, 95% CI: 0.626-4.078; very preterm: 12 days (IQR: 10-14) as compared with 16 days (IQR 15-17), HR: 1.89, 95% CI: 1.011-3.555]. There was no difference in the incidence of NEC, FI and combined outcome of NEC and FI. Early feeding in preterm IUGR neonates with AREDF on antenatal UA Doppler allowed earlier discontinuation of PN, allowing birth weight to be regained earlier and did not increase the incidence of NEC and

  7. Randomized open-label phase II study comparing oxycodone-naloxone with oxycodone in early return of gastrointestinal function after laparoscopic colorectal surgery.

    Science.gov (United States)

    Creamer, F; Balfour, A; Nimmo, S; Foo, I; Norrie, J D; Williams, L J; Fearon, K C; Paterson, H M

    2017-01-01

    Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection. In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance. Secondary endpoints included a composite endpoint of gut function (tolerance of solid food, low nausea/vomiting score, passage of flatus or faeces). Eighty-two patients were screened and 62 randomized (76 per cent); the attrition rate was 19 per cent (12 of 62), leaving 50 patients who received the allocated intervention with 100 per cent follow-up and retention (modified intention-to-treat cohort). Protocol compliance was more than 90 per cent. Return of gut function by day 3 was similar in the two groups: 13 (48 per cent) of 27 in the oxycodone-naloxone group and 15 (65 per cent) of 23 in the control group (95 per cent c.i. for difference -10·0 to 40·7 per cent; P = 0·264). However, patients in the oxycodone-naloxone group had a shorter time to first bowel movement (mean(s.d.) 87(38) h versus 111(37) h in the control group; 95 per cent c.i. for difference 2·3 to 45·4 h, P = 0·031) and reduced total (oral plus parenteral) opioid consumption (mean(s.d.) 78(36) versus 94(56) mg respectively; 95 per cent c.i. for difference -10·2 to 42·8 mg, P = 0·222). High participation, retention and protocol compliance confirmed feasibility. Potential benefits of oxycodone-naloxone in reducing time to bowel movement and total opioid consumption could be tested in a randomized trial. Registration number: NCT02109640 (https://www.clinicaltrials.gov/). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  8. Quantification of Valleys of Randomly Textured Substrates as a Function of Opening Angle: Correlation to the Defect Density in Intrinsic nc-Si:H.

    Science.gov (United States)

    Kim, Do Yun; Hänni, Simon; Schüttauf, Jan-Willem; van Swaaij, René A C M M; Zeman, Miro

    2016-08-17

    Optical and electrical properties of hydrogenated nanocrystalline silicon (nc-Si:H) solar cells are strongly influenced by the morphology of underlying substrates. By texturing the substrates, the photogenerated current of nc-Si:H solar cells can increase due to enhanced light scattering. These textured substrates are, however, often incompatible with defect-less nc-Si:H growth resulting in lower Voc and FF. In this study we investigate the correlation between the substrate morphology, the nc-Si:H solar-cell performance, and the defect density in the intrinsic layer of the solar cells (i-nc-Si:H). Statistical surface parameters representing the substrate morphology do not show a strong correlation with the solar-cell parameters. Thus, we first quantify the line density of potentially defective valleys of randomly textured ZnO substrates where the opening angle is smaller than 130° (ρSi:H (ρdefect), which is obtained by fitting external photovoltaic parameters from experimental results and simulations. We confirm that when ρ<130 increases the Voc and FF significantly drops. It is also observed that ρdefect increases following a power law dependence of ρ<130. This result is attributed to more frequently formed defective regions for substrates having higher ρ<130.

  9. Clinical efficacy comparison of Saccharomyces boulardii and yogurt fluid in acute non-bloody diarrhea in children: a randomized, controlled, open label study.

    Science.gov (United States)

    Eren, Makbule; Dinleyici, Ener C; Vandenplas, Yvan

    2010-03-01

    The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 +/- 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, although these differences were not significant. However, diarrhea had resolved in significantly more children on day 3 in the S. boulardii group (48.5% versus 25.5%; P yogurt treatment was cheaper than S. boulardii whereas in hospitalized patients, treatment cost was similar. In conclusion, the effect of daily freshly prepared YF was comparable to S. boulardii in the treatment of acute non-bloody diarrhea in children. The duration of diarrhea was shorter in the S. boulardii group, expressed as a significantly higher number of patients with normal stools on day 3.

  10. Comparing blastocyst quality and live birth rates of intravaginal culture using INVOcell™ to traditional in vitro incubation in a randomized open-label prospective controlled trial.

    Science.gov (United States)

    Doody, Kevin J; Broome, E Jason; Doody, Kathleen M

    2016-04-01

    The purpose of this study is to to compare the efficacy of intravaginal culture (IVC) of embryos in INVOcell™ (INVO Bioscience, MA, USA) to traditional in vitro fertilization (IVF) incubators in a laboratory setting using a mild pre-determined stimulation regimen based solely on anti-mullerian hormone (AMH) and body weight with minimal ultrasound monitoring. The primary endpoint examined was total quality blastocysts expressed as a percentage of total oocytes placed in incubation. Secondary endpoints included percentage of quality blastocysts transferred, pregnancy, and live birth rates. In this prospective randomized open-label controlled single-center study, 40 women aged culture. IVF produced a greater percentage of total quality embryos as compared to IVC (50.6 vs. 30.7 %, p = 0.0007, respectively). There was no significant difference between in IVF and IVC in the percentage of quality blastocysts transferred (97.5 vs. 84.9 %, p = 0.09) or live birth rate (60 % IVF, 55 % IVC). IVF was shown to be superior to IVC in creating quality blastocysts. However, both IVF and IVC produced identical blastocysts for transfer resulting in similar live birth rates. IVC using INVOcell™ is effective and may broaden access to fertility care in selected patient populations by ameliorating the need for a traditional IVF laboratory setting. Further studies will help elucidate the potential physiological, psychological, geographic, and financial impact of IVC on the delivery of fertility care.

  11. Clinical effectiveness and safety of escitalopram and desvenlafaxine in patients of depression with anxiety: a randomized, open-label controlled trial.

    Science.gov (United States)

    Maity, Nabakumar; Ghosal, Malay Kumar; Gupta, Anupam; Sil, Amrita; Chakraborty, Sushmita; Chatterjee, Suparna

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are effective in treating anxiety disorders associated with major depressive disorder (MDD). This randomized, controlled, parallel-group, open-label, phase 4 trial (CTRI/2012/08/002895) was undertaken to compare the effectiveness and safety of desvenlafaxine versus escitalopram, a standard antidepressant. Effectiveness was assessed using the Hamilton Depression Rating Scale (HAM-D17) and Hamilton Anxiety Rating Scale (HAM-A). Response to treatment was assessed by ≥50% decrease of baseline scores (responder rate). Safety and tolerability was evaluated by changes in routine laboratory parameters, vital signs, and adverse events reported by the subject and/or observed by the clinician. Responder rates for both HAM-A and HAM-D scores at 8 weeks were better in the escitalopram group compared to the desvenlafaxine group (HAM-A 76.92% vs. 71.05%; HAM-D 79.48% vs 73.68%) but the differences were not statistically significant (P = 0.59 and P = 0.61). Within group changes of both scores, from baseline to subsequent visits in both treatment arms were statistically significant (P desvenlafaxine was comparable to escitalopram, but escitalopram was better tolerated.

  12. Recombinant fusion ESAT6-CFP10 immunogen as a skin test reagent for tuberculosis diagnosis: an open-label, randomized, two-centre phase 2a clinical trial.

    Science.gov (United States)

    Li, F; Xu, M; Qin, C; Xia, L; Xiong, Y; Xi, X; Fan, X; Gu, J; Pu, J; Wu, Q; Lu, S; Wang, G

    2016-10-01

    We sought to assess the accuracy and safety of the ESAT6-CFP10 reagent in diagnosing tuberculosis (TB) disease. An open-label, randomized phase 2a trial was conducted in 56 healthy adults and 88 TB patients at one medical centre and one teaching hospital in China. All participants received 0.1, 0.5, 1 or 2 μg ESAT6-CFP10 in their right forearm. Moreover, 56 healthy volunteers and 56 patients were given tuberculin-purified protein derivative (TB-PPD) in their left forearm. The remaining 32 patients were administered placebo. The main outcome measure was induration diameter. An enzyme-linked immunospot (ELISPOT) assay was conducted before the skin test. The ESAT6-CFP10 test caused a higher positivity rate than placebo (81.2% (26/32) vs. 3.1% (1/32); p skin test appears to be a safe and promising tool; further testing will confirm its efficacy in identifying TB disease. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Eunice Kazue Kano

    2015-03-01

    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  14. Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy

    Directory of Open Access Journals (Sweden)

    Jahan Ara Ainuddin

    2015-01-01

    Full Text Available Aims. To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. Methods. In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycemic control. The patients were followed up till delivery. Maternal, and perinatal outcomes and pharmacotherapeutic characteristics were recorded on a proforma. Results. Maternal characteristics were comparable in metformin and insulin treated group. 84.9% patients in metformin group required add-on insulin therapy at mean gestational age of 26.58 ± 3.85 weeks. Less maternal weight gain (P24 hours in metformin group (P<0.01. Significant reduction in cost of treatment was found in metformin group. Conclusion. Metformin alone or with add-on insulin is an effective and cheap treatment option for patients with type 2 diabetes in pregnancy. This trial is registered with clinical trial registration number: Clinical trials.gov NCT01855763.

  15. Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema - An open-label randomized controlled trial of efficacy

    NARCIS (Netherlands)

    van Coevorden, AM; Kamphof, WG; van Sonderen, E; Bruynzeel, DP; Coenraads, PJ

    2004-01-01

    Objective: To study whether oral psoralen-UV-A (PUVA) with a portable tanning unit at home is as effective as hospital-administered bath PUVA in patients with chronic hand eczema. Design: Open-label randomized controlled trial, with a 10-week treatment period and an 8-week follow-up period. Setting:

  16. Comparison of the Effect of PRP, PRF and Induced Bleeding in the Revascularization of Teeth with Necrotic Pulp and Open Apex: A Triple Blind Randomized Clinical Trial.

    Science.gov (United States)

    Shivashankar, Vasundara Yayathi; Johns, Dexton Antony; Maroli, Ramesh Kumar; Sekar, Mahalaxmi; Chandrasekaran, Rathinavel; Karthikeyan, Shanmugavel; Renganathan, Senthil Kumar

    2017-06-01

    Treatment of a tooth with necrotic pulp and open apex is a special challenge to the clinicians. Apexification with calcium hydroxide and MTA barrier technique fails to induce continued root maturation which makes the tooth susceptible to root fracture. Hence, an ideal outcome for such a tooth should be regeneration of pulp like tissue into the root canal capable of continuing normal root maturation. This study aims to compare the effect of Platelet Rich Fibrin (PRF), induced bleeding technique and Platelet Rich Plasma (PRP) in the revascularization of tooth with necrotic pulp and open apex. The main objectives of the study were to: (a) Radiographically evaluate the continuation of root development, increase in the dentin wall thickness and narrowing of canal space, apical closure and resolution of the periapical lesion; and to (b) To clinically evaluate the response to pulp sensibility testing and response to percussion and palpation tests. Sixty patients (6 to 28 years) with necrotic immature permanent tooth were randomly categorised into three groups after the root canal disinfection procedure. PRF as scaffolding material (Group A: n=20), revascularization with conventional induced bleeding technique (Group B: n=20), and PRP as the biomaterial (Group C: n=20). The primary outcome variable was measured using Periapical Index (PAI) (for periapical healing), Chen and Chen index (for apical responses), Schei's ruler (for root lengthening and root thickening) and other clinical parameters. The Chi-square test was used to interpret the data among the three groups at the end of 12 months for the variables root lengthening and lateral wall thickness. ANOVA test was performed to compare the mean of the PAI scores of the three groups at preoperative stage and 12 months. If statistically significant, Bonferroni test was done to compare the outcome among the three groups. The significant level was set at pPRF and induced bleeding technique with respect to periapical wound

  17. A randomized control trial to evaluate the effect of adjuvant selective laser trabeculoplasty versus medication alone in primary open-angle glaucoma: preliminary results

    Directory of Open Access Journals (Sweden)

    Lee JWY

    2014-09-01

    Full Text Available Jacky WY Lee,1,2 Catherine WS Chan,2 Mandy OM Wong,3 Jonathan CH Chan,3 Qing Li,2 Jimmy SM Lai2 1The Department of Ophthalmology, Caritas Medical Centre, 2The Department of Ophthalmology, The University of Hong Kong, 3The Department of Ophthalmology, Queen Mary Hospital, Hong Kong Background: The objective of this study was to investigate the effects of adjuvant selective laser trabeculoplasty (SLT versus medication alone on intraocular pressure (IOP control, medication use, and quality of life in patients with primary open-angle glaucoma.Methods: This prospective, randomized control study recruited 41 consecutive primary open-angle glaucoma subjects with medically-controlled IOP ≤21 mmHg. The SLT group (n=22 received a single 360-degree SLT treatment. The medication-only group (n=19 continued with their usual treatment regimen. In both groups, medication was titrated to maintain a target IOP defined as a 25% reduction from baseline IOP without medication, or <18 mmHg, whichever was lower. Outcomes, which were measured at baseline and at 6 months, included the Glaucoma Quality of Life-15 (GQL-15 and Comparison of Ophthalmic Medications for Tolerability (COMTOL survey scores, IOP, and the number of antiglaucoma medicines. Results: The baseline IOP was 15.8±2.7 mmHg and 14.5±2.5 mmHg in the SLT and medication-only groups, respectively (P=0.04. Both groups had a comparable number of baseline medication (P=0.2, GQL-15 (P=0.3 and COMTOL scores (P=0.7. At 6 months, the SLT group had a lower IOP (P=0.03 and required fewer medications compared with both baseline (P<0.0001 and with the medication-only group (P=0.02. There was no statistically significant difference in the 6-month GQL-15 or COMTOL score as compared to baseline (P≥0.4 or between the two treatment groups (P≥0.2.Conclusion: A single session of adjuvant SLT provided further reductions in IOP and medication without substantial changes in quality of life or medication tolerability at 6

  18. An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Martin-Martin LS

    2017-03-01

    Full Text Available LS Martin-Martin,1 F Giovannangeli,2 E Bizzi,2 U Massafra,2 E Ballanti,2 M Cassol,3 A Migliore2 1Department of Internal Medicine, Regina Apostolorum Hospital, 2Operative Unit of Rheumatology, 3Department of Internal Medicine, San Pietro Fatebenefratelli Hospital, Rome, Italy Background: Biologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA. One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA. The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL in patients affected by RA in maintaining LDA or remission obtained after biological therapy. Method: This is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28, clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months. Results: The rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups. Conclusion: This is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA

  19. Efficacy and safety of a flexible extended regimen of ethinylestradiol/drospirenone for the treatment of dysmenorrhea: a multicenter, randomized, open-label, active-controlled study.

    Science.gov (United States)

    Momoeda, Mikio; Kondo, Masami; Elliesen, Joerg; Yasuda, Masanobu; Yamamoto, Shigetomo; Harada, Tasuku

    2017-01-01

    Dysmenorrhea is a common condition in women, which is characterized by menstrual pain. Low-dose estrogen/progestin combined oral contraceptives have been shown to reduce the severity of dysmenorrhea symptoms, and a 28-day cyclic regimen of ethinylestradiol/drospirenone (28d regimen) is approved for this indication in Japan. The aim of this study was to assess the safety and efficacy of a flexible extended regimen of ethinylestradiol/drospirenone (flexible regimen) in Japanese women with dysmenorrhea. This multicenter, open-label study was performed in Japanese women with dysmenorrhea who, after a baseline observational phase, were randomized to receive ethinylestradiol 20 μg/drospirenone 3 mg in a flexible regimen (one tablet each day for 24-120 days followed by a 4-day tablet-free interval) or in the standard 28d regimen (one tablet each day for 24 days, followed by 4 days of placebo tablets for six cycles). The primary endpoint was the number of days with dysmenorrhea of at least mild intensity over a 140-day evaluation period. Dysmenorrhea scores, bleeding patterns, and other pain-related parameters were also assessed. A total of 216 women (mean age 29.7 years) were randomized to the flexible regimen (n=108) or 28d regimen (n=108) and 212 were included in the full analysis sets (flexible regimen, n=105; 28d regimen, n=107). Women in the flexible-regimen group reported a mean of 3.4 fewer days with dysmenorrheic pain than women in the 28d-regimen group, with similar decreases in disease severity reported in both treatment groups. According to the investigators, 64.8% and 59.4% of women in the flexible-regimen and 28d-regimen treatment groups had "very much improved" or "much improved" disease, while 54.3% and 50.9% of patients reported being "very much satisfied" or "much satisfied" with their treatment, respectively. In Japanese women with dysmenorrhea, a flexible extended regimen of ethinylestradiol/drospirenone decreased the number of days with dysmenorrheic

  20. Use of a cognitive ergonomics approach to compare usability of a multidose dry powder inhaler and a capsule dry powder inhaler: an open-label, randomized, controlled study.

    Science.gov (United States)

    Franks, Mark; Briggs, Pamela

    2004-11-01

    Usability (ease of use) is an important feature of inhalers to ensure optimal dose delivery The aim of this study was to compare the usability of a multidose dry powder inhaler (mDPI) and a capsule dry powder inhaler (cDPI) in older individuals, using a range of qualitative and quantitative techniques from the field of cognitive ergonomics. Participants aged >50 years were enrolled in this 2-visit, open-label, randomized, controlled, parallel-group study conducted at Northumbria University, Newcastle upon Tyne, United Kingdom. Participants who had used an inhaler or were inhaler naive were randomized to use the mDPI or cDPI. At visit 1, the inhaler procedure was demonstrated twice by the investigator. Participants then repeated the procedure (although they were not expected to inhale because no drug was to be administered) until they made 3 consecutive correct attempts. They also undertook a range of tests to assess their confidence in using the device, manual dexterity, and self-efficacy At visit 2 (2 days later), participants made a single inhaler attempt before receiving any demonstrations from the investigator; this was intended to simulate clinical practice, in which the patient may not use an inhaler for a few days after it is prescribed. Participants then completed the inhaler procedure 10 times while undertaking a concurrent distracter task. The number of critical errors (ie, those having a high impact on dose delivery) was recorded for all attempts. To facilitate subsequent correlation analyses, an overall performance measure was derived from a combination of the results of the single inhaler trial and the 10 trials with a distracter. Eighty individuals (51 women, 29 men; mean [SD] age, 74.1 [7.5] years) participated in the study(40 participants per device). Forty of the participants (50%) had used an inhaler previously; 40 (50%) were inhaler naive. Based on the overall performance measure, participants testing the mDPI made significantly fewer critical

  1. Bioavailability of orally administered rhGM-CSF: a single-dose, randomized, open-label, two-period crossover trial.

    Directory of Open Access Journals (Sweden)

    Wenping Zhang

    Full Text Available BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF is usually administered by injection, and its oral administration in a clinical setting has been not yet reported. Here we demonstrate the bioavailability of orally administered rhGM-CSF in healthy volunteers. The rhGM-CSF was expressed in Bombyx mori expression system (BmrhGM-CSF. METHODS AND FINDINGS: Using a single-dose, randomized, open-label, two-period crossover clinical trial design, 19 healthy volunteers were orally administered with BmrhGM-CSF (8 microg/kg and subcutaneously injected with rhGM-CSF (3.75 microg/kg respectively. Serum samples were drawn at 0.0h, 0.5h ,0.75h,1.0h,1.5h,2.0h ,3.0h,4.0h,5.0h,6.0h,8.0h,10.0h and 12.0h after administrations. The hGM-CSF serum concentrations were determined by ELISA. The AUC was calculated using the trapezoid method. The relative bioavailability of BmrhGM-CSF was determined according to the AUC ratio of both orally administered and subcutaneously injected rhGM-CSF. Three volunteers were randomly selected from 15 orally administrated subjects with ELISA detectable values. Their serum samples at the 0.0h, 1.0h, 2.0h, 3.0h and 4.0h after the administrations were analyzed by Q-Trap MS/MS TOF. The different peaks were revealed by the spectrogram profile comparison of the 1.0h, 2.0h, 3.0h and 4.0h samples with that of the 0.0h sample, and further analyzed using both Enhanced Product Ion (EPI scanning and Peptide Mass Fingerprinting Analysis. The rhGM-CSF was detected in the serum samples from 15 of 19 volunteers administrated with BmrhGM-CSF. Its bioavailability was observed at an average of 1.0%, with the highest of 3.1%. The rhGM-CSF peptide sequences in the serum samples were detected by MS analysis, and their sizes ranging from 2,039 to 7,336 Da. CONCLUSIONS: The results demonstrated that the oral administered BmrhGM-CSF was absorbed into the blood. This study provides an approach for an oral administration of

  2. Acti-Tape™ (elastic therapeutic tape as compared with a knee guard in providing support to the knee joint: an open-label, randomized, crossover study

    Directory of Open Access Journals (Sweden)

    Hui HK

    2014-04-01

    Full Text Available Hoong Keong Hui,1 Narayan J Karne,2 Navneet Sonawane31Nutriworks Ltd, Kowloon, Hong Kong; 2Karne Hospital, Pune, India; 3Vedic Lifesciences Pvt Ltd, Mumbai, IndiaStudy design: Randomized, open-label, crossover, controlled study.Background: Elastic taping methods are used to provide support to the musculoskeletal system in athletes. Acti-Tape™ (an elastic therapeutic tape has been marketed for the last 2–3 years and has shown good results in providing support to the joints. This pilot study was planned to collect data on the clinical outcomes and to assess if a single tape application of Acti-Tape over the knee joint could provide benefits similar to a traditionally used knee guard.Methods: Thirteen subjects aged 30–65 years visiting an orthopedic center in Pune, India who were suffering from osteoarthritis were randomly assigned to either Acti-Tape (n=6 or a knee guard (n=7 in the first intervention period (6 days and were crossed over to the other group in the second intervention period (6 days after a washout of 1 day. Main outcome measures were change from day 0 to day 6 in pain visual analog score (VAS; timed up and go (TUG, medial step down (MSD, and unilateral anterior reach (UAR tests; and subject's preference.Results: Data for all the 13 subjects were pooled and analyzed by Student's t-test as treatment-by-period interaction was not significant by analysis of variance (P>0.05. The changes (mean ± standard deviation after using Acti-Tape and a knee guard, respectively, were pain VAS, –10±5.4 versus (vs –11.5±5.83; TUG, –0.62±1.33 vs –0.46±1.56; UAR, 0.15±1.07 vs 0.75±0.44; and MSD, 1.08±095 vs 0.85±1.14. These were statistically significant with both devices for pain VAS, UAR, and MSD, but not for TUG. Between the treatments however, no statistically significant difference was seen. Eleven of 13 (85% subjects preferred Acti-Tape for future use (P<0.05 by McNemar’s χ2 test. No safety concerns were reported by the

  3. An open randomized controlled trial to compare the efficacy of two fixed dose combinations of artemesinin based combinations for uncomplicated falciparum malaria in Bangladesh.

    Science.gov (United States)

    Samad, R; Rahman, M R; Yunus, E B; Hussain, M A; Arif, S M; Islam, M N; Hafiz, S A M M A; Hossain, M M; Faiz, M A

    2013-12-01

    National Malaria Control Program (NMCP) of Bangladesh has introduced Artemisinin Based Combination (ACT), Coartem(R) (Artemether-Lumefantrine (AL), fixed dose combination, in the confirmed cases of uncomplicated P. falciparum malaria since 2004. Despite the reduction of mortality due to malaria, the development and spread of anti-malarial drug resistance wordwide posing a threat to the health services and will make it difficult to control malaria in Bangladesh in future. We need to have an alternative to Coartem which could be Artesunate-amodiaquine (AA) in a fixed dose combination (FDC), a cheaper altenative not yet evidenced to be effective and safe to our population. In this study we compared the efficacy and safety of Artemether + Lumefantrene (FDC, Coartem) with Artesunate +Amodiaquine tablets (100/270 mg FDC) for the treatment of uncomplicated P. falciparum malaria in three high risk multi-drug resistant malaria prevalent areas of Bangladesh. It was an open label randomized controlled trial conducted between December 2008 and November 2009 in 4 upazillas in patients over the age 12 to 60 years diagnosed as a case of uncomplicated P. falciparum malaria. The outcome of the cases were measured as clinical response, parasitological response, defervescence time and parasite clearance time. Drug safety was assessed by comparing the adverse events. A total of 252 cases were randomized to receive Artesunate + Amodiaquine (AA group, 147 cases) and Artemether + Lumefantrene (AL group, 106 cases), one lost to follow up at day 28 in AA group. The distribution of the cases was comparable by age, sex and study sites. Treatment success' response was observed 100% in the AL group and AA group had 99%, two failures with AA were late treatment failures and the difference was not statistically significant (p > .1). The parasitological sensitive (S) response was observed in 97% of cases in AL group and 95% in the AA group, and was not a statistically significant difference

  4. A randomized trial comparing concise and standard consent forms in the START trial.

    Science.gov (United States)

    Grady, Christine; Touloumi, Giota; Walker, A Sarah; Smolskis, Mary; Sharma, Shweta; Babiker, Abdel G; Pantazis, Nikos; Tavel, Jorge; Florence, Eric; Sanchez, Adriana; Hudson, Fleur; Papadopoulos, Antonios; Emanuel, Ezekiel; Clewett, Megan; Munroe, David; Denning, Eileen

    2017-01-01

    Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed. We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin). 77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups. An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient. Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008-006439-12.

  5. An open cluster-randomized, 18-month trial to compare the effectiveness of educational outreach visits with usual guideline dissemination to improve family physician prescribing.

    Science.gov (United States)

    Pinto, Daniel; Heleno, Bruno; Rodrigues, David S; Papoila, Ana Luísa; Santos, Isabel; Caetano, Pedro A

    2014-01-15

    The Portuguese National Health Directorate has issued clinical practice guidelines on prescription of anti-inflammatory drugs, acid suppressive therapy, and antiplatelets. However, their effectiveness in changing actual practice is unknown. The study will compare the effectiveness of educational outreach visits regarding the improvement of compliance with clinical guidelines in primary care against usual dissemination strategies. A cost-benefit analysis will also be conducted. We will carry out a parallel, open, superiority, randomized trial directed to primary care physicians. Physicians will be recruited and allocated at a cluster-level (primary care unit) by minimization. Data will be analyzed at the physician level. Primary care units will be eligible if they use electronic prescribing and have at least four physicians willing to participate. Physicians in intervention units will be offered individual educational outreach visits (one for each guideline) at their workplace during a six-month period. Physicians in the control group will be offered a single unrelated group training session. Primary outcomes will be the proportion of cyclooxygenase-2 inhibitors prescribed in the anti-inflammatory class, and the proportion of omeprazole in the proton pump inhibitors class at 18 months post-intervention. Prescription data will be collected from the regional pharmacy claims database. We estimated a sample size of 110 physicians in each group, corresponding to 19 clusters with a mean size of 6 physicians. Outcome collection and data analysis will be blinded to allocation, but due to the nature of the intervention, physicians and detailers cannot be blinded. This trial will attempt to address unresolved issues in the literature, namely, long term persistence of effect, the importance of sequential visits in an outreach program, and cost issues. If successful, this trial may be the cornerstone for deploying large scale educational outreach programs within the Portuguese

  6. Effect of phenylephrine vs. ephedrine on frontal lobe oxygenation during caesarean section with spinal anesthesia: an open label randomized controlled trial

    Science.gov (United States)

    Foss, Visti T.; Christensen, Robin; Rokamp, Kim Z.; Nissen, Peter; Secher, Niels H.; Nielsen, Henning B.

    2014-01-01

    Background: During caesarean section spinal anesthesia may provoke maternal hypotension that we prevent by administration of phenylephrine and/or ephedrine. Phenylephrine is however reported to reduce the near infrared spectroscopy-determined frontal lobe oxygenation (ScO2) but whether that is the case for patients exposed to spinal anesthesia is not known. Objectives: To evaluate the impact of phenylephrine vs. ephedrine on ScO2during caesarean section with spinal anesthesia in a single center, open-label parallel-group study with balanced randomization of 24 women (1:1). Secondary aims were to compare the effect of the two drugs on maternal hemodynamics and fetal heart rate. Intervention: Ephedrine (0.8–3.3 mg/min) vs. phenylephrine infusion (0.02–0.07 mg/min). Results: For the duration of surgery, administration of ephedrine maintained ScO2 (compared to baseline +2.1 ± 2.8%; mean ± SE, while phenylephrine reduced ScO2 (−8.6 ± 2.8%; p = 0.005) with a 10.7% difference in ScO2between groups (p = 0.0106). Also maternal heart rate was maintained with ephedrine (+3 ± 3 bpm) but decreased with phenylephrine (−11 ± 3 bpm); difference 14 bpm (p = 0.0053), but no significant difference in mean arterial pressure (p = 0.1904) or CO (p = 0.0683) was observed between groups. The two drugs also elicited an equal increase in fetal heart rate (by 19 ± 3 vs. 18 ± 3 bpm; p = 0.744). Conclusion: In the choice between phenylephrine and ephedrine for maintenance of blood pressure during caesarean section with spinal anesthesia, ephedrine maintains frontal lobe oxygenation and maternal heart rate with a similar increase in fetal heart rate as elicited by phenylephrine. Trial registration: Clinical trials NCT 01509521 and EudraCT 2001 006103 35. PMID:24624090

  7. Comparative randomized open-label trial on efficacy and safety of Persen® and Persen® Night herbal extracts in patients with short-term insomnia

    Directory of Open Access Journals (Sweden)

    A. P. Rachin

    2016-01-01

    Full Text Available Herbal sedatives serve an alternative to antipsychotics and hypnotics aimed to alleviate symptoms of anxious disorders and insomnia. Valeriana officinalis L., Mentha piperita L. and Melissa officinalis are most widely used in neurology as sedatives of herbal origin. We present the results of a randomized open-label trial on efficiency and safety of Persen® and Persen® Night containing extracts of the above mentioned plants in patients with short-term insomnia. The study consisted of 60 subjects of 18–65 y.o. (mean 42.4 ± 6.9 y.o. with short-term insomnia due to adjustment disorder or mixed anxiety-depressive disorders: 30 of them got Persen® 2 tablets a day and 30 – Persen® Night, 1 capsule 30–60 min before sleep during 4 weeks. The majority (76.5 % of patients referred the onset of insomnia with psychosocial traumatic stressor. Persen® Night’s main action was found on superficial sleep, number of night awakenings, sleep onset rate. At the end of the therapy with this substance 39.7 % of patients fell asleep in 10–15 min, and 92.2 % – in 30 min, accordingly, while for Persen® at 17.4 and 80.3 % accordingly (р < 0.05. In the meantime Persen® decreased the bad sleep perception at awakening and day somnolence, mostly attributed to the mood improvement and decrease of anxiety. Levels of efficacy and safety for both substances were significant, allowing to regard them as potential phytotherapeutic agent in the treatment of insomnia and mixed anxiety-depressive disorders.

  8. Phacoemulsification versus phacoemulsification with micro-bypass stent implantation in primary open-angle glaucoma: randomized double-masked clinical trial.

    Science.gov (United States)

    Fea, Antonio M

    2010-03-01

    To compare phacoemulsification alone and phacoemulsification with micro-bypass stent implantation in eyes with primary open-angle glaucoma. Instituto di Fisiopatologia Clinica, Clinica Oculistica, Universita' di Torino, Torino, Italy. In this prospective double-masked randomized clinical trial, patients had phacoemulsification alone (control group) or phacoemulsification with iStent implantation (combined group). Primary outcomes were intraocular pressure (IOP) and reduction in medication use over 15 months and IOP after a 1-month washout of ocular hypotensive agents (ie, 16 months postoperatively). The baseline IOP was similar between groups (combined group: 17.9 mm Hg +/- 2.6 [SD]; control group: 17.3 +/- 3.0 mm Hg) (P = .512). Three patients in the control group were lost to follow-up. The mean IOP was 14.8 +/- 1.2 mm Hg in the combined group and 15.7 +/- 1.1 mm Hg in the control group at 15 months and 16.6 +/- 3.1 mm Hg and 19.2 +/- 3.5 mm Hg, respectively, after washout; the IOP was statistically significantly lower in the combined group than in the control group at both time points (P = .031 and P = .042, respectively). At 15 months, the mean number of medications was lower in the combined group than in the control group (0.4 +/- 0.7 and 1.3 +/- 1.0, respectively; P = .007), as was the proportion of patients on ocular hypotensive medication (33% and 76%, respectively). Phacoemulsification with stent implantation was more effective in controlling IOP than phacoemulsification alone; the safety profiles were similar. Copyright 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  9. Efficacy of single-injection unilateral thoracic paravertebral block for post open cholecystectomy pain relief: a prospective randomized study at Gondar University Hospital

    Science.gov (United States)

    Fentie, Demeke Yilkal; Gebremedhn, Endale Gebreegziabher; Denu, Zewditu Abdissa; Gebreegzi, Amare Hailekiros

    2017-01-01

    Background Cholecystectomy can be associated with considerable postoperative pain. While the benefits of paravertebral block (PVB) on pain after thoracotomy and mastectomy have been demonstrated, not enough investigations on the effects of PVB on pain after open cholecystectomy have been conducted. We tested the hypothesis that a single-injection thoracic PVB reduces pain scores, decreases opioid consumption, and prolongs analgesic request time after cholecystectomy. Methods Of 52 patients recruited, 50 completed the study. They were randomly allocated into two groups: the paravertebral group and the control group. The outcome measures were the severity of pain measured on numeric pain rating scale, total opioid consumption, and first analgesic request time during the first postoperative 24 hours. Result The main outcomes recorded during 24 hours after surgery were Numerical Rating Scale (NRS) pain scores (NRS, 0–10), cumulative opioid consumption, and the first analgesic request time. Twenty four hours after surgery, NRS at rest was 4 (3–6) vs 5 (5–7) and at movement 4 (4–7) vs 6 (5–7.5) for the PVB and control groups, respectively. The difference between the groups over the whole observation period was statistically significant (Ptramadol consumption was 200 (150–250) mg vs 300 (200–350) mg in the paravertebral and in the control group, respectively (P=0.003). After surgery, the median (25th–75th percentile) first analgesic requirement time was prolonged in the PVB group in statistically significant fashion (P<0.0001). Conclusion and recommendations Single-shot thoracic PVB as a component of multi-modal analgesic regimen provided superior analgesia when compared with the control group up to 24 postoperative hours after cholecystectomy, and we recommend this block for post cholecystectomy pain relief. PMID:28744155

  10. INFLUENCE OF GRADED AEROBIC EXERCISE ON QUALITY OF LIFE IN POST SURGICAL MITRAL VALVE DISEASE INDIVIDUAL A PROSPECTIVE RANDOMIZED OPEN LABEL STUDY

    Directory of Open Access Journals (Sweden)

    Shanthi C

    2016-10-01

    Full Text Available Background: Post surgical mitral valve disease individual focus their cardiac rehabilitation training on two major goal that is to improve cardiac output response exercises and place an important role in determining exercise tolerance and to improve quality of life. Cardiac rehabilitation programs involve prescribed exercise and education however various other method are being used to improve quality of life. But our study to find out the effectiveness of graded aerobic exercise protocol on ejection fraction and quality of life in post surgical mitral valve disease individuals. Methods: The study design was open label studies total of 100 post surgical mitral valve disease individuals patients from the age group of 20-60 years were recruited from SVIMS hospital. They were randomly divided into two groups. Group I underwent a twelve week structured graded individually tailored exercises. The group II received only none graded (not individualized exercise training. The ejection fraction and quality of life was measured before and after 12 weeks of exercise training for two groups. Results: Repeated measures ANOVA was used to compare mean values of continuous variables between baseline and at the time of discharge and three months after surgery for each parameter. Comparison of means between groups was done by the unpaired student t test. Mean age of the subjects was 40.18±10.29. There was a significant increase in the ejection fraction in the group I(61.34±2.49 to 64.4±3.31 compared to with the group II (61.06±2.51. to 61.62 ±2.37. QOL had improved in group I than group II at p<0.05. Conclusion: A 12 week structured graded aerobic exercise training significantly improved ejection fraction and quality of life in post surgical mitral valve disease individuals.

  11. Impact on quality of life of a nursing intervention programme for patients with chronic non-cancer pain: an open, randomized controlled parallel study protocol.

    Science.gov (United States)

    Morales-Fernandez, Angeles; Morales-Asencio, Jose Miguel; Canca-Sanchez, Jose Carlos; Moreno-Martin, Gabriel; Vergara-Romero, Manuel

    2016-05-01

    To determine the effect of a nurse-led intervention programme for patients with chronic non-cancer pain. Chronic non-cancer pain is a widespread health problem and one that is insufficiently controlled. Nurses can play a vital role in pain management, using best practices in the assessment and management of pain under a holistic approach where the patient plays a proactive role in addressing the disease process. Improving the quality of life, reducing disability, achieving acceptance of health status, coping and breaking the vicious circle of pain should be the prime objectives of our care management programme. Open randomized parallel controlled study. The experimental group will undertake one single initial session, followed by six group sessions led by nurses, aimed at empowering patients for the self-management of pain. Healthy behaviours will be encouraged, such as sleep and postural hygiene, promotion of physical activity and healthy eating. Educational interventions on self-esteem, pain-awareness, communication and relaxing techniques will be carried out. As primary end points, quality of life, perceived level of pain, anxiety and depression will be evaluated. Secondary end points will be coping and satisfaction. Follow-up will be performed at 12 and 24 weeks. The study was approved by the Ethics and Research Committee Costa del Sol. If significant effects were detected, impact on quality of life through a nurse-led programme would offer a complementary service to existing pain clinics for a group of patients with frequent unmet needs. © 2016 John Wiley & Sons Ltd.

  12. Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study.

    Science.gov (United States)

    Chopra, Arvind; Chandrashekara, S; Iyer, Rajgopalan; Rajasekhar, Liza; Shetty, Naresh; Veeravalli, Sarathchandra Mouli; Ghosh, Alakendu; Merchant, Mrugank; Oak, Jyotsna; Londhey, Vikram; Barve, Abhijit; Ramakrishnan, M S; Montero, Enrique

    2016-04-01

    The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period. (Clinical Trial Registry of India, http://ctri.nic.in/Clinicaltrials/login.php , CTRI/2008/091/000295).

  13. Open-Label, Randomized, 6-Way Crossover, Single-Dose Study to Determine the Pharmacokinetics of Batefenterol (GSK961081) and Fluticasone Furoate When Administered Alone or in Combination.

    Science.gov (United States)

    Ambery, Claire; Riddell, Kylie; Daley-Yates, Peter

    2016-09-01

    To investigate the pharmacokinetics of inhaled batefenterol (BAT) and fluticasone furoate (FF) given alone or in combination via ELLIPTA® dry powder inhaler (DPI-E), and BAT monotherapy via DISKUS® DPI (DPI-D). In this open-label, 6-way crossover study, 48 healthy subjects were randomized to 1 of 6 treatment sequences, comprising 6 single-dose treatment regimens: (1) BAT 1200 μg via DPI-D; (2) BAT 1200 μg via DPI-E without a lactose-filled second strip; (3) BAT 1200 μg via DPI-E with a lactose-filled second strip; (4) BAT/FF 1200/300 μg via DPI-E; (5) FF 300 μg via DPI-E with a lactose-filled second strip; and (6) BAT/FF 900/300 μg via DPI-E. Pharmacokinetic data were analyzed using noncompartmental methods. Plasma BAT area under the curve (AUC) and maximum plasma concentration (Cmax ) were similar for all treatments containing BAT 1200 μg (geometric least-squares means [GLSM] ratio, 0.90-1.06). Plasma FF AUC and Cmax were reduced following BAT/FF 1200/300 μg and 900/300 μg versus FF 300 μg monotherapy (GLSM ratio, 0.62-0.77). BAT 1200 μg administered via DPI-E, alone or in combination with FF, resulted in similar systemic exposure versus BAT administered by DPI-D. FF exposure was reduced when administered in combination with BAT compared with FF alone. © 2016, The American College of Clinical Pharmacology.

  14. Superiority of dutasteride over finasteride in hair regrowth and reversal of miniaturization in men with androgenetic alopecia: A randomized controlled open-label, evaluator-blinded study.

    Science.gov (United States)

    Shanshanwal, Sujit J S; Dhurat, Rachita S

    2017-01-01

    Finasteride and dutasteride are inhibitors of the enzyme 5-alpha-reductase which inhibits the conversion of testosterone to dihydrotestosterone. Dutasteride inhibits both type I and type II 5-alpha-reductase while finasteride inhibits only the type II enzyme. As both isoenzymes are present in hair follicles, it is likely that dutasteride is more effective than finasteride. To compare the efficacy, safety and tolerability of dutasteride and finasteride in men with androgenetic alopecia. Men with androgenetic alopecia between 18 and 40 years of age were randomized to receive 0.5 mg dutasteride or 1 mg finasteride daily for 24 weeks. The primary efficacy variables were hair counts (thick and thin) in the target area from modified phototrichograms and global photography evaluation by blinded and non-blinded investigators. The secondary efficacy variable was subjective assessment using a preset questionnaire. Patients were assessed monthly for side effects. Ninety men with androgenetic alopecia were recruited. The increase in total hair count per cm[2] representing new growth was significantly higher in dutasteride group (baseline- 223 hair; at 24 weeks- 246 hair) compared to finasteride group (baseline- 227 hair; at 24 weeks- 231 hair). The decrease in thin hair count per cm[2] suggestive of reversal of miniaturization was significantly higher in dutasteride group (baseline- 65 hair; at 24 weeks- 57 hair) compared to finasteride group (baseline- 67 hair; at 24 weeks- 66 hair). Both the groups showed a similar side effect profile with sexual dysfunction being the most common and reversible side effect. Limitations include the short duration of the study (6 months), the small sample size and the fact that it was an open-label study. Dutasteride was shown to be more efficacious than finasteride and the side-effect profiles were comparable.

  15. Pharmacokinetic interaction between rosuvastatin and olmesartan: a randomized, open-label, 3-period, multiple-dose crossover study in healthy Korean male subjects.

    Science.gov (United States)

    Roh, Hyerang; Son, Hankil; Lee, Donghwan; Chang, HeeChul; Yun, Chohee; Park, Kyungsoo

    2014-08-01

    Rosuvastatin has been widely used in combination with olmesartan for the treatment of dyslipidemia accompanied by hypertension. With no information currently available on the interaction between the 2 drugs, a pharmacokinetic study was conducted to investigate the influence of rosuvastatin on olmesartan and vice versa when the 2 drugs were coadministered. The purpose of this study was to investigate the pharmacokinetic profile of coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet and the associated drug-drug interaction in healthy Korean male volunteers. This was a randomized, open-label, 3-period, multiple-dose crossover study. Eligible subjects were aged 20 to 50 years and within 20% of their ideal body weight. After being randomly assigned to 6 groups of equal number, subjects received each of the following 3 formulations once a day for 7 consecutive days with an 8-day washout period between the formulations: rosuvastatin 20-mg tablet, olmesartan 40-mg tablet, and coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet. Blood samples were collected up to 72 hours after dosing, and pharmacokinetic parameters were determined for rosuvastatin, its active metabolite (N-desmethyl rosuvastatin), and olmesartan. Adverse events were evaluated based on subject interviews and physical examinations. Among the 36 enrolled subjects, 34 completed the study (mean [range] age, 28.6 [23-49] y; mean [range] weight, 66.4 [52.2-78.7] kg). The 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters for the coadministration of the 2 drugs to the mono-administration of each drug were 85.14% to 96.08% for AUCτ and 81.41% to 97.48% for Css,max for rosuvastatin, and 77.55% to 89.48% for AUCτ and 75.62% to 90.12% for Css,max for N-desmethyl rosuvastatin; those values were 95.61% to 102.57% for AUCτ and 91.73% to 102.98% for Css,max for olmesartan. Dizziness was the most frequently noted adverse drug

  16. Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

    Directory of Open Access Journals (Sweden)

    Babu KG

    2014-06-01

    Full Text Available K Govind Babu,1 Kumar Prabhash,2 Ashok K Vaid,3 Bhawna Sirohi,3 Ravi B Diwakar,4 Raghunadha Rao,5 Madhuchanda Kar,6 Hemant Malhotra,7 Shona Nag,8 Chanchal Goswami,9 Vinod Raina,10 Ravi Mohan111Kidwai Memorial Institute of Oncology, Bangalore, 2Tata Memorial Hospital, Mumbai, 3Artemis Health Institute, Delhi, 4Bangalore Institute of Oncology, Bangalore, 5Nizam Institute of Medical Sciences, Hyderabad, 6B R Singh Hospital, Kolkata, 7Birla Cancer Centre, Jaipur, 8Jehangir Hospital, Pune, 9B P Poddar Hospital and Medical Research Ltd, Kolkata, 10Institute Rotary Cancer Hospital, New Delhi, 11King George Hospital, Visakhapatnam, IndiaBackground: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.Methods: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group or chemotherapy alone (control group, and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response. Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.Results: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04. A complete response and partial response were achieved in 3

  17. Pharmacokinetics of rosuvastatin/olmesartan fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

    Science.gov (United States)

    Son, Hankil; Roh, Hyerang; Lee, Donghwan; Chang, Heechul; Kim, Junku; Yun, Chohee; Park, Kyungsoo

    2013-07-01

    Rosuvastatin, a lipid-lowering agent, has been widely used with olmesartan, a long-acting angiotensin II receptor blocker, indicated for the treatment of dyslipidemia accompanied by hypertension. A fixed-dose combination (FDC) tablet of these 2 drugs was recently developed to enhance the dosing convenience and to increase patient compliance while yielding pharmacokinetic profiles comparable to coadministration of each drug as individual tablets. The goal of present study was to compare the pharmacokinetic profiles of single-dose administration of an FDC tablet containing rosuvastatin/olmesartan 20/40 mg (test formulation) with coadministration of a rosuvastatin 20-mg tablet and a olmesartan 40-mg tablet (reference formulation) in healthy Korean male volunteers, for the purpose of determining bioequivalence. This single-dose, randomized, open-label, 2-period crossover study enrolled subjects aged 20 to 50 years and within 20% of ideal body weight. Each subject received a single dose of the test and reference formulations orally in a fasted state, with a 7-day washout period between the administrations. Blood samples were collected up to 72 hours after dosing, and pharmacokinetic parameters were determined for rosuvastatin, its active metabolite (N-desmethyl rosuvastatin), and olmesartan. Bioequivalence was concluded if the 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters were within the predetermined range of 80% to 125%. Adverse events (AEs) were evaluated based on subject interviews and physical examinations. Among the 58 enrolled subjects, 54 completed the study. The 90% CIs of the geometric mean ratios of the primary pharmacokinetic parameters were as follows: rosuvastatin: AUC(last), 85.60% to 97.40% and C(max), 83.16% to 98.21%; N-desmethyl rosuvastatin: AUC(last), 82.08% to 93.45% and C(max), 79.23% to 93.41%; and olmesartan: AUC(last), 97.69% to 105.69% and C(max), 100.35% to 109.42%. The most frequently noted AE was headache

  18. Nitrous oxide-oxygen mixture during care of bedsores and painful ulcers in the elderly: a randomized, crossover, open-label pilot study.

    Science.gov (United States)

    Paris, Adeline; Horvath, Rémi; Basset, Pierre; Thiery, Stéphane; Couturier, Pascal; Franco, Alain; Bosson, Jean-Luc

    2008-02-01

    Bedsore and ulcer care can often be painful and no standardized analgesic method exists today for pain relief during treatment in adults and the elderly. To evaluate the analgesic efficacy of a nitrous oxide-oxygen mixture vs. morphine during painful bedsore and ulcer care in adult and elderly patients, we conducted a randomized, crossover, multicenter, prospective, open-label, pilot study. Thirty-four inpatients, aged 53-96 years (median 84 years), were recruited in Grenoble University Hospital, Annecy Hospital and Chambéry Hospital, France, from January to June 2001. Each of the 34 patients received morphine (M), nitrous oxide-oxygen mixture (E), or morphine+nitrous oxide-oxygen mixture (ME) during painful care in a crossover protocol. Treatments were changed every two days and the study duration was six days. Analgesia was evaluated before and after each care session using a behavioral scale to evaluate pain in noncommunicating adults (ECPA), a visual analog scale (VAS), a global hetero-evaluation scale (GHES), and the DOLOPLUS-2 scale. There was a significant overall difference (P<0.01) among the three treatments. On the ECPA, the average difference after and before care was +5.2+/-8.6 (M), -0.3+/-8 (E), and -0.6+/-7.4 (ME), respectively. There was a significant difference between M and E, and M and ME (each P<0.01). No difference was found between E and ME (P=0.97). There were similar significant differences in the GHES and DOLOPLUS-2 scales (all tests P<0.01). Post hoc comparisons showed a significant difference (P<0.01) between M and E, and between M and ME without any additional effect for M+E. No differences were found with regard to safety or tolerability. This pilot study demonstrates the superiority of nitrous oxide-oxygen mixture over morphine for analgesia. This experience suggests that this mixture has ease of use, rapid effect, and limited contraindications when used during painful bedsore and ulcer care in elderly patients. Furthermore, it is well

  19. Pharmacokinetic interaction between rosuvastatin and telmisartan in healthy Korean male volunteers: a randomized, open-label, two-period, crossover, multiple-dose study.

    Science.gov (United States)

    Son, Mijeong; Kim, Yukyung; Lee, Donghwan; Roh, Hyerang; Son, Hankil; Guk, Jinju; Jang, Seong Bok; Nam, Su Youn; Park, Kyungsoo

    2014-08-01

    Rosuvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, and telmisartan, an angiotensin receptor blocker, are commonly prescribed in combination for the treatment of dyslipidemia accompanied by hypertension. However, the nature of the pharmacokinetic interaction between the 2 drugs is not clearly understood. The goal of the present study was to investigate the pharmacokinetic drug-drug interaction between rosuvastatin and telmisartan in a healthy Korean population. This was a randomized, 2-part, open-label, 2-period, crossover, multiple-dose study, with each part composed of different subjects between the ages of 20 and 55 years. In part 1, each subject received rosuvastatin 20 mg with and without telmisartan 80 mg once daily for 6 consecutive days. In part 2, each subject received telmisartan 80 mg with and without rosuvastatin 20 mg once daily for 6 consecutive days. In both parts, there was a 16-day washout period between mono- and coadministration. Blood samples were collected up to 72 hours after the last dose. Adverse events (AEs) were evaluated through interviews and physical examinations. In part 1, the 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters for coadministration of the 2 drugs to monoadministration of each drug were 1.0736-1.2932 for AUCτ and 1.7442-2.3229 for Cmax,ss for rosuvastatin and 0.9942-1.1594 for AUCτ and 1.3593-1.7169 for Cmax,ss for N-desmethyl rosuvastatin, whereas in part 2, the CIs were 1.0834-1.2672 for AUCτ and 1.1534-1.5803 for Cmax,ss for telmisartan. The most frequently noted AE was cough in part 1, which occurred in 2 subjects receiving the combination therapy, and oropharyngeal pain in part 2, which occurred in 3 subjects receiving the combination therapy. All reported AEs were mild or moderate, and there was no significant difference in incidence between the treatments. These findings demonstrated that rosuvastatin and telmisartan mutually affected each other

  20. Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

    Science.gov (United States)

    Chae, Dong Woo; Son, Mijeong; Kim, Yukyung; Son, Hankil; Jang, Seong Bok; Seo, Jeong Min; Nam, Su Youn; Park, Kyungsoo

    2015-10-01

    As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 - 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0-∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ were 0.9262-1.1498, 0.9294-1.0313, and 0.9312-1.0320 for telmisartan, 0.9041-1.0428, 0.9262-1.0085, and 0.9307-1.0094 for rosuvastatin, and 0.8718-1.0022, 0.8901-0.9904, and 0.8872-0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test

  1. Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study

    Directory of Open Access Journals (Sweden)

    Wani RA

    2015-03-01

    Full Text Available Rayees Ahmad Wani, Mansoor Ahmad Dar, Rajesh Kumar Chandel, Yasir Hassan Rather, Inaamul Haq, Arshad Hussain, Altaf Ahmad MallaDepartment of Psychiatry, Government Medical College, Srinagar, Jammu and Kashmir, IndiaBackground: Patients with schizophrenia suffer high rates of metabolic derangements on some antipsychotic medications that predispose them to cardiovascular diseases. Keeping this fact in mind, we planned this open-label study to see the effect on various metabolic parameters after switching stable schizophrenia subjects, who had developed metabolic syndrome on olanzapine, to aripiprazole.Methods: Sixty-two patients with schizophrenia who were stable on olanzapine and were fulfilling modified National Cholesterol Education Program (NCEP Adult Treatment Panel III (ATP-III criteria for the presence of metabolic syndrome were enrolled on the study. Patients were randomly assigned either to switch to aripiprazole or to stay on olanzapine, on a 1:1 basis. Cross-tapering over a period of 1 month was done while switching patients to aripiprazole. Laboratory assessment for metabolic parameters was done at baseline, 8 weeks, and 24 weeks after enrollment; efficacy assessment was done using the Positive and Negative Syndrome Scale (PANSS at baseline and 24 weeks, the Clinical Global Impressions severity subscale (CGI-S at baseline, and the Clinical Global Impressions improvement subscale (CGI-I at 24 weeks.Results: All parameters of metabolic syndrome (waist circumference, blood pressure, triglyceride level, fasting blood glucose, and high-density lipoprotein cholesterol kept deteriorating in the stay group, compared with a continuous improvement in the switch group over time. At the end of the study, 26 patients (100% from the stay group and 15 patients (42.8% from switch group met the modified NCEP ATP-III criteria for presence of metabolic syndrome (P<0.001. There were no statistically significant differences between groups in

  2. Factors Influencing the Placebo Effect in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: An Analysis of Two Randomized Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Taichi Kawamura

    Full Text Available To explore factors related to the placebo effect in patients with primary open-angle glaucoma (POAG or ocular hypertension (OH.This was a retrospective cohort study of patients with POAG and patients with OH who were treated with placebo. The patients' data were extracted from two randomized, double-masked, parallel, multicenter clinical trials (trial 1 and trial 2 in Japan. We explored the baseline factors that were associated with the intraocular pressure (IOP-lowering effect of placebo ophthalmic solution after 4 weeks of instillation treatment at two time points by using multivariable models. The time points were Hour 0 (between 08:30 and 10:30 before instillation and Hour 2 (within 1.5 to 2.5 h after instillation and by 12:30 at the baseline date and after 4 weeks. The changes in IOP from baseline to 4 weeks at the two time points were evaluated for the IOP-lowering effect induced by placebo instillation.Of the 330 patients included in the two trials, 89 patients were eligible for the analysis. The results of the multivariable analysis for Hour 0 indicated a high IOP at the baseline date (coefficient: 0.24, 95% confidence interval (CI: 0.02 to 0.46, P = 0.03, and the magnitude of the IOP fluctuation at the baseline date (coefficient: 0.57, 95% CI: 0.24 to 0.90, P = 0.001 was associated with the IOP-lowering effect after 4 weeks. With respect to Hour 2, the trial type was associated with the IOP-lowering effect (coefficient: -1.15, 95% CI: -2.14 to -0.16, P = 0.02.A large fluctuation in IOP during the day is associated with the IOP-lowering effect induced by placebo in patients with POAG or OH. This finding would be helpful to researchers when designing studies related to glaucoma in the early stages of clinical development of drugs.

  3. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.

    Science.gov (United States)

    Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

    2016-03-01

    The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder.

  4. Prospective unmasked randomized evaluation of the iStent inject® versus two ocular hypotensive agents in patients with primary open-angle glaucoma

    Science.gov (United States)

    Fea, Antonio M; Belda, Jose I; Rękas, Marek; Jünemann, Anselm; Chang, Lydia; Pablo, Luis; Voskanyan, Lilit; Katz, L Jay

    2014-01-01

    Purpose The purpose of this study was to compare outcomes of subjects with open-angle glaucoma (OAG) not controlled on one medication who underwent either implantation of two iStent inject® trabecular micro-bypass devices or received medical therapy consisting of a fixed combination of latanoprost/timolol. Patients and methods Of 192 subjects who qualified for the study and were enrolled, 94 were randomized to surgery with implantation of two iStent inject® devices in the treated eye and 98 to receive medical therapy. Results At the month 12 visit, 94.7% of eyes (89/94) in the stent group reported an unmedicated intraocular pressure (IOP) reduction of ≥20% versus baseline unmedicated IOP, and 91.8% of eyes (88/98) in the medical therapy group reported an IOP reduction ≥20% versus baseline unmedicated IOP. A 17.5% between-group treatment difference in favor of the iStent inject group was statistically significant (P=0.02) at the ≥50% level of IOP reduction. An IOP ≤18 mmHg was reported in 92.6% of eyes (87/94) in the iStent inject group and 89.8% of eyes (88/98) in the medical therapy group. Mean (standard deviation) IOP decreases from screening of 8.1 (2.6) mmHg and 7.3 (2.2) mmHg were reported in the iStent inject and medical therapy groups, respectively. A high safety profile was also noted in this study in both the iStent inject and medical therapy groups, as measured by stable best corrected visual acuity, cup-to-disc ratio, and adverse events. Conclusion These data show that the use of iStent inject is at least as effective as two medications, with the clinical benefit of reducing medication burden and assuring continuous treatment with full compliance to implant therapy as well as having a highly favorable safety profile. PMID:24855336

  5. Effect of Oral Beta-Hydroxy-Beta-Methylbutyrate (HMB Supplementation on Physical Performance in Healthy Old Women Over 65 Years: An Open Label Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Linda Berton

    Full Text Available Although older people are particularly liable to sarcopenia, limited research is available on beta-hydroxy-beta-methylbutyrate (HMB supplementation in this population, particularly in healthy subjects. In this parallel-group, randomized, controlled, open-label trial, we aimed to evaluate whether an oral supplement containing 1.5 g of calcium HMB for 8 weeks could improve physical performance and muscle strength parameters in a group of community-dwelling healthy older women. Eighty healthy women attending a twice-weekly mild fitness program were divided into two equal groups of 40, and 32 of the treated women and 33 control completed the study. We considered a change in the Short Physical Performance Battery (SPPB score as the primary outcome and changes in the peak torque (PT isometric and isokinetic strength of the lower limbs, 6-minute walking test (6MWT, handgrip strength and endurance as secondary outcomes. Body composition was assessed with dual-energy X-ray absorptiometry (DXA and peripheral quantitative computerized tomography (pQCT. The mean difference between the two groups on pre-post change were finally calculated (delta for each outcome. After 8 weeks, there were no significant differences between the groups’ SPPB, handgrip strength or DXA parameters. The group treated with HMB scored significantly better than the control group for PT isokinetic flexion (delta = 1.56±1.56 Nm; p = 0.03 and extension (delta = 3.32±2.61 Nm; p = 0.03, PT isometric strength (delta = 9.74±3.90 Nm; p = 0.02, 6MWT (delta = 7.67±8.29 m; p = 0.04, handgrip endurance (delta = 21.41±16.28 s; p = 0.02, and muscle density assessed with pQCT. No serious adverse effects were reported in either group. In conclusion, a nutritional supplement containing 1.5 g of calcium HMB for 8 weeks in healthy elderly women had no significant effects on SPPB, but did significantly improve several muscle strength and physical performance parameters.ClinicalTrials.gov NCT

  6. Hemostatic efficacy of TachoSil in liver resection compared with argon beam coagulator treatment: An open, randomized, prospective, multicenter, parallel-group trial

    DEFF Research Database (Denmark)

    Fischer, Lars; Seiler, Christoph M.; Broelsch, Christoph E.

    2011-01-01

    surgical trial with 2 parallel groups. Patients were eligible for intra-operative randomization after elective resection of ≥1 liver segment and primary hemostasis. The primary end point was the time to hemostasis after starting the randomized intervention to obtain secondaty hemostasis. Secondary end...

  7. Safety and efficacy of bimatoprost/timolol fixed combination in Chinese patients with open-angle glaucoma or ocular hypertension

    Institute of Scientific and Technical Information of China (English)

    Ling Zhihong; Zhang Mingchang; Hu Yizhen; Yin Zhengqin; Xing Yiqiao; Fang Aiwu; Ye Jian

    2014-01-01

    Background Lowering intraocular pressure (lOP) is currently the only therapeutic approach in primary open-angle glaucoma.and the fixed-combination medications are needed to achieve sufficiently low target lOP.A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China.In this study,we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.Methods In this multicenter,randomized,double-masked,parallel controlled study,patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments.Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03% bimatoprost and 0.5% timolol (followed by vehicle for masking) once daily at 19:00 P.M.and concurrent treatment was 0.03% bimatoprost followed by 0.5% timolol once daily at 19:00 P.M.The primary efficacy variable was change from baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent-to-treat (ITr) population.Primary analysis evaluated the non-inferiority of bimatoprost/timolol fixed combination to concurrent with respect to the primary variable using a confidence interval (CI) approach.Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95% CI for the between-treatment (bimatoprost/timolol fixed combination minus concurrent) difference was-≤1.5 mmHg.Adverse events were collected and slit-lamp examinations were performed to assess safety.Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher's exact test

  8. Neridronate improves bone mineral density and reduces back pain in β-thalassaemia patients with osteoporosis: results from a phase 2, randomized, parallel-arm, open-label study.

    Science.gov (United States)

    Forni, Gian Luca; Perrotta, Silverio; Giusti, Andrea; Quarta, Giovanni; Pitrolo, Lorella; Cappellini, Maria Domenica; D'Ascola, Domenico Giuseppe; Borgna Pignatti, Caterina; Rigano, Paolo; Filosa, Aldo; Iolascon, Giovanni; Nobili, Bruno; Baldini, Marina; Rosa, Alessandra; Pinto, Valeria; Palummeri, Ernesto

    2012-07-01

    Neridronate is a third generation bisphosphonate with established efficacy in metabolic bone disease. In this randomized, open-label study, 118 adults with β-thalassaemia and bone mineral density (BMD) Z scores ≤-2·0 were randomized 1:1-500 mg calcium with 400 international unis (iu) vitamin D daily or 500 mg calcium with 400 iu vitamin D daily plus neridronate 100 mg intravenously every 90 d. Significant increases in BMD at the lumbar spine and total hip were noted in the neridronate group at 6 and 12 months from baseline (P back pain and analgesic use were also evident, starting 3 months from commencing treatment. Treatment was well tolerated by all patients. In this largest randomized trial in thalassaemia-induced osteoporosis to date, neridronate was safe and effective in reducing bone resorption and increasing BMD. The associated reduction in back pain and improved quality of life will encourage adherence to therapy. (Clinicaltrials.gov identifier NCT01140321.).

  9. Comparison of different dosing regimens (once weekly vs. twice weekly, and once weekly vs. once every two weeks with epoetin delta in patients with chronic kidney disease: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Macdougall Iain C

    2007-11-01

    Full Text Available Abstract Background Anaemia is a common complication of chronic kidney disease and prevalence increases with declining renal function. Renal anaemia has significant implications for the well-being and quality of life of patients and impacts on morbidity and mortality. Anaemia can be well managed by therapy with erythropoiesis-stimulating agents (ESAs. Previous clinical trials have shown that the only human cell-line-derived ESA, epoetin delta, is well tolerated and effective in maintaining haemoglobin levels in anaemic patients with chronic kidney disease. The half-life of epoetin delta suggests that administration of this agent is feasible once weekly and once every two weeks. We report on the design and rationale of a trial to compare once weekly vs. twice weekly, and once weekly vs. once every two weeks dosing of epoetin delta. Design and methods This is a randomized, open-label, multicentre trial. Patients aged 18 years or above with chronic kidney disease (Stages 3–5 are eligible to enter this trial. Two groups of patients form the trial population, those naïve to ESA therapy and those previously stable on ESA therapy. There are two primary objectives of this trial: 1 to demonstrate non-inferiority between twice weekly and once weekly dosing of epoetin delta in previously naïve patients (assessed by haemoglobin at Week 24; 2 to demonstrate non-inferiority between once weekly and once every two weeks dosing in previously stable patients (assessed by average haemoglobin over Weeks 16–24. Among the secondary analyses will be assessments of haematocrit, number(% of patients meeting predefined targets for haemoglobin and haematocrit levels, and comparisons of average dose. All patients will receive study medication for 24 weeks and dose will be adjusted according to a predefined algorithm to achieve and maintain haemoglobin ≥ 11 g/dL. All patients completing this trial are eligible to enter a 2-year follow-up study to enable monitoring

  10. Cranialization of the frontal sinus for secondary mucocele prevention following open surgery for benign frontal lesions.

    Directory of Open Access Journals (Sweden)

    Gilad Horowitz

    Full Text Available OBJECTIVE: To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus. STUDY DESIGN: Retrospective case series. SETTING: Tertiary academic medical center. PATIENTS: Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011. INTERVENTIONS: Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59% or frontal cranialization (n = 28, 41%. MAIN OUTCOME MEASURES: The prevalence of post-surgical complications and secondary mucocele formation were compiled. RESULTS: Pathologies included osteoma (n = 34, 49%, mucocele (n = 27, 39%, fibrous dysplasia (n = 6, 9%, and encephalocele (n = 2, 3%. Complications included skin infections (n = 6, postoperative cutaneous fistula (n = 1, telecanthus (n = 4, diplopia (n = 3, nasal deformity (n = 2 and epiphora (n = 1. None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (P<0.0001. CONCLUSION: Cranialization of the frontal sinus appears to be a good option for prevention of secondary mucocele development after open excision of benign frontal sinus lesions.

  11. Cranialization of the frontal sinus for secondary mucocele prevention following open surgery for benign frontal lesions.

    Science.gov (United States)

    Horowitz, Gilad; Amit, Moran; Ben-Ari, Oded; Gil, Ziv; Abergel, Abraham; Margalit, Nevo; Cavel, Oren; Wasserzug, Oshri; Fliss, Dan M

    2013-01-01

    To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus. Retrospective case series. Tertiary academic medical center. Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011. Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59%) or frontal cranialization (n = 28, 41%). The prevalence of post-surgical complications and secondary mucocele formation were compiled. Pathologies included osteoma (n = 34, 49%), mucocele (n = 27, 39%), fibrous dysplasia (n = 6, 9%), and encephalocele (n = 2, 3%). Complications included skin infections (n = 6), postoperative cutaneous fistula (n = 1), telecanthus (n = 4), diplopia (n = 3), nasal deformity (n = 2) and epiphora (n = 1). None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (Pmucocele development after open excision of benign frontal sinus lesions.

  12. Effectiveness of percutaneous laser disc decompression versus conventional open discectomy in the treatment of lumbar disc herniation; Design of a prospective randomized controlled trial

    NARCIS (Netherlands)

    P.A. Brouwer (Patrick); W.C. Peul (Wilco); R. Brand (René); M.P. Arts (Mark); B.W. Koes (Bart); A.A. van den Berg (Annette); M.A. van Buchem (Mark)

    2009-01-01

    textabstractBackground. The usual surgical treatment of refractory sciatica caused by lumbar disc herniation, is open discectomy. Minimally invasive procedures, including percutaneous therapies under local anesthesia, are increasingly gaining attention. One of these treatments is Percutaneous Laser

  13. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kayentao Kassoum

    2012-10-01

    Full Text Available Abstract Background Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. Methods This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to P. falciparum malaria. Patients were randomized (2:1 to pyronaridine-artesunate granules (60/20 mg once daily or artemether-lumefantrine crushed tablets (20/120 mg twice daily, both dosed by bodyweight, orally (liquid suspension for three days. Results Of 535 patients randomized, 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate clinical and parasitological response (ACPR, corrected for re-infection using polymerase chain reaction (PCR genotyping (per-protocol population was 97.1% (329/339; 95% CI 94.6, 98.6 for pyronaridine-artesunate; 98.8% (165/167; 95% CI 95.7, 99.9 for artemether-lumefantrine. The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P 3 times the upper limit of normal (ULN and peak total bilirubin >2xULN (i.e. within the Hy’s law definition. Conclusions The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine. The adverse event profile was similar for the two comparators. Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes. Trial registration ClinicalTrials.gov: identifier NCT00541385

  14. Prospective unmasked randomized evaluation of the iStent inject® versus two ocular hypotensive agents in patients with primary open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    Fea AM

    2014-05-01

    Full Text Available Antonio M Fea,1 Jose I Belda,2 Marek Rękas,3 Anselm Jünemann,4 Lydia Chang,5 Luis Pablo,6 Lilit Voskanyan,7 L Jay Katz81Università degli Studi di Torino, Clinica Oculistica, Torino, Italy; 2Hospital Torrevieja Salud, UTE, Servicio de Oftalmologia, Alicante, Spain; 3Military Institute of Medicine, Department of Ophthalmology, Warsaw, Poland; 4Universitätsaugenklinik, Erlangen, Germany; 5Hinchingbrooke Hospital NHS Trust and Moorfields Bedford Hospital NHS Trust, United Kingdom; 6Hospital Universitario Miguel Servet, Servicio Oftalmologico, Zaragoza, Spain; 7SV Malayan Ophthalmological Center, Yerevan, Armenia; 8Wills Eye Institute, Jefferson Medical College, Philadelphia, PA, USAPurpose: The purpose of this study was to compare outcomes of subjects with open-angle glaucoma (OAG not controlled on one medication who underwent either implantation of two iStent inject® trabecular micro-bypass devices or received medical therapy consisting of a fixed combination of latanoprost/timolol.Patients and methods: Of 192 subjects who qualified for the study and were enrolled, 94 were randomized to surgery with implantation of two iStent inject® devices in the treated eye and 98 to receive medical therapy.Results: At the month 12 visit, 94.7% of eyes (89/94 in the stent group reported an unmedicated intraocular pressure (IOP reduction of ≥20% versus baseline unmedicated IOP, and 91.8% of eyes (88/98 in the medical therapy group reported an IOP reduction ≥20% versus baseline unmedicated IOP. A 17.5% between-group treatment difference in favor of the iStent inject group was statistically significant (P=0.02 at the ≥50% level of IOP reduction. An IOP ≤18 mmHg was reported in 92.6% of eyes (87/94 in the iStent inject group and 89.8% of eyes (88/98 in the medical therapy group. Mean (standard deviation IOP decreases from screening of 8.1 (2.6 mmHg and 7.3 (2.2 mmHg were reported in the iStent inject and medical therapy groups, respectively. A high

  15. Relative bioavailability of levodropropizine 60 mg capsule and syrup formulations in healthy male Korean volunteers: a singledose, randomized-sequence, open-label, two-way crossover study.

    Science.gov (United States)

    Jang, Jae-Won; Seo, Ji-Hyung; Jo, Min-Ho; Lee, Young-Joo; Cho, Young-Wuk; Yim, Sung-Vin; Lee, Kyung-Tae

    2013-02-01

    Levodropropizine is an oral non-opioid anti-tussive drug used in treatment of cough. A new generic 60 mg capsule formulation of levodropropizine has recently been developed. The aim of this study was to assess the pharmacokinetics and bioequivalence of the test (capsule) formulation and reference (syrup) formulation of levodropropizine (60 mg) in healthy, fasted, male Korean volunteers. This was a single-dose, randomized sequence, open-label, 2-period crossover study conducted in healthy male Korean volunteers in the fasted state at Kyung Hee University Medical Center (Seoul, Republic of Korea). A single oral dose of the test or reference formulation was followed by a 1-week washout period, after which subjects received the alternative formulation. Blood samples were collected at 0 (predose), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after study drug administration. Plasma concentration of levodropropizine was determined using a validated liquid chromatography tandem mass spectrometry (LCMS/ MS) method. The formulations were considered bioequivalent if the 90% CIs for C(max), AUC(0-12h) and AUC(0-∞) were within the predetermined bioequivalence range (80 - 125%, according to the guidelines of the Korea Food and Drug Administration (Korea FDA)). Tolerability was evaluated throughout the study based on vital sign measurements, laboratory analysis (blood biochemistry, hematology, hepatic function and urinalysis) and subject interviews concerning adverse events (AEs). A total of 36 male Korean subjects (mean (SD) age, 23.9 (2.4) years (range 19 - 30 years); height, 176.2 (6.1) cm (range 161 - 190 cm); weight, 69.8 (9.1) kg (range 54.0 - 92.2 kg); body mass index, 22.4 (2.1) kg/m2 (range 19.1 - 28.3 kg/m2)) was enrolled and completed the study. The mean values for C(max), t(max), AUC(0-12h), and AUC(0-∞) with the test formulation of levodropropizine were 331.51 ng/ml, 0.60 hours, 784.32 ng×h/ml, and 825.82 ng×h/ml, respectively; for the reference

  16. Prospective, randomized study of one, two, or three trabecular bypass stents in open-angle glaucoma subjects on topical hypotensive medication

    Directory of Open Access Journals (Sweden)

    Katz LJ

    2015-12-01

    Full Text Available L Jay Katz,1 Carl Erb,2 Amadeu Carceller Guillamet,3 Antonio M Fea,4 Lilit Voskanyan,5 Jeffrey M Wells,6 Jane Ellen Giamporcaro6 1Wills Eye Hospital, Jefferson Medical College, Philadelphia, PA, USA; 2Eye Clinic Wittenbergplatz, Berlin, Germany; 3Department of Ophthalmology, Hospital d’Hebron, Barcelona, Spain; 4University Eye Clinic of the University of Turin, Turin, Italy; 5SV Malayan Opthalmology Centre, Yerevan, Armenia; 6Glaukos Corporation, Laguna Hills, CA, USA Purpose: To assess the safety and efficacy of one, two, or three trabecular microbypass stents in eyes with primary open-angle glaucoma (OAG not controlled on ocular hypotensive medication. A total of 119 subjects were followed for 18 months postoperatively.Materials and methods: Subjects with medicated intraocular pressure (IOP 18–30 mmHg and postmedication-washout baseline IOP 22–38 mmHg were randomized to implantation of one, two, or three stents. Ocular hypotensive medication was to be used if postoperative IOP exceeded 18 mmHg.Results: A total of 38 subjects were implanted with one stent, 41 subjects with two stents, and 40 subjects with three stents. Both month 12 IOP reduction ≥20% without ocular hypotensive medication vs baseline unmedicated IOP and month 12 unmedicated IOP ≤18 mmHg were achieved by 89.2%, 90.2%, and 92.1% of one-, two-, and three-stent eyes, respectively. Furthermore, 64.9%, 85.4%, and 92.1% of the three respective groups achieved unmedicated IOP ≤15 mmHg. Over the 18-month follow-up period, medication was required in seven one-stent subjects, four two-stent subjects, and three three-stent subjects. At 18 months, mean unmedicated IOP was 15.9±0.9 mmHg in one-stent subjects, 14.1±1.0 mmHg in two-stent subjects, and 12.2±1.1 mmHg in three-stent subjects. Month 18 IOP reduction was significantly greater (P<0.001 with implantation of each additional stent, with mean differences in reduction of 1.84 mmHg (95% confidence interval 0.96

  17. Fecal Microbiota Transplant for Relapsing Clostridium difficile Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized, Open-Label, Controlled Pilot Study

    OpenAIRE

    Youngster, Ilan; Sauk, Jenny; Pindar, Christina; Wilson, Robin G; Kaplan, Jess L.; Smith, Mark B.; Alm, Eric J; Gevers, Dirk; Russell, George H.; Hohmann, Elizabeth L.

    2014-01-01

    Fecal microbiota transplant is increasingly used to treat recurrent or relapsing Clostridium difficile infection. In this randomized controlled study, using a frozen inoculum from unrelated donors was safe and effective, whether administered by nasogastric tube or by colonoscopy.

  18. Clinical and radiographic evaluation of periodontal intrabony defects by open flap surgery alone or in combination with Biocollagen ? membrane: A randomized clinical trial

    National Research Council Canada - National Science Library

    Essam Elkhatat; Amr Elkhatat; Saleh Azzeghaiby; Bassel Tarakji; Khaled Beshr; Hossam Mossa

    2015-01-01

    ...) in the treatment of intrabony defects. Materials and Methods: A total of 16 patients of both sexes satisfying the criteria of chronic periodontitis and each of whom displayed one intrabony defect were randomly assigned to two groups, i.e...

  19. A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia.

    Science.gov (United States)

    Derman, Richard; Roman, Eloy; Modiano, Manuel R; Achebe, Maureen M; Thomsen, Lars L; Auerbach, Michael

    2017-03-01

    Iron deficiency anemia (IDA) is common in many chronic diseases, and intravenous (IV) iron offers a rapid and efficient iron correction. This trial compared the efficacy and safety of iron isomaltoside and iron sucrose in patients with IDA who were intolerant of, or unresponsive to, oral iron. The trial was an open-label, comparative, multi-center trial. Five hundred and eleven patients with IDA from different causes were randomized 2:1 to iron isomaltoside or iron sucrose and followed for 5 weeks. The cumulative dose of iron isomaltoside was based on body weight and hemoglobin (Hb), administered as either a 1000 mg infusion over more than 15 minutes or 500 mg injection over 2 minutes. The cumulative dose of iron sucrose was calculated according to Ganzoni and administered as repeated 200 mg infusions over 30 minutes. The mean cumulative dose of iron isomaltoside was 1640.2 (standard deviation (SD): 357.6) mg and of iron sucrose 1127.9 (SD: 343.3) mg. The primary endpoint was the proportion of patients with a Hb increase ≥2 g/dL from baseline at any time between weeks 1-5. Both non-inferiority and superiority were confirmed for the primary endpoint, and a shorter time to Hb increase ≥2 g/dL was observed with iron isomaltoside. For all biochemical efficacy parameters, faster and/or greater improvements were found with iron isomaltoside. Both treatments were well tolerated; 0.6% experienced a serious adverse drug reaction. Iron isomaltoside was more effective than iron sucrose in achieving a rapid improvement in Hb. Furthermore, iron isomaltoside has an advantage over iron sucrose in allowing higher cumulative dosing in fewer administrations. Both treatments were well tolerated in a broad population with IDA.

  20. Efficacy and Safety of Once-Daily Insulin Degludec/Insulin Aspart versus Insulin Glargine (U100) for 52 Weeks in Insulin-Naïve Patients with Type 2 Diabetes: A Randomized Controlled Trial

    Science.gov (United States)

    Kumar, Ajay; Franek, Edward; Wise, Jonathan; Niemeyer, Marcus; Mersebach, Henriette; Simó, Rafael

    2016-01-01

    Purpose The efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily (OD) compared with insulin glargine U100 (IGlar) OD over 52 weeks in insulin-naïve adults with type 2 diabetes mellitus (T2DM) was investigated. Methods In this open-label, parallel-group treat-to-target trial, participants were randomized (1:1) to receive IDegAsp OD (breakfast, n = 266) or IGlar OD (as per label, n = 264). Participants then entered a 26-week extension phase (IDegAsp OD, n = 192; IGlar OD, n = 221). The primary endpoint was change from baseline to Week 26 in HbA1c. Results After 26 and 52 weeks, mean HbA1c decreased to similar levels in both groups. After 52 weeks, the mean estimated treatment difference was –0.08% (–0.26, 0.09 95%CI), confirming the non-inferiority of IDegAsp OD versus IGlar OD evaluated at Week 26. After 52 weeks, there was a similar reduction in mean fasting plasma glucose in both treatment groups. The rate of confirmed hypoglycemic episodes was 86% higher (p administration of IDegAsp with the main meal of the day, tailored to the individual patient’s needs. Trial Registration ClinicalTrials.gov: NCT01045707 [core]) and NCT01169766 [ext] PMID:27760129

  1. A comparison between intravenous lidocaine and ketamine on acute and chronic pain after open nephrectomy: A prospective, double-blind, randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Ali Jendoubi

    2017-01-01

    Conclusion: Ketamine and lidocaine are safe and effective adjuvants to decrease opioid consumption and control early pain. We also suggest that lidocaine infusion serves as an interesting alternative to improve the functional walking capacity and prevent chronic neuropathic pain at 3 months after open nephrectomy.

  2. Effectiveness of antipsychotics in first-episode schizophrenia and schizophreniform disorder on response and remission : An open randomized clinical trial (EUFEST)

    NARCIS (Netherlands)

    Boter, Han; Peuskens, Joseph; Libiger, Jan; Fleischhacker, W. Wolfgang; Davidson, Michael; Galderisi, Silvana; Kahn, Rene S.

    2009-01-01

    Background: Predefined response and remission criteria may hold more clinical relevance than mean scores on rating scales. We compared the effectiveness of low doses of haloperidol and regular doses of second generation antipsychotics (SGAs) on >= 50% response and remission. Methods: In an open rand

  3. Pharmacokinetics of armodafinil and modafinil after single and multiple doses in patients with excessive sleepiness associated with treated obstructive sleep apnea: a randomized, open-label, crossover study.

    Science.gov (United States)

    Darwish, Mona; Kirby, Mary; D'Andrea, Denise M; Yang, Ronghua; Hellriegel, Edward T; Robertson, Philmore

    2010-11-01

    Armodafinil (the R-isomer of racemic modafinil) and modafinil are wakefulness-promoting medications for excessive sleepiness associated with treated obstructive sleep apnea (OSA). The R-isomer of racemic modafinil has a half-life of approximately15 hours; the S-isomer has a half-life of 4 to 5 hours. The R-and S-isomers are equipotent, producing equivalent pharmacologic activity at equal concentrations. The aim of this work was to compare the pharmacokinetic profiles of armodafinil (R-modafinil) and modafinil (racemic mixture with equal quantities of R- and S-isomers) at equal doses in patients with residual excessive sleepiness associated with continuous positive airway pressure-treated OSA. This open-label study was conducted at 5 US centers from July 2008 to March 2009. Patients were randomized to 1 of 2 crossover administration sequences, ABCD or BADC, where A was a single armodafinil 200-mg dose, B was a single modafinil 200-mg dose, C was multiple daily modafinil 200-mg doses, and D was multiple daily armodafinil 200-mg doses. During multiple-dose administration, patients received 100 mg once daily for days 1 and 2, and 200 mg once daily for days 3 through 10. The pharmacokinetic parameters of principal interest for assessing the bioequivalence of armodafinil and modafinil were maximum concentration at 7 to 11 hours after dosing and the concentration-versus-time curve for this period. Analysis was performed via achiral high-performance liquid chromatography with ultraviolet detection using blood samples obtained over 72 hours after single-dose administration and over 24 hours after the multiple-dose regimen. For post hoc evaluation of bioequivalence, 90% CI values were also constructed for the geometric mean ratios of armodafinil to modafinil. Tolerability was assessed by the reported adverse events, clinical laboratory testing, vital sign measurements, ECGs, and physical exams. The study population was 83.3% male (35/42) and 76.2% white (32/42) with a mean

  4. A single center, open, randomized study investigating the clinical safety and the endothelial modulating effects of a prostacyclin analog in combination with eptifibatide in patients having undergone primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Holmvang, Lene; Ostrowski, Sisse Rye; Dridi, Nadia Paarup

    2012-01-01

    Treatment with the endothelial modulator prostacyclin may be beneficial in patients with endothelial dysfunction. The primary aim of the present pilot study was to evaluate the safety and the potential endothelial modulating affect of the prostacyclin analog iloprost in patients with a recent ST...... segment elevation myocardial infarction (STEMI). Seventeen patients were randomized to either 24h of iloprost infusion in combination with low dose eptifibatide infusion or saline infusion+eptifibatide. The study was randomized and open labeled. None of the patients experienced any bleeding complications...... and vital signs were stable throughout the entire study period in both groups. None of the functional hemostatic whole blood assays applied in the present study differed between the active treatment and the placebo group. The endothelial marker, sE-selectin, displayed a decrease over time in the iloprost...

  5. A randomized, double-blind, placebo-controlled multicenter trial evaluating topical zinc oxide for acute open wounds following pilonidal disease excision

    DEFF Research Database (Denmark)

    Agren, Magnus S; Ostenfeld, Ulla; Kallehave, Finn;

    2006-01-01

    The purpose of this randomized, double-blind, placebo-controlled multicenter trial was to compare topical zinc oxide with placebo mesh on secondary healing pilonidal wounds. Sixty-four (53 men) consecutive patients, aged 17-60 years, were centrally randomized to either treatment with 3% zinc oxide...... range 42-71 days) for the zinc and 62 days (55-82 days) for the placebo group (p = 0.32). Topical zinc oxide increased (p wound fluid zinc levels to 1,540 (1,035-2,265) microM and decreased (p wounds. Fewer zinc oxide (n = 3) than placebo...... abnormalities by histopathological examination of wound biopsies, or other harmful effects. Larger clinical trials will be required to show definitive effects of topical zinc oxide on wound healing and infection....

  6. Hemostatic efficacy of TachoSil in liver resection compared with argon beam coagulator treatment: an open, randomized, prospective, multicenter, parallel-group trial

    DEFF Research Database (Denmark)

    Fischer, Lars; Seiler, Christoph M; Broelsch, Christoph E;

    2011-01-01

    surgical trial with 2 parallel groups. Patients were eligible for intra-operative randomization after elective resection of = 1 liver segment and primary hemostasis. The primary end point was the time to hemostasis after starting the randomized intervention to obtain secondary hemostasis. Secondary end...... time to hemostasis was less when TachoSil was used (3.6 minutes) compared with ABC (5.0 minutes; P = .0018). The estimated ratio of mean time to hemostasis for TachoSil/ABC was 0.61 (95% confidence interval, 0.47-0.80; P = .0003). Postoperative drainage volume, drainage fluid, and drainage duration did...... not differ between the 2 groups. Mortality (2 vs 4 patients) and adverse reactions (24 vs 28 patients) for TachoSil versus ABC did not differ. CONCLUSION: This trial confirmed that TachoSil achieved significantly faster hemostasis after liver resection compared with ABC. Postoperative morbidity and mortality...

  7. A randomized, double-blind, placebo-controlled multicenter trial evaluating topical zinc oxide for acute open wounds following pilonidal disease excision

    DEFF Research Database (Denmark)

    Friis-Møller, Alice; Agren, MS; Ostenfeld, U;

    2006-01-01

    The purpose of this randomized, double-blind, placebo-controlled multicenter trial was to compare topical zinc oxide with placebo mesh on secondary healing pilonidal wounds. Sixty-four (53 men) consecutive patients, aged 17-60 years, were centrally randomized to either treatment with 3% zinc oxide...... range 42-71 days) for the zinc and 62 days (55-82 days) for the placebo group (p = 0.32). Topical zinc oxide increased (p zinc levels to 1,540 (1,035-2,265) microM and decreased (p zinc oxide (n = 3) than placebo......-treated patients (n = 12) were prescribed postoperative antibiotics (p = 0.005). Serum-zinc levels increased (p Zinc oxide was not associated with increased pain by the visual analog scale, cellular...

  8. Value of first day angiography/angioplasty in evolving Non-ST segment elevation myocardial infarction: an open multicenter randomized trial. The VINO Study.

    Science.gov (United States)

    Spacek, R; Widimský, P; Straka, Z; Jiresová, E; Dvorák, J; Polásek, R; Karel, I; Jirmár, R; Lisa, L; Budesínský, T; Málek, F; Stanka, P

    2002-02-01

    Direct angioplasty is an effective treatment for ST-elevation myocardial infarction. The role of very early angioplasty in non-ST-elevation infarction is not known. Thus, a randomized study of first day angiography/angioplasty vs early conservative therapy of evolving myocardial infarction without persistent ST-elevation was conducted. One hundred and thirty-one patients with confirmed acute myocardial infarction without ST-segment elevations were randomized within 24 h of last rest chest pain: 64 in the first day angiography/angioplasty group and 67 in the early conservative group (coronary angiography only after recurrent or stress induced myocardial ischaemia). All patients in the invasive group underwent coronary angiography on the day of admission (mean randomization-angiography time 6.2 h). First day angioplasty of the infarct related artery was performed in 47% of the patients and bypass surgery in 35%. In the conservative group, 55% underwent coronary angiography, 10% angioplasty and 30% bypass surgery within 6 months. The primary end-point (death/reinfarction) at 6 months occurred in 6.2% vs 22.3% (P<0.001). Six month mortality in the first day angiography/angioplasty group was 3.1% vs 13.4% in the conservative group (P<0.03). Non-fatal reinfarction occurred in 3.1% vs. 14.9% (P<0.02). First day coronary angiography followed by angioplasty whenever possible reduces mortality and reinfarction in evolving myocardial infarction without persistent ST-elevation, in comparison with an early conservative treatment strategy. Copyright 2001 The European Society of Cardiology.

  9. A randomized, open, parallel group, multicenter trial to investigate analgesic efficacy and safety of a new transdermal fentanyl patch compared to standard opioid treatment in cancer pain

    DEFF Research Database (Denmark)

    Kress, Hans G; Von der Laage, Dorothea; Hoerauf, Klaus H

    2008-01-01

    trial, in which 220 patients were randomized to receive either the fentanyl patch or standard opioid treatment for 30 days. The primary efficacy variable, pain intensity (PI) on a 0-10-point numerical rating scale, was recorded once daily. The primary endpoint was the relative area under the curve of PI...... expressed as a percentage of the maximum possible PI area under the curve. Any adverse events were recorded; four tolerability endpoints, constipation, nausea, daytime drowsiness, and sleeping disturbances, were assessed daily. Noninferiority was shown; the upper 95% confidence interval limits of the mean...

  10. A randomized, open, parallel group, multicenter trial to investigate analgesic efficacy and safety of a new transdermal fentanyl patch compared to standard opioid treatment in cancer pain

    DEFF Research Database (Denmark)

    Kress, H.G.; Laage, D. Von der; Hoerauf, K.H.

    2008-01-01

    , in which 220 patients were randomized to receive either the fentanyl patch or standard opioid treatment for 30 days. The primary efficacy variable, pain intensity (PI) on a 0-10-point numerical rating scale, was recorded once daily. The primary endpoint was the relative area under the curve of PI expressed...... as a percentage of the maximum possible PI area under the curve. Any adverse events were recorded; four tolerability endpoints, constipation, nausea, daytime drowsiness, and sleeping disturbances, were assessed daily. Noninferiority was shown; the upper 95% confidence interval limits os the mean difference...

  11. Efficacy of a standardized extract of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) in infantile colic: An open randomized controlled trial.

    Science.gov (United States)

    Martinelli, M; Ummarino, D; Giugliano, F P; Sciorio, E; Tortora, C; Bruzzese, D; De Giovanni, D; Rutigliano, I; Valenti, S; Romano, C; Campanozzi, A; Miele, E; Staiano, A

    2017-06-30

    Infant colic (IC) is a prevalent physiological event of infants, which can disrupt the child's home environment. We aimed to investigate the effectiveness of a mixture of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) compared with Lactobacillus reuteri DSM 17938 and with simethicone for the treatment of IC. A multicenter randomized comparative study was conducted in infants with colic, according to Rome III criteria, who were randomly assigned to receive M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) (Colimil(®) Plus(®) ; Milte Italia Spa, Milan, Italy) (Group A), L. reuteri DSM 17938 (Group B) and simethicone (Group C). Treatment was given to subjects for 28 days. One-hundred and seventy-six patients completed the study. Mean daily crying time at day 28 was significantly lower in group A (-44, 95% CI: -58 to -30, Pofficinalis L. and tyndallized L. acidophilus (HA122) and L. reuteri DSM 17938 are significantly more effective than simethicone in IC. ClinicalTrials.gov: NCT02708238. © 2017 John Wiley & Sons Ltd.

  12. Biofilm formation in long-term central venous catheters in children with cancer: a randomized controlled open-labelled trial of taurolidine versus heparin.

    Science.gov (United States)

    Handrup, Mette Møller; Fuursted, Kurt; Funch, Peter; Møller, Jens Kjølseth; Schrøder, Henrik

    2012-10-01

    Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty-eight children with cancer were randomized to catheter locking by heparin (n = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi-quantitative cultures were also performed. Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group. A positive culture was made of six of the catheters locked with taurolidine and heparin, respectively (p = 0.78). The rate of catheter-related bloodstream infections (CRBSI) was 0.1 per 1000 catheter-days using taurolidine and 0.9 per 1000 catheter-days using heparin (p = 0.03). This randomized trial confirmed that the use of taurolidine as catheter-lock compared with heparin reduced the rate of CRBSIs; this reduction was not related to a reduction in the intraluminal biofilm formation and the rate of bacterial colonization detected by scanning electron microscopy in the two groups.

  13. School-based mindfulness intervention for stress reduction in adolescents: Design and methodology of an open-label, parallel group, randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Jeanette M. Johnstone

    2016-12-01

    Full Text Available Adolescents are in a high-risk period developmentally, in terms of susceptibility to stress. A mindfulness intervention represents a potentially useful strategy for developing cognitive and emotion regulation skills associated with successful stress coping. Mindfulness strategies have been used successfully for emotional coping in adults, but are not as well studied in youth. This article details a novel proposal for the design of an 8-week randomized study to evaluate a high school-based mindfulness curriculum delivered as part of a two semester health class. A wellness education intervention is proposed as an active control, along with a waitlist control condition. All students enrolled in a sophomore (10th grade health class at a private suburban high school will be invited to participate (n = 300. Pre-test assessments will be obtained by youth report, parent ratings, and on-site behavioral testing. The assessments will evaluate baseline stress, mood, emotional coping, controlled attention, and working memory. Participants, divided into 13 classrooms, will be randomized into one of three conditions, by classroom: A mindfulness intervention, an active control (wellness education, and a passive control (waitlist. Waitlisted participants will receive one of the interventions in the following term. Intervention groups will meet weekly for 8 weeks during regularly scheduled health classes. Immediate post-tests will be conducted, followed by a 60-day post-test. It is hypothesized that the mindfulness intervention will outperform the other conditions with regard to the adolescents' mood, attention and response to stress.

  14. One-year, randomized, open trial comparing olanzapine, quetiapine, risperidone and ziprasidone effectiveness in antipsychotic-naive patients with a first-episode psychosis.

    Science.gov (United States)

    San, Luis; Arranz, Belen; Perez, Victor; Safont, Gemma; Corripio, Iluminada; Ramirez, Nicolas; Dueñas, Rosa; Alvarez, Enric

    2012-12-30

    The aim of this study was to compare the 12-month effectiveness of several second-generation antipsychotic drugs, with that of haloperidol in never-treated patients with first-episode psychosis. In total, 114 patients without life time exposure to any psychotropic medication were randomized to haloperidol, olanzapine, risperidone, quetiapine or ziprasidone. Primary outcome was time to all-cause discontinuation. Secondary outcomes included discontinuation rates and symptom change as measured by the Positive and Negative Syndrome Scale (PANSS). The overall discontinuation rate 64%. At 12 months, the proportion of patients discontinuing treatment was 40.0% for olanzapine, 56.5% for quetiapine, 64.0% for risperidone, 80.0% for ziprasidone and 85.7% for haloperidol. Mean time to antipsychotic discontinuation was higher in patients randomized to second-generation antipsychotics than in those taking haloperidol. Significantly lower discontinuation was noted in patients on olanzapine than on haloperidol, or ziprasidone. Our results suggest that olanzapine might lead to longer treatment continuation in treatment naïve FEP patients than haloperidol and, possibly ziprasidone. Global psychopathology was significantly less reduced by haloperidol than with each individual SGA in this earliest phase of treatment. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    William Eardley

    2010-04-01

    Full Text Available William Eardley, Cory TothDepartment of Clinical Neurosciences and the University of Calgary, Calgary, AB, CanadaAbstract: Although many therapies are used in the management of neuropathic pain (NeP due to polyneuropathy (PN, few comparison studies exist. We performed a prospective, non-randomized, unblended, efficacy comparison of the serotonin-norepinephrine reuptake inhibitor venlafaxine, as either monotherapy or adjuvant therapy, with a first-line medication for NeP, gabapentin, in patients with PN-related NeP. VAS pain scores were assessed after 3 and 6 months in intervention groups and in a cohort of patients receiving no pharmacotherapy. In a total of 223 patients, we analyzed pain quantity and quality (visual analogue scale [VAS] score, Brief Pain Inventory [BPI], quality of life and health status measures [EuroQol 5 Domains, EQ-5D], Medical Outcomes Sleep Study Scale [MOSSS], Hospital Anxiety and Depression Scale [HADS] and Short Form 36 Health Survey [SF-36] after 6 months of therapy. Significant improvements in VAS pain scores occurred for all treatment groups after 6 months. Improvements in aspects of daily life and anxiety were identified in all treatment groups. Our data suggest that monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for NeP management. We advocate for head-to-head, randomized, double-blinded studies of current NeP therapies.Keywords: peripheral neuropathy, neuropathic pain, pharmacotherapy, venlafaxine, gabapentin

  16. RING-OPENING POLYMERIZAION OF 2,2-DIMETHYLTRIMETHYLENE CARBONATE INITIATED BY IN SITU GENERATED, TETRAHYDROSALEN STABLIZED YTTRIUM BOROHYDRIDE COMPLEX AND RANDOM COPOLYMERIZATION WITH ε-CAPROLACTONE

    Institute of Scientific and Technical Information of China (English)

    Jing Huang; Jian-fang Yu; Han-jian Yu; Wei-lin Sun; Zhi-quan Shen

    2011-01-01

    The poly(2,2-dimethyltrimethylene carbonate) (PDTC) with one hydroxyl and one formate tenninal fimctions was synthesized by in situ generated, tetrahydrosalen stabilized yttrium borohydride complex. The influences of monomer/initiator molar ratio, temperature and reaction time on polymerization of DTC were investigated. Under the condition: [DTC]/[I] = 500, 55℃, toluene: 0.5 mL, DTC: 0.6 g, PDTC with Mn = 15600 and PDI = 2.15 was obtained.Through 1H-NMR and 13C-NMR analyses, the structure of PDTC was characterized and a coordination-insertion mechanism was proposed. In addition, the random copolymerization of DTC and caprolactone (CL) initiated by rare-earth borohydride compound was studied. The microstructure of PDTC-co-PCL includes four diads: DTC-CL, CL-CL, DTC-DTC and CLDTC, which were determined by the specific signals in 1H-NMR spectra. Based on the typical signals of the formate (δ=8.08) and hydroxyl (δ = 3.34) end groups of PDTC-co-PCL, a mechanism involving DTC monomer inserts before CL during the initiation process was presumed. Furthermore, the thermal properties of amorphous copolymer were characterized by differential scanning calorimetry (DSC). The results support the random structure of PDTC-co-PCL.

  17. Biofilm formation in long-term central venous catheters in children with cancer: a randomized controlled open-labelled trial of taurolidine versus heparin

    DEFF Research Database (Denmark)

    Handrup, Mette Møller; Fuursted, Kurt; Funch, Peter;

    2012-01-01

    Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty-eight children with cancer were randomized to catheter locking by heparin (n...... = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi......-quantitative cultures were also performed. Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group. A positive culture was made of six of the catheters locked with taurolidine and heparin, respectively (p = 0.78). The rate of catheter-related bloodstream...

  18. Hemostatic efficacy of TachoSil in liver resection compared with argon beam coagulator treatment: An open, randomized, prospective, multicenter, parallel-group trial

    DEFF Research Database (Denmark)

    Fischer, Lars; Seiler, Christoph M.; Broelsch, Christoph E.

    2011-01-01

    points were drainage duration, volume, and content. Adverse events were collected to evaluate the safety of treatments. The trial was registered internationally (Eudract number 2008-006407-23). Results: Among 119 patients (60 TachoSil and 59 ABC) randomized in 10 tertiary care centers in Europe, the mean...... time to hemostasis was less when TachoSil was used (3.6 minutes) compared with ABC (5.0 minutes; P = .0018). The estimated ratio of mean time to hemostasis for TachoSil/ABC ws 0.61 (95% confidence interval, 0.47-0.80; P = .0003). Postoperative drainage volume, drainage fluid, and drainage duration did...... not differ between the 2 groups. Mortality (2 vs. 4 patients) and adverse reactions (24 vs. 28 patients) for TachoSil versus ABC did not differ. Conclusion: This trial confirmed that TachoSil achieved significantly faster hemostasis after liver resection compared with ABC. Postoperative morbidity...

  19. A randomized open-label controlled trial of chlorhexidine-alcohol vs povidone-iodine for cesarean antisepsis: the CAPICA trial.

    Science.gov (United States)

    Springel, Edward H; Wang, Xiao-Yu; Sarfoh, Vanessa M; Stetzer, Bradley P; Weight, Steven A; Mercer, Brian M

    2017-06-07

    Identification of optimal surgical site antisepsis preparations may reduce cesarean-related surgical site infections. Two recently published investigations examined efficacy of chlorhexidine-alcohol and iodine-alcohol preparations. No previous randomized controlled trial has compared chlorhexidine-alcohol to povidone-iodine aqueous scrub and paint in reduction of cesarean-related surgical site infection. The purpose of the study was to determine if chlorhexidine-alcohol would result in fewer surgical site infections than povidone-iodine when used as skin antisepsis preparation prior to cesarean delivery. This study was a single-center pragmatic randomized controlled trial at an urban tertiary care institution to compare chlorhexidine-alcohol 26-mL single-step applicator to povidone-iodine aqueous scrub and paint 236-mL wet skin tray as preoperative skin antiseptic preparation for women undergoing cesarean delivery. Patients were eligible for study participation if they could provide informed consent in English or Spanish, were ≥18 years of age, did not have clinical chorioamnionitis, were unlikely to be lost to follow-up, and had no sensitivities to chlorhexidine, betadine, or iodine. Treatment was assigned by computer-generated simple 1:1 randomization immediately before skin preparation. The primary outcome was surgical site infection occurring within 30 days of cesarean delivery including ≥1 of: superficial or deep surgical site infection, or endometritis, according to Centers for Disease Control and Prevention definitions. Analysis was by intent to treat. Categorical outcomes were compared using Fisher exact test. The Wilcoxon rank-sum test was performed for continuous outcomes. This trial was institutional review board approved and registered at ClinicalTrials.gov (NCT02202577). In all, 932 subjects (461 assigned to chlorhexidine-alcohol, 471 assigned to povidone-iodine) were randomized from February 2013 through May 2016. Rate of follow-up evaluation

  20. A Multicenter, Randomized, Open-Labeled, Parallel Group Trial of Sildenafil in Alcohol-Associated Erectile Dysfunction: The Impact on Psychosocial Outcomes

    Directory of Open Access Journals (Sweden)

    Alexander Grinshpoon

    2009-09-01

    Full Text Available To examine the effect of sildenafil on erectile dysfunction (ED and psychosocial outcomes in alcohol-dependent (AD men, 108 men with these diagnoses were randomly assigned to either take sildenafil (50 mg as add-on to standard treatment for AD, or the same treatment without sildenafil, for 12 weeks. Only 50 patients in sildenafil group and 51 in control group twice completed the International Index of Erectile Function (IIEF and a battery of self-report questionnaires. IIEF scores and psychosocial functioning, self-esteem and support from friends improved only for sildenafil-treated patients (P < 0.001. The high effect sizes suggest that the observed benefits are unlikely to be a placebo effect, although their unspecific nature could not be ruled out. In men with ED associated with AD, sildenafil improves both ED and psychosocial outcomes. Further placebo-controlled clinical trial is warranted.

  1. Amisulpride plus valproate vs haloperidol plus valproate in the treatment of acute mania of bipolar I patients: a multicenter, open-label, randomized, comparative trial

    Directory of Open Access Journals (Sweden)

    Pierre Thomas

    2008-06-01

    Full Text Available Pierre Thomas1, Eduard Vieta2 for the SOLMANIA study group1Department of Psychiatry, Fontan Hospital CHRU Lille, University of Lille 2, France; 2Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, SpainAbstract: The primary objective of this study was to compare the effectiveness of combination treatment of valproate and amisulpride with that of valproate and haloperidol in bipolar I disorder. Adult inpatients with a current manic episode fulfilling DSM-IV-TR diagnostic criteria for bipolar type I disorder were included. Patients were randomized to amisulpride (400–800 mg/day or haloperidol (5–15 mg/day for 3 months and all received valproate. The primary effectiveness criterion was the percentage of responders (defined by a decrease of ≥50% of the Y-MRS in patients completing the study. Safety was evaluated by adverse event reporting, determination of extrapyramidal function and clinical examination. Sixty-two patients were randomized to receive valproate-amisulpride, and 61 to receive valproate-haloperidol. At study end, responder rates were 72.6% in the amisulpride group and 65.5% in the haloperidol group. Remission rates were 83.9% and 89.7%, respectively. At study end, neither response rates nor remission rates differed significantly between groups. Treatment-emergent adverse events occurred significantly (p = 0.009 more frequently in the haloperidol group (86.4% than in the amisulpride group (66.1%. In conclusion, the valproate–amisulpride combination was as effective as the valproate – haloperidol combination in bipolar I patients, with a better safety profile.Keywords: amisulpride, valproate, haloperidol, clinical trial, mania, bipolar disorder

  2. 计量资料非劣效临床试验样本量及把握度的计算与SAS程序实现%SAS programming for sample size and power calculation of measurement data in non-inferior trials

    Institute of Scientific and Technical Information of China (English)

    文世梅; 陈云飞; 刘华

    2013-01-01

    AIM: To calculate sample size and power of measurement data in non-inferior trials using SAS programming. METHODS;Two cal culation method, formula and SAS program ming, were compared based on examples and the SAS macro for power was given as well. RE SULTS: The calculation results of SAS program ming was consistent with the formula, and SAS programming can directly give the result was more convenient without looking-up table to ob tain the relevant parameters. CONCLUSION: It is helpful for investigator to have a better under standing at this programming to calculate sample size and power provided in this paper.%目的:利用SAS简易快速对计量资料非劣效临床试验进行样本量及把握度的计算.方法:比较公式及SAS编程两种计算方法,同时给出反推把握度的SAS宏程序.结果:公式和SAS程序两种计算方法的结果一致,利用SAS程序可以直接给出结果,无需要再进行查表获得相关参数,更简单、快捷.结论:利用本文提供的程序可以更好地帮助研究者理解与运用此程序进行样本量和把握度的估算,为此类新药临床试验服务.

  3. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD

    Directory of Open Access Journals (Sweden)

    Tara Rheault

    2016-04-01

    Full Text Available This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611. Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1 at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0–24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score. Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: −50 mL to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: −5–54. Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37% and glycopyrronium (36%. Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

  4. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD.

    Science.gov (United States)

    Rheault, Tara; Khindri, Sanjeev; Vahdati-Bolouri, Mitra; Church, Alison; Fahy, William A

    2016-04-01

    This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0-24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score). Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: -50 mL) to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: -5-54). Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37%) and glycopyrronium (36%). Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

  5. Does a laparoscopic approach attenuate the body weight loss and lean body mass loss observed in open distal gastrectomy for gastric cancer? a single-institution exploratory analysis of the JCOG 0912 phase III trial.

    Science.gov (United States)

    Aoyama, Toru; Sato, Tsutomu; Hayashi, Tsutomu; Yamada, Takanobu; Cho, Haruhiko; Ogata, Takashi; Oba, Koji; Yoshikawa, Takaki

    2017-06-16

    Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer may prevent the loss of body weight and lean body mass resulting from reduced surgical stress in comparison to open distal gastrectomy (ODG). A multicenter phase III trial conducted by the Japan Clinical Oncology Group (JCOG0912 trial) was performed to confirm the non-inferiority of LADG to ODG for stage I gastric cancer in terms of relapse-free survival. This study was performed as a single-institution exploratory analysis using the data of the patients from our hospital who were enrolled in the JCOG0912 phase III trial. Body weight and lean body mass were evaluated using a bioelectrical impedance analyzer within 1 week before and at 1 week, 1 month, and 3 months after surgery. One-hundred six patients were randomized to undergo ODG (54 patients) or LADG (51 patients). Body weight loss at 1 week, 1 month, and 3 months was -3.0%, -4.9%, and -5.4%, respectively, in the ODG group and -2.7%, -4.3%, and -5.7%, respectively, in the LADG group; the differences were not statistically significant (p = 0.330, 0.166, and 0.656, respectively). Lean body mass loss at 1 week, 1 month, and 3 months was -2.8%, -4.1%, and -2.3%, respectively, in the ODG group and -2.7%, -2.9%, and -3.0%, respectively, in the LADG group; the differences were not statistically significant (p = 0.610, 0.413, and 0.925, respectively). The laparoscopic approach did not attenuate the loss of body weight and lean body mass in comparison to patients who underwent open distal gastrectomy for gastric cancer.

  6. Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labeled randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Sandeep Chaudhary

    2016-01-01

    Full Text Available Background and Aims: Although Vitamin D deficiency has been linked to autoimmune thyroid disorders (AITD, the impact of Vitamin D supplementation on thyroid autoimmunity is not known. This study aimed to evaluate the impact of Vitamin D supplementation on thyroid autoimmunity (thyroid peroxidase antibody [TPO-Ab] titers in patients with newly diagnosed AITD in a randomized controlled trial. Materials and Methods: One hundred two patients with newly diagnosed AITD (TPO-Ab > 34 kIU/L and/or sonographic evidence of thyroiditis patients were randomized into Group-1 (intervention group and Group-2 (control group. Group-1 received cholecalciferol 60,000 IU weekly and calcium 500 mg/day for 8 weeks; Group-2 received calcium 500 mg/day for 8 weeks. Responders were defined as ≥25% fall in TPO-Ab titers. Individuals with at least 3-month follow-up were analyzed. Trial is registered at ctri.nic.in (CTRI/2015/04/005713. Results: Data from 100 AITD patients (68 with thyroid stimulating hormone [TSH] ≤10 mIU/L, 32 with TSH > 10 mIU/L, 93% having Vitamin D insufficiency, were analyzed. TPO-Ab titers were highest among patients in the lowest 25-hydroxyvitamin D quartile (P = 0.084. At 3 months follow-up, there was significant fall in TPO-Ab in Group-1 (−46.73% as compared to Group-2 (−16.6% (P = 0.028. Sixty-eight percentage patients in Group-1 were responders compared to 44% in Group-2 (P = 0.015. Kaplan–Meier analysis revealed significantly higher response rate in Group-1 (P = 0.012. Significantly greater reduction in TPO-Ab titers was observed in AITD with TSH ≤ 10 mIU/L compared to TSH > 10 mIU/L. Cox regression revealed Group-1 followed by TPO-Ab and free tetraiodothyronine levels to be a good predictor of response to therapy (P = 0.042, 0.069, and 0.074, respectively. Conclusion: Vitamin D supplementation in AITD may have a beneficial effect on autoimmunity as evidence by significant reductions in TPO-Ab titers.

  7. Comparison of 532 nm Potassium Titanyl Phosphate Laser and 595 nm Pulsed Dye Laser in the Treatment of Erythematous Surgical Scars: A Randomized, Controlled, Open-Label Study.

    Science.gov (United States)

    Keaney, Terrence C; Tanzi, Elizabeth; Alster, Tina

    2016-01-01

    The pulsed dye laser (PDL) has long been used for treatment of erythematous and hypertrophic scars. Its effectiveness has been attributed in large part to its vascular-specificity. The vascular-specific potassium titanyl phosphate (KTP) laser has also been reported to be clinically effective for scars, but has not been compared to the PDL. To compare the safety and clinical efficacy of a 532-nm KTP laser versus a 595-nm PDL in improving the appearance of erythematous surgical scars. Twenty patients with matched bilateral erythematous surgical scars or a single linear erythematous scar measuring longer than 5 cm were enrolled in the study. Single scars were divided into equal halves with each half randomized to receive 3 successive treatments at 6-week intervals with either a 532-nm KTP laser (Excel V; Brisbane, CA) or a 595-nm PDL (Cynergy; Cynosure Inc., Chelmsford, MA) at equivalent laser parameters. Bilateral matched scars were similarly randomized to receive three 532-nm KTP or 595-nm PDL treatments. Clinical efficacy was evaluated 12 weeks after the third (final) laser treatment by independent, blinded photographic scar assessments. Secondary evaluations included final investigator and subject treatment/satisfaction assessments, Vancouver scar scale (VSS) scores, subject scar symptoms, intraoperative pain scores, and incidence of side effects. Clinical improvement of erythematous surgical scars was observed with both 532-nm KTP and 595-nm PDL systems. No statistically significant differences between the 2 treatment arms were noted in the independent, blinded photographic scar assessments, investigator and subject treatment/satisfaction assessments, subject scar symptoms, and intraoperative pain scores. The KTP arm produced statistically significant improvement for the vascularity component of the VSS only. Side effects were limited to mild treatment discomfort and minimal transient post-treatment erythema and purpura. No vesiculation, infection, scarring or

  8. A Meta-Analysis of the Short- and Long-Term Results of Randomized Controlled Trials That Compared Laparoscopy-Assisted and Conventional Open Surgery for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Hiroshi Ohtani, Yutaka Tamamori, Yuichi Arimoto, Yukio Nishiguchi, Kiyoshi Maeda, Kosei Hirakawa

    2011-01-01

    Full Text Available Purpose: We conducted a meta-analysis to evaluate and compare the short- and long-term results of laparoscopic colorectal surgery (LCRS and conventional open surgery (OCRS for colorectal cancer (CRC.Methods: We searched relevant papers published between January 1990 and May 2011. We analyzed the outcomes of each type of surgery over the short- and long-term periods.Results: In the short-term period, we found no significant differences in overall perioperative complications and anastomotic leakage between LCRS and OCRS groups. We found no significant differences in overall, distant, local and wound-site recurrence, overall mortality, 3 and 5 year disease-free survival rate, and cancer-related mortality between the 2 groups.Conclusions: LCRS has the benefits of reducing intraoperative blood loss, earlier resumption of oral intake, and shorter duration of hospital stay in the short-term. The long-term outcomes of LCRS seem to be similar to those of OCRS.

  9. Early individualised manipulative rehabilitation following lumbar open laser microdiscectomy improves early post-operative functional disability: A randomized, controlled pilot study.

    Science.gov (United States)

    Kim, Byungho J; Ahn, Junghoon; Cho, Heecheol; Kim, Dongyun; Kim, Taeyeong; Yoon, Bumchul

    2016-01-01

    Lumbar open laser microdiscectomy has been shown to be an effective intervention and safe approach for lumbar disc prolapse. However early post-operative physical disability affecting daily activities have been sporadically reported. To evaluate the feasibility of using early individualised manipulative rehabilitation to improve early post-operative functional disability following lumbar discectomy. Randomised controlled pilot trial. Setting at a major metropolitan spine surgery hospital. Twenty-one patients aged 25-69 years who underwent lumbar microdiscectomy were randomised to either the manipulative rehabilitation treatment group or the active control group. Rehabilitation was initiated 2-3 weeks after surgery, twice a week for 4 weeks. Each session was for 30 minutes. Primary outcomes were the Roland-Morris disability questionnaire and the visual analogue pain scale. Outcome measures were assessed at baseline and post-intervention. Early post-operative physical disability was improved with a 55% reduction by early individualised manipulative rehabilitation, compared to that of control care with a 5% increase. Early post-operative residual leg pain decreased with rehabilitation (55%) and control care (9%). This pilot study supports the feasibility of a future definitive randomised control trial and indicates this type of rehabilitation may be an important option for post-operative management after spinal surgery.

  10. Switching to aripiprazole in outpatients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues with risperidone: a randomized, multicentre, open-label study.

    Science.gov (United States)

    Ryckmans, V; Kahn, J P; Modell, S; Werner, C; McQuade, R D; Kerselaers, W; Lissens, J; Sanchez, R

    2009-05-01

    This study evaluated the safety/tolerability and effectiveness of aripiprazole titrated-dose versus fixed-dose switching strategies from risperidone in patients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues. Patients were randomized to an aripiprazole titrated-dose (starting dose 5 mg/day) or fixed-dose (dose 15 mg/day) switching strategy with risperidone down-tapering. Primary endpoint was rate of discontinuation due to adverse events (AEs) during the 12-week study. Secondary endpoints included positive and negative syndrome scale (PANSS), clinical global impressions - improvement of illness scale (CGI-I), preference of medication (POM), subjective well-being under neuroleptics (SWN-K) and GEOPTE (Grupo Español para la Optimización del Tratamiento de la Esquizofrenia) scales. Rates of discontinuations due to AEs were similar between titrated-dose and fixed-dose strategies (3.5% vs. 5.0%; p=0.448). Improvements in mean PANSS total scores were similar between aripiprazole titrated-dose and fixed-dose strategies (-14.8 vs. -17.2; LOCF), as were mean CGI-I scores (2.9 vs. 2.8; p=0.425; LOCF) and SWN-K scores (+8.6 vs.+10.3; OC,+7.8 vs.+9.8; LOCF). Switching can be effectively and safely achieved through a titrated-dose or fixed-dose switching strategy for aripiprazole, with down-titration of risperidone.

  11. Efficacy and safety of escitalopram versus desvenlafaxine in the treatment of major depression: A preliminary 1-year prospective randomized open label comparative trial

    Directory of Open Access Journals (Sweden)

    Brij Mohan Gupta

    2016-01-01

    Full Text Available Aim and Objective: To compare efficacy and safety of escitalopram with desvenlafaxine in the treatment of major depression.Materials and Methods: A total of 60 patients of depression were randomized into two groups after meeting inclusion criterion. In the first 3 weeks, escitalopram 10 mg/day was given and then 20 mg/day for the next 3 weeks in group 1 (n = 30. Desvenlafaxine in the first 3 weeks was given 50 mg/day and 100 mg/day for the next 3 weeks in group 2 (n = 30. The parameters evaluated during the study were efficacy assessments byHamilton Scale of Rating Depression (HAM-D, Hamilton Rating Scale of Anxiety (HAM-A, and Clinical Global Impression (CGI. Safety assessments were done by UKU-scale. Results: Escitalopram and desvenlafaxine significantly (P < 0.001, reduced HAM-D, HAM-A, and CGI scores from their respective base lines. However, on comparison failed show any statistical difference at 3 and 6 weeks of treatment. Escitalopram and desvenlafaxine were both found to be safe and well-tolerated and there was not much difference between the two groups as evident from UKU Scale and their effect on various biochemical parameters. Conclusion: The present study demonstrated similar efficacy and safety in reducing depression and anxiety with both escitalopram and desvenlafaxine, but clinical superiority of one drug over the other cannot be concluded due to limitations of the small sample size.

  12. A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP.

    Science.gov (United States)

    Zhou, Hai; Xu, Miao; Qin, Ping; Zhang, Hai-yan; Yuan, Cheng-lu; Zhao, Hong-guo; Cui, Zhong-guang; Meng, Yue-sheng; Wang, Lei; Zho