The work of forensic physicians with police detainees in the Canberra City Watchhouse.

Science.gov (United States)

Sturgiss, Elizabeth Ann; Parekh, Vanita

2011-02-01

Forensic physicians provide both medical care and forensic consultations to detainees in police custody. There is a paucity of Australian data regarding characteristics of detainees and the type of work provided by forensic physicians in this setting. This retrospective audit of a clinical forensic service in Canberra, Australia will assist with service planning, future data collection and the training of forensic physicians. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Health problems among detainees in Switzerland: a study using the ICPC-2 classification

Directory of Open Access Journals (Sweden)

Bertrand Dominique

2011-04-01

Full Text Available Abstract Background Little is known about the health status of prisoners in Switzerland. The aim of this study was to provide a detailed description of the health problems presented by detainees in Switzerland's largest remand prison. Methods In this retrospective cross-sectional study we reviewed the health records of all detainees leaving Switzerland's largest remand prison in 2007. The health problems were coded using the International Classification for Primary Care (ICPC-2. Analyses were descriptive, stratified by gender. Results A total of 2195 health records were reviewed. Mean age was 29.5 years (SD 9.5; 95% were male; 87.8% were migrants. Mean length of stay was 80 days (SD 160. Illicit drug use (40.2% and mental health problems (32.6% were frequent, but most of these detainees (57.6% had more generic primary care problems, such as skin (27.0%, infectious diseases (23.5%, musculoskeletal (19.2%, injury related (18.3%, digestive (15.0% or respiratory problems (14.0%. Furthermore, 7.9% reported exposure to violence during arrest by the police. Conclusion Morbidity is high in this young, predominantly male population of detainees, in particular in relation to substance abuse. Other health problems more commonly seen in general practice are also frequent. These findings support the further development of coordinated primary care and mental health services within detention centers.

Recent Trends in Alcohol and Other Drug Use Among Police Detainees in New Zealand, 2010-2015.

Science.gov (United States)

Wilkins, Chris; Prasad, Jitesh; Parker, Karl; Rychert, Marta; Barnes, Helen Moewaka

New Zealand has unusual patterns of recreational substance use by international standards including low levels of cocaine and heroin use, and high methamphetamine use. This paper examines recent trends in alcohol and other drug use among police detainees in New Zealand over the past six years. The paper utilises data from the New Zealand Arrestee Drug Use Monitoring (NZ-ADUM) study. NZ-ADUM interviewed approximately 800 police detainees each year at four central city police watch houses (i.e. Whangarei, Auckland, Wellington, Christchurch) from 2010 to 2015. The proportion of police detainees who had used methamphetamine in the previous year increased from 28% in 2012 to 36% in 2015. Drinking prior to arrest declined from 41% in 2013 to 28% in 2015. The use of cannabis in the past year declined slightly from 76% in 2011 to 69% in 2015. The proportion using ecstasy in the previous year steadily declined from 28% in 2011 to 19% in 2015. Only small minorities had recently used cocaine or an opioid. Use of methamphetamine and ecstasy increased in Christchurch. Growing methamphetamine use is consistent with record seizures of methamphetamine over the past 2-3 years. Increasing drug use in Christchurch may reflect factors related to the devastating earthquakes in 2011 and the subsequent city rebuild, including an influx of construction workers, more organised trafficking groups and earthquake-related stress. The decline in cannabis use may be related to the emergence of 'legal' synthetic cannabinoids. The decline in ecstasy use may be the result of recent domestic enforcement operations and the overall global shortage of MDMA. The decline in alcohol drinking may be due to the introduction of pre-charge formal warnings for minor alcohol and disorder offences, and new restrictions on alcohol premise opening hours. Acknowledgements: The New Zealand Drug Use Monitoring (NZ-ADUM) research study is funded by the New Zealand Police and is conducted by SHORE and Whariki Research

Enemy Combatant Detainees: Habeas Corpus Challenges in Federal Court

Science.gov (United States)

2006-09-26

Separation of Powers Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Eliminating Federal Court Jurisdiction Where There Is No State Court Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 1 542 U.S. 466 (2004). Enemy Combatant Detainees: Habeas Corpus Challenges in Federal Court In Rasul v. Bush,1 a divided Supreme Court declared that “a state

Brain structural abnormalities and mental health sequelae in South Vietnamese ex-political detainees who survived traumatic head injury and torture.

Science.gov (United States)

Mollica, Richard F; Lyoo, In Kyoon; Chernoff, Miriam C; Bui, Hoan X; Lavelle, James; Yoon, Sujung J; Kim, Jieun E; Renshaw, Perry F

2009-11-01

A pilot study of South Vietnamese ex-political detainees who had been incarcerated in Vietnamese reeducation camps and resettled in the United States disclosed significant mental health problems associated with torture and traumatic head injury (THI). To identify structural brain alterations associated with THI and to investigate whether these deficits are associated with posttraumatic stress disorder and depression. Cross-sectional neuroimaging study. Massachusetts General Hospital and McLean Hospital. A subsample of Vietnamese ex-political detainees (n = 42) and comparison subjects (n = 16) selected from a community study of 337 ex-political detainees and 82 comparison subjects. Scores on the Vietnamese versions of the Hopkins Symptom Checklist-25 (HSCL) and Harvard Trauma Questionnaire for depression and posttraumatic stress disorder, respectively; cerebral regional cortical thickness; and manual volumetric morphometry of the amygdala, hippocampus, and thalamus. Ex-political detainees exposed to THI (n = 16) showed a higher rate of depression (odds ratio, 10.2; 95% confidence interval, 1.2-90.0) than those without THI exposure (n = 26). Ex-political detainees with THI had thinner prefrontotemporal cortices than those without THI exposure (P brain map) in the left dorsolateral prefrontal and bilateral superior temporal cortices, controlling for age, handedness, and number of trauma/torture events (left superior frontal cortex [SFC], P = .006; left middle frontal cortex, P = .01; left superior temporal cortex [STC], P = .007; right STC, P = .01). Trauma/torture events were associated with bilateral amygdala volume loss (left, P = .045; right, P = .003). Cortical thinning associated with THI in the left SFC and bilateral STC was related to HSCL depression scores in THI-exposed (vs non-THI-exposed) ex-political detainees (left SFC, P for interaction = .007; left STC, P for interaction = .03; right STC, P for interaction = .02). Structural deficits in

When the War Doesn’t End: Detainees in Legal Limbo

Science.gov (United States)

2014-05-01

it most. While the images of Abu Ghraib may have been forgotten by many, the limitless detention laws provide a legal basis that allows many to...11 Detainee Policy: Popular President Meets Unified Government. Universitat der Bundeswehr 2013, 92. 35 Strasser, Steven 2004. The Abu Ghraib

Changing the face of Abu Ghraib through mental health intervention: U.S. Army mental health team conducts debriefing with military policemen and Iraqi detainees.

Science.gov (United States)

Smith, Marshall H; Brady, Patrick J

2006-12-01

A critical incident stress debriefing (CISD) was conducted with two U.S. Army military police officers (MPs) and 11 Iraqi detainees who experienced the untimely death of a detainee. The CISD was conducted by a psychiatrist and a psychologist, who used the seven-step debriefing model created by Jeffrey Mitchell in 1983. A primary goal of CISD is to diminish the impact of a traumatic event and ultimately to prevent the onset of post-traumatic stress disorder. An unexpected finding was that the debriefing provided an opportunity for the MPs and detainees to clear preconceived notions about each other, enhancing mutual collaboration. The purpose of this article is to describe how a mental health team used a CISD as an intervention in treating MPs and detainees who experienced a common tragic event.

Indefinite Detention / Enduring Freedom: What Former Detainees' Experiences Can Teach Us About Institutional Violence, Resistance and the Law

OpenAIRE

Koenig, Kimberly Alexa

2013-01-01

This dissertation focuses on the experiences of former Guantánamo detainees as communicated in 78 interviews. An analysis of those interviews centers on former detainees' worst experiences to parse how those experiences might inform society's understanding of cruel, inhuman and degrading treatment. The dissertation is organized into nine chapters.Chapter one situates this study in the context of the United States' response to the events of 9/11, with an emphasis on the imprisonment of indivi...

Are the American Psychological Association’s Detainee Interrogation Policies Ethical and Effective?

Science.gov (United States)

Pope, Kenneth S.

2011-01-01

After 9–11, the United States began interrogating detainees at settings such as Abu Ghraib, Bagram, and Guantanamo. The American Psychological Association (APA) supported psychologists’ involvement in interrogations, adopted formal policies, and made an array of public assurances. This article’s purpose is to highlight key APA decisions, policies, procedures, documents, and public statements in urgent need of rethinking and to suggest questions that may be useful in a serious assessment, such as, “However well intended, were APA’s interrogation policies ethically sound?”; “Were they valid, realistic, and able to achieve their purpose?”; “Were other approaches available that would address interrogation issues more directly, comprehensively, and actively, that were more ethically and scientifically based, and that would have had a greater likelihood of success?”; and “Should APA continue to endorse its post-9–11 detainee interrogation policies?” PMID:22096660

Euthanasia for Detainees in Belgium.

Science.gov (United States)

Devolder, Katrien

2016-07-01

In 2011, Frank Van Den Bleeken became the first detainee to request euthanasia under Belgium's Euthanasia Act of 2002. This article investigates whether it would be lawful and morally permissible for a doctor to accede to this request. Though Van Den Bleeken has not been held accountable for the crimes he committed, he has been detained in an ordinary prison, without appropriate psychiatric care, for more than 30 years. It is first established that Van Den Bleeken's euthanasia request plausibly meets the relevant conditions of the Euthanasia Act and that, consequently, a doctor could lawfully fulfill it. Next, it is argued that autonomy-based reasons for euthanizing him outweigh complicity-based reasons against doing so, and that, therefore, it is also morally permissible for a doctor to carry out the euthanasia request.

A phase I trial of pre-operative radiotherapy for prostate cancer: Clinical and translational studies

International Nuclear Information System (INIS)

Supiot, Stephane; Shubbar, Shubber; Fleshner, Neil; Warde, Padraig; Hersey, Karen; Wallace, Kris; Cole, Heather; Sweet, Joan; Tsihlias, John; Jewett, Michael A.S.; Klotz, Laurence; Bristow, Robert G.

2008-01-01

Background and purpose: Selected patients undergoing radical prostatectomy for localized prostate cancer can be at high-risk for pT3 disease and require subsequent radiotherapy. In a phase I trial, we investigated the feasibility of pre-operative radiotherapy for this patient subset. Materials and methods: Eligibility criteria were: T1/T2N0M0 tumors plus (i) Gleason ≥ 7, PSA > 10 ng/ml and 15 ng/ml and less WAF associated with reduced cell proliferation. Conclusion: Intra-operative morbidity is low following short-course, pre-operative radiotherapy. A phase II trial is planned to fully document biochemical response with this combined-modality approach

Interrogation of Detainees: Overview of the McCain Amendment

Science.gov (United States)

2006-10-23

shocks in one circumstance might not be considered so egregious in another); Miller v. City of Philadelphia, 174 F. 3d 368, 375 (3rd Cir.1999) (“The...concurring). 15 Hope v. Pelzer, 536 U.S. 730 (2002). 16 Chandler v. Crosby, 379 F. 3d 1278 (11th Cir. 2004). 17 Haynes v. Washington, 373 U.S. 503 (1963...and that taken by S. 3861, S. 3886, and H.R. 6054. Kate Zernike & Sheryl Gay Stolberg, Differences Settled in Deal Over Detainee Treatment, NY

Physical restraint and the protection of the human rights of immigration detainees in hospitals.

Science.gov (United States)

Pickles, Hilary; Norton, Emma; Ginn, Emma; Schleicher, Theresa

2015-08-01

Immigration detainees, like prisoners, are entitled to the same standard of healthcare as non-detained patients. When hospital attendance or admission is required, the priority for custodial staff (who for purposes of this article we refer to as 'escorts') is to prevent absconding. For that reason, they may wish to use physical restraints, such as handcuffs, and remain with the detainee at all times. This can be degrading for the patient and breach their human rights. Clinicians have professional obligations to all their patients and must object to any restraint methods that risk damaging the patient's right to confidentiality, treatment, health or the therapeutic relationship itself. The starting presumption is that restraints ought not to be used during treatment and only in the most exceptional cases ought escorts to be present during clinical examination or treatment. © Royal College of Physicians 2015. All rights reserved.

The psychiatric profession and the Australian government: the debate over collective depression syndrome among asylum-seeking detainees.

Science.gov (United States)

Bostock, William W

2009-01-01

Psychiatrists have long had involvement with the political process, both individually and as a profession. They have made valuable contributions to debate over such issues as war, conflict, terrorism, torture, human rights abuse, drug abuse, suicide and other public health issues. However, they have also been complicit in some gross atrocities. Over several years there has been debate over the Australian Government's treatment of asylum seekers, and the Royal Australian and New Zealand College of Psychiatrists took the unusual step of publicly criticizing the Australian Government's policy on grounds of its toxicity leading to a diagnosis of collective depression syndrome, particularly among child detainees, but also adult detainees. The official Ministerial response was to deny that collective depression exists and to assert that the concept is meaningless. Can this intervention by psychiatrists be interpreted as a product of earlier political behaviors by psychiatrists? The willingness of psychiatrists to cooperate with other professions, notably psychologists, pediatricians, physicians and lawyers, is noted, as is presence of minority voices within the Australian psychiatric profession. The significance of the debate over the mental condition of asylum-seeking detainees is that its outcome has implications for how Australia sees itself and is seen by the rest of the world, that is, its national identity.

The quest for significance model of radicalization: implications for the management of terrorist detainees.

Science.gov (United States)

Dugas, Michelle; Kruglanski, Arie W

2014-01-01

Radicalization and its culmination in terrorism represent a grave threat to the security and stability of the world. A related challenge is effective management of extremists who are detained in prison facilities. The major aim of this article is to review the significance quest model of radicalization and its implications for management of terrorist detainees. First, we review the significance quest model, which elaborates on the roles of motivation, ideology, and social processes in radicalization. Secondly, we explore the implications of the model in relation to the risks of prison radicalization. Finally, we analyze the model's implications for deradicalization strategies and review preliminary evidence for the effectiveness of a rehabilitation program targeting components of the significance quest. Based on this evidence, we argue that the psychology of radicalization provides compelling reason for the inclusion of deradicalization efforts as an essential component of the management of terrorist detainees. Copyright © 2014 John Wiley & Sons, Ltd.

CTC Sentinel. Volume 1, Issue 12, November 2008. The Dilemma of the Yemeni Detainees at Guantanamo Bay

National Research Council Canada - National Science Library

Johnsen, Gregory D; Boucek, Christopher

2008-01-01

.... Other countries, most notably Saudi Arabia, have successfully repatriated many of their nationals, but Yemen has been unable to convince the United States to release detainees into its custody...

Are the American Psychological Association's Detainee Interrogation Policies Ethical and Effective?: Key Claims, Documents, and Results.

Science.gov (United States)

Pope, Kenneth S

2011-01-01

After 9-11, the United States began interrogating detainees at settings such as Abu Ghraib, Bagram, and Guantanamo. The American Psychological Association (APA) supported psychologists' involvement in interrogations, adopted formal policies, and made an array of public assurances. This article's purpose is to highlight key APA decisions, policies, procedures, documents, and public statements in urgent need of rethinking and to suggest questions that may be useful in a serious assessment, such as, "However well intended, were APA's interrogation policies ethically sound?"; "Were they valid, realistic, and able to achieve their purpose?"; "Were other approaches available that would address interrogation issues more directly, comprehensively, and actively, that were more ethically and scientifically based, and that would have had a greater likelihood of success?"; and "Should APA continue to endorse its post-9-11 detainee interrogation policies?"

Forensic age estimation in anti-piracy trials in Seychelles: Experiences and challenges faced.

Science.gov (United States)

Gunawardena, S A; Liyanage, U A; Weeratna, J B; Mendis, N D N A; Perera, H J M; Jayasekara, R W; Fernando, R

2017-01-01

Forensic age estimation (FAE) was conducted using a multifactorial method on thirteen Somali detainees claiming juvenile status during the anti-piracy trials of the Seychelles Supreme Court in 2014/2015. A multidisciplinary team, comprising of four of the authors covering specialties in forensic medicine, forensic odontology and radiology, conducted the FAE using a five-stage protocol. Each detainee was interviewed with an interpreter and examined for disorders affecting dental/skeletal development and for assessment of genital development through Tanner staging. Dental maturity was assessed clinically and radiologically. Eruption stage was assessed using Olze et al. and mandibular third-molar maturity was assessed using Demirjian's classification. Skeletal maturity was assessed from hand-wrist X-rays according to Greulich & Pyle and from CT-clavicle according to Kellinghaus et al. and Schultz et al. Interpretation of findings was done using reference population data from similar ethnic and social backgrounds wherever possible. Final age-ranges were calculated by combining dental and clavicle maturity stages using the regression formula developed by Bassed et al. followed by a 10% correction factor. The team later testified on their findings under cross-examination. The protocol adopted by the authors increased the scientific validity of the findings and was useful in addressing cross-examination queries on exclusion of developmental disorders, ethnic/socioeconomic variability and maintaining chain of custody. Unforeseen jurisdictional and practical limitations were experienced but did not affect the outcome. Combining dental and clavicle developmental data provided the court with a much clearer picture on the likelihood of the detainees' juvenile status which emphasizes the importance of conducting more population studies using combinations of different developmental sites. The authors note that available reference data is mostly from affluent populations whereas

Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

Science.gov (United States)

Lawrie, Theresa A; Betrán, Ana Pilar; Singata-Madliki, Mandisa; Ciganda, Alvaro; Hofmeyr, G Justus; Belizán, José M; Purnat, Tina Dannemann; Manyame, Sarah; Parker, Catherine; Cormick, Gabriela

2017-10-26

The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low

The psychiatric profession and the Australian government: the debate over collective depression syndrome among asylum-seeking detainees

Directory of Open Access Journals (Sweden)

William W Bostock

2009-11-01

Full Text Available William W BostockSchool of Government, University of Tasmania, Hobart, Tasmania, AustraliaAbstract: Psychiatrists have long had involvement with the political process, both individually and as a profession. They have made valuable contributions to debate over such issues as war, conflict, terrorism, torture, human rights abuse, drug abuse, suicide and other public health issues. However, they have also been complicit in some gross atrocities. Over several years there has been debate over the Australian Government’s treatment of asylum seekers, and the Royal Australian and New Zealand College of Psychiatrists took the unusual step of publicly criticizing the Australian Government’s policy on grounds of its toxicity leading to a diagnosis of collective depression syndrome, particularly among child detainees, but also adult detainees. The official Ministerial response was to deny that collective depression exists and to assert that the concept is meaningless. Can this intervention by psychiatrists be interpreted as a product of earlier political behaviors by psychiatrists? The willingness of psychiatrists to cooperate with other professions, notably psychologists, pediatricians, physicians and lawyers, is noted, as is presence of minority voices within the Australian psychiatric profession. The significance of the debate over the mental condition of asylum-seeking detainees is that its outcome has implications for how Australia sees itself and is seen by the rest of the world, that is, its national identity.Keywords: collective depression syndrome, psychiatric profession, political intervention, asylum seeker, Australian national identity

Detainee Healthcare in Theater Hospitals: Are Air Force Medics Prepared for the Challenge

Science.gov (United States)

2009-04-01

hostility could include not having same sex medical personnel for detainees, which can be challenging, due to staffing limitations. Muslim males, and...set of problems called ethnocentrism . What it boils down to is the belief that your own culture is the normal and right way of doing things and...population itself, but more so with first identifying our own preconceptions, ethnocentrisms , as well as our propensity to push our own cultural

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

Science.gov (United States)

McNicholl, Janet M

2016-12-01

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

Commentary (Pre-Trial Detention in the Extraordinary Chambers in the Courts of Cambodia )

DEFF Research Database (Denmark)

Marchuk, Iryna

2015-01-01

Most international criminal courts and tribunals find provisional detention absolutely necessary to ensure the swift delivery of justice. A decision on pre-trial detention must be in conformity with well-recognized human rights standards, thus respecting the person’s right to a fair trial...... and upholding the presumption of evidence. Although the general assumption in criminal law is that pre-trial detention is the exception and not the rule, a number of factors, such as the gravity of the crimes, as well as heightened flight risk of the accused, appear to have reversed the test employed...... in international criminal courts and tribunals. To date, all provisional detention orders against former members of the inner circle of Pol Pot, except for one, have been re-affirmed on appeal in the ECCC. This commentary appraises the ECCC case law on pre-trial detention from the standpoint of its conformity...

Using a network-based approach and targeted maximum likelihood estimation to evaluate the effect of adding pre-exposure prophylaxis to an ongoing test-and-treat trial.

Science.gov (United States)

Balzer, Laura; Staples, Patrick; Onnela, Jukka-Pekka; DeGruttola, Victor

2017-04-01

Several cluster-randomized trials are underway to investigate the implementation and effectiveness of a universal test-and-treat strategy on the HIV epidemic in sub-Saharan Africa. We consider nesting studies of pre-exposure prophylaxis within these trials. Pre-exposure prophylaxis is a general strategy where high-risk HIV- persons take antiretrovirals daily to reduce their risk of infection from exposure to HIV. We address how to target pre-exposure prophylaxis to high-risk groups and how to maximize power to detect the individual and combined effects of universal test-and-treat and pre-exposure prophylaxis strategies. We simulated 1000 trials, each consisting of 32 villages with 200 individuals per village. At baseline, we randomized the universal test-and-treat strategy. Then, after 3 years of follow-up, we considered four strategies for targeting pre-exposure prophylaxis: (1) all HIV- individuals who self-identify as high risk, (2) all HIV- individuals who are identified by their HIV+ partner (serodiscordant couples), (3) highly connected HIV- individuals, and (4) the HIV- contacts of a newly diagnosed HIV+ individual (a ring-based strategy). We explored two possible trial designs, and all villages were followed for a total of 7 years. For each village in a trial, we used a stochastic block model to generate bipartite (male-female) networks and simulated an agent-based epidemic process on these networks. We estimated the individual and combined intervention effects with a novel targeted maximum likelihood estimator, which used cross-validation to data-adaptively select from a pre-specified library the candidate estimator that maximized the efficiency of the analysis. The universal test-and-treat strategy reduced the 3-year cumulative HIV incidence by 4.0% on average. The impact of each pre-exposure prophylaxis strategy on the 4-year cumulative HIV incidence varied by the coverage of the universal test-and-treat strategy with lower coverage resulting in a larger

A Single-Blind randomized controlled trial to evaluate the effect of extended counseling on uptake of pre-antiretroviral care in eastern uganda

Directory of Open Access Journals (Sweden)

Marrone Gaetano

2011-07-01

Full Text Available Abstract Background Many newly screened people living with HIV (PLHIV in Sub-Saharan Africa do not understand the importance of regular pre-antiretroviral (ARV care because most of them have been counseled by staff who lack basic counseling skills. This results in low uptake of pre-ARV care and late treatment initiation in resource-poor settings. The effect of providing post-test counseling by staff equipped with basic counseling skills, combined with home visits by community support agents on uptake of pre-ARV care for newly diagnosed PLHIV was evaluated through a randomized intervention trial in Uganda. Methods An intervention trial was performed consisting of post-test counseling by trained counselors, combined with monthly home visits by community support agents for continued counseling to newly screened PLHIV in Iganga district, Uganda between July 2009 and June 2010, Participants (N = 400 from three public recruitment centres were randomized to receive either the intervention, or the standard care (the existing post-test counseling by ARV clinic staff who lack basic training in counseling skills, the control arm. The outcome measure was the proportion of newly screened and counseled PLHIV in either arm who had been to their nearest health center for clinical check-up in the subsequent three months +2 months. Treatment was randomly assigned using computer-generated random numbers. The statistical significance of differences between the two study arms was assessed using chi-square and t-tests for categorical and quantitative data respectively. Risk ratios and 95% confidence intervals were used to assess the effect of the intervention. Results Participants in the intervention arm were 80% more likely to accept (take up pre-ARV care compared to those in the control arm (RR 1.8, 95% CI 1.4-2.1. No adverse events were reported. Conclusions Provision of post-test counseling by staff trained in basic counseling skills, combined with home visits by

Combined Screening for Early Detection of Pre-Eclampsia

Directory of Open Access Journals (Sweden)

Hee Jin Park

2015-08-01

Full Text Available Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers.

The Value of Pre-Screening in the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease Trial.

Science.gov (United States)

Rios-Romenets, S; Giraldo-Chica, M; López, H; Piedrahita, F; Ramos, C; Acosta-Baena, N; Muñoz, C; Ospina, P; Tobón, C; Cho, W; Ward, M; Langbaum, J B; Tariot, P N; Reiman, E M; Lopera, F

2018-01-01

The Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) trial evaluates the anti-amyloid-β antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30-60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD.

Psychologists abandon the Nuremberg ethic: concerns for detainee interrogations.

Science.gov (United States)

Pope, Kenneth S; Gutheil, Thomas G

2009-01-01

In the aftermath of 9-11, the American Psychological Association, one of the largest U.S. health professions, changed its ethics code so that it now runs counter to the Nuremberg Ethic. This historic post-9-11 change allows psychologists to set aside their ethical responsibilities whenever they are in irreconcilable conflict with military orders, governmental regulations, national and local laws, and other forms of governing legal authority. This article discusses the history, wording, rationale, and implications of the ethical standard that U.S. psychologists adopted 7 years ago, particularly in light of concerns over health care professionals' involvement in detainee interrogations and the controversy over psychologists' prominent involvement in settings like the Guantánamo Bay Detainment Camp and the Abu Ghraib prison. It discusses possible approaches to the complex dilemmas arising when ethical responsibilities conflict with laws, regulations, or other governing legal authority.

HIV pre-exposure prophylaxis trials: socio-economic and ethical ...

African Journals Online (AJOL)

The advent of HIV pre-exposure prophylaxis (PrEP) as a HIV-prevention strategy has received optimistic support among HIV researchers. However, discourse on PrEP trials has tended to be dominated by the disputes arising between some activist groups and researchers about the research methodologies. Instead, this ...

The pre-trial procedures and principles of the International Criminal ...

African Journals Online (AJOL)

The pre-trial procedures and principles of the International Criminal Court. ... the accused persons were done ex-post facto and devoid of any country's law. ... Against this background, this paper attempts to put the ambiguities aside and ...

PRE-TRIAL SUPPORT OF YOUNG OFFENDERS (EFFECTIVENESS OF IMPLEMENTATION IN ARKHANGELSK REGION

Directory of Open Access Journals (Sweden)

Yana Korneeva

2015-09-01

Full Text Available Sophisticated criminal situation with juvenile delinquency in Arkhangelsk region has prompted practitioners to find new ways to counteract. The basis for the acquisition of new knowledge in the field of prevention of juvenile delinquency was the phased introduction of social support for the pre-trial juvenile in conflict with the law. Based on the survey of investigators, investigators, judges and social workers involved in the experiment, the analysis of materials of criminal cases involving young offender’s conclusions about the positive results of the experiment revealed the difficulties and challenges faced by law enforcers. The article provides suggestions for optimizing the procedure of pre-trial support.

Psychologists and detainee interrogations: key decisions, opportunities lost, and lessons learned.

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Pope, Kenneth S

2011-01-01

After the 9-11 terrorist attacks, U.S. psychologists faced hard choices about what roles, if any, were appropriate for psychologists in the detainee interrogations conducted in settings such as the Bagram Airbase, the Abu Ghraib Prison, and the Guantanamo Bay Detention Camps. The American Psychological Association (APA) sparked intense controversy with its policies and public statements. This article reviews APA decisions, documents, and public statements in this area, in the context of major criticisms and responses to those criticisms. The review focuses on key issues: how the APA created and reported policies in the areas of ethics and national security; transparency; psychologists' professional identities; psychologists' qualifications; ethical-legal conflicts; policies opposing torture; interpretations of avoiding harm; and effective interrogations. It suggests lessons learned, missed opportunities, and questions in need of a fresh approach. © 2011 by Annual Reviews. All rights reserved

Mental Rehabilitation of Juvenile Girl Detainees for Increasing Their Self-Esteem Through the Self Knowledge Sources

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Shiva Saeghi Mameghani

2011-04-01

Full Text Available Objectives: The main purpose of the present study is to consider the rate of impression in group mental rehabilitation based on the regulation of self recognition sources on augmentation of self-respect among 14- to 18-year old female prisoners. Methods: 30 female social seekers were randomly selected from the whole population, 15 of which were gathered in control group and the rest 15 within evidence group. First, GHQ papers (General Health Questionnaire were distributed among the girls in order to evaluate their mental status. Pre- and Post- Cooper Smith self-respect tests were formulated both before and after interventions on experiment group. Interventions were accomplished during 9 sessions within three months by group consulting based on the configuration of self-recognition (collected by Younesi 2007. Considering the point that remedy plans are not utilized for the evidence group and they are evaluated by gathered marks achieved by the two tests to compare average discriminations. Results: After applying remedy interventions, social seekers from experimental group manifested meaningful augmentation during the test of self-esteem invented by Cooper Smith compared with social help seekers from control group. Discussion: The findings indicated that group mental rehabilitation would increase self-esteem in its four dimensions among the subjects. The findings showed that mental rehabilitation based on self knowledge resources is useful for improvement of juvenile detainee's self-esteem.

Aspects regarding the hope for successful reintegration of female detainees.

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Enache, Alexandra; Pasca, Viorel; Luta, Veronica; Ciopec, Flavius; Ursachi, Georgeta; Radu, Daniel; Stratul, Stefan; Zarie, Gabriela; Mutiu, Florentina

2009-04-01

We investigated in the female inmate population whether they had and which were the foundations of hope for a better future after liberation. We created and applied a questionnaire structured on four general information chapters regarding health, attitude and spiritual life. In total, 67 questions with 293 items. For this study, we selected 62 items. Hope for better reintegration was layed on family support and (re)imployment. The majority considered that the length of the detention influences the chances for social reintegration. The family perception was clarified and the relationship with the parents and spouse was tightened. The spiritual questions reflected a moderate return to religion. The study proved that the female detainees have a positive perception on the role of education and that the efforts of different educational factors during detention was strongly positive. The development of moral, family, social and spiritual values was beneficial and raised the hopes of social reintegration.

Defendant’s free will in legal collaboration and its relation with pre-trial detention

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Antonio Henrique Graciano Suxberger

2017-03-01

Full Text Available The legal collaboration, a type of evidence used on organized crime prosecutions, demands free will of the defendant. Appraising the defendant’s free will, many critics cover the deals made with an arrested defendant during the negotiation of the legal collaboration. These two institutes — legal collaboration and pre-trial detention —, although they do not present themselves as a cause-effect relation, commonly are approached in practice as associated. This essay intends to evaluate the defendant’s free will during pre-trial detention and the legal collaboration’s bargaining. It asserts a strict and clear relation between pre-trial detention and the legal collaboration bargaining. Identifying occasional problems do not imply the conclusion on the existence of a structural problem to legal collaboration institute. This consideration is relevant to avoid superficial solutions that could fragilize even more the held defendant. Methodologically, from a literature review and document analysis about the subject, the paper clarifies what is a “criminal case” and what it means to the study.

Does the bracket–ligature combination affect the amount of orthodontic space closure over three months? A randomized controlled trial

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Wong, Henry; Collins, Jill; Tinsley, David; Sandler, Jonathan; Benson, Philip

2013-01-01

Objective: To investigate the effect of bracket–ligature combination on the amount of orthodontic space closure over three months. Design: Randomized clinical trial with three parallel groups. Setting: A hospital orthodontic department (Chesterfield Royal Hospital, UK). Participants: Forty-five patients requiring upper first premolar extractions. Methods: Informed consent was obtained and participants were randomly allocated into one of three groups: (1) conventional pre-adjusted edgewise bra...

Pre-Exposure Prophylaxis for HIV Prevention: Safety Concerns.

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Tetteh, Raymond A; Yankey, Barbara A; Nartey, Edmund T; Lartey, Margaret; Leufkens, Hubert G M; Dodoo, Alexander N O

2017-04-01

Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present challenges in the implementation and use of PrEP. The aim of this review is to discuss safety concerns observed in completed clinical trials on the use of PrEP. We performed a literature search on PrEP in PubMed, global advocacy for HIV prevention (Aids Vaccine Advocacy Coalition) database, clinical trials registry " http://www.clinicaltrials.gov " and scholar.google, using combination search terms 'pre-exposure prophylaxis', 'safety concerns in the use of pre-exposure prophylaxis', 'truvada use as PrEP', 'guidelines for PrEP use', 'HIV pre-exposure prophylaxis' and 'tenofovir' to identify clinical trials and literature on PrEP. We present findings associated with safety issues on the use of PrEP based on a review of 11 clinical trials on PrEP with results on safety and efficacy as at April 2016. We also reviewed findings from routine real-life practice reports. The pharmacological intervention for PrEP was tenofovir disoproxil fumarate/emtricitabine in a combined form as Truvada ® or tenofovir as a single entity. Both products are efficacious for PrEP and seem to have a good safety profile. Regular monitoring is recommended to prevent long-term toxic effects. The main adverse effects observed with PrEP are gastrointestinal related; basically mild to moderate nausea, vomiting and diarrhea. Other adverse drug effects worth monitoring are liver enzymes, renal function and bone mineral density. PrEP as an intervention to reduce HIV transmission appears to have a safe benefit-risk profile in clinical trials. It is recommended for widespread use but adherence monitoring and real-world safety surveillance are critical in the post-marketing phase to ensure that the benefits

The costs and effectiveness of large Phase III pre-licensure vaccine clinical trials.

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Black, Steven

2015-01-01

Prior to the 1980s, most vaccines were licensed based upon safety and effectiveness studies in several hundred individuals. Beginning with the evaluation of Haemophilus influenzae type b conjugate vaccines, much larger pre-licensure trials became common. The pre-licensure trial for Haemophilus influenzae oligosaccharide conjugate vaccine had more than 60,000 children and that of the seven-valent pneumococcal conjugate vaccine included almost 38,000 children. Although trial sizes for both of these studies were driven by the sample size required to demonstrate efficacy, the sample size requirements for safety evaluations of other vaccines have subsequently increased. With the demonstration of an increased risk of intussusception following the Rotashield brand rotavirus vaccine, this trend has continued. However, routinely requiring safety studies of 20,000-50,000 or more participants has two major downsides. First, the cost of performing large safety trials routinely prior to licensure of a vaccine is very large, with some estimates as high at US$200 million euros for one vaccine. This high financial cost engenders an opportunity cost whereby the number of vaccines that a company is willing or able to develop to meet public health needs becomes limited by this financial barrier. The second downside is that in the pre-licensure setting, such studies are very time consuming and delay the availability of a beneficial vaccine substantially. One might argue that in some situations, this financial commitment is warranted such as for evaluations of the risk of intussusception following newer rotavirus vaccines. However, it must be noted that while an increased risk of intussusception was not identified in large pre-licensure studies, in post marketing evaluations an increased risk of this outcome has been identified. Thus, even the extensive pre-licensure evaluations conducted did not identify an associated risk. The limitations of large Phase III trials have also been

HIV and tuberculosis in prisons in sub-Saharan Africa.

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Telisinghe, Lilanganee; Charalambous, Salome; Topp, Stephanie M; Herce, Michael E; Hoffmann, Christopher J; Barron, Peter; Schouten, Erik J; Jahn, Andreas; Zachariah, Rony; Harries, Anthony D; Beyrer, Chris; Amon, Joseph J

2016-09-17

Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are

Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

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Minsky, B.D.; Cohen, A.M.; Kemeny, N.; Enker, W.E.; Kelsen, D.P.; Schwartz, G.; Saltz, L.; Dougherty, J.; Frankel, J.; Wiseberg, J.

1993-01-01

The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs

Knowledge, Attitudes, and Experiences of HIV Pre-Exposure Prophylaxis (PrEP) Trial Participants in Botswana.

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Toledo, Lauren; McLellan-Lemal, Eleanor; Henderson, Faith L; Kebaabetswe, Poloko M

2015-03-01

Recent clinical trials have shown that a daily dose of oral TDF/FTC pre-exposure prophylaxis (PrEP) is effective in reducing human immunodeficiency (HIV) risk. Understanding trial participants' perspectives about retention and PrEP adherence is critical to inform future PrEP trials and the scale-up and implementation of PrEP programs. We analyzed 53 in-depth interviews conducted in April 2010 with participants in the TDF2 study, a Phase 3, randomized, double-blind, placebo-controlled clinical trial of daily oral TDF/FTC with heterosexual men and women in Francistown and Gaborone, Botswana. We examined participants' knowledge, attitudes, and experiences of the trial, identified facilitators and barriers to enrollment and retention, and compared participant responses by study site, sex, and study drug adherence. Our findings point to several factors to consider for participant retention and adherence in PrEP trials and programs, including conducting pre-enrollment education and myth reduction counseling, providing accurate estimates of participant obligations and side effect symptoms, ensuring participant understanding of the effects of non-adherence, gauging personal commitment and interest in study outcomes, and developing a strong external social support network for participants.

Maximising the value of combining qualitative research and randomised controlled trials in health research: the QUAlitative Research in Trials (QUART) study--a mixed methods study.

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O'Cathain, Alicia; Thomas, Kate J; Drabble, Sarah J; Rudolph, Anne; Goode, Jackie; Hewison, Jenny

2014-06-01

Researchers sometimes undertake qualitative research with randomised controlled trials (RCTs) of health interventions. To systematically explore how qualitative research is being used with trials and identify ways of maximising its value to the trial aim of providing evidence of effectiveness of health interventions. A sequential mixed methods study with four components. (1) Database search of peer-reviewed journals between January 2008 and September 2010 for articles reporting the qualitative research undertaken with specific trials, (2) systematic search of database of registered trials to identify studies combining qualitative research and trials, (3) survey of 200 lead investigators of trials with no apparent qualitative research and (4) semistructured telephone interviews with 18 researchers purposively sampled from the first three methods. Qualitative research was undertaken with at least 12% of trials. A large number of articles reporting qualitative research undertaken with trials (n=296) were published between 2008 and 2010. A total of 28% (82/296) of articles reported qualitative research undertaken at the pre-trial stage and around one-quarter concerned drugs or devices. The articles focused on 22 aspects of the trial within five broad categories. Some focused on more than one aspect of the trial, totalling 356 examples. The qualitative research focused on the intervention being trialled (71%, 254/356), the design and conduct of the trial (15%, 54/356), the outcomes of the trial (1%, 5/356), the measures used in the trial (3%, 10/356), and the health condition in the trial (9%, 33/356). The potential value of the qualitative research to the trial endeavour included improving the external validity of trials and facilitating interpretation of trial findings. This value could be maximised by using qualitative research more at the pre-trial stage and reporting findings with explicit attention to the implications for the trial endeavour. During interviews

Improving the sludge disintegration efficiency of sonication by combining with alkalization and thermal pre-treatment methods.

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Şahinkaya, S; Sevimli, M F; Aygün, A

2012-01-01

One of the most serious problems encountered in biological wastewater treatment processes is the production of waste activated sludge (WAS). Sonication, which is an energy-intensive process, is the most powerful sludge pre-treatment method. Due to lack of information about the combined pre-treatment methods of sonication, the combined pre-treatment methods were investigated and it was aimed to improve the disintegration efficiency of sonication by combining sonication with alkalization and thermal pre-treatment methods in this study. The process performances were evaluated based on the quantities of increases in soluble chemical oxygen demand (COD), protein and carbohydrate. The releases of soluble COD, carbohydrate and protein by the combined methods were higher than those by sonication, alkalization and thermal pre-treatment alone. Degrees of sludge disintegration in various options of sonication were in the following descending order: sono-alkalization > sono-thermal pre-treatment > sonication. Therefore, it was determined that combining sonication with alkalization significantly improved the sludge disintegration and decreased the required energy to reach the same yield by sonication. In addition, effects on sludge settleability and dewaterability and kinetic mathematical modelling of pre-treatment performances of these methods were investigated. It was proven that the proposed model accurately predicted the efficiencies of ultrasonic pre-treatment methods.

Pre-treating Seed to Enhance Germination of Desert Shrubs

Energy Technology Data Exchange (ETDEWEB)

W. K. Ostler; D. C. Anderson; D. J. Hansen

2002-06-01

Creosotebush [Larrea tridentata (D.C.) Cav.] and white bursage [Ambrosia dumosa (A. Gray) W.W. Payne] seeds were subjected to pre-treatments of rinsing and soaking in water and thiourea to enhance germination in laboratory experiments. The effects of darkness, temperature, seed source, and soil moisture were also evaluated in the laboratory. The best pre-treatment from the laboratory experiments, rinsing with water for 36 hours followed by drying, was field-tested at Fort Irwin, California. Two sites and two seeding dates (early March and mid April) were determined for each site. Five mulch treatments (no mulch, straw, gravel, chemical stabilizer, and plastic) were evaluated in combination with the seed pre-treatments. Field emergence was greatly enhanced with the seed pre-treatment for white bursage during the March (18-42% increase in germination) and April seedings (16-23% increase in germination). Creosotebush showed poor germination during March (2-5%) when soil temperatures averaged 15 C, but germination increased during the April trials (6-43%) when soil temperatures averaged 23 C. The seed pre-treatment during the April trials increased germination from 16-23%. The plastic mulch treatment increased germination dramatically during both the March and April trials. The plastic mulch increased soil temperatures (8-10 C)and maintained high humidity during germination. Both the chemical stabilizer and the gravel mulches improved germination over the control while the straw mulch decreased germination. These results suggest that seed pre-treatments combined with irrigation and mulch are effective techniques to establish these two dominant Mojave Desert species from seed.

Current clinical trials testing combinations of immunotherapy and radiation.

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Crittenden, Marka; Kohrt, Holbrook; Levy, Ronald; Jones, Jennifer; Camphausen, Kevin; Dicker, Adam; Demaria, Sandra; Formenti, Silvia

2015-01-01

Preclinical evidence of successful combinations of ionizing radiation with immunotherapy has inspired testing the translation of these results to the clinic. Interestingly, the preclinical work has consistently predicted the responses encountered in clinical trials. The first example came from a proof-of-principle trial started in 2001 that tested the concept that growth factors acting on antigen-presenting cells improve presentation of tumor antigens released by radiation and induce an abscopal effect. Granulocyte-macrophage colony-stimulating factor was administered during radiotherapy to a metastatic site in patients with metastatic solid tumors to translate evidence obtained in a murine model of syngeneic mammary carcinoma treated with cytokine FLT-3L and radiation. Subsequent clinical availability of vaccines and immune checkpoint inhibitors has triggered a wave of enthusiasm for testing them in combination with radiotherapy. Examples of ongoing clinical trials are described in this report. Importantly, most of these trials include careful immune monitoring of the patients enrolled and will generate important data about the proimmunogenic effects of radiation in combination with a variety of immune modulators, in different disease settings. Results of these studies are building a platform of evidence for radiotherapy as an adjuvant to immunotherapy and encourage the growth of this novel field of radiation oncology. Copyright © 2015 Elsevier Inc. All rights reserved.

Randomized controlled trial of fish oil and montelukast and their combination on airway inflammation and hyperpnea-induced bronchoconstriction.

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Sandra Tecklenburg-Lund

2010-10-01

Full Text Available Both fish oil and montelukast have been shown to reduce the severity of exercise-induced bronchoconstriction (EIB. The purpose of this study was to compare the effects of fish oil and montelukast, alone and in combination, on airway inflammation and bronchoconstriction induced by eucapnic voluntary hyperpnea (EVH in asthmatics.In this model of EIB, twenty asthmatic subjects with documented hyperpnea-induced bronchoconstriction (HIB entered a randomized double-blind trial. All subjects entered on their usual diet (pre-treatment, n = 20 and then were randomly assigned to receive either one active 10 mg montelukast tablet and 10 placebo fish oil capsules (n = 10 or one placebo montelukast tablet and 10 active fish oil capsules totaling 3.2 g EPA and 2.0 g DHA (n = 10 taken daily for 3-wk. Thereafter, all subjects (combination treatment; n = 20 underwent another 3-wk treatment period consisting of a 10 mg active montelukast tablet or 10 active fish oil capsules taken daily.While HIB was significantly inhibited (p0.017 between treatment groups; percent fall in forced expiratory volume in 1-sec was -18.4 ± 2.1%, -9.3±2.8%, -11.6 ± 2.8% and -10.8 ± 1.7% on usual diet (pre-treatment, fish oil, montelukast and combination treatment respectively. All three treatments were associated with a significant reduction (p0.017 in these biomarkers between treatments.While fish oil and montelukast are both effective in attenuating airway inflammation and HIB, combining fish oil with montelukast did not confer a greater protective effect than either intervention alone. Fish oil supplementation should be considered as an alternative treatment for EIB.ClinicalTrials.gov NCT00676468.

Avoiding Systematic Errors in Isometric Squat-Related Studies without Pre-Familiarization by Using Sufficient Numbers of Trials

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Pekünlü Ekim

2014-10-01

Full Text Available There is no scientific evidence in the literature indicating that maximal isometric strength measures can be assessed within 3 trials. We questioned whether the results of isometric squat-related studies in which maximal isometric squat strength (MISS testing was performed using limited numbers of trials without pre-familiarization might have included systematic errors, especially those resulting from acute learning effects. Forty resistance-trained male participants performed 8 isometric squat trials without pre-familiarization. The highest measures in the first “n” trials (3 ≤ n ≤ 8 of these 8 squats were regarded as MISS obtained using 6 different MISS test methods featuring different numbers of trials (The Best of n Trials Method [BnT]. When B3T and B8T were paired with other methods, high reliability was found between the paired methods in terms of intraclass correlation coefficients (0.93-0.98 and coefficients of variation (3.4-7.0%. The Wilcoxon’s signed rank test indicated that MISS obtained using B3T and B8T were lower (p < 0.001 and higher (p < 0.001, respectively, than those obtained using other methods. The Bland- Altman method revealed a lack of agreement between any of the paired methods. Simulation studies illustrated that increasing the number of trials to 9-10 using a relatively large sample size (i.e., ≥ 24 could be an effective means of obtaining the actual MISS values of the participants. The common use of a limited number of trials in MISS tests without pre-familiarization appears to have no solid scientific base. Our findings suggest that the number of trials should be increased in commonly used MISS tests to avoid learning effect-related systematic errors

The Principle of Justice Administered Only by the Court When Making a Pre-Trial Cooperation Agreement and Special Trial Order

Directory of Open Access Journals (Sweden)

Suvorova A. A.

2015-01-01

Full Text Available The article investigates the problems of realization of the principle of justice administered only by the court in special conditions of judicial proceedings, suggests the ways of optimizing the procedure of making a pre-trial cooperation agreement.

PP22. PROGRESSING RADIOTHERAPY-DRUG COMBINATIONS TOWARDS EARLY PHASE CLINICAL TRIALS

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Jones, Dr Hazel; Stock, Dr Julie; Chalmers, Prof Anthony

2017-01-01

Abstract The Radiotherapy-Drug Combinations consortium (RaDCom) works with UK-based investigators to design and deliver high quality preclinical projects evaluating specific radiotherapy-drug combinations. We have several collaborations with industry, from in vitro projects to understand the novel agent in the context of radiobiology, through to preclinical studies that will generate data to support the development of radiotherapy combination trials. RaDCom facilitates the coordination of industry interactions, triage new proposals, monitor active projects, and engages with the radiotherapy community to promote collaboration and networking (via a capability map). The CRUK New Agents Committee Preclinical Combination Grant scheme provides one of the funding options for these studies, with the potential to feed into early phase clinical trials via the ECMC Combinations Alliance. RaDCom also supports broader radiotherapy research initiatives, by working to improve preclinical quality assurance and identifying a route to registration for radiotherapy-drug treatments. These activities will place the UK at the forefront of radiotherapy-drug preclinical research and provide a significant incentive for pharmaceutical companies to invest in this area and utilise the RaDCom network. Further information can be found on our webpage: http://ctrad.ncri.org.uk/research-support/radiation-drug-combinations-radcom Successful projects from RaDCom can then move into early phase combinations trials within the Combinations Alliance. The Combinations Alliance supports early phase combination studies in the UK via the ECMC (Experimental Cancer Medicine Centres) network. It focuses on translational research, and enables clinical project teams to work with disease experts to set up investigator led trials. The CRUK Centre of Drug Development (CDD) supports these studies with further management and coordination ensuring more robust timelines and delivery. The Combinations Alliance framework

Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain.

Science.gov (United States)

Moore, R Andrew; Gay-Escoda, C; Figueiredo, R; Tóth-Bagi, Z; Dietrich, T; Milleri, S; Torres-Lagares, D; Hill, C M; García-García, A; Coulthard, P; Wojtowicz, A; Matenko, D; Peñarrocha-Diago, M; Cuadripani, S; Pizà-Vallespir, B; Guerrero-Bayón, C; Bertolotti, M; Contini, M P; Scartoni, S; Nizzardo, A; Capriati, A; Maggi, C A

2015-01-01

Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective. This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72%) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95% confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. EudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).

SMS text pre-notification and delivery of reminder e-mails to increase response rates to postal questionnaires in the SUSPEND trial: a factorial design, randomised controlled trial.

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Starr, Kathryn; McPherson, Gladys; Forrest, Mark; Cotton, Seonaidh C

2015-07-08

Patient-reported outcomes are vital in informing randomised controlled trials (RCTs) and health-care interventions and policies from the patient's perspective. However, participant non-response may introduce bias and can affect the generalisability of the trial. This study evaluates two interventions aimed at increasing response rates to postal questionnaires within a large, UK-wide RCT: pre-notification via short messenger service (SMS) text prior to sending the initial mailing of trial questionnaires versus no pre-notification; for non-responders to the initial mailing of the questionnaires, an e-mail reminder (containing a hyperlink to complete the questionnaire online) versus a postal reminder. This study is a 2 × 2 partial factorial design RCT nested within an RCT of medical expulsive therapy for ureteric stone disease. Participants who supplied a mobile telephone number were randomly assigned to receive an SMS text pre-notification of questionnaire delivery or no pre-notification. Those who supplied an e-mail address were randomly assigned to receive a questionnaire reminder by e-mail or post. Participants could be randomly assigned to the pre-notification comparison or the reminder comparison or both. The primary outcome measure was response rate at each questionnaire time point. Four hundred eighteen participants were randomly assigned to the SMS pre-notification comparison (80% were male, and the mean age was 41 years with a standard deviation (SD) of 11.1). The intervention had no effect on response rate at either questionnaire time point. In subgroup analyses, SMS pre-notification increased response rates in women but only at the first questionnaire time point. One hundred nineteen participants were randomly assigned to the reminder comparison (80% were male, and the mean age was 42 years with an SD of 12.1). There was no difference in response rate in those who received an e-mail reminder compared with those who received a postal reminder. SMS text pre

From subjects to relations: Bioethics and the articulation of postcolonial politics in the Cambodia Pre-Exposure Prophylaxis trial.

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Grant, Jenna M

2016-04-01

Controversies about global clinical trials, particularly HIV trials, tend to be framed in terms of ethics. In this article, I explore debates about ethics in the Cambodia Pre-Exposure Prophylaxis trial, which was designed to test the safety and efficacy of tenofovir as a prevention for HIV infection. Bringing together studies of public participation in science with studies of bioethics, I show how activists around the Cambodian Pre-Exposure Prophylaxis trial circulated and provoked debates about standards of research ethics, as opposed to research methodology. This postcolonial bioethics was configured through the circulation of and debate about ethics guidelines, and historically and culturally specific relations of vulnerability and responsibility between foreigners and Cambodians and between Cambodian leaders and Cambodian subjects. I argue that this shift in the object of ethical concern, from the experimental human subject to the relation between subjects and researchers, illustrates how a postcolonial field of articulation reformulates classical bioethics.

Anxiety Sensitivity and Pre-Cessation Smoking Processes: Testing the Independent and Combined Mediating Effects of Negative Affect–Reduction Expectancies and Motives

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Farris, Samantha G.; Leventhal, Adam M.; Schmidt, Norman B.; Zvolensky, Michael J.

2015-01-01

Objective: Anxiety sensitivity appears to be relevant in understanding the nature of emotional symptoms and disorders associated with smoking. Negative-reinforcement smoking expectancies and motives are implicated as core regulatory processes that may explain, in part, the anxiety sensitivity–smoking interrelations; however, these pathways have received little empirical attention. Method: Participants (N = 471) were adult treatment-seeking daily smokers assessed for a smoking-cessation trial who provided baseline data; 157 participants provided within-treatment (pre-cessation) data. Anxiety sensitivity was examined as a cross-sectional predictor of several baseline smoking processes (nicotine dependence, perceived barriers to cessation, severity of prior withdrawal-related quit problems) and pre-cessation processes including nicotine withdrawal and smoking urges (assessed during 3 weeks before the quit day). Baseline negative-reinforcement smoking expectancies and motives were tested as simultaneous mediators via parallel multiple mediator models. Results: Higher levels of anxiety sensitivity were related to higher levels of nicotine dependence, greater perceived barriers to smoking cessation, more severe withdrawal-related problems during prior quit attempts, and greater average withdrawal before the quit day; effects were indirectly explained by the combination of both mediators. Higher levels of anxiety sensitivity were not directly related to pre-cessation smoking urges but were indirectly related through the independent and combined effects of the mediators. Conclusions: These empirical findings bolster theoretical models of anxiety sensitivity and smoking and identify targets for nicotine dependence etiology research and cessation interventions. PMID:25785807

Pre-treatment of Biomass By Rolling - A Combined Experimental and Numerical Analysis

DEFF Research Database (Denmark)

Hansen, Klaus Schütt; Ravn, Christian; Nielsen, Emil Krabbe

2017-01-01

Pre-treatment of bulk straw material by rolling is studied as a possible method to prepare for subsequent biogas production. A combined experimental and theoretical study is presented. A pilot rolling mill with a double screw feeder is designed and constructed for crushing of bulk straw. Experime...... process window for pre-treatment of wheat straw by roll pressing varying the feed, the roll gap, the roll speed and the moisture content of the bulk straw.......Pre-treatment of bulk straw material by rolling is studied as a possible method to prepare for subsequent biogas production. A combined experimental and theoretical study is presented. A pilot rolling mill with a double screw feeder is designed and constructed for crushing of bulk straw....... Experiments show that the roll speed and the roll reduction should be chosen within a specific range depending on the injection screw speed to avoid blocking or insufficient compaction. A mechanical testing procedure of the bulk straw material including closed die compaction testing as well as simple...

Combined radiotherapy and chemotherapy for head and neck cancer

International Nuclear Information System (INIS)

Inuyama, Yukio; Fujii, Masato; Tanaka, Juichi; Takaoka, Tetsuro; Hosoda, Hyonosuke; Kawaura, Mitsuhiro; Toji, Masao

1988-01-01

There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neo-adjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary. (author)

Design of Phase I Combination Trials: Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee

Science.gov (United States)

Paller, Channing J.; Bradbury, Penelope A.; Ivy, S. Percy; Seymour, Lesley; LoRusso, Patricia M.; Baker, Laurence; Rubinstein, Larry; Huang, Erich; Collyar, Deborah; Groshen, Susan; Reeves, Steven; Ellis, Lee M.; Sargent, Daniel J.; Rosner, Gary L.; LeBlanc, Michael L.; Ratain, Mark J.

2014-01-01

Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to maximize the pharmacodynamic effect. The development of combination regimens, while desirable, poses unique challenges. These include the selection of agents for combination therapy that may lead to improved efficacy while maintaining acceptable toxicity, the design of clinical trials that provide informative results for individual agents and combinations, and logistical and regulatory challenges. The phase 1 trial is often the initial step in the clinical evaluation of a combination regimen. In view of the importance of combination regimens and the challenges associated with developing them, the Clinical Trial Design (CTD) Task Force of the National Cancer Institute (NCI) Investigational Drug Steering Committee developed a set of recommendations for the phase 1 development of a combination regimen. The first two recommendations focus on the scientific rationale and development plans for the combination regimen; subsequent recommendations encompass clinical design aspects. The CTD Task Force recommends that selection of the proposed regimens be based on a biological or pharmacological rationale supported by clinical and/or robust and validated preclinical evidence, and accompanied by a plan for subsequent development of the combination. The design of the phase 1 clinical trial should take into consideration the potential pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity. Depending on the specific hypothesized interaction, the primary endpoint may be dose optimization, pharmacokinetics, and/or pharmacodynamic (i.e., biomarker). PMID:25125258

Imipramine and Pregabalin Combination for Painful Polyneuropathy. A Randomized Controlled Trial

DEFF Research Database (Denmark)

Holbech, Jakob V; Bach, Flemming W; Finnerup, Nanna B

2015-01-01

Monotherapy with first-line drugs for neuropathic pain often fails to provide sufficient pain relief or has unacceptable side effects because of the need for high doses. The aim of this trial was to test whether the combination of imipramine and pregabalin in moderate doses would relieve pain more...... effectively than monotherapy with either of the drugs. This was a randomized, double-blind, placebo-controlled, crossover, multicenter trial consisting of four 5-week treatment periods in patients with painful polyneuropathy. Treatment arms were imipramine 75 mg/d vs pregabalin 300 mg/d vs combination therapy...... randomized, and 69 patients were included in the data analysis. The effect on average pain in comparison with placebo was: combination (-1.67 NRS points, P pregabalin (-0.48 NRS points, P = 0.03). The combination therapy had significantly lower pain...

The design and development of a complex multifactorial falls assessment intervention for falls prevention: The Prevention of Falls Injury Trial (PreFIT).

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Bruce, Julie; Ralhan, Shvaita; Sheridan, Ray; Westacott, Katharine; Withers, Emma; Finnegan, Susanne; Davison, John; Martin, Finbarr C; Lamb, Sarah E

2017-06-01

This paper describes the design and development of a complex multifactorial falls prevention (MFFP) intervention for implementation and testing within the framework of a large UK-based falls prevention randomised controlled trial (RCT). A complex intervention was developed for inclusion within the Prevention of Falls Injury Trial (PreFIT), a multicentre pragmatic RCT. PreFIT aims to compare the clinical and cost-effectiveness of three alternative primary care falls prevention interventions (advice, exercise and MFFP), on outcomes of fractures and falls. Community-dwelling adults, aged 70 years and older, were recruited from primary care in the National Health Service (NHS), England. Development of the PreFIT MFFP intervention was informed by the existing evidence base and clinical guidelines for the assessment and management of falls in older adults. After piloting and modification, the final MFFP intervention includes seven falls risk factors: a detailed falls history interview with consideration of 'red flags'; assessment of balance and gait; vision; medication screen; cardiac screen; feet and footwear screen and home environment assessment. This complex intervention has been fully manualised with clear, documented assessment and treatment pathways for each risk factor. Each risk factor is assessed in every trial participant referred for MFFP. Referral for assessment is based upon a screening survey to identify those with a history of falling or balance problems. Intervention delivery can be adapted to the local setting. This complex falls prevention intervention is currently being tested within the framework of a large clinical trial. This paper adheres to TIDieR and CONSORT recommendations for the comprehensive and explicit reporting of trial interventions. Results from the PreFIT study will be published in due course. The effectiveness and cost-effectiveness of the PreFIT MFFP intervention, compared to advice and exercise, on the prevention of falls and

Assessing Odor Level when Using PrePex for HIV Prevention: A Prospective, Randomized, Open Label, Blinded Assessor Trial to Improve Uptake of Male Circumcision.

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Vincent Mutabazi

Full Text Available The PrePex is a WHO--prequalified medical device for adult male circumcision for HIV prevention. The Government of Rwanda was the first country to implement the PrePex device and acts as the leading center of excellence providing training and formal guidelines. As part of the Government's efforts to improve PrePex implementation, it made efforts to improve the psychological acceptability of device by men, thus increasing uptake with VMMC in sub-Saharan Africa. Some men who underwent the PrePex procedure complained of foreskin odor while wearing the PrePex 3-7 days after it was placed. This complaint was identified as potential risk for uptake of the device. Researchers from Rwanda assumed there is a possible relation between the level of foreskin odor and patient foreskin hygiene technique. The Government of Rwanda decided to investigate those assumptions in a scientific way and conduct a trial to test different hygiene-cleaning methods in order to increase the acceptability of PrePex and mitigate the odor concern. The main objective of the trial was to compare odor levels between three arms, having identical personal hygiene but different foreskin hygiene techniques using either clear water with soap during a daily shower, soapy water using a syringe, or chlorhexidine using a syringe. One hundred and one subjects were enrolled to the trial and randomly allocated into three trial arms. Using chlorhexidine solution daily almost completely eliminated odor, and was statistically significant more effective that the other two arms. The trial results suggest that odor from the foreskin, while wearing the PrePex device, could be related to the growth of anaerobic bacteria, which can be prevented by a chlorhexidine cleaning method. This finding can be used to increase acceptability by men when considering PrePex as one of the leading methods for HIV prevention in VMMC programs.

Combinations of Personal Responsibility: Differences on Pre-service and Practicing Teachers' Efficacy, Engagement, Classroom Goal Structures and Wellbeing.

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Daniels, Lia M; Radil, Amanda I; Goegan, Lauren D

2017-01-01

Pre-service and practicing teachers feel responsible for a range of educational activities. Four domains of personal responsibility emerging in the literature are: student achievement, student motivation, relationships with students, and responsibility for ones own teaching. To date, most research has used variable-centered approaches to examining responsibilities even though the domains appear related. In two separate samples we used cluster analysis to explore how pre-service ( n = 130) and practicing ( n = 105) teachers combined personal responsibilities and their impact on three professional cognitions and their wellbeing. Both groups had low and high responsibility clusters but the third cluster differed: Pre-service teachers combined responsibilities for relationships and their own teaching in a cluster we refer to as teacher-based responsibility; whereas, practicing teachers combined achievement and motivation in a cluster we refer to as student-outcome focused responsibility. These combinations affected outcomes for pre-service but not practicing teachers. Pre-service teachers in the low responsibility cluster reported less engagement, less mastery approaches to instruction, and more performance goal structures than the other two clusters.

Which Fall Ascertainment Method Captures Most Falls in Pre-Frail and Frail Seniors?

Science.gov (United States)

Teister, Corina J; Chocano-Bedoya, Patricia O; Orav, Endel J; Dawson-Hughes, Bess; Meyer, Ursina; Meyer, Otto W; Freystaetter, Gregor; Gagesch, Michael; Rizzoli, Rene; Egli, Andreas; Theiler, Robert; Kanis, John A; Bischoff-Ferrari, Heike A

2018-06-15

There is no consensus on most reliable falls ascertainment method. Therefore, we investigated which method captures most falls among pre-frail and frail seniors from two randomized controlled trials conducted in Zurich, Switzerland, a 18-month trial (2009-2010) including 200 community-dwelling pre-frail seniors with a prior fall and a 12-month trial (2005-2008) including 173 frail seniors with acute hip fracture. Both included the same fall ascertainment methods: monthly active-asking, daily self-report diary, and a call-in hotline. We compared number of falls reported and estimated overall and positive percent agreement between methods. Pre-frail seniors reported 499 falls (rate = 2.5/year) and frail seniors reported 205 falls (rate = 1.4/year). Most falls were reported by active-asking: 81% of falls in pre-frail, and 78% in frail seniors. Among pre-frail seniors, diaries captured additional 19% falls, while hotline added none. Among frail seniors, hotline added 16% falls, while diaries added 6%. The positive percent agreement between active-asking and diary was 100% among pre-frail and 88% among frail seniors. While monthly active-asking captures most falls in both groups, this method alone missed 19% of falls in pre-frail and 22% in frail seniors. Thus, a combination of active-asking and diaries for pre-frail, and active-asking and the hotline for frail seniors is warranted.

SU-F-T-351: Establishing a Workflow for IMRT Pre-Treatment Reviews for NRG-GY006 Clinical Trial

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Giaddui, T [Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Li, N; Moore, K; Mell, L [University of California, San Diego, San Diego, CA (United States); Curry, K [MIM Software, Inc., Clevealand, OH (United States); Leath, C [University of Alabama at Birmingham, Birmingham, AL (United States); Kunos, C [Northeastern Ohio University College, Clevealand, OH (United States); Xiao, Y [University of Pennsylvania, Philadelphia, PA (United States)

2016-06-15

Purpose: To establish a workflow for NRG-GY006 IMRT pre-treatment reviews, incorporating advanced radiotherapy technologies being evaluated as part of the clinical trial. Methods: Pre-Treatment reviews are required for every IMRT case as part of NRG-GY006 (a randomized phase II trial of radiation therapy and cisplatin alone or in combination with intravenous triapine in women with newly diagnosed bulky stage I B2, stage II, IIIB, or IVA cancer of the uterine cervix or stage II-IVA vaginal cancer. The pretreatment review process includes structures review and generating an active bone marrow(ABM)- to be used as an avoidance structure during IMRT optimization- and evaluating initial IMRT plan quality using knowledgeengineering based planning (KBP). Institutions will initially submit their simulation CT scan, structures file and PET/CT to IROC QA center for generating ABM. The ABM will be returned to the institution for use in planning. Institutions will then submit an initial IMRT plan for review and will receive information back following implementation of a KBP algorithm, for use in re-optimization, before submitting the final IMRT used for treatment. Results: ABM structure is generated using MIM vista software (Version 6.5, MIM corporation, Inc.). Here, the planning CT and the diagnostic PET/CT are fused and a sub threshold structure is auto segmented above the mean value of the SUV of the bone marrow. The generated ABM were compared with those generated with other software system (e.g. Velocity, Varian) and Dice coefficient (reflects the overlap of structures) ranged between 80 – 90% was achieved. A KBP model was built in Varian Eclipse TPS using the RapidPlan KBP software to perform plan quality assurance. Conclusion: The workflow for IMRT pretreatment reviews has been established. It represents a major improvement of NRG Oncology clinical trial quality assurance and incorporates the latest radiotherapy technologies as part of NCI clinical trials. This project

SU-F-T-351: Establishing a Workflow for IMRT Pre-Treatment Reviews for NRG-GY006 Clinical Trial

International Nuclear Information System (INIS)

Giaddui, T; Li, N; Moore, K; Mell, L; Curry, K; Leath, C; Kunos, C; Xiao, Y

2016-01-01

Purpose: To establish a workflow for NRG-GY006 IMRT pre-treatment reviews, incorporating advanced radiotherapy technologies being evaluated as part of the clinical trial. Methods: Pre-Treatment reviews are required for every IMRT case as part of NRG-GY006 (a randomized phase II trial of radiation therapy and cisplatin alone or in combination with intravenous triapine in women with newly diagnosed bulky stage I B2, stage II, IIIB, or IVA cancer of the uterine cervix or stage II-IVA vaginal cancer. The pretreatment review process includes structures review and generating an active bone marrow(ABM)- to be used as an avoidance structure during IMRT optimization- and evaluating initial IMRT plan quality using knowledgeengineering based planning (KBP). Institutions will initially submit their simulation CT scan, structures file and PET/CT to IROC QA center for generating ABM. The ABM will be returned to the institution for use in planning. Institutions will then submit an initial IMRT plan for review and will receive information back following implementation of a KBP algorithm, for use in re-optimization, before submitting the final IMRT used for treatment. Results: ABM structure is generated using MIM vista software (Version 6.5, MIM corporation, Inc.). Here, the planning CT and the diagnostic PET/CT are fused and a sub threshold structure is auto segmented above the mean value of the SUV of the bone marrow. The generated ABM were compared with those generated with other software system (e.g. Velocity, Varian) and Dice coefficient (reflects the overlap of structures) ranged between 80 – 90% was achieved. A KBP model was built in Varian Eclipse TPS using the RapidPlan KBP software to perform plan quality assurance. Conclusion: The workflow for IMRT pretreatment reviews has been established. It represents a major improvement of NRG Oncology clinical trial quality assurance and incorporates the latest radiotherapy technologies as part of NCI clinical trials. This project

The effect of a pre- and post-operative orthogeriatric service on cognitive function in patients with hip fracture. The protocol of the Oslo Orthogeriatrics Trial

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Wyller Torgeir

2012-07-01

Full Text Available Abstract Background Hip fractures mainly affect older people. It is associated with high morbidity and mortality, and in particular a high frequency of delirium. Incident delirium following hip fracture is associated with an increased risk of dementia in the following months, but it is still not firmly established whether this is an association or a causal relationship. Orthogeriatric units vary with respect to content and timing of the intervention. One main effect of orthogeriatric care may be the prevention of delirium, especially if preoperative and postoperative care are provided. Thus, the aim of Oslo Orthogeriatric Trial, is to assess whether combined preoperative and postoperative orthogeriatric care can reduce the incidence of delirium and improve cognition following hip fracture. Methods/design Inclusion and randomisation will take place in the Emergency Department, as soon as possible after admission. All patients with proximal femur fractures are eligible, irrespective of age, pre-fracture function and accommodation, except if the fracture is caused by a high energy trauma or the patient is terminally ill. The intervention is pre-and post-operative orthogeriatric care delivered on a dedicated acute geriatric ward. The primary outcome measure is a composite endpoint combining the Clinical Dementia Rating Scale (CDR and the 10 word memory task at four months after surgery. Secondary outcomes comprise incident delirium, length of stay, cognition, mobility, place of residence, activities of daily living and mortality, measured at 4 and 12 months after surgery. We have included 332 patients in the period 17th September 2009 to 5th January 2012. Discussion Our choice of outcome measures and our emphasis of orthogeriatric care in the preoperative as well as the postoperative phase will enable us to provide new knowledge on the impact of orthogeriatric care on cognition. Trials registration ClinicalTrials.gov NCT01009268

Effects of Whey Protein Supplementation Pre- or Post-Resistance Training on Muscle Mass, Muscular Strength, and Functional Capacity in Pre-Conditioned Older Women: A Randomized Clinical Trial

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Hellen C. G. Nabuco

2018-05-01

Full Text Available Aging is associated with sarcopenia and dynapenia, with both processes contributing to functional dependence and mortality in older adults. Resistance training (RT and increased protein intake are strategies that may contribute to health improvements in older adults. Therefore, the aim was to investigate the effects of whey protein (WP supplementation consumed either immediately pre- or post-RT on skeletal muscle mass (SMM, muscular strength, and functional capacity in pre-conditioned older women. Seventy older women participated in this investigation and were randomly assigned to one of three groups: whey protein pre-RT and placebo post-RT (WP-PLA, n = 24, placebo pre-RT and whey protein post-RT (PLA-WP, n = 23, and placebo pre- and post-RT (PLA-PLA, n = 23. Each group ingested 35 g of WP or PLA. The RT program was carried out over 12 weeks (three times per week; 3 × 8–12 repetition maximum. Body composition, muscular strength, functional capacity, and dietary intake were assessed pre- and post-intervention. Two-way analysis of covariance (ANCOVA for repeated measures, with baseline scores as covariates were used for data analysis. A time vs. group interaction (p < 0.05 was observed with WP-PLA and PLA-WP presenting greater increases compared with PLA-PLA for SMM (WP-PLA = 3.4%; PLA-WP = 4.2%; PLA-PLA = 2.0%, strength (WP-PLA = 8.1%; PLA-WP = 8.3%; PLA-PLA = 7.0%, and the 10-m walk test (WP-PLA = −10.8%; PLA-WP = −11.8%; PLA-PLA = −4.3%. Whey protein supplementation was effective in promoting increases in SMM, muscular strength, and functional capacity in pre-conditioned older women, regardless of supplementation timing. This trial was registered at ClinicalTrials.gov: NCT03247192.

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

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Neto José

2011-03-01

Full Text Available Abstract Background Blood pressure (BP within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage. Methods This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution. Discussion The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe

Proximal, but not distal, pre-exposure reduces serial overshadowing in one-trial taste aversion learning.

Science.gov (United States)

Kwok, Dorothy W S; Boakes, Robert A

2015-09-01

This experiment tested whether pre-exposing a taste would reduce its ability to overshadow conditioning to a target taste and whether this effect would depend on the delay between pre-exposure and conditioning. Two groups of rats were pre-exposed to an interfering taste (HCl) either a week before conditioning (Group Distal) or the day preceding conditioning (Group Proximal). In the single conditioning trial, rats were given the target taste (sucrose) and 65min later were injected with lithium. The groups differed as to what they were given to drink 50min after sucrose: The Distal, Proximal and Novel groups were given HCl, while the Control group was given water. Pre-exposure to HCl reduced overshadowing of the sucrose aversion by HCl in Group Proximal but not in Group Distal. Possible explanations for the latter result include extinction of the context-HCl association and loss of context control over an HCl-no outcome association. Copyright © 2015 Elsevier B.V. All rights reserved.

Pre-operative biliary drainage for obstructive jaundice

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Fang, Yuan; Gurusamy, Kurinchi Selvan; Wang, Qin; Davidson, Brian R; Lin, He; Xie, Xiaodong; Wang, Chaohua

2014-01-01

Background Patients with obstructive jaundice have various pathophysiological changes that affect the liver, kidney, heart, and the immune system. There is considerable controversy as to whether temporary relief of biliary obstruction prior to major definitive surgery (pre-operative biliary drainage) is of any benefit to the patient. Objectives To assess the benefits and harms of pre-operative biliary drainage versus no pre-operative biliary drainage (direct surgery) in patients with obstructive jaundice (irrespective of a benign or malignant cause). Search methods We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2012. Selection criteria We included all randomised clinical trials comparing biliary drainage followed by surgery versus direct surgery, performed for obstructive jaundice, irrespective of the sample size, language, and publication status. Data collection and analysis Two authors independently assessed trials for inclusion and extracted data. We calculated the risk ratio (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence intervals (CI) based on the available patient analyses. We assessed the risk of bias (systematic overestimation of benefit or systematic underestimation of harm) with components of the Cochrane risk of bias tool. We assessed the risk of play of chance (random errors) with trial sequential analysis. Main results We included six trials with 520 patients comparing pre-operative biliary drainage (265 patients) versus no pre-operative biliary drainage (255 patients). Four trials used percutaneous transhepatic biliary drainage and two trials used endoscopic sphincterotomy and stenting as the method of pre-operative biliary drainage. The risk of bias was high in all trials. The proportion of patients with malignant obstruction varied between 60

Pre-trial Intervention: The Manhattan Court Employment Project of the Vera Institute of Justice. Final Report.

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Vera Inst. of Justice, New York, NY.

The final report of an experimental pre-trial intervention program of intensive manpower services (individual and group counseling and job, training, or academic placement with the help of career developers) for selected defendants in Manhattan covers the period November 1967 through October 1970. After three years and 1,300 participants,…

The PACOVAR-trial: A phase I/II study of pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant recurrent, pre-treated ovarian cancer

International Nuclear Information System (INIS)

Eichbaum, Michael; Fersis, Nikos; Schmidt, Marcus; Wallwiener, Markus; Schneeweiss, Andreas; Sohn, Christof; Mayer, Christine; Eickhoff, Regina; Bischofs, Esther; Gebauer, Gerhard; Fehm, Tanja; Lenz, Florian; Fricke, Hans-Christian; Solomayer, Erich

2011-01-01

The prognosis of patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC) is poor. There is no standard treatment available. Emerging evidence suggests a major role for antiangiogenic treatment modalities in EOC, in particular in combination with the metronomic application of low dose chemotherapy. The novel, investigational oral antiangiogenic agent pazopanib targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit is currently being studied in different tumour types and is already used as first line therapy in recurrent renal cell carcinoma. A combined therapy consisting of pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, pretreated EOC. This study is designed as a multicenter phase I/II trial evaluating the optimal dose for pazopanib (phase I) as well as activity and tolerability of a combination regimen consisting of pazopanib and metronomic cyclophosphamide in the palliative treatment of patients with recurrent, platinum-resistant, pre-treated ovarian cancer (phase II). The patient population includes patients with histologically or cytologically confirmed diagnosis of EOC, cancer of the fallopian tube or peritoneal cancer which is platinumresistant or -refractory. Patients must have measurable disease according to RECIST criteria and must have failed available standard chemotherapy. Primary objectives are determination of the optimal doses for pazopanib (phase I) and the overall response rate according to RECIST criteria (phase II). Secondary objectives are time to progression, overall survival, safety and tolerability. The treatment duration is until disease progression or intolerability of study drug regimen (with a maximum of 13 cycles up to 52 weeks per subject). The current phase I/II trial shall clarify the potential of the multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 (pazopanib) in

Modern dose-finding designs for cancer phase I trials drug combinations and molecularly targeted agents

CERN Document Server

Hirakawa, Akihiro; Daimon, Takashi; Matsui, Shigeyuki

2018-01-01

This book deals with advanced methods for adaptive phase I dose-finding clinical trials for combination of two agents and molecularly targeted agents (MTAs) in oncology. It provides not only methodological aspects of the dose-finding methods, but also software implementations and practical considerations in applying these complex methods to real cancer clinical trials. Thus, the book aims to furnish researchers in biostatistics and statistical science with a good summary of recent developments of adaptive dose-finding methods as well as providing practitioners in biostatistics and clinical investigators with advanced materials for designing, conducting, monitoring, and analyzing adaptive dose-finding trials. The topics in the book are mainly related to cancer clinical trials, but many of those topics are potentially applicable or can be extended to trials for other diseases. The focus is mainly on model-based dose-finding methods for two kinds of phase I trials. One is clinical trials with combinations of tw...

A randomized controlled trial of pre-conception treatment for periodontal disease to improve periodontal status during pregnancy and birth outcomes.

Science.gov (United States)

Jiang, Hong; Xiong, Xu; Su, Yi; Zhang, Yiming; Wu, Hongqiao; Jiang, Zhijun; Qian, Xu

2013-12-09

Evidence has suggested that periodontal disease is associated with an increased risk of various adverse pregnancy and birth outcomes. However, several large clinical randomized controlled trials failed to demonstrate periodontal therapy during pregnancy reduced the incidence of adverse pregnancy and birth outcomes. It has been suggested that the pre-conception period may be an optimal period for periodontal disease treatment rather than during pregnancy. To date, no randomized controlled trial (RCT) has examined if treating periodontal disease before pregnancy reduces adverse birth outcomes. This study aims to examine if the pre-conception treatment of periodontal disease will lead to improved periodontal status during late pregnancy and subsequent birth outcomes. A sample of 470 (235 in each arm of the study) pre-conception women who plan to conceive within one year and with periodontal disease will be recruited for the study. All participants will be randomly allocated to the intervention or control group. The intervention group will receive free therapy including dental scaling and root planning (the standard therapy), supragingival prophylaxis, and oral hygiene education. The control group will only receive supragingival prophylaxis and oral hygiene education. Women will be followed throughout their pregnancy and then to childbirth. The main outcomes include periodontal disease status in late pregnancy and birth outcomes measured such as mean birth weight (grams), and mean gestational age (weeks). Periodontal disease will be diagnosed through a dental examination by measuring probing depth, clinical attachment loss and percentage of bleeding on probing (BOP) between gestational age of 32 and 36 weeks. Local and systemic inflammatory mediators are also included as main outcomes. This will be the first RCT to test whether treating periodontal disease among pre-conception women reduces periodontal disease during pregnancy and prevents adverse birth outcomes. If

SPECIAL RULES OF MITIGATION OF PUNISHMENT IN CASE OF THE CONCLUSION OF THE PRE-TRIAL COOPERATION AGREEMENT, AT THE SPECIAL PROCEDURE OF FOR THE TRIAL AND AT THE SHORTENED ORDER OF INQUIRY

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Tatiana Nepomnyashchaya

2017-01-01

Full Text Available The subject. The article analyzes the rules for the appointment of punishment in the case of a pre-trial cooperation agreement, with a special procedure for the trial and with a shortened procedure of conducting inquiry, regulated by art. 62 of the RF Criminal Code “Turning out a Sentence when Mitigating Circumstances Exist”. The authors give an answer to two questions: 1 Does the legal nature of these institutions correspond to the legal nature of mitigating circumstances; 2 Is it advisable to consolidate in a one article of the law different legal regulations.Methodology. Authors use such researching methods as analysis and synthesis, formally legal, comparative legal.Results. Rules for the appointment of punishment in the conclusion of a pre-trial cooperation agreement, stipulated by the pt. 2, 4 of art. 62 of the RF Criminal Code, regulate not the order of accounting for mitigating circumstances, but the legal consequences associated with the promotion of a person, which concluded and executed a pre-trial cooperation agreement, that does not correspond to the legal nature of the pt. 1, 3 of art. 62 of the RF Criminal Code.The legal nature of the rules for the appointment of punishment, established in pt. 5 of art. 62 of the RF Criminal Code, also does not correspond to the legal nature of the rules for the imposition of punishment in the presence of mitigating circumstances, because mitigation of punishment occurs on criminal procedural grounds, which are not mitigating circumstances.Conclusions. In authors opinion, fastening in art. 62 of the RF Criminal Code of three independent rules for the imposition of punishment, namely, the rules for the imposition of punishment in the presence of mitigating circumstances (pt. 1, 3 of art. 62 of the Criminal Code, at the conclusion of a pre-trial cooperation agreement (pt. 2, 4 of art. 62 of the Crim-inal Code, with a special order of the trial and a shortened procedure for conducting an inquiry

Same day ART initiation versus clinic-based pre-ART assessment and counselling for individuals newly tested HIV-positive during community-based HIV testing in rural Lesotho - a randomized controlled trial (CASCADE trial).

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Labhardt, Niklaus Daniel; Ringera, Isaac; Lejone, Thabo Ishmael; Masethothi, Phofu; Thaanyane, T'sepang; Kamele, Mashaete; Gupta, Ravi Shankar; Thin, Kyaw; Cerutti, Bernard; Klimkait, Thomas; Fritz, Christiane; Glass, Tracy Renée

2016-04-14

Achievement of the UNAIDS 90-90-90 targets in Sub-Sahara Africa is challenged by a weak care-cascade with poor linkage to care and retention in care. Community-based HIV testing and counselling (HTC) is widely used in African countries. However, rates of linkage to care and initiation of antiretroviral therapy (ART) in individuals who tested HIV-positive are often very low. A frequently cited reason for non-linkage to care is the time-consuming pre-ART assessment often requiring several clinic visits before ART-initiation. This two-armed open-label randomized controlled trial compares in individuals tested HIV-positive during community-based HTC the proposition of same-day community-based ART-initiation to the standard of care pre-ART assessment at the clinic. Home-based HTC campaigns will be conducted in catchment areas of six clinics in rural Lesotho. Households where at least one individual tested HIV positive will be randomized. In the standard of care group individuals receive post-test counselling and referral to the nearest clinic for pre-ART assessment and counselling. Once they have started ART the follow-up schedule foresees monthly clinic visits. Individuals randomized to the intervention group receive on the spot point-of-care pre-ART assessment and adherence counselling with the proposition to start ART that same day. Once they have started ART, follow-up clinic visits will be less frequent. First primary outcome is linkage to care (individual presents at the clinic at least once within 3 months after the HIV test). The second primary outcome is viral suppression 12 months after enrolment in the study. We plan to enrol a minimum of 260 households with 1:1 allocation and parallel assignment into both arms. This trial will show if in individuals tested HIV-positive during community-based HTC campaigns the proposition of same-day ART initiation in the community, combined with less frequent follow-up visits at the clinic could be a pragmatic approach to

Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED trial: A multi-centre, double-masked, factorial randomised controlled trial

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Kingston Laura

2008-01-01

Full Text Available Abstract Background Medical management of thyroid eye disease remains controversial due to a paucity of high quality evidence on long-term treatment outcomes. Glucocorticoids are known to be effective initially but have significant side-effects with long-term use and recrudescence can occur on cessation. Current evidence is conflicting on the efficacy of radiotherapy and non-steroid systemic immunosuppression, and the majority of previous studies have been retrospective, uncontrolled, small or poorly designed. The Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease (CIRTED trial was designed to investigate the efficacy of radiotherapy and azathioprine in combination with a standard course of oral prednisolone in patients with active thyroid eye disease. Methods/design Patients with active thyroid eye disease will be randomised to receive (i azathioprine or oral placebo and (ii radiotherapy or sham-radiotherapy in this multi-centre, factorial randomised control trial. The primary outcome is improvement in disease severity (assessed using a composite binary measure at 12 months and secondary end-points include quality of life scores and health economic measures. Discussion The CIRTED trial is the first study to evaluate the role of radiotherapy and azathioprine as part of a long-term, combination immunosuppressive treatment regime for Thyroid Eye Disease. It will provide evidence for the role of radiotherapy and prolonged immunosuppression in the management of this condition, as well as pilot data on their use in combination. We have paid particular attention in the trial design to establishing (a robust placebo controls and masking protocols which are effective and safe for both radiotherapy and the systemic administration of an antiproliferative drug; (b constructing effective inclusion and exclusion criteria to select for active disease; and (c selecting pragmatic outcome measures. Trial registration Current controlled trials

Emissions of ammonia and greenhouse gases during combined pre-composting and vermicomposting of duck manure

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Wang, Jinzhi; Hu, Zhengyi; Xu, Xingkai; Jiang, Xia; Zheng, Binghui; Liu, Xiaoning; Pan, Xubin; Kardol, Paul

2014-01-01

Highlights: • Earthworms significantly decreased emissions of N 2 O and CH 4 , but had a marginal effect on CO 2 emission. • NH 3 , N 2 O, and CH 4 emissions were significantly reduced by reed straw and zeolite, CO 2 emission was increased by reed straw. • Combined pre-composting and vermicomposting with reed straw and zeolite would be recommended for disposal of duck manure. - Abstract: Combined pre-composting and vermicomposting has shown potential for reclamation of solid wastes, which is a significant source of ammonia (NH 3 ), and greenhouse gases (GHG), including nitrous oxide (N 2 O), methane (CH 4 ), and carbon dioxide (CO 2 ). Earthworms and amendments may both affect physico-chemical characteristics that control gas-producing processes, and thus affect NH 3 and GHG emissions. Here, we used two-way ANOVA to test the effects of addition of reed straw and combined addition of reed straw and zeolite on NH 3 and GHG emissions during pre-composting of duck manure, either with or without a follow-up phase of vermicomposting. Results showed that cumulative N 2 O, CH 4 , and CO 2 emissions during pre-composting and vermicomposting ranged from 92.8, 5.8, and 260.6 mg kg −1 DM to 274.2, 30.4, and 314.0 mg kg −1 DM, respectively. Earthworms and amendments significantly decreased N 2 O and CH 4 emissions. Emission of CO 2 was not affected by earthworms, but increased in responses to addition of reed straw. Cumulative NH 3 emission ranged from 3.0 to 8.1 g kg −1 DM, and was significantly decreased by reed straw and zeolite addition. In conclusion, combined pre-composting and vermicomposting with reed straw and zeolite addition would be strongly recommended in mitigating emissions of N 2 O, CH 4 , and NH 3 from duck manure. Moreover, this method also provides nutrient-rich products that can be used as a fertilizer

Reducing child abuse amongst adolescents in low- and middle-income countries: A pre-post trial in South Africa.

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Cluver, Lucie; Meinck, Franziska; Yakubovich, Alexa; Doubt, Jenny; Redfern, Alice; Ward, Catherine; Salah, Nasteha; De Stone, Sachin; Petersen, Tshiamo; Mpimpilashe, Phelisa; Romero, Rocio Herrero; Ncobo, Lulu; Lachman, Jamie; Tsoanyane, Sibongile; Shenderovich, Yulia; Loening, Heidi; Byrne, Jasmina; Sherr, Lorraine; Kaplan, Lauren; Gardner, Frances

2016-07-13

No known studies have tested the effectiveness of child abuse prevention programmes for adolescents in low- or middle-income countries. 'Parenting for Lifelong Health' ( http://tiny.cc/whoPLH ) is a collaborative project to develop and rigorously test abuse-prevention parenting programmes for free use in low-resource contexts. Research aims of this first pre-post trial in South Africa were: i) to identify indicative effects of the programme on child abuse and related outcomes; ii) to investigate programme safety for testing in a future randomised trial, and iii) to identify potential adaptations. Two hundred thirty participants (adolescents and their primary caregivers) were recruited from schools, welfare services and community-sampling in rural, high-poverty South Africa (no exclusion criteria). All participated in a 12-week parenting programme, implemented by local NGO childcare workers to ensure real-world external validity. Standardised pre-post measures with adolescents and caregivers were used, and paired t-tests were conducted for primary outcomes: abuse (physical, emotional abuse and neglect), adolescent behaviour problems and parenting (positive and involved parenting, poor monitoring and inconsistent discipline), and secondary outcomes: mental health, social support and substance use. Participants reported high levels of socio-economic deprivation, e.g. 60 % of adolescents had either an HIV-positive caregiver or were orphaned by AIDS, and 50 % of caregivers experienced intimate partner violence. i) indicative effects: Primary outcomes comparing pre-test and post-test assessments showed reductions reported by adolescents and caregivers in child abuse (adolescent report 63.0 % pre-test to 29.5 % post-test, caregiver report 75.5 % pre-test to 36.5 % post-test, both p child abuse and improved caregiver and adolescent outcomes. It showed high acceptability and unexpected community-level diffusion. Findings indicate needs for adaptations, and

Influence of Combined Ultrasound With Pre modulated interferential Current in Discogenic Sciatica

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Selem, A.I.; El Hafez, H.M.; Alshatoury, H.A.; Ismail, G.

2016-01-01

Background and purpose : Lumbar- spine disorders rank fifth among disease categories in the cost of hospital care and account for higher costs resulting in absence from work and disability than any other category. Sciatica is a common clinical condition that can be extremely painful, disabling and life changing. This study was conducted to find out the effectiveness of adding interferential current therapy to conventional treatment and to compare with conventional treatment only in patients with chronic discogenic sciatica. Methods : This randomized controlled trial was conducted at Ismailia General Hospital. Sixty patients (22 males and 38 females) aged between 20 and 40 years old and duration of illness of more than 3 months. They were classified randomly into two groups of equal number. The Experimental Group received interferential therapy (IFT) combined with conventional therapy while control Group received conventional therapy only, 3 times/ week for 4 weeks. Outcome measures : back and leg pain intensity was measured by numeric pain rating scale (0 - 10), functional disability was measured by Roland Morris disability questionnaire, range of motion (Rom) was measured by inclinometer and latency of H- reflex was measured by electromyography. The assessment was done twice for every subject (pre and post the treatment program). Results : Statistical interpretation showed significant improvement of both groups. But in case of experimental group, the amount of improvement was higher with decrease in pain, increasing functional ability, increasing range of motion and improvement in H- reflex latency when compared to control group

Emissions of ammonia and greenhouse gases during combined pre-composting and vermicomposting of duck manure.

Science.gov (United States)

Wang, Jinzhi; Hu, Zhengyi; Xu, Xingkai; Jiang, Xia; Zheng, Binghui; Liu, Xiaoning; Pan, Xubin; Kardol, Paul

2014-08-01

Combined pre-composting and vermicomposting has shown potential for reclamation of solid wastes, which is a significant source of ammonia (NH3), and greenhouse gases (GHG), including nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2). Earthworms and amendments may both affect physico-chemical characteristics that control gas-producing processes, and thus affect NH3 and GHG emissions. Here, we used two-way ANOVA to test the effects of addition of reed straw and combined addition of reed straw and zeolite on NH3 and GHG emissions during pre-composting of duck manure, either with or without a follow-up phase of vermicomposting. Results showed that cumulative N2O, CH4, and CO2 emissions during pre-composting and vermicomposting ranged from 92.8, 5.8, and 260.6 mg kg(-)(1) DM to 274.2, 30.4, and 314.0 mg kg(-1) DM, respectively. Earthworms and amendments significantly decreased N2O and CH4 emissions. Emission of CO2 was not affected by earthworms, but increased in responses to addition of reed straw. Cumulative NH3 emission ranged from 3.0 to 8.1 g kg(-1) DM, and was significantly decreased by reed straw and zeolite addition. In conclusion, combined pre-composting and vermicomposting with reed straw and zeolite addition would be strongly recommended in mitigating emissions of N2O, CH4, and NH3 from duck manure. Moreover, this method also provides nutrient-rich products that can be used as a fertilizer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Magpie Trial in the UK: methods and additional data for women and children at 2 years following pregnancy complicated by pre-eclampsia

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Armstrong Nina

2009-04-01

Full Text Available Abstract Background The Magpie Trial, a randomised trial comparing magnesium sulphate with placebo for women with pre-eclampsia. This paper describes methods used for follow up in the UK, and presents additional data collected. Methods In the UK 774 women and their 827 children were included; excluded were women discharged without a surviving child and families who opted out. General practitioners were sent a questionnaire when the child was around 18 months old. When the child was two years, or older, questionnaires asking about the health of the women and children were posted to families. A sample of families was offered a home visit, during which the child was assessed using the Bayley Scales of Infant Development. Results Of the women, 12 were lost to follow up and three died. Of the children, 12 were lost to follow up, 5 were excluded and 19 died. General practitioners returned 688/759 (91% questionnaires, as did 619/759 (82% women. Responses were largely comparable. 32 women had serious morbidity potentially related to pre-eclampsia. 30% of children were reported to have been admitted to hospital. There were no clear differences between the randomised groups in the child's behaviour, women's fertility or use of health service resources. Conclusion Data presented here provide further reassurance about the longer term safety of magnesium sulphate when used for women with pre-eclampsia. Postal questionnaires in the UK to assess the longer term health and wellbeing of women and children recruited to trials are feasible, and can achieve a high response rate. Responses from families and general practitioners were comparable Trial registration Trial registration number of the Magpie Trial [ISRCTN86938761

Emissions of ammonia and greenhouse gases during combined pre-composting and vermicomposting of duck manure

Energy Technology Data Exchange (ETDEWEB)

Wang, Jinzhi [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environment Sciences, Beijing 100012 (China); College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049 (China); Hu, Zhengyi, E-mail: zhyhu@ucas.ac.cn [College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049 (China); Xu, Xingkai [State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029 (China); Jiang, Xia; Zheng, Binghui [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environment Sciences, Beijing 100012 (China); Liu, Xiaoning [College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049 (China); Pan, Xubin [Institute of Plant Quarantine, Chinese Academy of Inspection and Quarantine, Beijing 100029 (China); Kardol, Paul [Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, S 90183 Umeå (Sweden)

2014-08-15

Highlights: • Earthworms significantly decreased emissions of N{sub 2}O and CH{sub 4}, but had a marginal effect on CO{sub 2} emission. • NH{sub 3}, N{sub 2}O, and CH{sub 4} emissions were significantly reduced by reed straw and zeolite, CO{sub 2} emission was increased by reed straw. • Combined pre-composting and vermicomposting with reed straw and zeolite would be recommended for disposal of duck manure. - Abstract: Combined pre-composting and vermicomposting has shown potential for reclamation of solid wastes, which is a significant source of ammonia (NH{sub 3}), and greenhouse gases (GHG), including nitrous oxide (N{sub 2}O), methane (CH{sub 4}), and carbon dioxide (CO{sub 2}). Earthworms and amendments may both affect physico-chemical characteristics that control gas-producing processes, and thus affect NH{sub 3} and GHG emissions. Here, we used two-way ANOVA to test the effects of addition of reed straw and combined addition of reed straw and zeolite on NH{sub 3} and GHG emissions during pre-composting of duck manure, either with or without a follow-up phase of vermicomposting. Results showed that cumulative N{sub 2}O, CH{sub 4}, and CO{sub 2} emissions during pre-composting and vermicomposting ranged from 92.8, 5.8, and 260.6 mg kg{sup −1} DM to 274.2, 30.4, and 314.0 mg kg{sup −1} DM, respectively. Earthworms and amendments significantly decreased N{sub 2}O and CH{sub 4} emissions. Emission of CO{sub 2} was not affected by earthworms, but increased in responses to addition of reed straw. Cumulative NH{sub 3} emission ranged from 3.0 to 8.1 g kg{sup −1} DM, and was significantly decreased by reed straw and zeolite addition. In conclusion, combined pre-composting and vermicomposting with reed straw and zeolite addition would be strongly recommended in mitigating emissions of N{sub 2}O, CH{sub 4}, and NH{sub 3} from duck manure. Moreover, this method also provides nutrient-rich products that can be used as a fertilizer.

Sample size requirements for separating out the effects of combination treatments: randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis.

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Wolbers, Marcel; Heemskerk, Dorothee; Chau, Tran Thi Hong; Yen, Nguyen Thi Bich; Caws, Maxine; Farrar, Jeremy; Day, Jeremy

2011-02-02

In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 x 2 factorial design. We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 x 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the

Pre-Combustion Carbondioxide Capture in Integrated Gasification Combined Cycles

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M. Zeki YILMAZOĞLU

2010-02-01

Full Text Available Thermal power plants have a significant place big proportion in the production of electric energy. Thermal power plants are the systems which converts heat energy to mechanical energy and also mechanical energy to electrical energy. Heat energy is obtained from combustion process and as a result of this, some harmful emissions, like CO2, which are the reason for global warming, are released to atmosphere. The contribution of carbondioxide to global warming has been exposed by the previous researchs. Due to this fact, clean energy technologies are growing rapidly all around the world. Coal is generally used in power plants and when compared to other fossil energy sources unit electricity production cost is less than others. When reserve rate is taken into account, coal may be converted to energy in a more efficient and cleaner way. The aim for using the clean coal technologies are to eradicate the harmful emissions of coal and to store the carbondioxide, orginated from combustion, in different forms. In line with this aim, carbondioxide may be captured by either pre-combustion, by O2/CO2 recycling combustion systems or by post combustion. The integrated gasification combined cycles (IGCC are available in pre-combustion capture systems, whereas in O2/CO2 recycling combustion systems there are ultrasuper critical boiler technologies and finally flue gas washing systems by amines exists in post combustion systems. In this study, a pre-combustion CO2 capture process via oxygen blown gasifiers is compared with a conventional power plant in terms of CO2 emissions. Captured carbondioxide quantity has been presented as a result of the calculations made throughout the study.

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

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L John Hoffer

Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

Science.gov (United States)

Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

2015-01-01

Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy

Sample size requirements for separating out the effects of combination treatments: Randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis

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Farrar Jeremy

2011-02-01

Full Text Available Abstract Background In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 × 2 factorial design. Methods We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. Results In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Conclusions Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 × 2 factorial design to detect effects of

An interdisciplinary intervention to prevent falls in community-dwelling elderly persons: protocol of a cluster-randomized trial [PreFalls

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Schuster Tibor

2011-02-01

Full Text Available Abstract Background Prevention of falls in the elderly is a public health target in many countries around the world. While a large number of trials have investigated the effectiveness of fall prevention programs, few focussed on interventions embedded in the general practice setting and its related network. In the Prevent Falls (PreFalls trial we aim to investigate the effectiveness of a pre-tested multi-modal intervention compared to usual care in this setting. Methods/Design PreFalls is a controlled multicenter prospective study with cluster-randomized allocation of about 40 general practices to an experimental or a control group. We aim to include 382 community dwelling persons aged 65 and older with an increased risk of falling. All participating general practitioners are trained to systematically assess the risk of falls using a set of validated tests. Patients from intervention practices are invited to participate in a 16-weeks exercise program with focus on fall prevention delivered by specifically trained local physiotherapists. Patients from practices allocated to the control group receive usual care. Main outcome measure is the number of falls per individual in the first 12 months (analysis by negative binomial regression. Secondary outcomes include falls in the second year, the proportion of participants falling in the first and the second year, falls associated with injury, risk of falls, fear of falling, physical activity and quality of life. Discussion Reducing falls in the elderly remains a major challenge. We believe that with its strong focus on a both systematic and realistic fall prevention strategy adapted to primary care setting PreFalls will be a valuable addition to the scientific literature in the field. Trial registration NCT01032252

PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours

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McKeage Mark J

2012-10-01

Full Text Available Abstract Background The purpose of this phase Ib clinical trial was to determine the maximum tolerated dose (MTD of PR-104 a bioreductive pre-prodrug given in combination with gemcitabine or docetaxel in patients with advanced solid tumours. Methods PR-104 was administered as a one-hour intravenous infusion combined with docetaxel 60 to 75 mg/m2 on day one given with or without granulocyte colony stimulating factor (G-CSF on day two or administrated with gemcitabine 800 mg/m2 on days one and eight, of a 21-day treatment cycle. Patients were assigned to one of ten PR-104 dose-levels ranging from 140 to 1100 mg/m2 and to one of four combination groups. Pharmacokinetic studies were scheduled for cycle one day one and 18F fluoromisonidazole (FMISO positron emission tomography hypoxia imaging at baseline and after two treatment cycles. Results Forty two patients (23 females and 19 males were enrolled with ages ranging from 27 to 85 years and a wide range of advanced solid tumours. The MTD of PR-104 was 140 mg/m2 when combined with gemcitabine, 200 mg/m2 when combined with docetaxel 60 mg/m2, 770 mg/m2 when combined with docetaxel 60 mg/m2 plus G-CSF and ≥770 mg/m2 when combined with docetaxel 75 mg/m2 plus G-CSF. Dose-limiting toxicity (DLT across all four combination settings included thrombocytopenia, neutropenic fever and fatigue. Other common grade three or four toxicities included neutropenia, anaemia and leukopenia. Four patients had partial tumour response. Eleven of 17 patients undergoing FMISO scans showed tumour hypoxia at baseline. Plasma pharmacokinetics of PR-104, its metabolites (alcohol PR-104A, glucuronide PR-104G, hydroxylamine PR-104H, amine PR-104M and semi-mustard PR-104S1, docetaxel and gemcitabine were similar to that of their single agents. Conclusions Combination of PR-104 with docetaxel or gemcitabine caused dose-limiting and severe myelotoxicity, but prophylactic G-CSF allowed PR-104 dose escalation with docetaxel. Dose

PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours

International Nuclear Information System (INIS)

McKeage, Mark J; Jameson, Michael B; Ramanathan, Ramesh K; Rajendran, Joseph; Gu, Yongchuan; Wilson, William R; Melink, Teresa J; Tchekmedyian, N Simon

2012-01-01

The purpose of this phase Ib clinical trial was to determine the maximum tolerated dose (MTD) of PR-104 a bioreductive pre-prodrug given in combination with gemcitabine or docetaxel in patients with advanced solid tumours. PR-104 was administered as a one-hour intravenous infusion combined with docetaxel 60 to 75 mg/m 2 on day one given with or without granulocyte colony stimulating factor (G-CSF) on day two or administrated with gemcitabine 800 mg/m 2 on days one and eight, of a 21-day treatment cycle. Patients were assigned to one of ten PR-104 dose-levels ranging from 140 to 1100 mg/m 2 and to one of four combination groups. Pharmacokinetic studies were scheduled for cycle one day one and 18 F fluoromisonidazole (FMISO) positron emission tomography hypoxia imaging at baseline and after two treatment cycles. Forty two patients (23 females and 19 males) were enrolled with ages ranging from 27 to 85 years and a wide range of advanced solid tumours. The MTD of PR-104 was 140 mg/m 2 when combined with gemcitabine, 200 mg/m 2 when combined with docetaxel 60 mg/m 2 , 770 mg/m 2 when combined with docetaxel 60 mg/m 2 plus G-CSF and ≥770 mg/m 2 when combined with docetaxel 75 mg/m 2 plus G-CSF. Dose-limiting toxicity (DLT) across all four combination settings included thrombocytopenia, neutropenic fever and fatigue. Other common grade three or four toxicities included neutropenia, anaemia and leukopenia. Four patients had partial tumour response. Eleven of 17 patients undergoing FMISO scans showed tumour hypoxia at baseline. Plasma pharmacokinetics of PR-104, its metabolites (alcohol PR-104A, glucuronide PR-104G, hydroxylamine PR-104H, amine PR-104M and semi-mustard PR-104S1), docetaxel and gemcitabine were similar to that of their single agents. Combination of PR-104 with docetaxel or gemcitabine caused dose-limiting and severe myelotoxicity, but prophylactic G-CSF allowed PR-104 dose escalation with docetaxel. Dose-limiting thrombocytopenia prohibited further

Effects of Peer-Facilitated, Video-Based and Combined Peer-and-Video Education on Anxiety Among Patients Undergoing Coronary Angiography: Randomised controlled trial.

Science.gov (United States)

Habibzadeh, Hosein; Milan, Zahra D; Radfar, Moloud; Alilu, Leyla; Cund, Audrey

2018-02-01

Coronary angiography can be stressful for patients and anxiety-caused physiological responses during the procedure increase the risk of dysrhythmia, coronary artery spasms and rupture. This study therefore aimed to investigate the effects of peer, video and combined peer-and-video training on anxiety among patients undergoing coronary angiography. This single-blinded randomised controlled clinical trial was conducted at two large educational hospitals in Iran between April and July 2016. A total of 120 adult patients undergoing coronary angiography were recruited. Using a block randomisation method, participants were assigned to one of four groups, with those in the control group receiving no training and those in the three intervention groups receiving either peer-facilitated training, video-based training or a combination of both. A Persian-language validated version of the State-Trait Anxiety Inventory was used to measure pre- and post-intervention anxiety. There were no statistically significant differences in mean pre-intervention anxiety scores between the four groups (F = 0.31; P = 0.81). In contrast, there was a significant reduction in post-intervention anxiety among all three intervention groups compared to the control group (F = 27.71; P <0.01); however, there was no significant difference in anxiety level in terms of the type of intervention used. Peer, video and combined peer-and-video education were equally effective in reducing angiography-related patient anxiety. Such techniques are recommended to reduce anxiety amongst patients undergoing coronary angiography in hospitals in Iran.

Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment.

Science.gov (United States)

Gordon, Michael S; Vocci, Frank J; Fitzgerald, Terrence T; O'Grady, Kevin E; O'Brien, Charles P

2017-02-01

Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases has been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. We describe the background and rationale for the study, its aims, hypotheses, and study design. The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. ClinicalTrials.gov: NCT02867124. Copyright © 2016 Elsevier Inc. All rights reserved.

Completeness of reporting in abstracts from clinical trials of pre-harvest interventions against foodborne pathogens.

Science.gov (United States)

Snedeker, Kate G; Canning, Paisley; Totton, Sarah C; Sargeant, Jan M

2012-04-01

Abstracts are the most commonly read part of a journal article, and play an important role as summaries of the articles, and search and screening tools. However, research on abstracts in human biomedicine has shown that abstracts often do not report key methodological features and results. Little research has been done to examine reporting of such features in abstracts from papers detailing pre-harvest food safety trials. Thus, the objective of this study was to assess the quality of reporting of key factors in abstracts detailing trials of pre-harvest food safety interventions. A systematic search algorithm was used to identify all in vivo trials of pre-harvest interventions against foodborne pathogens in PubMed and CAB Direct published from 1999 to October 2009. References were screened for relevance, and 150 were randomly chosen for inclusion in the study. A checklist based on the CONSORT abstract extension and the REFLECT Statement was used to assess the reporting of methodological features and results. All screening and assessment was performed by two independent reviewers with disagreements resolved by consensus. The systematic search returned 3554 unique citations; 356 were found to be relevant and 150 were randomly selected for inclusion. The abstracts were from 51 different journals, and 13 out of 150 were structured. Of the 124 abstracts that reported whether the trial design was deliberate disease challenge or natural exposure, 113 were deliberate challenge and 11 natural exposure. 103 abstracts detailed studies involving poultry, 20 cattle and 15 swine. Most abstracts reported the production stage of the animals (135/150), a hypothesis or objective (123/150), and results for all treatment groups (136/150). However, few abstracts reported on how animals were grouped in housing (25/150), the location of the study (5/150), the primary outcome (2/126), level of treatment allocation (15/150), sample size (63/150) or whether study units were lost to follow up

Adaptive clinical trial designs with pre-specified rules for modifying the sample size: understanding efficient types of adaptation.

Science.gov (United States)

Levin, Gregory P; Emerson, Sarah C; Emerson, Scott S

2013-04-15

Adaptive clinical trial design has been proposed as a promising new approach that may improve the drug discovery process. Proponents of adaptive sample size re-estimation promote its ability to avoid 'up-front' commitment of resources, better address the complicated decisions faced by data monitoring committees, and minimize accrual to studies having delayed ascertainment of outcomes. We investigate aspects of adaptation rules, such as timing of the adaptation analysis and magnitude of sample size adjustment, that lead to greater or lesser statistical efficiency. Owing in part to the recent Food and Drug Administration guidance that promotes the use of pre-specified sampling plans, we evaluate alternative approaches in the context of well-defined, pre-specified adaptation. We quantify the relative costs and benefits of fixed sample, group sequential, and pre-specified adaptive designs with respect to standard operating characteristics such as type I error, maximal sample size, power, and expected sample size under a range of alternatives. Our results build on others' prior research by demonstrating in realistic settings that simple and easily implemented pre-specified adaptive designs provide only very small efficiency gains over group sequential designs with the same number of analyses. In addition, we describe optimal rules for modifying the sample size, providing efficient adaptation boundaries on a variety of scales for the interim test statistic for adaptation analyses occurring at several different stages of the trial. We thus provide insight into what are good and bad choices of adaptive sampling plans when the added flexibility of adaptive designs is desired. Copyright © 2012 John Wiley & Sons, Ltd.

Pre-exposure and postexposure prophylaxes and the combination HIV prevention methods (The Combine! Study): protocol for a pragmatic clinical trial at public healthcare clinics in Brazil.

Science.gov (United States)

Grangeiro, Alexandre; Couto, Márcia Thereza; Peres, Maria Fernanda; Luiz, Olinda; Zucchi, Eliana Miura; de Castilho, Euclides Ayres; Estevam, Denize Lotufo; Alencar, Rosa; Wolffenbüttel, Karina; Escuder, Maria Mercedes; Calazans, Gabriela; Ferraz, Dulce; Arruda, Érico; Corrêa, Maria da Gloria; Amaral, Fabiana Rezende; Santos, Juliane Cardoso Villela; Alvarez, Vivian Salles; Kietzmann, Tiago

2015-08-25

Few results from programmes based on combination prevention methods are available. We propose to analyse the degree of protection provided by postexposure prophylaxis (PEP) for consensual sexual activity at healthcare clinics, its compensatory effects on sexual behaviour; and the effectiveness of combination prevention methods and pre-exposure prophylaxis (PrEP), compared with exclusively using traditional methods. A total of 3200 individuals aged 16 years or older presenting for PEP at 5 sexually transmitted disease (STD)/HIV clinics in 3 regions of Brazil will be allocated to one of two groups: the PEP group-individuals who come to the clinic within 72 h after a sexual exposure and start PEP; and the non-PEP group-individuals who come after 72 h but within 30 days of exposure and do not start PEP. Clinical follow-up will be conducted initially for 6 months and comprise educational interventions based on information and counselling for using prevention methods, including PrEP. In the second study phase, individuals who remain HIV negative will be regrouped according to the reported use of prevention methods and observed for 18 months: only traditional methods; combined methods; and PrEP. Effectiveness will be analysed according to the incidence of HIV, syphilis and hepatitis B and C and protected sexual behaviour. A structured questionnaire will be administered to participants at baseline and every 6 months thereafter. Qualitative methods will be employed to provide a comprehensive understanding of PEP-seeking behaviour, preventive choices and exposure to HIV. This study will be conducted in accordance with the resolution of the School of Medicine Research Ethics Commission of Universidade de São Paulo (protocol no. 251/14). The databases will be available for specific studies, after management committee approval. Findings will be presented to researchers, health managers and civil society members by means of newspapers, electronic media and scientific journals

Large-scale exploration and analysis of drug combinations.

Science.gov (United States)

Li, Peng; Huang, Chao; Fu, Yingxue; Wang, Jinan; Wu, Ziyin; Ru, Jinlong; Zheng, Chunli; Guo, Zihu; Chen, Xuetong; Zhou, Wei; Zhang, Wenjuan; Li, Yan; Chen, Jianxin; Lu, Aiping; Wang, Yonghua

2015-06-15

Drug combinations are a promising strategy for combating complex diseases by improving the efficacy and reducing corresponding side effects. Currently, a widely studied problem in pharmacology is to predict effective drug combinations, either through empirically screening in clinic or pure experimental trials. However, the large-scale prediction of drug combination by a systems method is rarely considered. We report a systems pharmacology framework to predict drug combinations (PreDCs) on a computational model, termed probability ensemble approach (PEA), for analysis of both the efficacy and adverse effects of drug combinations. First, a Bayesian network integrating with a similarity algorithm is developed to model the combinations from drug molecular and pharmacological phenotypes, and the predictions are then assessed with both clinical efficacy and adverse effects. It is illustrated that PEA can predict the combination efficacy of drugs spanning different therapeutic classes with high specificity and sensitivity (AUC = 0.90), which was further validated by independent data or new experimental assays. PEA also evaluates the adverse effects (AUC = 0.95) quantitatively and detects the therapeutic indications for drug combinations. Finally, the PreDC database includes 1571 known and 3269 predicted optimal combinations as well as their potential side effects and therapeutic indications. The PreDC database is available at http://sm.nwsuaf.edu.cn/lsp/predc.php. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of physical training with the Nintendo Wii Fit Plus® and protein supplementation on musculoskeletal function and the risk of falls in pre-frail older women: Protocol for a randomized controlled clinical trial (the WiiProtein study).

Science.gov (United States)

Vojciechowski, Audrin Said; Biesek, Simone; Melo Filho, Jarbas; Rabito, Estela Iraci; Amaral, Maryelle Paula do; Gomes, Anna Raquel Silveira

2018-05-01

Frailty is one of the key geriatric syndromes and is related to the loss of functional independence. However, the practice of physical training (PT) combined with protein supplementation (PS) may improve musculoskeletal function (MF). To verify the effect of PT using 'exergames' with or without PS on MF, nutritional status, and risk of falls in pre-frail older women. The protocol is for a randomized controlled clinical trial with a sample of pre-frail older women, divided into 5 groups: control group; PT using exergames; PS; PT using exergames combined with PS; PT using exergames combined with isoenergetic supplementation. The primary outcomes will be: the strength and power of the lower limbs, assessed by isokinetic dynamometer and the sit-and-stand test carried out 5 times; muscle architecture, assessed by ultrasound; body composition, assessed by anthropometric measurements, bioelectrical impedance and dual energy X-ray absorptiometry; and functional mobility and risk of falls, assessed using the Timed-Up and Go test. The secondary outcomes will be: centre of pressure (CoP), assessed using a force plate; and fear of falling, assessed using the Falls Efficacy Scale - International, Brazil. PT using exergames with a gradual increase in the mass weighted vest will be carried out twice a week for 50 min over 3 months. The supplements will be ingested 5 days a week for 3 months. All outcomes will be assessed before and after 3 months. The WiiProtein study will be the first clinical trial to examine the effects of PT using exergames with progressive resistance, which may or may not be combined with PS, on MF, nutritional status, and risk of falls in pre-frail older women. Copyright © 2018 Elsevier B.V. All rights reserved.

Addressing All Heads of the Hydra: Reframing Safeguards for Mentally Impaired Detainees in Immigration Removal Proceedings.

Science.gov (United States)

Wilson, Amelia; Prokop, Natalie H; Robins, Stephanie

2015-01-01

This article concerns the constitutional rights of detained, mentally impaired non-citizens in defending against deportation. Due process requires that such detainees receive a full and fair hearing. However, until recently, they were not provided an attorney to assist them in navigating our extremely complicated immigration system. Mentally impaired detainees were expected to proceed alone in proving the elements of their claims against skilled government attorneys--a daunting task even for those unencumbered by a mental disorder. On December 31, 2013, the Department of Justice ("DOJ") released guidelines detailing new procedures for how immigration courts should handle these cases, including the provision of counsel upon a finding of mental incompetence. The guidelines were issued as a direct response to Franco-Gonzales v. Holder, a class action lawsuit brought by the American Civil Liberties Union in federal district court in California seeking appointed counsel for detained, unrepresented, mentally impaired non-citizens. The guidelines created a three-stage process for assessing competency. Only at the end of this process--and after an individual is declared incompetent--is counsel appointed. This article argues that the DOJ guidelines fall far short of Franco's promise of due process for this particularly vulnerable population. It proposes an alternative model wherein counsel is appointed the moment the court is presented with "indicia" of incompetence, rather than after an adjudication of incompetence. "Indicia" should create a presumption of incompetency that can be rebutted only after a forensic evaluation is conducted and the court holds a robust hearing into the matter. This article reveals, through empirical evidence, the critical role that counsel plays in the investigation of a respondent's ability to participate in the proceedings, and how an attorney is often the only party positioned to marshal all the evidence relevant to the question of competency

Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial.

Science.gov (United States)

Margolis, Karen L; O'Connor, Patrick J; Morgan, Timothy M; Buse, John B; Cohen, Robert M; Cushman, William C; Cutler, Jeffrey A; Evans, Gregory W; Gerstein, Hertzel C; Grimm, Richard H; Lipkin, Edward W; Narayan, K M Venkat; Riddle, Matthew C; Sood, Ajay; Goff, David C

2014-06-01

To compare effects of combinations of standard and intensive treatment of glycemia and either blood pressure (BP) or lipids in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. ACCORD enrolled 10,251 type 2 diabetes patients aged 40-79 years at high risk for cardiovascular disease (CVD) events. Participants were randomly assigned to hemoglobin A1c goals of risk of the primary outcome was lower in the groups intensively treated for glycemia (hazard ratio [HR] 0.67; 95% CI 0.50-0.91), BP (HR 0.74; 95% CI 0.55-1.00), or both (HR 0.71; 95% CI 0.52-0.96) compared with combined standard BP and glycemia treatment. For secondary outcomes, MI was significantly reduced by intensive glycemia treatment and stroke by intensive BP treatment; most other HRs were neutral or favored intensive treatment groups. In the lipid trial, the general pattern of results showed no evidence of benefit of intensive regimens (whether single or combined) compared with combined standard lipid and glycemia treatment. The mortality HR was 1.33 (95% CI 1.02-1.74) in the standard lipid/intensive glycemia group compared with the standard lipid/standard glycemia group. In the ACCORD BP trial, compared with combined standard treatment, intensive BP or intensive glycemia treatment alone improved major CVD outcomes, without additional benefit from combining the two. In the ACCORD lipid trial, neither intensive lipid nor glycemia treatment produced an overall benefit, but intensive glycemia treatment increased mortality. © 2014 by the American Diabetes Association.

Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotid-sparing IMRT for locally advanced head and neck cancer.

Science.gov (United States)

Clark, C H; Miles, E A; Urbano, M T Guerrero; Bhide, S A; Bidmead, A M; Harrington, K J; Nutting, C M

2009-07-01

The purpose of this study was to compare conventional radiotherapy with parotid gland-sparing intensity-modulated radiation therapy (IMRT) using the PARSPORT trial. The validity of such a trial depends on the radiotherapy planning and delivery meeting a defined standard across all centres. At the outset, many of the centres had little or no experience of delivering IMRT; therefore, quality assurance processes were devised to ensure consistency and standardisation of all processes for comparison within the trial. The pre-trial quality assurance (QA) programme and results are described. Each centre undertook exercises in target volume definition and treatment planning, completed a resource questionnaire and produced a process document. Additionally, the QA team visited each participating centre. Each exercise had to be accepted before patients could be recruited into the trial. 10 centres successfully completed the quality assurance exercises. A range of treatment planning systems, linear accelerators and delivery methods were used for the planning exercises, and all the plans created reached the standard required for participation in this multicentre trial. All 10 participating centres achieved implementation of a comprehensive and robust IMRT programme for treatment of head and neck cancer.

Single-trial lie detection using a combined fNIRS-polygraph system

Science.gov (United States)

Bhutta, M. Raheel; Hong, Melissa J.; Kim, Yun-Hee; Hong, Keum-Shik

2015-01-01

Deception is a human behavior that many people experience in daily life. It involves complex neuronal activities in addition to several physiological changes in the body. A polygraph, which can measure some of the physiological responses from the body, has been widely employed in lie-detection. Many researchers, however, believe that lie detection can become more precise if the neuronal changes that occur in the process of deception can be isolated and measured. In this study, we combine both measures (i.e., physiological and neuronal changes) for enhanced lie-detection. Specifically, to investigate the deception-related hemodynamic response, functional near-infrared spectroscopy (fNIRS) is applied at the prefrontal cortex besides a commercially available polygraph system. A mock crime scenario with a single-trial stimulus is set up as a deception protocol. The acquired data are classified into “true” and “lie” classes based on the fNIRS-based hemoglobin-concentration changes and polygraph-based physiological signal changes. Linear discriminant analysis is utilized as a classifier. The results indicate that the combined fNIRS-polygraph system delivers much higher classification accuracy than that of a singular system. This study demonstrates a plausible solution toward single-trial lie-detection by combining fNIRS and the polygraph. PMID:26082733

Single-trial lie detection using a combined fNIRS-polygraph system

Directory of Open Access Journals (Sweden)

M. Raheel eBhutta

2015-06-01

Full Text Available Deception is a human behavior that many people experience in daily life. It involves complex neuronal activities in addition to several physiological changes in the body. A polygraph, which can measure some of the physiological responses from the body, has been widely employed in lie-detection. Many researchers, however, believe that lie detection can become more precise if the neuronal changes that occur in the process of deception can be isolated and measured. In this study, we combine both measures (i.e., physiological and neuronal changes for enhanced lie-detection. Specifically, to investigate the deception-related hemodynamic response, functional near-infrared spectroscopy (fNIRS is applied at the prefrontal cortex besides a commercially available polygraph system. A mock crime scenario with a single-trial stimulus is set up as a deception protocol. The acquired data are classified into true and lie classes based on the fNIRS-based hemoglobin-concentration changes and polygraph-based physiological signal changes. Linear discriminant analysis is utilized as a classifier. The results indicate that the combined fNIRS-polygraph system delivers much higher classification accuracy than that of a singular system. This study demonstrates a plausible solution toward single-trial lie-detection by combining fNIRS and the polygraph.

Self-stigma and empowerment in combined-CMHA and consumer-run services: two controlled trials.

Science.gov (United States)

Segal, Steven P; Silverman, Carol J; Temkin, Tanya L

2013-10-01

Self-help agencies (SHAs) are consumer-operated service organizations managed as participatory democracies involving members in all management tasks. Hierarchically organized board- and staff-run consumer-operated service programs (BSR-COSPs) are consumer managed, but they afford members less decision-making power. This study considered the relative effectiveness of SHAs and BSR-COSPs working jointly with community mental health agencies (CMHAs) and the role of organizational empowerment in reducing self-stigma. Clients seeking CMHA services were assigned in separate randomized controlled trials to a trial of combined SHA and CMHA services versus regular CMHA services (N=505) or to a trial of combined BSR-COSP and CMHA services versus regular CMHA services (N=139). Self-stigma, organizational empowerment, and self-efficacy were assessed at baseline and eight months with the Attitudes Toward Persons With Mental Illness Scale, the Organizationally Mediated Empowerment Scale, and the Self-Efficacy Scale. Outcomes were evaluated with fully recursive path analysis models. SHA-CMHA participants experienced greater positive change in self-stigma than CMHA-only participants, a result attributable to participation in the combined condition (b=1.20, p=.016) and increased organizational empowerment (b=.27, p=.003). BSR-COSP-CMHA participants experienced greater negative change in self-stigma than CMHA-only participants, a result attributable to participation in the combined service (b=-4.73, p=.031). In the SHA-CMHA trial, participants showed positive change in self-efficacy, whereas the change among BSR-COSP-CMHA participants was negative. Differential organizational empowerment efforts in the SHA and BSR-COSP appeared to account for the differing outcomes. Members experienced reduced self-stigma and increases in self-efficacy when they were engaged in responsible roles.

A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

Energy Technology Data Exchange (ETDEWEB)

Hiniker, Susan M., E-mail: shiniker@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center and Cancer Institute, Stanford, California (United States); Reddy, Sunil A. [Division of Oncology, Department of Medicine, Stanford University Medical Center and Cancer Institute, Stanford, California (United States); Maecker, Holden T.; Subrahmanyam, Priyanka B.; Rosenberg-Hasson, Yael [Human Immune Monitoring Center, Institute for Immunity, Transplantation, and Infection, Stanford University Medical Center, Stanford, California (United States); Swetter, Susan M. [Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center and Cancer Institute, Stanford, California (United States); Dermatology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California (United States); Saha, Saurabh [Atlas Venture, Cambridge, Massachusetts (United States); Shura, Lei; Knox, Susan J. [Department of Radiation Oncology, Stanford University Medical Center and Cancer Institute, Stanford, California (United States)

2016-11-01

Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasis measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the

A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

International Nuclear Information System (INIS)

Hiniker, Susan M.; Reddy, Sunil A.; Maecker, Holden T.; Subrahmanyam, Priyanka B.; Rosenberg-Hasson, Yael; Swetter, Susan M.; Saha, Saurabh; Shura, Lei; Knox, Susan J.

2016-01-01

Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasis measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the

The Combination of Pixantrone, Etoposide, Bendamustine and, in CD20+ Tumors, Rituximab (PREBEN) Shows Promising Feasibility/Efficacy in Heavily Pre-Treated Aggressive Lymphomas of B- and T-Cell Phenotype - Results of the Pre-Trial Experience Leading to a Nordic Phase 1/2 Study (the PREBEN Trial)

DEFF Research Database (Denmark)

Clausen, Michael Roost; Leppa, Sirpa; Brown, Peter de Nully

2016-01-01

Background: Aggressive non-Hodgkin lymphoma (aNHL) relapsing after high-dose therapy or, in not transplant-eligible patients, after 1st-line chemotherapy represents an unmet clinical need. Therefore, we aimed at evaluating a salvage combination regimen based on pixantrone, an aza-anthracenadione ......Background: Aggressive non-Hodgkin lymphoma (aNHL) relapsing after high-dose therapy or, in not transplant-eligible patients, after 1st-line chemotherapy represents an unmet clinical need. Therefore, we aimed at evaluating a salvage combination regimen based on pixantrone, an aza......IND developed acute myeloid leukemia with therapy-related cytogenetic features.Conclusions: The PREBEN/PEBEN salvage regimen was feasible in a heavily pre-treated cohort of elderly patients with high-risk aNHL. In individual patients it elicited substantial and durable responses early in the course of therapy...

Combining dosimetry and toxicity: analysis of two UK phase III clinical trials

International Nuclear Information System (INIS)

Gulliford, Sarah L

2014-01-01

There are many advantages to performing a clinical trial when implementing a novel radiotherapy technique. The clinical trials framework enables the safety and efficacy of the 'experimental arm' to be tested and ensures practical support, rigorous quality control and data monitoring for participating centres. In addition to the clinical and follow-up data collected from patients within the trial, it is also possible to collect 3-D dosimetric information from the corresponding radiotherapy treatment plans. Analysing the combination of dosimetric, clinical and follow-up data enhances the understanding of the relationship between the dose delivered to both the target and normal tissue structures and reported outcomes and toxicity. Aspects of the collection, collation and analysis of data from two UK multicentre Phase III radiotherapy trials are presented here. MRC-RT01 dose-escalation prostate radiotherapy trial ISRCTN47772397 was one of the first UK multi-centre radiotherapy trials to collect 3-D dosimetric data. A number of different analysis methodologies were implemented to investigate the relationship between the dose distribution to the rectum and specific rectal toxicities. More recently data was collected from the PARSPORT trial (Parotid Sparing IMRT vs conventional head and neck radiotherapy) ISRCTN48243537. In addition to the planned analysis, dosimetric analysis was employed to investigate an unexpected finding that acute fatigue was more prevalent in the IMRT arm of the trial. It can be challenging to collect 3-D dosimetric information from multicentre radiotherapy trials. However, analysing the relationship between dosimetric and toxicity data provides invaluable information which can influence the next generation of radiotherapy techniques.

Effects of exercise programs on falls and mobility in frail and pre-frail older adults: A multicenter randomized controlled trial

NARCIS (Netherlands)

Faber, M.J.; Bosscher, R.J.; Chin, A.P.M.J.; van Wieringen, P.C.W.

2006-01-01

Faber MJ, Bosscher RJ, Chin A Paw MJ, van Wieringen PC. Effects of exercise programs on falls and mobility in frail and pre-frail older adults: a multicenter randomized controlled trial. Objectives: To determine the effects of moderate intensity group-exercise programs on falls, functional

CREDITOR DEBTS PRE-TRIAL SETTLEMENT BY PARTICIPANTS OF FINANCIAL AND CREDIT RELATIONS: IMPROVEMENT MECHANISMS

Directory of Open Access Journals (Sweden)

V. N. Alferov

2012-01-01

Full Text Available If a borrower who is in the state of insolvency performs his obligations under loan agreements, cases of challenging the debtor’s transactions may arise. It is expedient to use in Russia international experience of informal financial recovery for pre-trial financial rehabilitation of debtors. The rehabilitation includes three steps: continuous monitoring of the borrowers’ financial state by regional councils of directors and the court (or only by creditors; development and signing of rehabilitation plan and peaceful agreement; control over performance of the agreement by thedebtor. Anti-crisis management expert’s services may be helpful.

Comparing the validity of the K6 when assessing depression, anxiety, and PTSD among male and female jail detainees.

Science.gov (United States)

Kubiak, Sheryl Pimlott; Beeble, Marisa; Bybee, Deborah

2012-12-01

A lack of a consistent and valid approach to screening within the jail often hinders identification and treatment. Furthermore, screening instruments developed for jail populations are often inadequate in detecting serious depression and anxiety disorders in women. While the remedy thus far has been the use of separate screening instruments for men and women, others have suggested that the K6, a six-item measure validated in large epidemiologic studies, may hold promise. Building on prior research, this study assesses the validity of the K6 in detecting depression, posttraumatic stress disorder, and anxiety disorders among 494 male and 515 female jail detainees. The authors found that 15% of males and 36% of females meet criteria for serious mental illness on the K6, with receiver operating characteristics--area under the curve scores of .84 and .93, respectively. This study not only establishes the validity and efficiency of using the K6 for screening within jails but also suggests a need for adjusting scale cut points.

Changes in Sprint and Jump Performances After Traditional, Plyometric, and Combined Resistance Training in Male Youth Pre- and Post-Peak Height Velocity.

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Lloyd, Rhodri S; Radnor, John M; De Ste Croix, Mark B A; Cronin, John B; Oliver, Jon L

2016-05-01

The purpose of this study was to compare the effectiveness of 6-week training interventions using different modes of resistance (traditional strength, plyometric, and combined training) on sprinting and jumping performances in boys before and after peak height velocity (PHV). Eighty school-aged boys were categorized into 2 maturity groups (pre- or post-PHV) and then randomly assigned to (a) plyometric training, (b) traditional strength training, (c) combined training, or (d) a control group. Experimental groups participated in twice-weekly training programs for 6 weeks. Acceleration, maximal running velocity, squat jump height, and reactive strength index data were collected pre- and postintervention. All training groups made significant gains in measures of sprinting and jumping irrespective of the mode of resistance training and maturity. Plyometric training elicited the greatest gains across all performance variables in pre-PHV children, whereas combined training was the most effective in eliciting change in all performance variables for the post-PHV cohort. Statistical analysis indicated that plyometric training produced greater changes in squat jump and acceleration performances in the pre-PHV group compared with the post-PHV cohort. All other training responses between pre- and post-PHV cohorts were not significant and not clinically meaningful. The study indicates that plyometric training might be more effective in eliciting short-term gains in jumping and sprinting in boys who are pre-PHV, whereas those who are post-PHV may benefit from the additive stimulus of combined training.

The assessment of field trials in GMO research around the world and their possible integration in field trials for variety registration.

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Slot, M M; van de Wiel, C C M; Kleter, G A; Visser, R G F; Kok, E J

2018-05-04

Most regulations worldwide stipulate that a new genetically modified (GM) crop event has to be compared to its closest non-GM counterpart as a corner stone of the pre-market risk assessment. To this end the GM crop and its comparator should be grown in field trials for a phenotypic comparison as well as for subsequent detailed analysis of the composition of the two crop varieties. A more in-depth globally harmonised approach for the conduct of these field trials is lacking. Only a few countries have formulated detailed protocols for the set-up of GM field trials. In some countries, commercial non-GM reference varieties need to be included in a field study to compile reliable data that indicate the range of natural variation for the compounds tested at the specific location. Detailed analysis of pre-market assessment reports have so far not shown the added value of including these reference varieties in the field trials. In all cases where specific values were found to be outside of the range of the reference varieties, it proved possible to draw conclusions on the part of the pre-market risk assessment that relates to the compositional analysis, on the basis of already available compositional data. With the increasing quality of several databases on compositional data of a growing number of crop species, it seems unlikely that reference varieties will become more important on future occasions. It was furthermore investigated whether this part of the risk assessment can be related to field trial requirements for variety registration with the explicit intention of reducing the data burden on producers of new GM plant varieties. Field trials for variety registration so far include an assessment of phenotypic characteristics that do not cover safety aspects, with the exception of establishment of the glycoalkaloid content in potatoes in the Netherlands and Sweden. It may, however, under certain conditions be relatively easy to exchange data from compositional

Malignant mesothelioma clinical trial combines immunotherapy drugs.

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Chatwal, Monica S; Tanvetyanon, Tawee

2018-04-01

Immunotherapy by checkpoint inhibitor is effective for a number of solid tumors including malignant mesothelioma. Studies utilizing single-agent PD-1 or PD-L1 inhibitor for mesothelioma have reported tumor response rates in approximately 10-20% of patients treated. Given the success of combining these agents with CTLA-4 inhibitor in melanoma, there is a strong rationale to study it in mesothelioma. Recently results from clinical trials investigating this approach have been released. Though limited by small sample size, the studies conclusively demonstrated feasibility and suggested a modestly higher tumor response rate than one would expect from treatment with single-agent PD-1 or PD-L1 inhibitor. Nevertheless, toxicity was also increased. Immunotherapy-related deaths due to encephalitis, renal failure and hepatitis were observed. Further studies are warranted.

The Combination of Pixantrone, Etoposide, Bendamustine and, in CD20+ Tumors, Rituximab (PREBEN) Shows Promising Feasibility/Efficacy in Heavily Pre-Treated Aggressive Lymphomas of B- and T-Cell Phenotype - Results of the Pre-Trial Experience Leading to a Nordic Phase 1/2 Study (the PREBEN Trial)

DEFF Research Database (Denmark)

Clausen, Michael Roost; Leppa, Sirpa; Brown, Peter de Nully

2016-01-01

-anthracenadione recently approved in Europe for patients with multiply relapsed aNHL. Etoposide and bendamustine were chosen as companion compounds due to available feasibility data in combination with anthracenadions, and a well-documented efficacy in salvage regimens for relapsed aNHL. Rituximab was added......IND developed acute myeloid leukemia with therapy-related cytogenetic features.Conclusions: The PREBEN/PEBEN salvage regimen was feasible in a heavily pre-treated cohort of elderly patients with high-risk aNHL. In individual patients it elicited substantial and durable responses early in the course of therapy...

What is the place of pre-exposure prophylaxis in HIV prevention?

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De Man, Jeroen; Colebunders, Robert; Florence, Eric; Laga, Marie; Kenyon, Christopher

2013-01-01

New tools are needed to bring down ongoing high HIV incidence. This review aims to evaluate the place of one of these new tools (pre-exposure prophylaxis) in a comprehensive prevention strategy. Several trials have demonstrated the safety and the efficacy of pre-exposure prophylaxis in HIV prevention. Two large trials have, however, failed to show such efficacy. This was likely due to poor adherence in these trials. New forms of long-acting pre-exposure prophylaxis currently in trials may deal with these problems of low adherence. Pre-exposure prophylaxis has been demonstrated to be cost-effective within certain settings. The introduction of pre-exposure prophylaxis into prevention programs needs to be carefully thought through. For example, pre-exposure prophylaxis-induced risk compensation, at both an individual and population level, could undermine other aspects of a comprehensive HIV prevention program. In conclusion, pre-exposure prophylaxis could be a useful additional tool for the prevention of HIV in specific high-risk groups. It should be implemented in a way that deals with issues such as ensuring high adherence and ensuring that pre-exposure prophylaxis does not detract from, but complements, other more fundamental elements of HIV prevention programs.

Hydrolysis of Miscanthus for bioethanol production using dilute acid presoaking combined with wet explosion pre-treatment and enzymatic treatment

DEFF Research Database (Denmark)

Sørensen, Annette; Teller, Philip Johan; Hilstrøm, Troels

2008-01-01

xylose prior to wet explosion. The acid presoaking extracted 63.2% xylose and 5.2% glucose. Direct enzymatic hydrolysis of the presoaked biomass was found to give only low sugar yields of 24-26% glucose. Wet explosion is a pre-treatment method that combines wet-oxidation and steam explosion. The effect...... of wet explosion on non-presoaked and presoaked Miscanthus was investigated using both atmospheric air and hydrogen peroxide as the oxidizing agent. All wet explosion pre-treatments showed to have a disrupting effect on the lignocellulosic biomass, making the sugars accessible for enzymatic hydrolysis......Miscanthus is a high yielding bioenergy crop. In this study we used acid presoaking, wet explosion, and enzymatic hydrolysis to evaluate the combination of the different pre-treatment methods for bioethanol production with Miscanthus. Acid presoaking is primarily carried out in order to remove...

Pre-exposure prophylaxis of HIV

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Naswa, Smriti; Marfatia, Y. S.

2011-01-01

Pre-exposure prophylaxis (PrEP) is an experimental approach to HIV prevention and consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection and continued during periods of risk. An effective PrEP could provide an additional safety net to sexually active persons at risk, when combined with other prevention strategies. Women represent nearly 60% of adults infected with HIV and PrEP can be a female-controlled prevention method for women who are unable to negotiate condom use. Two antiretroviral nucleoside analog HIV-1 reverse transcriptase inhibitor drugs are currently under trial as PrEP drugs, namely tenofovirdisoproxilfumarate (TDF) alone and TDF in combination with emricitabine (FTC), to be taken as daily single dose oral drugs. There are 11 ongoing trials of ARV-based prevention in different at risk populations across the world. The iPrex trial showed that daily use of oral TDF/FTC by MSM resulted in 44% reduction in the incidence of HIV. This led to publication of interim guidance by CDC to use of PrEP by health providers for MSM. Few other trials are Bangkok Tenofovir Study, Partners PrEP Study, FEM-PrEP study, and VOICE (MTN-003) study. Future trials are being formulated for intermittent PrEP (iPrEP) where drugs are taken before and after sex, “stand-in dose” iPrEP, vaginal or rectal PrEP, etc. There are various issues/concerns with PrEP such as ADRs and resistance to TDF/FTC, adherence to drugs, acceptability, sexual disinhibition, use of PrEP as first line of defense for HIV without other prevention strategies, and cost. The PrEP has a potential to address unmet need in public health if delivered as a part of comprehensive toolkit of prevention services, including risk-reduction, correct and consistent use of condoms, and diagnosis and treatment of sexually transmitted infections. PMID:21799568

Combined effects of functionally-oriented exercise regimens and nutritional supplementation on both the institutionalised and free-living frail elderly (double-blind, randomised clinical trial

Directory of Open Access Journals (Sweden)

Grodzicki Tomasz

2009-01-01

Full Text Available Abstract Background Consistently swelling proportion of the frail elderly within a modern society challenges the overstrained public health sector to provide both adequate medical care and comprehensive assistance in their multiple functional deficits of daily living. Easy-to-apply and task-specific ways of addressing this issue are being sought out, with a view to proposing systemic solutions for nationwide application. Methods The present randomised, double-blind, placebo-controlled, 7-week clinical trial aimed to determine whether specifically structured, intensive exercise regimens, combined with nutritional supplementation, might improve and help sustain individual muscle strength and mobility, and possibly enhance individual functional capabilities in an on-going quest for active prevention of care-dependency. Ninety-one frail elderly (F 71 M 20; mean age 79 years were recruited from both nursing home residents and community dwellers and randomly split into four groups: Group I – progressive resistance exercises (PRE + functionally-oriented exercises (FOE + nutritional supplementation (NS, Group II – PRE + FOE + placebo, Group III – standard exercises (SE + FOE + NS, Group IV – SE + FOE + placebo. Each group pursued a 45 min. exercise session 5 times weekly. The subjects' strength with regard to four muscle groups, i.e. hip and knee extensors and flexons, was assessed at 80% (1 RM weekly, whereas their balance and mobility at baseline and at the end of the study. Results The study was completed by 80 subjects. Despite its relatively short duration significant differences in muscle strength were noted both in Group I and Group II (p = 0.01; p = 0.04; respectively, although this did not translate directly into perceptible improvement in individual mobility. Notable improvements in individual mobility were reported in Group III and Group IV (p = 0.002, although without positive impact on individual muscle strength. Conclusion

Evaluation of the Prevention and Reactivation Care Program (PReCaP for the hospitalized elderly: a prospective nonrandomized controlled trial

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Asmus-Szepesi KJ

2015-03-01

Full Text Available Kirsten J Asmus-Szepesi,1 Linda E Flinterman,1 Marc A Koopmanschap,2 Anna P Nieboer,2 Ton J Bakker,3 Johan P Mackenbach,1 Ewout W Steyerberg1 1Department of Public Health, Erasmus University Medical Center, 2Institute of Health Policy and Management, Erasmus University, 3Stichting Wetenschap Balans, Rotterdam, the Netherlands Background: The hospitalized elderly are at risk of functional decline. We evaluated the effects and care costs of a specialized geriatric rehabilitation program aimed at preventing functional decline among at-risk hospitalized elderly.Methods: The prospective nonrandomized controlled trial reported here was performed in three hospitals in the Netherlands. One hospital implemented the Prevention and Reactivation Care Program (PReCaP, while two other hospitals providing usual care served as control settings. Within the PReCaP hospital we compared patients pre-implementation with patients post-implementation of the PReCaP (“within-hospital analysis”, while our nonrandomized controlled trial compared patients of the PReCaP hospital post-implementation with patients from the two control hospitals providing usual care (“between-hospital analysis”. Hospitalized patients 65 years or older and at risk of functional decline were interviewed at baseline and at 3 and 12 months using validated questionnaires to score functioning, depression, and health-related quality of life (HRQoL. We estimated costs per unit of care from hospital information systems and national data sources. We used adjusted general linear mixed models to analyze functioning and HRQoL.Results: Between-hospital analysis showed no difference in activities of daily living (ADL or instrumental activities of daily living (IADL between PReCaP patients and control groups. PReCaP patients did have slightly better cognitive functioning (Mini Mental State Examination; 0.4 [95% confidence interval (CI 0.2–0.6], lower depression (Geriatric Depression Scale 15; -0

Combination Analgesia for Neonatal Circumcision: A Randomized Controlled Trial.

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Sharara-Chami, Rana; Lakissian, Zavi; Charafeddine, Lama; Milad, Nadine; El-Hout, Yaser

2017-12-01

There is no consensus on the most effective pain management for neonatal circumcision. We sought to compare different modalities. This is a double-blinded randomized controlled trial comparing 3 combination analgesics used during circumcision (EMLA + sucrose; EMLA + sucrose + dorsal penile nerve block [DPNB]; EMLA + sucrose + ring block [RB]) with the traditional topical analgesic cream EMLA alone. The trial was set in the normal nursery of a teaching hospital. The sample included 70 healthy male newborns, randomly assigned to intervention and control groups at a 2:1 ratio. Infants were videotaped (face and torso) during the procedure for assessment of pain by 2 blinded, independent reviewers. The primary outcome measure is the Neonatal Infant Pain Scale score. Secondary outcomes include heart rate, oxygen saturation, and crying time. Neonatal Infant Pain Scale scores were significantly lower in the intervention groups (EMLA + sucrose, mean [SD]: 3.1 [1.33]; EMLA + sucrose + DPNB: 3 [1.33]; EMLA + sucrose + RB: 2.45 [1.27]) compared with the control (5.5 [0.53]). Between-group analyses showed RB + EMLA + sucrose to be significantly more effective than EMLA + sucrose; EMLA + sucrose + DPNB ( P = .009 and P = .002, respectively). Interrater reliability was κ = 0.843. Significant increase in heart rate (139.27 [9.63] to 163 [13.23] beats per minute) and crying time (5.78 [6.4] to 45.37 [12.39] seconds) were noted in the EMLA group. During neonatal circumcision in boys, the most effective analgesia is RB combined with oral sucrose and EMLA cream. Copyright © 2017 by the American Academy of Pediatrics.

The promises and challenges of pre-exposure prophylaxis as part of the emerging paradigm of combination HIV prevention.

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Cáceres, Carlos F; Koechlin, Florence; Goicochea, Pedro; Sow, Papa-Salif; O'Reilly, Kevin R; Mayer, Kenneth H; Godfrey-Faussett, Peter

2015-01-01

Towards the end of the twentieth century, significant success was achieved in reducing incidence in several global HIV epidemics through ongoing prevention strategies. However, further progress in risk reduction was uncertain. For one thing, it was clear that social vulnerability had to be addressed, through research on interventions addressing health systems and other structural barriers. As soon as antiretroviral treatment became available, researchers started to conceive that antiretrovirals might play a role in decreasing either susceptibility in uninfected people or infectiousness among people living with HIV. In this paper we focus on the origin, present status, and potential contribution of pre-exposure prophylaxis (PrEP) within the combination HIV prevention framework. After a phase of controversy, PrEP efficacy trials took off. By 2015, daily oral PrEP, using tenofovir alone or in combination with emtricitabine, has been proven efficacious, though efficacy seems heavily contingent upon adherence to pill uptake. Initial demonstration projects after release of efficacy results have shown that PrEP can be implemented in real settings and adherence can be high, leading to high effectiveness. Despite its substantial potential, beliefs persist about unfeasibility in real-life settings due to stigma, cost, adherence, and potential risk compensation barriers. The strategic synergy of behavioural change communication, biomedical strategies (including PrEP), and structural programmes is providing the basis for the combination HIV prevention framework. If PrEP is to ever become a key component of that framework, several negative beliefs must be confronted based on emerging evidence; moreover, research gaps regarding PrEP implementation must be filled, and appropriate prioritization strategies must be set up. Those challenges are significant, proportional to the impact that PrEP implementation may have in the global response to HIV.

Interventions for hyperthyroidism pre-pregnancy and during pregnancy.

Science.gov (United States)

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2013-11-19

Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. To identify interventions used in the management of hyperthyroidism pre-pregnancy or during pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). We planned to include randomised controlled trials, quasi-randomised controlled trials, and cluster-randomised trials comparing antithyroid interventions for hyperthyroidism pre-pregnancy or during pregnancy with another intervention or no intervention (placebo or no treatment). Two review authors assessed trial eligibility and planned to assess trial quality and extract the data independently. No trials were included in the review. As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid interventions for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.

Trial-to-Trial Fluctuations in Attentional State and Their Relation to Intelligence

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Unsworth, Nash; McMillan, Brittany D.

2014-01-01

Trial-to-trial fluctuations in attentional state while performing measures of intelligence were examined in the current study. Participants performed various measures of fluid and crystallized intelligence while also providing attentional state ratings prior to each trial. It was found that pre-trial attentional state ratings strongly predicted…

The recursive combination filter approach of pre-processing for the estimation of standard deviation of RR series.

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Mishra, Alok; Swati, D

2015-09-01

Variation in the interval between the R-R peaks of the electrocardiogram represents the modulation of the cardiac oscillations by the autonomic nervous system. This variation is contaminated by anomalous signals called ectopic beats, artefacts or noise which mask the true behaviour of heart rate variability. In this paper, we have proposed a combination filter of recursive impulse rejection filter and recursive 20% filter, with recursive application and preference of replacement over removal of abnormal beats to improve the pre-processing of the inter-beat intervals. We have tested this novel recursive combinational method with median method replacement to estimate the standard deviation of normal to normal (SDNN) beat intervals of congestive heart failure (CHF) and normal sinus rhythm subjects. This work discusses the improvement in pre-processing over single use of impulse rejection filter and removal of abnormal beats for heart rate variability for the estimation of SDNN and Poncaré plot descriptors (SD1, SD2, and SD1/SD2) in detail. We have found the 22 ms value of SDNN and 36 ms value of SD2 descriptor of Poincaré plot as clinical indicators in discriminating the normal cases from CHF cases. The pre-processing is also useful in calculation of Lyapunov exponent which is a nonlinear index as Lyapunov exponents calculated after proposed pre-processing modified in a way that it start following the notion of less complex behaviour of diseased states.

Assessment of Oral Fluid HIV Test Performance in an HIV Pre-Exposure Prophylaxis Trial in Bangkok, Thailand.

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Pravan Suntharasamai

Full Text Available Rapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs.The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants' oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive.We screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5% were confirmed HIV-infected, 10 (2.2% HIV-uninfected, and one (0.2% had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days than participants receiving placebo (16.8 days (p = 0.02 and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04.The oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice.ClinicalTrials.gov NCT00119106.

Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy.

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Paul D Griffiths

Full Text Available To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml of whole blood.Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A. A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml or less than 3000 genomes/ml were obtained (Part B. For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml.In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56% in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37% in the immediate treatment arm (p = 0.193. However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022. In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35% in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45% among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322. However, the duration of antiviral treatment was significantly shorter (p = 0.0012 in those randomized to stop treatment when viraemia was less than 3000 genomes/ml.The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy.

Does a pre-hospital emergency pathway improve early diagnosis and referral in suspected stroke patients? – Study protocol of a cluster randomised trial [ISRCTN41456865

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Lori Giuliano

2005-10-01

Full Text Available Abstract Background Early interventions proved to be able to improve prognosis in acute stroke patients. Prompt identification of symptoms, organised timely and efficient transportation towards appropriate facilities, become essential part of effective treatment. The implementation of an evidence based pre-hospital stroke care pathway may be a method for achieving the organizational standards required to grant appropriate care. We performed a systematic search for studies evaluating the effect of pre-hospital and emergency interventions for suspected stroke patients and we found that there seems to be only a few studies on the emergency field and none about implementation of clinical pathways. We will test the hypothesis that the adoption of emergency clinical pathway improves early diagnosis and referral in suspected stroke patients. We designed a cluster randomised controlled trial (C-RCT, the most powerful study design to assess the impact of complex interventions. The study was registered in the Current Controlled Trials Register: ISRCTN41456865 – Implementation of pre-hospital emergency pathway for stroke – a cluster randomised trial. Methods/design Two-arm cluster-randomised trial (C-RCT. 16 emergency services and 14 emergency rooms were randomised either to arm 1 (comprising a training module and administration of the guideline, or to arm 2 (no intervention, current practice. Arm 1 participants (152 physicians, 280 nurses, 50 drivers attended an interactive two sessions course with continuous medical education CME credits on the contents of the clinical pathway. We estimated that around 750 patients will be met by the services in the 6 months of observation. This duration allows recruiting a sample of patients sufficient to observe a 30% improvement in the proportion of appropriate diagnoses. Data collection will be performed using current information systems. Process outcomes will be measured at the cluster level six months after the

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT).

Science.gov (United States)

Bruce, Julie; Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

2016-01-18

Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver 'active' interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to 'active' intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the

Combining task-evoked and spontaneous activity to improve pre-operative brain mapping with fMRI

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Fox, Michael D.; Qian, Tianyi; Madsen, Joseph R.; Wang, Danhong; Li, Meiling; Ge, Manling; Zuo, Huan-cong; Groppe, David M.; Mehta, Ashesh D.; Hong, Bo; Liu, Hesheng

2016-01-01

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20 years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional localization, and can be combined to improve identification of eloquent motor cortex. Accuracy, sensitivity, and specificity of our approach are quantified through comparison with electrical cortical stimulation mapping in eight patients with intractable epilepsy. Broad applicability and reproducibility of our approach is demonstrated through prospective replication in an independent dataset of six patients from a different center. In both cohorts and every individual patient, we see a significant improvement in signal to noise and mapping accuracy independent of threshold, quantified using receiver operating characteristic curves. Collectively, our results suggest that modifying the processing of fMRI data to incorporate both task-based and spontaneous activity significantly improves functional localization in pre-operative patients. Because this method requires no additional scan time or modification to conventional pre-operative data acquisition protocols it could have widespread utility. PMID:26408860

From Famine to Feast: Developing Early-Phase Combination Immunotherapy Trials Wisely.

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Day, Daphne; Monjazeb, Arta M; Sharon, Elad; Ivy, S Percy; Rubin, Eric H; Rosner, Gary L; Butler, Marcus O

2017-09-01

Not until the turn of this century has immunotherapy become a fundamental component of cancer treatment. While monotherapy with immune modulators, such as immune checkpoint inhibitors, provides a subset of patients with durable clinical benefit and possible cure, combination therapy offers the potential for antitumor activity in a greater number of patients. The field of immunology has provided us with a plethora of potential molecules and pathways to target. This abundance makes it impractical to empirically test all possible combinations efficiently. We recommend that potential immunotherapy combinations be chosen based on sound rationale and available data to address the mechanisms of primary and acquired immune resistance. Novel trial designs may increase the proportion of patients receiving potentially efficacious treatments and, at the same time, better define the balance of clinical activity and safety. We believe that implementing a strategic approach in the early development of immunotherapy combinations will expedite the delivery of more effective therapies with improved safety and durable outcomes. ©2017 American Association for Cancer Research.

Perspective: Recommendations for benchmarking pre-clinical studies of nanomedicines

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Dawidczyk, Charlene M.; Russell, Luisa M.; Searson, Peter C.

2015-01-01

Nanoparticle-based delivery systems provide new opportunities to overcome the limitations associated with traditional small molecule drug therapy for cancer, and to achieve both therapeutic and diagnostic functions in the same platform. Pre-clinical trials are generally designed to assess therapeutic potential and not to optimize the design of the delivery platform. Consequently, progress in developing design rules for cancer nanomedicines has been slow, hindering progress in the field. Despite the large number of pre-clinical trials, several factors restrict comparison and benchmarking of different platforms, including variability in experimental design, reporting of results, and the lack of quantitative data. To solve this problem, we review the variables involved in the design of pre-clinical trials and propose a protocol for benchmarking that we recommend be included in in vivo pre-clinical studies of drug delivery platforms for cancer therapy. This strategy will contribute to building the scientific knowledge base that enables development of design rules and accelerates the translation of new technologies. PMID:26249177

Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

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Julia L. Hurwitz

2010-02-01

Full Text Available Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.

The International (Ludwig) Breast Cancer Study Group Trials I-IV: 15 years follow-up.

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Castiglione-Gertsch, M; Johnsen, C; Goldhirsch, A; Gelber, R D; Rudenstam, C M; Collins, J; Lindtner, J; Hacking, A; Cortes-Funes, H; Forbes, J

1994-10-01

Adjuvant systemic therapy prolongs disease-free and overall survival in both pre- and postmenopausal patients. Available data shown benefit from multi-agent chemotherapy, prolonged tamoxifen treatment, and ovarian ablation, and that the combination of chemo- and endocrine therapy might be advantageous. In 1978 the International (Ludwig) Breast Cancer Study Group (IBCSG) initiated four complementary randomized controlled clinical trials to evaluate the roles of chemo-endocrine combinations or endocrine therapy alone in specific populations defined by risk (for pre- and perimenopausal patients) or by age (for postmenopausal patients). The results at 10 and 13 years' median follow-up for these trials are summarized in this report and are compared to those of the Overview meta-analysis with regard to chemo-endocrine or endocrine therapy combinations. Furthermore, types of first relapses by sites and second malignant diseases are reported. 1601 evaluable patients with node positive disease were included into the studies I-IV. In Trial I (491 premenopausal patients with 1-3 positive axillary nodes) we studied the addition of low-dose continuous prednisone (p) to a cyclophosphamide-methotrexate-fluorouracil (CMF) combination. In Trial II 327 premenopausal patients with four or more positive axillary nodes were randomized to one year CMFp or to a surgical oophorectomy followed by CMFp. In Trial III (463 postmenopausal patients 65 years old or younger), combined chemoendocrine therapy (one year of CMFp plus tamoxifen (T)) was compared to endocrine therapy (1 year of p + T) or to surgery alone. In Trial IV 320 postmenopausal patients 66 to 80 years old were treated either by surgery alone or by surgery followed by 1 year prednisone and tamoxifen. In Trial I the addition of prednisone allowed a higher dose of cytotoxics to be administered compared with CMF alone. Despite this increased dose intensity, 13-year disease-free survival (DFS) and overall survival (OS) were similar

Reducing child abuse amongst adolescents in low- and middle-income countries: A pre-post trial in South Africa

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Lucie Cluver

2016-07-01

Full Text Available Abstract Background No known studies have tested the effectiveness of child abuse prevention programmes for adolescents in low- or middle-income countries. ‘Parenting for Lifelong Health’ ( http://tiny.cc/whoPLH is a collaborative project to develop and rigorously test abuse-prevention parenting programmes for free use in low-resource contexts. Research aims of this first pre-post trial in South Africa were: i to identify indicative effects of the programme on child abuse and related outcomes; ii to investigate programme safety for testing in a future randomised trial, and iii to identify potential adaptations. Methods Two hundred thirty participants (adolescents and their primary caregivers were recruited from schools, welfare services and community-sampling in rural, high-poverty South Africa (no exclusion criteria. All participated in a 12-week parenting programme, implemented by local NGO childcare workers to ensure real-world external validity. Standardised pre-post measures with adolescents and caregivers were used, and paired t-tests were conducted for primary outcomes: abuse (physical, emotional abuse and neglect, adolescent behaviour problems and parenting (positive and involved parenting, poor monitoring and inconsistent discipline, and secondary outcomes: mental health, social support and substance use. Results Participants reported high levels of socio-economic deprivation, e.g. 60 % of adolescents had either an HIV-positive caregiver or were orphaned by AIDS, and 50 % of caregivers experienced intimate partner violence. i indicative effects: Primary outcomes comparing pre-test and post-test assessments showed reductions reported by adolescents and caregivers in child abuse (adolescent report 63.0 % pre-test to 29.5 % post-test, caregiver report 75.5 % pre-test to 36.5 % post-test, both p < 0.001 poor monitoring/inconsistent discipline (p < .001, adolescent delinquency/aggressive behaviour (both p < .001, and

Unsaturated Fatty Acid, cis-2-Decenoic Acid, in Combination with Disinfectants or Antibiotics Removes Pre-Established Biofilms Formed by Food-Related Bacteria

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Sepehr, Shayesteh; Rahmani-Badi, Azadeh; Babaie-Naiej, Hamta; Soudi, Mohammad Reza

2014-01-01

Biofilm formation by food-related bacteria and food-related pathogenesis are significant problems in the food industry. Even though much disinfection and mechanical procedure exist for removal of biofilms, they may fail to eliminate pre-established biofilms. cis-2 decenoic acid (CDA), an unsaturated fatty acid messenger produced by Pseudomonas aeruginosa, is reportedly capable of inducing the dispersion of established biofilms by multiple types of microorganisms. However, whether CDA has potential to boost the actions of certain antimicrobials is unknown. Here, the activity of CDA as an inducer of pre-established biofilms dispersal, formed by four main food pathogens; Staphylococcus aureus, Bacillus cereus, Salmonella enterica and E. coli, was measured using both semi-batch and continuous cultures bioassays. To assess the ability of CDA combined biocides treatments to remove pre-established biofilms formed on stainless steel discs, CFU counts were performed for both treated and untreated cultures. Eradication of the biofilms by CDA combined antibiotics was evaluated using crystal violet staining. The effect of CDA combined treatments (antibiotics and disinfectants) on biofilm surface area and bacteria viability was evaluated using fluorescence microscopy, digital image analysis and LIVE/DEAD staining. MICs were also determined to assess the probable inhibitory effects of CDA combined treatments on the growth of tested microorganisms' planktonic cells. Treatment of pre-established biofilms with only 310 nM CDA resulted in at least two-fold increase in the number of planktonic cells in all cultures. While antibiotics or disinfectants alone exerted a trivial effect on CFU counts and percentage of surface area covered by the biofilms, combinational treatments with both 310 nM CDA and antibiotics or disinfectants led to approximate 80% reduction in biofilm biomass. These data suggests that combined treatments with CDA would pave the way toward developing new strategies

Unsaturated fatty acid, cis-2-decenoic acid, in combination with disinfectants or antibiotics removes pre-established biofilms formed by food-related bacteria.

Directory of Open Access Journals (Sweden)

Shayesteh Sepehr

Full Text Available Biofilm formation by food-related bacteria and food-related pathogenesis are significant problems in the food industry. Even though much disinfection and mechanical procedure exist for removal of biofilms, they may fail to eliminate pre-established biofilms. cis-2 decenoic acid (CDA, an unsaturated fatty acid messenger produced by Pseudomonas aeruginosa, is reportedly capable of inducing the dispersion of established biofilms by multiple types of microorganisms. However, whether CDA has potential to boost the actions of certain antimicrobials is unknown. Here, the activity of CDA as an inducer of pre-established biofilms dispersal, formed by four main food pathogens; Staphylococcus aureus, Bacillus cereus, Salmonella enterica and E. coli, was measured using both semi-batch and continuous cultures bioassays. To assess the ability of CDA combined biocides treatments to remove pre-established biofilms formed on stainless steel discs, CFU counts were performed for both treated and untreated cultures. Eradication of the biofilms by CDA combined antibiotics was evaluated using crystal violet staining. The effect of CDA combined treatments (antibiotics and disinfectants on biofilm surface area and bacteria viability was evaluated using fluorescence microscopy, digital image analysis and LIVE/DEAD staining. MICs were also determined to assess the probable inhibitory effects of CDA combined treatments on the growth of tested microorganisms' planktonic cells. Treatment of pre-established biofilms with only 310 nM CDA resulted in at least two-fold increase in the number of planktonic cells in all cultures. While antibiotics or disinfectants alone exerted a trivial effect on CFU counts and percentage of surface area covered by the biofilms, combinational treatments with both 310 nM CDA and antibiotics or disinfectants led to approximate 80% reduction in biofilm biomass. These data suggests that combined treatments with CDA would pave the way toward

Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy.

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Haussmann, Ursula; Fischer, Joachim; Eber, Stefan; Scherer, Franziska; Seger, Reinhard; Gungor, Tayfun

2006-06-01

Hepatic veno-occlusive disease (VOD) remains a serious complication after hematopoietic stem cell transplantation (HSCT). Based on a protective effect of antithrombin III (ATIII) on endothelial cells, we assessed the incidence of VOD after pre-emptive ATIII replacement and the outcome of VOD after combined high dose defibrotide (DF) and ATIII therapy. This prospective case series comprised two phases. In the first phase 71 children did not receive any specific VOD prophylaxis or therapy (controls). In the second phase 91 children were given pre-emptive ATIII replacement in case of decreased ATIII activity (defibrotide (60 mg/day) and ATIII replacement therapy were combined. The severity of VOD was determined according to the degree of multiple organ dysfunction. The incidence of VOD was similar in both groups (13/71, 18% vs. 14/91, 15%). All 14 patients in the second group who developed VOD showed decreased ATIII activity not more than 1 day prior to the clinical diagnosis of VOD. The resulting short duration of pre-emptive ATIII therapy failed to prevent VOD (OR 0.96). None of the patients (n=72) maintaining normal ATIII levels developed VOD. All 14 patients with VOD who received combined therapy achieved complete remission and 93 % (13/14) survived until day +100, compared to six survivors (46%) in the first group. Pre-emptive ATIII administration did not alter the incidence of VOD. Combination treatment with ATIII and defibrotide was safe and yielded excellent remission and survival rates.

Combining task-evoked and spontaneous activity to improve pre-operative brain mapping with fMRI.

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Fox, Michael D; Qian, Tianyi; Madsen, Joseph R; Wang, Danhong; Li, Meiling; Ge, Manling; Zuo, Huan-Cong; Groppe, David M; Mehta, Ashesh D; Hong, Bo; Liu, Hesheng

2016-01-01

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional localization, and can be combined to improve identification of eloquent motor cortex. Accuracy, sensitivity, and specificity of our approach are quantified through comparison with electrical cortical stimulation mapping in eight patients with intractable epilepsy. Broad applicability and reproducibility of our approach are demonstrated through prospective replication in an independent dataset of six patients from a different center. In both cohorts and every individual patient, we see a significant improvement in signal to noise and mapping accuracy independent of threshold, quantified using receiver operating characteristic curves. Collectively, our results suggest that modifying the processing of fMRI data to incorporate both task-based and spontaneous activity significantly improves functional localization in pre-operative patients. Because this method requires no additional scan time or modification to conventional pre-operative data acquisition protocols it could have widespread utility. Copyright © 2015. Published by Elsevier Inc.

A complex behavioural change intervention to reduce the risk of diabetes and prediabetes in the pre-conception period in Malaysia: study protocol for a randomised controlled trial.

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Skau, Jutta K H; Nordin, Awatef Binti Amer; Cheah, Julius C H; Ali, Roslinah; Zainal, Ramli; Aris, Tahir; Ali, Zainudin Mohd; Matzen, Priya; Biesma, Regien; Aagaard-Hansen, Jens; Hanson, Mark A; Norris, Shane A

2016-04-27

Over the past two decades, the population of Malaysia has grown rapidly and the prevalence of diabetes mellitus in Malaysia has dramatically increased, along with the frequency of obesity, hyperlipidaemia and hypertension. Early-life influences play an important role in the development of non-communicable diseases. Indeed, maternal lifestyle and conditions such as gestational diabetes mellitus or obesity can affect the risk of diabetes in the next generation. Lifestyle changes can help to prevent the development of type 2 diabetes mellitus. This is a protocol for an unblinded, community-based, randomised controlled trial in two arms to evaluate the efficacy of a complex behavioural change intervention, combining motivational interviewing provided by a community health promoter and access to a habit formation mobile application, among young Malaysian women and their spouses prior to pregnancy. Eligible subjects will be Malaysian women in the age group 20 to 39 years, who are nulliparous, not diagnosed with diabetes and own a smartphone. With an alpha-value of 0.05, a statistical power of 90 %, 264 subjects will need to complete the study. Subjects with their spouses will be randomised to either the intervention or the control arm for an 8-month period. The primary endpoint is change in waist circumference from baseline to end of intervention period and secondary endpoints are changes in anthropometric parameters, biochemical parameters, change in health literacy level, dietary habits, physical activity and stress level. Primary endpoint and the continuous secondary endpoints will be analysed in a linear regression model, whereas secondary endpoints on an ordinal scale will be analysed by using the chi-squared test. A multivariate linear model for the primary endpoint will be undertaken to account for potential confounders. This study has been approved by the Medical Research and Ethics Committee of the Ministry of Health Malaysia (protocol number: NMRR-14

Combining escitalopram and cognitive-behavioural therapy for social anxiety disorder: randomised controlled fMRI trial.

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Gingnell, Malin; Frick, Andreas; Engman, Jonas; Alaie, Iman; Björkstrand, Johannes; Faria, Vanda; Carlbring, Per; Andersson, Gerhard; Reis, Margareta; Larsson, Elna-Marie; Wahlstedt, Kurt; Fredrikson, Mats; Furmark, Tomas

2016-09-01

Selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioural therapy (CBT) are often used concomitantly to treat social anxiety disorder (SAD), but few studies have examined the effect of this combination. To evaluate whether adding escitalopram to internet-delivered CBT (ICBT) improves clinical outcome and alters brain reactivity and connectivity in SAD. Double-blind, randomised, placebo-controlled neuroimaging trial of ICBT combined either with escitalopram (n = 24) or placebo (n = 24), including a 15-month clinical follow-up (trial registration: ISRCTN24929928). Escitalopram+ICBT, relative to placebo+ICBT, resulted in significantly more clinical responders, larger reductions in anticipatory speech state anxiety at post-treatment and larger reductions in social anxiety symptom severity at 15-month follow-up and at a trend-level (P = 0.09) at post-treatment. Right amygdala reactivity to emotional faces also decreased more in the escitalopram+ICBT combination relative to placebo+ICBT, and in treatment responders relative to non-responders. Adding escitalopram improves the outcome of ICBT for SAD and decreased amygdala reactivity is important for anxiolytic treatment response. © The Royal College of Psychiatrists 2016.

Does the bracket-ligature combination affect the amount of orthodontic space closure over three months? A randomized controlled trial.

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Wong, Henry; Collins, Jill; Tinsley, David; Sandler, Jonathan; Benson, Philip

2013-06-01

To investigate the effect of bracket-ligature combination on the amount of orthodontic space closure over three months. Randomized clinical trial with three parallel groups. A hospital orthodontic department (Chesterfield Royal Hospital, UK). Forty-five patients requiring upper first premolar extractions. Informed consent was obtained and participants were randomly allocated into one of three groups: (1) conventional pre-adjusted edgewise brackets and elastomeric ligatures; (2) conventional pre-adjusted edgewise brackets and Super Slick(®) low friction elastomeric ligatures; (3) Damon 3MX(®) passive self-ligating brackets. Space closure was undertaken on 0·019×0·025-inch stainless steel archwires with nickel-titanium coil springs. Participants were recalled at four weekly intervals. Upper alginate impressions were taken at each visit (maximum three). The primary outcome measure was the mean amount of space closure in a 3-month period. A one-way ANOVA was undertaken [dependent variable: mean space closure (mm); independent variable: group allocation]. The amount of space closure was very similar between the three groups (1 mm per 28 days); however, there was a wide variation in the rate of space closure between individuals. The differences in the amount of space closure over three months between the three groups was very small and non-significant (P = 0·718). The hypothesis that reducing friction by modifying the bracket/ligature interface increases the rate of space closure was not supported. The major determinant of orthodontic tooth movement is probably the individual patient response.

A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens.

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Sanchez, Larysa; Vesole, David H; Richter, Joshua R; Biran, Noa; Bilotti, Elizabeth; McBride, Laura; Anand, Palka; Ivanovski, Kristin; Siegel, David S

2017-02-01

Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open-label, single-institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide-refractory patients. Patients were considered lenalidomide-refractory if they had no clinical response (vorinostat 400 mg days 1-7 and 15-21, lenalidomide 25 mg days 1-21, and dexamethasone 40 mg days 1, 8, 15 and 22 in 28-day cycles. Twenty-five patients were enrolled, median age was 65 years and patients had received a median of 5 prior regimens. The overall response rate was 24% (6 partial responses) and clinical benefit rate (≥stable disease) was 80%. Median time to a partial response was 1·9 months and median duration of response was 3·3 months. Median progression-free survival was 5·3 months. Most common grade 3/4 adverse events were neutropenia (48%), thrombocytopenia (32%), anaemia (20%) and gastrointestinal toxicities (16%). In this heavily pre-treated population, vorinostat in combination with lenalidomide and dexamethasone was active in lenalidomide-refractory patients. © 2016 John Wiley & Sons Ltd.

Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy.

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Palmer, Adam C; Sorger, Peter K

2017-12-14

Combination cancer therapies aim to improve the probability and magnitude of therapeutic responses and reduce the likelihood of acquired resistance in an individual patient. However, drugs are tested in clinical trials on genetically diverse patient populations. We show here that patient-to-patient variability and independent drug action are sufficient to explain the superiority of many FDA-approved drug combinations in the absence of drug synergy or additivity. This is also true for combinations tested in patient-derived tumor xenografts. In a combination exhibiting independent drug action, each patient benefits solely from the drug to which his or her tumor is most sensitive, with no added benefit from other drugs. Even when drug combinations exhibit additivity or synergy in pre-clinical models, patient-to-patient variability and low cross-resistance make independent action the dominant mechanism in clinical populations. This insight represents a different way to interpret trial data and a different way to design combination therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

WITHDRAWN: Exercise for treating anterior cruciate ligament injuries in combination with collateral ligament and meniscal damage of the knee in adults.

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Trees, Amanda H; Howe, Tracey E; Grant, Margaret; Gray, Heather G

2011-05-11

The anterior cruciate ligament (ACL) is the most frequently injured ligament of the knee. The ACL may be damaged in isolation but often other ligaments and menisci are implicated. The injury may be managed surgically or conservatively. Injury causes pain, effusion and inflammation leading to alteration in muscle function. Regaining muscular control is essential if the individual wishes to return to pre-injury level of function and patients will invariably be referred for rehabilitation. To present the best evidence for effectiveness of exercise used in the treatment of ACL injuries in combination with collateral ligament and meniscal damage to the knee in adults, on return to work and pre-injury levels of activity. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (October 2006), Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 3), MEDLINE (1996 to October 2006), EMBASE (1980 to October 2006), other databases and reference lists of articles. We included randomised controlled trials and quasi-randomised trials testing exercise programmes designed to treat adults with ACL injuries in combination with collateral ligament and meniscal damage. Included trials randomised participants to receive any combination of the following: no care, usual care, a single-exercise intervention, and multiple-exercise interventions. The primary outcome measures of interest were returning to work and return to pre-injury level of activity post treatment, at six months and one year. Two authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. Five trials (243 participants) evaluated different exercise programmes following ACL reconstruction and one trial (100 participants) compared supervised with self-monitored exercises as part of conservative treatment. No study compared the effect of exercise versus

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

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

2016-02-01

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

Adding a post-training FIFA 11+ exercise program to the pre-training FIFA 11+ injury prevention program reduces injury rates among male amateur soccer players: a cluster-randomised trial

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Wesam Saleh A Al Attar

2017-10-01

Trial registration: ACTRN12615001206516. [Al Attar WSA, Soomro N, Pappas E, Sinclair PJ, Sanders RH (2017 Adding a post-training FIFA 11+ exercise program to the pre-training FIFA 11+ injury prevention program reduces injury rates among male amateur soccer players: a cluster-randomised trial. Journal of Physiotherapy 63: 235–242

A randomized controlled trial of pre-conception treatment for periodontal disease to improve periodontal status during pregnancy and birth outcomes

OpenAIRE

Jiang, Hong; Xiong, Xu; Su, Yi; Zhang, Yiming; Wu, Hongqiao; Jiang, Zhijun; Qian, Xu

2013-01-01

Background Evidence has suggested that periodontal disease is associated with an increased risk of various adverse pregnancy and birth outcomes. However, several large clinical randomized controlled trials failed to demonstrate periodontal therapy during pregnancy reduced the incidence of adverse pregnancy and birth outcomes. It has been suggested that the pre-conception period may be an optimal period for periodontal disease treatment rather than during pregnancy. To date, no randomized cont...

Evaluation of the Prevention and Reactivation Care Program (PReCaP) for the hospitalized elderly: A prospective nonrandomized controlled trial

OpenAIRE

Asmus-Szepesi, Kirsten; Flinterman, Linda; Koopmanschap, Marc; Nieboer, Anna; Bakker, Ton; Mackenbach, Johan; Steyerberg, Ewout

2015-01-01

textabstractBackground: The hospitalized elderly are at risk of functional decline. We evaluated the effects and care costs of a specialized geriatric rehabilitation program aimed at preventing functional decline among at-risk hospitalized elderly. Methods: The prospective nonrandomized controlled trial reported here was performed in three hospitals in the Netherlands. One hospital implemented the Prevention and Reactivation Care Program (PReCaP), while two other hospitals providing usual car...

Pre-Meal Effect of Whey Proteins on Metabolic Parameters in Subjects with and without Type 2 Diabetes: A Randomized, Crossover Trial

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Ann Bjørnshave

2018-01-01

Full Text Available Diabetic dyslipidemia with elevated postprandial triglyceride (TG responses is characteristic in type 2 diabetes (T2D. Diet and meal timing can modify postprandial lipemia (PPL. The impact of a pre-meal of whey proteins (WP on lipid metabolism is unidentified. We determined whether a WP pre-meal prior to a fat-rich meal influences TG and apolipoprotein B-48 (ApoB-48 responses differentially in patients with and without T2D. Two matched groups of 12 subjects with and without T2D accomplished an acute, randomized, cross-over trial. A pre-meal of WP (20 g or water (control was consumed 15 min before a fat-rich meal (supplemented with 20 g WP in case of water pre-meal. Postprandial responses were examined during a 360-min period. A WP pre-meal significantly increased postprandial concentrations of insulin (P < 0.0001, glucagon (P < 0.0001 and glucose-dependent insulinotropic peptide (GIP (P < 0.0001 in subjects with and without T2D. We detected no effects of the WP pre-meal on TG, ApoB-48, or non-esterified fatty acids (NEFA responses to the fat-rich meal in either group. Paracetamol absorption i.e. gastric emptying was delayed by the WP pre-meal (P = 0.039. In conclusion, the WP pre-meal induced similar hormone and lipid responses in subjects with and without T2D. Thus, the WP pre-meal enhanced insulin, glucagon and GIP responses but did not influence lipid or glucose responses. In addition, we demonstrated that a WP pre-meal reduced gastric emptying in both groups.

Interactions between ibrutinib and anti-CD20 antibodies; competing effects on the outcome of combination therapy

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Skarzynski, Martin; Niemann, Carsten U; Lee, Yuh Shan; Martyr, Sabrina; Maric, Irina; Salem, Dalia; Stetler-Stevenson, Maryalice; Marti, Gerald E; Calvo, Katherine R; Yuan, Constance; Valdez, Janet; Soto, Susan; Farooqui, Mohammed Z.H.; Herman, Sarah E.M.; Wiestner, Adrian

2015-01-01

Purpose Clinical trials of ibrutinib combined with anti-CD20 monoclonal antibodies (mAbs) for chronic lymphocytic leukemia (CLL) report encouraging results. Paradoxically, in pre-clinical studies in vitro ibrutinib was reported to decrease CD20 expression and inhibits cellular effector mechanisms. We therefore set out to investigate effects of in vivo ibrutinib treatment that could explain this paradox. Experimental Design Patients received single agent ibrutinib (420mg daily) on an investigator-initiated phase 2 trial. Serial blood samples were collected pre-treatment and during treatment for ex vivo functional assays to examine the effects on CLL cell susceptibility to anti-CD20 mAbs. Results We demonstrate that CD20 expression on ibrutinib was rapidly and persistently down-regulated (median reduction 74%, day 28, Pibrutinib were less susceptible to anti-CD20 mAb-mediated complement-dependent cytotoxicity than pre-treatment cells (median reduction 75%, Pibrutinib, providing a likely mechanism for the preserved C3d opsonization. Additionally, ibrutinib significantly inhibited trogocytosis, a major contributor to antigen loss and tumor escape during mAb therapy. Conclusions Our data indicate that ibrutinib promotes both positive and negative interactions with anti-CD20 mAbs, suggesting that successfully harnessing maximal anti-tumor effects of such combinations requires further investigation. PMID:26283682

Effect of Seed Quality and Combination Fungicide-Trichoderma spp. Seed Treatments on Pre- and Postemergence Damping-Off in Cotton.

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Howell, Charles R

2007-01-01

ABSTRACT Good quality seeds of cotton cultivars often escaped pre-emergence damping-off incited by Pythium spp. and Rhizopus oryzae, and they were resistant to postemergence damping-off incited by Rhizoctonia solani. Poor quality seeds, however, were highly susceptible to both phases of seedling disease and required seed treatment in order to survive. Pre-emergence damping-off incited by Pythium spp. and Rhizopus oryzae could be controlled by seed treatment with biocontrol preparations of a number of Trichoderma spp., but these treatments were much less effective in controlling postemergence disease incited by Rhizoctonia solani. Postemergence seedling disease can be controlled by fungicides, but they were much less effective in controlling the pre-emergence phase of the disease. Combination seed treatments of poor quality cotton seeds with fungicides and Trichoderma spp. preparations, followed by planting in pathogen-infested soil, indicated that this technique will control both phases of seedling disease. Seed treatment with either the fungicides or the biocontrol agents alone did not achieve this goal. The optimum combination treatment for disease control was that of chloroneb plus Trichoderma spp., followed by chloroneb plus metalaxyl (Deltacoat AD) plus T. virens strain G-6.

Combining features from ERP components in single-trial EEG for discriminating four-category visual objects

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Wang, Changming; Xiong, Shi; Hu, Xiaoping; Yao, Li; Zhang, Jiacai

2012-10-01

Categorization of images containing visual objects can be successfully recognized using single-trial electroencephalograph (EEG) measured when subjects view images. Previous studies have shown that task-related information contained in event-related potential (ERP) components could discriminate two or three categories of object images. In this study, we investigated whether four categories of objects (human faces, buildings, cats and cars) could be mutually discriminated using single-trial EEG data. Here, the EEG waveforms acquired while subjects were viewing four categories of object images were segmented into several ERP components (P1, N1, P2a and P2b), and then Fisher linear discriminant analysis (Fisher-LDA) was used to classify EEG features extracted from ERP components. Firstly, we compared the classification results using features from single ERP components, and identified that the N1 component achieved the highest classification accuracies. Secondly, we discriminated four categories of objects using combining features from multiple ERP components, and showed that combination of ERP components improved four-category classification accuracies by utilizing the complementarity of discriminative information in ERP components. These findings confirmed that four categories of object images could be discriminated with single-trial EEG and could direct us to select effective EEG features for classifying visual objects.

Reporting Quality of Randomized, Controlled Trials Evaluating Combined Chemoradiotherapy in Nasopharyngeal Carcinoma

International Nuclear Information System (INIS)

Chen, Yu-Pei; Chen, Lei; Li, Wen-Fei; Lee, Anne W.M.; Vermorken, Jan B.; Wee, Joseph; O'Sullivan, Brian; Eisbruch, Avraham; Lin, Jin-Ching; Mai, Hai-Qiang; Zhang, Li; Guo, Ying; Lin, Ai-Hua; Sun, Ying

2017-01-01

Purpose: To comprehensively assess the reporting quality of randomized, controlled trials (RCTs) in nasopharyngeal carcinoma (NPC), and to identify significant predictors of quality. Methods and Materials: Two investigators searched MEDLINE and EMBASE for RCTs published between January 1988 and December 2015 that assessed the effect of combined chemoradiotherapy for NPC. The overall quality of each report was assessed using a 28-point overall quality score (OQS) based on the 2010 Consolidated Standards of Reporting Trials (CONSORT) statement. To provide baseline data for further evaluation, we also investigated the reporting quality of certain important issues in detail, including key methodologic items (allocation concealment, blinding, intention-to-treat principle), endpoints, follow-up, subgroup analyses, and adverse events. Results: We retrieved 24 relevant RCTs including 6591 patients. Median 2010 OQS was 15.5 (range, 10-24). Half of the items in the 2010 OQS were poorly reported in at least 40% of trials. Multivariable regression models revealed that publication after 2010 and high impact factor were significant predictors of improved 2010 OQS. Additionally, many issues that we consider significant were not reported adequately. Conclusions: Despite publication of the CONSORT statement more than a decade ago, overall reporting quality for RCTs in NPC was unsatisfactory. Additionally, substantial selectivity and heterogeneity exists in reporting of certain crucial issues. This survey provides the first prompt for NPC trial investigators to improve reporting quality according to the CONSORT statement; increased scrutiny and diligence by editors and peer reviewers is also required.

Reporting Quality of Randomized, Controlled Trials Evaluating Combined Chemoradiotherapy in Nasopharyngeal Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Chen, Yu-Pei; Chen, Lei; Li, Wen-Fei [Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); Lee, Anne W.M. [Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen (China); Vermorken, Jan B. [Department of Medical Oncology, Antwerp University Hospital, Edegem (Belgium); Wee, Joseph [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); O' Sullivan, Brian [Department of Radiation Oncology, University of Toronto, Ontario Cancer Institute, University Health Network, Toronto, Ontario (Canada); Eisbruch, Avraham [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Lin, Jin-Ching [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Mai, Hai-Qiang [Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); Zhang, Li [Department of Medical Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); Guo, Ying [Clinical Trials Centre, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); Lin, Ai-Hua [Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou (China); Sun, Ying [Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); and others

2017-05-01

Purpose: To comprehensively assess the reporting quality of randomized, controlled trials (RCTs) in nasopharyngeal carcinoma (NPC), and to identify significant predictors of quality. Methods and Materials: Two investigators searched MEDLINE and EMBASE for RCTs published between January 1988 and December 2015 that assessed the effect of combined chemoradiotherapy for NPC. The overall quality of each report was assessed using a 28-point overall quality score (OQS) based on the 2010 Consolidated Standards of Reporting Trials (CONSORT) statement. To provide baseline data for further evaluation, we also investigated the reporting quality of certain important issues in detail, including key methodologic items (allocation concealment, blinding, intention-to-treat principle), endpoints, follow-up, subgroup analyses, and adverse events. Results: We retrieved 24 relevant RCTs including 6591 patients. Median 2010 OQS was 15.5 (range, 10-24). Half of the items in the 2010 OQS were poorly reported in at least 40% of trials. Multivariable regression models revealed that publication after 2010 and high impact factor were significant predictors of improved 2010 OQS. Additionally, many issues that we consider significant were not reported adequately. Conclusions: Despite publication of the CONSORT statement more than a decade ago, overall reporting quality for RCTs in NPC was unsatisfactory. Additionally, substantial selectivity and heterogeneity exists in reporting of certain crucial issues. This survey provides the first prompt for NPC trial investigators to improve reporting quality according to the CONSORT statement; increased scrutiny and diligence by editors and peer reviewers is also required.

Combined Acupuncture and Auriculotherapy in Burning Mouth Syndrome Treatment: A Preliminary Single-Arm Clinical Trial.

Science.gov (United States)

Franco, Faraína Rodrigues Vasconcelos; Castro, Luciano Alberto; Borsatto, Maria Cristina; Silveira, Erika Aparecida; Ribeiro-Rotta, Rejane Faria

2017-02-01

Burning mouth syndrome (BMS) is a chronic pain disorder that is difficult to diagnose and refractory to treatment; it is more prevalent in pre- and postmenopausal women. Acupuncture and auriculotherapy have been suggested as options for the treatment of pain because they promote analgesia and allow for the reduction of symptoms with lower doses of drugs; this leads to greater patient compliance with treatment and has a positive effect on quality of life. Clinical trials investigating the effectiveness of acupuncture in the treatment of BMS are scarce in the literature. To investigate the effect of combined acupuncture and auriculotherapy on pain management and quality of life in patients with BMS. Sixty patients with BMS were subjected to a thorough differential diagnosis. Of these, 12 met the inclusion criteria and agreed to participate. Eight patients completed treatment with acupuncture and auriculotherapy using a previously established protocol. The outcome variables were analyzed before and after treatment: pain/burning (visual analog scale; VAS), salivary flow (unstimulated sialometry), and quality of life (Short-Form Oral Health Impact Profile [OHIP-14]). Two-year follow-up was carried out by assessing VAS and OHIP-14. The intensity of pain/burning decreased significantly after the first treatment sessions, as shown by low values on the VAS (0-2) and a subjective indicator of quality of life (mean = 5.37 ± 3.50). There was no relationship between salivary flow and the intensity of pain/burning. At 2-year follow-up, no statistically significant difference was observed for VAS, but improvement on OHIP-14 was seen. Combined acupuncture/auriculotherapy was effective in reducing the intensity of burning and improving quality of life. There was no relationship between salivary flow and the intensity of burning mouth. Patients' status improved after acupuncture and auriculotherapy at 2-year follow-up.

Relative Bioavailability of Fixed-Dose Combinations of Tamsulosin and Dutasteride: Results From 2 Randomized Trials in Healthy Male Volunteers.

Science.gov (United States)

Burns, Olivia; Zhu, John; Manyak, Michael J; Ravindranath, Ramiya; Koosha, Fariba; Haque, Nazneen; Chung, Sally

2018-05-01

The relative bioavailabilities of dutasteride/tamsulosin hydrochloride 0.5 mg/0.2 mg fixed-dose combination (FDC) capsules compared with coadministered reference products (1 dutasteride 0.5-mg capsule [Avodart ® ] + 1 tamsulosin hydrochloride 0.2-mg orally disintegrating tablet [Harnal D ® ]) were investigated in 2 clinical trials under fasted and fed conditions (ClinicalTrials.gov NCT02184585 and NCT02509104). Both trials were open-label, randomized, single-dose, crossover studies in healthy male adults aged 18-65 years. Trial 1 evaluated 2 formulations (FDC1 and FDC2), and trial 2 evaluated a third formulation (FDC3). The primary end points were dutasteride area under the concentration-time curve from time 0 to t (AUC (0-t) ) and peak plasma concentration (C max ) and tamsulosin AUC (0-∞) , AUC (0-t) , and C max . The formulations were considered to be bioequivalent if the 90%CIs for the geometric mean ratios for each end point were within the range of 0.80-1.25. For FDC1 in trial 1, bioequivalence criteria were not met for dutasteride C max or AUC in the fasted state or for tamsulosin C max in the fasted or fed states. For FDC2 in trial 1, all bioequivalence criteria were met except for tamsulosin C max in the fasted state. For FDC3 in trial 2, bioequivalence criteria were met for all dutasteride and tamsulosin end points in both the fed and fasted states. Safety profiles were similar for all FDC formulations and combination treatments. © 2017, The American College of Clinical Pharmacology.

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

Science.gov (United States)

Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

2018-01-30

It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

The incorporation of marine n-3 PUFA into platelets and adipose tissue in pre- and postmenopausal women: a randomised, double-blind, placebo-controlled trial

DEFF Research Database (Denmark)

Witt, Petra M; Christensen, Jeppe H; Ewertz, Marianne

2010-01-01

The primary aim of the trial was to investigate the influence of menopause on the incorporation of marine n-3 PUFA into platelets and adipose tissue. A secondary aim was to evaluate whether marine n-3 PUFA may change levels of circulating oestrogens in women. Ninety-two pre- and postmenopausal...

Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment

Science.gov (United States)

Gordon, Michael S.; Vocci, Frank J.; Fitzgerald, Terrence T.; O'Grady, Kevin E.; O'Brien, Charles P.

2017-01-01

Background Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases have been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Methods Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. Results We describe the background and rationale for the study, its aims, hypotheses, and study design. Conclusions The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. PMID:28011389

Sufentanil and Bupivacaine Combination versus Bupivacaine Alone for Spinal Anesthesia during Cesarean Delivery: A Meta-Analysis of Randomized Trials

Science.gov (United States)

Yan, Jianqin; Wang, Ruike; Wang, Ying; Xu, Mu

2016-01-01

Objective The addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted. Methods A comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I2 tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg’s funnel plots and Egger’s linear regression test were used to detect any publication bias. Results This study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P bupivacaine-alone group (WMD = −1.0 min, 95% CI −1.5 to −0.58, P Bupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus. PMID:27032092

Single and combined effects of beetroot juice and caffeine supplementation on cycling time trial performance.

Science.gov (United States)

Lane, Stephen C; Hawley, John A; Desbrow, Ben; Jones, Andrew M; Blackwell, James R; Ross, Megan L; Zemski, Adam J; Burke, Louise M

2014-09-01

Both caffeine and beetroot juice have ergogenic effects on endurance cycling performance. We investigated whether there is an additive effect of these supplements on the performance of a cycling time trial (TT) simulating the 2012 London Olympic Games course. Twelve male and 12 female competitive cyclists each completed 4 experimental trials in a double-blind Latin square design. Trials were undertaken with a caffeinated gum (CAFF) (3 mg·kg(-1) body mass (BM), 40 min prior to the TT), concentrated beetroot juice supplementation (BJ) (8.4 mmol of nitrate (NO3(-)), 2 h prior to the TT), caffeine plus beetroot juice (CAFF+BJ), or a control (CONT). Subjects completed the TT (females: 29.35 km; males: 43.83 km) on a laboratory cycle ergometer under conditions of best practice nutrition: following a carbohydrate-rich pre-event meal, with the ingestion of a carbohydrate-electrolyte drink and regular oral carbohydrate contact during the TT. Compared with CONT, power output was significantly enhanced after CAFF+BJ and CAFF (3.0% and 3.9%, respectively, p caffeine (-0.9%, p = 0.4 compared with CAFF). We conclude that caffeine (3 mg·kg(-1) BM) administered in the form of a caffeinated gum increased cycling TT performance lasting ∼50-60 min by ∼3%-4% in both males and females. Beetroot juice supplementation was not ergogenic under the conditions of this study.

A Comparative Investigation of the Combined Effects of Pre-Processing, Wavelength Selection, and Regression Methods on Near-Infrared Calibration Model Performance.

Science.gov (United States)

Wan, Jian; Chen, Yi-Chieh; Morris, A Julian; Thennadil, Suresh N

2017-07-01

Near-infrared (NIR) spectroscopy is being widely used in various fields ranging from pharmaceutics to the food industry for analyzing chemical and physical properties of the substances concerned. Its advantages over other analytical techniques include available physical interpretation of spectral data, nondestructive nature and high speed of measurements, and little or no need for sample preparation. The successful application of NIR spectroscopy relies on three main aspects: pre-processing of spectral data to eliminate nonlinear variations due to temperature, light scattering effects and many others, selection of those wavelengths that contribute useful information, and identification of suitable calibration models using linear/nonlinear regression . Several methods have been developed for each of these three aspects and many comparative studies of different methods exist for an individual aspect or some combinations. However, there is still a lack of comparative studies for the interactions among these three aspects, which can shed light on what role each aspect plays in the calibration and how to combine various methods of each aspect together to obtain the best calibration model. This paper aims to provide such a comparative study based on four benchmark data sets using three typical pre-processing methods, namely, orthogonal signal correction (OSC), extended multiplicative signal correction (EMSC) and optical path-length estimation and correction (OPLEC); two existing wavelength selection methods, namely, stepwise forward selection (SFS) and genetic algorithm optimization combined with partial least squares regression for spectral data (GAPLSSP); four popular regression methods, namely, partial least squares (PLS), least absolute shrinkage and selection operator (LASSO), least squares support vector machine (LS-SVM), and Gaussian process regression (GPR). The comparative study indicates that, in general, pre-processing of spectral data can play a significant

Pre-symptomatic increase in urine-orosomucoid excretion in pre-eclamptic women

DEFF Research Database (Denmark)

Kronborg, Camilla Skovhus; Allen, Jim; Vittinghus, Erik

2007-01-01

, 32 women developed pre-eclampsia, and 5 controls for every case of pre-eclampsia were found. Blood samples were collected 4 times and urine samples 6 times from the 18/19th week and throughout pregnancy. Orosomucoid and albumin in plasma were analysed by standard methods, and in urine by sandwich...... in orosomucoid. In the plasma samples, orosomucoid was significantly higher late in pre-eclamptic pregnancies (>or=36th week, p=0.0275). CONCLUSIONS: Pre-eclampsia is associated with a pre-symptomatic increase in the urine excretion of orosomucoid, and orosomucoid excretion precedes that of albumin. Orosomucoid...... excretion can probably be used as a prognostic tool in combination with other screening methods, and seems to be a more sensitive marker for evolving pre-eclampsia than albumin. Plasma orosomucoid is significantly increased late in pre-eclampsia. Thus, the increased excretion of orosomucoid must primarily...

Combined Pre-Precipitation, Biological Sludge Hydrolysis and Nitrogen Reduction - A Pilot Demonstration of Integrated Nutrient Removal

DEFF Research Database (Denmark)

Kristensen, G. H.; Jørgensen, P. E.; Strube, R.

1992-01-01

solubilization was 10-13% of the suspended COD. The liquid phase of the hydrolyzed sludge, the hydrolysate, was separated from the suspended fraction by centrifugation and added to the biological nitrogen removal stage to support denitrification. The hydrolysate COD consisted mainly of volatile fatty acids......A pilot study was performed to investigate advanced wastewater treatment by pre-precipitation in combination with biological nitrogen removal supported by biological sludge hydrolysis. The influent wastewater was pretreated by addition of a pre-polymerized aluminum salt, followed by flocculation......, resulting in high denitrification rates. Nitrogen reduction was performed based on the Bio-Denitro principle in an activated sludge system. Nitrogen was reduced from 45 mg/l to 9 mg/l and phosphorus was reduced from 11 mg/l to 0.5 mg/l. The sludge yield was low, approx. 0.3-0.4 gCOD/gCOD removed...

Pre-exposure to wheel running disrupts taste aversion conditioning.

Science.gov (United States)

Salvy, Sarah-Jeanne; Pierce, W David; Heth, Donald C; Russell, James C

2002-05-01

When rats are given access to a running wheel after drinking a flavored solution, they subsequently drink less of that flavor solution. It has been suggested that running produces a conditioned taste aversion (CTA). This study explored whether CTA is eliminated by prior exposure to wheel running [i.e., unconditioned stimulus (UCS) pre-exposure effect]. The rats in the experimental group (UW) were allowed to wheel run for 1 h daily for seven consecutive days of pre-exposure. Rats in the two other groups had either access to locked wheels (LW group) or were maintained in their home cages (HC group) during the pre-exposure days. All rats were then exposed to four paired and four unpaired trials using a "ABBAABBA" design. Conditioning trials were composed of one flavored liquid followed by 60-min access to wheel running. For the unpaired trials, rats received a different flavor not followed by the opportunity to run. All rats were then initially tested for water consumption followed by tests of the two flavors (paired or unpaired) in a counterbalanced design. Rats in the UW group show no CTA to the liquid paired with wheel running, whereas LW and HC groups developed CTA. These results indicate that pre-exposure to wheel running (i.e., the UCS), eliminates subsequent CTA.

The Effects of Combinations of Cognitive Impairment and Pre-frailty on Adverse Outcomes from a Prospective Community-Based Cohort Study of Older Chinese People.

Science.gov (United States)

Yu, Ruby; Morley, John E; Kwok, Timothy; Leung, Jason; Cheung, Osbert; Woo, Jean

2018-01-01

To examine how various combinations of cognitive impairment (overall performance and specific domains) and pre-frailty predict risks of adverse outcomes; and to determine whether cognitive frailty may be defined as the combination of cognitive impairment and the presence of pre-frailty. Community-based cohort study. Chinese men and women ( n  = 3,491) aged 65+ without dementia, Parkinson's disease and/or frailty at baseline. Frailty was characterized using the Cardiovascular Health Study criteria. Overall cognitive impairment was defined by a Cantonese Mini-Mental Status Examination (CMMSE) total score (impairment by a CMMSE delayed recall score (impairment by a CMMSE language and praxis score (impaired were more likely to develop pre-frailty/frailty after 4 years ( P  impairment had lower grip strength ( P  without cognitive impairment at baseline. Similar results were obtained with delayed recall and language and praxis impairments. Robust and cognitively impaired participants had higher risks of becoming pre-frail/frail over 4 years compared with those with normal cognition. Cognitive impairment characterized by the CMMSE overall score or its individual domain score improved the predictive power of pre-frailty for poor quality of life, incident physical limitation, increased cumulative hospital stay, and mortality. Our findings support to the concept that cognitive frailty may be defined as the occurrence of both cognitive impairment and pre-frailty, not necessarily progressing to dementia.

Adequacy of clinical trial evidence of metformin fixed-dose combinations for the treatment of type 2 diabetes mellitus in India.

Science.gov (United States)

Evans, Valerie; Roderick, Peter; Pollock, Allyson M

2018-01-01

There is growing national and international concern about the drug regulatory system in India. Parliamentary reports have highlighted the presence of high numbers of unapproved medicines and irrational combinations of both approved and unapproved drugs in the Indian market-place. Fixed-dose combinations (FDCs) are a peculiar feature of the Indian pharmaceutical landscape. Although metformin is a first-line treatment, FDCs for diabetes in India account for two-thirds of all diabetes medicine sales, and some have not been approved by the Central Drugs Standard Control Organization (CDSCO). This study examines the basis of efficacy and safety of top-selling metformin FDCs in India against four WHO criteria from clinical trials guidelines for the approval of FDCs. Data from a commercial drug sales database (PharmaTrac) were combined with searches through published literature, clinical trial registries, and published and unpublished trial websites of metformin FDCs in adults with type 2 diabetes mellitus. Five metformin FDCs in India from November 2011 to October 2012 accounted for 80% of all metformin FDC sales by value and volume. Although all five had obtained CDSCO approval, three had been sold and marketed prior to receiving this approval. Evaluation of published and unpublished clinical trials of these five FDCs found none provided robust evidence of safety and efficacy for the treatment of type 2 diabetes. Recommendations are made for publishing evidence that underpins drug approvals, marketing bans, greater transparency through updated clinical trials databases and legislative reform in order to prevent irrational FDCs from entering the market.

Aiming to increase birth weight: a randomised trial of pre-pregnancy information, advice and counselling in inner-urban Melbourne

Directory of Open Access Journals (Sweden)

Donohue Lisa

2006-12-01

Full Text Available Abstract Background In the 1980s there was substantial interest in early pregnancy and pre-pregnancy interventions to increase birth weight and reduce preterm birth. We developed an inter-pregnancy intervention, implemented in a randomised controlled trial, to be provided by midwives at home soon after women's first birth. Methods MCH nurses invited women to take part during their home visit to new mothers. Women's contact details, with their permission, were passed to the study midwife. She had a randomisation schedule to which women's names were added before she met the women or their partners. All women recruited had a home visit from the study midwife with a discussion of their first pregnancy, labour and birth and the postpartum experience. Women in the intervention arm received in addition a pre-pregnancy intervention with discussion of social, health or lifestyle problems, preparation and timing for pregnancy, family history, rubella immunisation, referrals for health problems, and a reminder card. The primary outcome was defined as a birth weight difference in the second birth of 100 g (one-sided in favour of the intervention. Additional data collected were gestational age, perinatal deaths and birth defects. Analyses used EPI-INFO and STATA. Results Intervention and comparison groups were comparable on socioeconomic factors, prior reproductive history and first birth outcomes. Infant birth weight in the second birth was lower (-97.4 g, among infants in the intervention arm. There were no significant differences between intervention and comparison arms in the proportion of women having a preterm birth, an infant with low birthweight, or an infant with a birth weight th percentile. There were more adverse outcomes in the intervention arm: ten births Conclusion As the primary outcome was envisaged to be either improved birth weight or no effect, the study was not designed to identify the alternative outcome with confidence. Despite

Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

Science.gov (United States)

Schaefer, S M; Süsal, C; Opelz, G; Döhler, B; Becker, L E; Klein, K; Sickmüller, S; Waldherr, R; Macher-Goeppinger, S; Schemmer, P; Beimler, J; Zeier, M; Morath, C

2016-02-01

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Achievement Place: experiments in self-government with pre-delinquents.

Science.gov (United States)

Fixsen, D L; Phillips, E L; Wolf, M M

1973-01-01

One of the goals of many treatment programs for pre-delinquent youths is the development of the skills involved in the democratic decision-making process. At Achievement Place, one aspect of the treatment program is a semi-self-government system whereby the seven pre-delinquent youths can democratically establish many of their own rules of behavior, monitor their peers' behavior to detect violations of their rules, and conduct a "trial" to determine a rule violator's guilt or innocence, and to determine the consequences for a youth who violates a rule. Two experiments were carried out to determine the role of some of the procedures in the boys' participation in the self-government system. Experiment I showed that more boys participated in the discussion of consequences for a rule violation when they had complete responsibility for setting the consequence during the trials than when the teaching-parents set the consequence for each rule violation before the trial. An analysis of the rule violations in this experiment indicated that the boys in Achievement Place reported more of the rule violations that resulted in trials than reported by the teaching-parents or school personnel. The boys reported rule violations that occurred in the community and school as well as at Achievement Place, including most of the serious rule violations that came to the attention of the teaching-parents. In Experiment II, the results indicated that more trials were called when the teaching-parents were responsible for calling trials on rule violations reported by the peers than when the boys were responsible for calling trials. When the youths earned points for calling trials the average number of trials per day increased, but more trivial rule violations were reported. These results suggest that aspects of the democratic decision-making process in a small group of pre-delinquents can be studied and variables that affect participation can be identified and evaluated.

Cost-effectiveness analysis of a communication-focused therapy for pre-school children with autism: results from a randomised controlled trial.

Science.gov (United States)

Byford, Sarah; Cary, Maria; Barrett, Barbara; Aldred, Catherine R; Charman, Tony; Howlin, Patricia; Hudry, Kristelle; Leadbitter, Kathy; Le Couteur, Ann; McConachie, Helen; Pickles, Andrew; Slonims, Vicky; Temple, Kathryn J; Green, Jonathan

2015-12-21

Autism is associated with impairments that have life-time consequences for diagnosed individuals and a substantial impact on families. There is growing interest in early interventions for children with autism, yet despite the substantial economic burden, there is little evidence of the cost-effectiveness of such interventions with which to support resource allocation decisions. This study reports an economic evaluation of a parent-mediated, communication-focused therapy carried out within the Pre-School Autism Communication Trial (PACT). 152 pre-school children with autism were randomly assigned to treatment as usual (TAU) or PACT + TAU. Primary outcome was severity of autism symptoms at 13-month follow-up. Economic data included health, education and social services, childcare, parental productivity losses and informal care. Clinically meaningful symptom improvement was evident for 53 % of PACT + TAU versus 41 % of TAU (odds ratio 1.91, p = 0.074). Service costs were significantly higher for PACT + TAU (mean difference £4,489, p < 0.001), but the difference in societal costs was smaller and non-significant (mean difference £1,385, p = 0.788) due to lower informal care rates for PACT + TAU. Improvements in outcome generated by PACT come at a cost. Although this cost is lower when burden on parents is included, the cost and effectiveness results presented do not support the cost-effectiveness of PACT + TAU compared to TAU alone. Current Controlled Trials ISRCTN58133827.

Aristotelian pre-Socratics, A glance at Aristotle's Narrative from pre-Socratics

OpenAIRE

Mehdi Qavam Safari; M.B Ghomi

2015-01-01

In this article, it's tried to study Aristotle's narrative of  pre-Socratics on the base of Aristotle's texts and mainly using  metaphysics, physics, genesis and decadence books. It is also tried to show how Aristotle has interpreted all the pre-Socratics in one way and on the base of his own philosophy framework. He interprets pre-Socratic Arche as an element that means comprehensive matter which is nothing itself, but everything is combination of it and even considers that as substance and ...

Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial

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Mordi, Natalie A; Mordi, Ify R; Singh, Jagdeep S; Baig, Fatima; Choy, Anna-Maria; McCrimmon, Rory J; Struthers, Allan D; Lang, Chim C

2017-01-01

Introduction Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium–glucose cotransporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters. The effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may underlie the cardiovascular and renal benefits demonstrated in the recent EMPA-REG study. Methods and analysis To assess the effect of SGLT2 inhibitors when used in combination with a loop diuretic, the RECEDE-CHF (Renal and Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure) trial is a single-centre, randomised, double-blind, placebo-controlled, cross-over trial conducted in a secondary care setting within NHS Tayside, Scotland. 34 eligible participants, aged between 18 and 80 years, with stable T2D and CHF will be recruited. Renal physiological testing will be performed at two points (week 1 and week 6) on each arm to assess the effect of 25 mg empagliflozin, on the primary and secondary outcomes. Participants will be enrolled in the trial for a total period between 14 and 16 weeks. The primary outcome will assess the effect of empagliflozin versus placebo on urine output. The secondary outcomes are to assess the effect of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium excretion, urinary protein/creatinine ratio and urinary albumin/creatinine ratio when compared with placebo. Ethics and dissemination Ethics approval was obtained by the East of Scotland Research Ethics Service. Results of the trial will be submitted for publication in a peer

Pre-task music improves swimming performance.

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Smirmaul, B P; Dos Santos, R V; Da Silva Neto, L V

2015-12-01

The purpose of this study was to investigate the effects of pre-task music on swimming performance and other psychological variables. A randomized counterbalanced within-subjects (experimental and control condition) design was employed. Eighteen regional level male swimmers performed two 200-m freestyle swimming time trials. Participants were exposed to either 5 minutes of self-selected music (pre-task music condition) or 5 minutes of silence (control condition) and, after 1 minute, performed the swimming task. Swimming time was significantly shorter (-1.44%) in the pre-task music condition. Listening to pre-task music increased motivation to perform the swimming task, while arousal remained unchanged. While fatigue increased after the swimming task in both conditions, vigor, ratings of perceived exertion and affective valence were unaltered. It is concluded, for the first time, that pre-task music improves swimming performance.

Assessment of a Standardized Pre-Operative Telephone Checklist Designed to Avoid Late Cancellation of Ambulatory Surgery: The AMBUPROG Multicenter Randomized Controlled Trial.

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Sonia Gaucher

Full Text Available To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial.Multicenter, two-arm, parallel-group, open-label randomized controlled trial.11 university hospital ambulatory surgery units in Paris, France.Patients scheduled for ambulatory surgery and able to be reached by telephone.A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults, was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone.Rate of cancellation on the day of surgery or the day before.The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6% vs. 113 (5.8%, adjusted odds ratio [95% confidence interval] = 0.91 [0.65-1.29], (p = 0.57. Checklist administration revealed that 355 patients (28.0% had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0% still had questions concerning the fasting state.A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes.ClinicalTrials.gov NCT01732159.

Involving older people in a multi-centre randomised trial of a complex intervention in pre-hospital emergency care: implementation of a collaborative model.

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Koniotou, Marina; Evans, Bridie Angela; Chatters, Robin; Fothergill, Rachael; Garnsworthy, Christopher; Gaze, Sarah; Halter, Mary; Mason, Suzanne; Peconi, Julie; Porter, Alison; Siriwardena, A Niroshan; Toghill, Alun; Snooks, Helen

2015-07-10

Health services research is expected to involve service users as active partners in the research process, but few examples report how this has been achieved in practice in trials. We implemented a model to involve service users in a multi-centre randomised controlled trial in pre-hospital emergency care. We used the generic Standard Operating Procedure (SOP) from our Clinical Trials Unit (CTU) as the basis for creating a model to fit the context and population of the SAFER 2 trial. In our model, we planned to involve service users at all stages in the trial through decision-making forums at 3 levels: 1) strategic; 2) site (e.g. Wales; London; East Midlands); 3) local. We linked with charities and community groups to recruit people with experience of our study population. We collected notes of meetings alongside other documentary evidence such as attendance records and study documentation to track how we implemented our model. We involved service users at strategic, site and local level. We also added additional strategic level forums (Task and Finish Groups and Writing Days) where we included service users. Service user involvement varied in frequency and type across meetings, research stages and locations but stabilised and increased as the trial progressed. Involving service users in the SAFER 2 trial showed how it is feasible and achievable for patients, carers and potential patients sharing the demographic characteristics of our study population to collaborate in a multi-centre trial at the level which suited their health, location, skills and expertise. A standard model of involvement can be tailored by adopting a flexible approach to take account of the context and complexities of a multi-site trial. Current Controlled Trials ISRCTN60481756. Registered: 13 March 2009.

A comprehensive combined experimental and computational framework for pre-clinical wear simulation of total knee replacements.

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Abdelgaied, A; Fisher, J; Jennings, L M

2018-02-01

A more robust pre-clinical wear simulation framework is required in order to simulate wider and higher ranges of activities, observed in different patient populations such as younger more active patients. Such a framework will help to understand and address the reported higher failure rates for younger and more active patients (National_Joint_Registry, 2016). The current study has developed and validated a comprehensive combined experimental and computational framework for pre-clinical wear simulation of total knee replacements (TKR). The input mechanical (elastic modulus and Poisson's ratio) and wear parameters of the moderately cross-linked ultra-high molecular weight polyethylene (UHMWPE) bearing material were independently measured from experimental studies under realistic test conditions, similar to the loading conditions found in the total knee replacements. The wear predictions from the computational wear simulation were validated against the direct experimental wear measurements for size 3 Sigma curved total knee replacements (DePuy, UK) in an independent experimental wear simulation study under three different daily activities; walking, deep squat, and stairs ascending kinematic conditions. The measured compressive mechanical properties of the moderately cross-linked UHMWPE material were more than 20% lower than that reported in the literature under tensile test conditions. The pin-on-plate wear coefficient of moderately cross-linked UHMWPE was significantly dependant of the contact stress and the degree of cross-shear at the articulating surfaces. The computational wear predictions for the TKR from the current framework were consistent and in a good agreement with the independent full TKR experimental wear simulation measurements, with 0.94 coefficient of determination of the framework. In addition, the comprehensive combined experimental and computational framework was able to explain the complex experimental wear trends from the three different daily

“Pre-schoolers in the playground” an outdoor physical activity intervention for children aged 18 months to 4 years old: study protocol for a pilot cluster randomised controlled trial

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2013-01-01

Background The pre-school years are considered critical for establishing healthy lifestyle behaviours such as physical activity. Levels of physical activity track through childhood into adulthood, thus establishing habitual physical activity early in life is vital. Time spent outdoors is associated with greater physical activity and playground interventions have been shown to increase physical activity in school aged children. There are few pre-school, playground-based interventions, and evaluations of these have found mixed results. A recent report published by the UK Chief Medical Officer (CMO) highlighted that new interventions to promote movement in the early years (0–5 years old) are needed. The aim of this study is to undertake a pilot cluster randomised controlled trial (RCT) of an outdoor playground-based physical activity intervention for parents and their children aged 18 months to 4 years old (“Pre-schoolers in the Playground”; PiP) and to assess the feasibility of conducting a full scale cluster RCT. The PiP intervention is grounded in behavioural theory (Social Cognitive Theory), and is in accordance with the CMO guidance for physical activity in the early years. It is informed by existing literature and data collected from focus groups with parents. Methods/Design One hundred and fifty pre-school children affiliated to 10 primary schools will be recruited. Schools will be randomised to either the PiP intervention arm or the control arm (usual practice). Children in the intervention arm will be invited to attend three 30 minute outdoor play sessions per week for 30 weeks (3 school terms) at the school. Feasibility will be assessed by examining recruitment rates, attendance, attrition, acceptability of the trial and of the PiP intervention to parents, fidelity of intervention implementation, capability and capacity for schools to deliver the intervention. Health outcomes and the feasibility of outcome measurement tools will be assessed. These

Pre-hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug administration In Cardiac arrest (PARAMEDIC-2): Trial protocol.

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Perkins, Gavin D; Quinn, Tom; Deakin, Charles D; Nolan, Jerry P; Lall, Ranjit; Slowther, Anne-Marie; Cooke, Matthew; Lamb, Sarah E; Petrou, Stavros; Achana, Felix; Finn, Judith; Jacobs, Ian G; Carson, Andrew; Smyth, Mike; Han, Kyee; Byers, Sonia; Rees, Nigel; Whitfield, Richard; Moore, Fionna; Fothergill, Rachael; Stallard, Nigel; Long, John; Hennings, Susie; Horton, Jessica; Kaye, Charlotte; Gates, Simon

2016-11-01

Despite its use since the 1960s, the safety or effectiveness of adrenaline as a treatment for cardiac arrest has never been comprehensively evaluated in a clinical trial. Although most studies have found that adrenaline increases the chance of return of spontaneous circulation for short periods, many studies found harmful effects on the brain and raise concern that adrenaline may reduce overall survival and/or good neurological outcome. The PARAMEDIC-2 trial seeks to determine if adrenaline is safe and effective in out-of-hospital cardiac arrest. This is a pragmatic, individually randomised, double blind, controlled trial with a parallel economic evaluation. Participants will be eligible if they are in cardiac arrest in the out-of-hospital environment and advanced life support is initiated. Exclusions are cardiac arrest as a result of anaphylaxis or life threatening asthma, and patient known or appearing to be under 16 or pregnant. 8000 participants treated by 5 UK ambulance services will be randomised between December 2014 and August 2017 to adrenaline (intervention) or placebo (control) through opening pre-randomised drug packs. Clinical outcomes are survival to 30 days (primary outcome), hospital discharge, 3, 6 and 12 months, health related quality of life, and neurological and cognitive outcomes (secondary outcomes). Trial registration (ISRCTN73485024). Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

Day care for pre-school children.

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Zoritch, B; Roberts, I; Oakley, A

2000-01-01

The debate about how, where and by whom young children should be looked after is one which has occupied much social policy and media attention in recent years. Mothers undertake most of the care of young children. Internationally, out-of-home day-care provision ranges widely. These different levels of provision are not simply a response to different levels of demand for day-care, but reflect cultural and economic interests concerning the welfare of children, the need to promote mothers' participation in paid work, and the importance of socialising children into society's values. At a time when a decline in family values is held responsible for a range of social problems, the day-care debate has a special prominence. To quantify the effects of out-of-home day-care for preschool children on educational, health and welfare outcomes for children and their families. Randomised controlled trials of day-care for pre-school children were identified using electronic databases, hand searches of relevant literature, and contact with authors. Studies were included in the review if the intervention involved the provision of non-parental day care for children under 5 years of age, and the evaluation design was that of a randomised or quasi-randomised controlled trial. A total of eight trials were identified after examining 920 abstracts and 19 books. The trials were assessed for methodological quality. Day-care increases children's IQ, and has beneficial effects on behavioural development and school achievement. Long-term follow up demonstrates increased employment, lower teenage pregnancy rates, higher socio-economic status and decreased criminal behaviour. There are positive effects on mothers' education, employment and interaction with children. Effects on fathers have not been examined. Few studies look at a range of outcomes spanning the health, education and welfare domains. Most of the trials combined non-parental day-care with some element of parent training or education

Combination therapy versus gemcitabine monotherapy in the treatment of elderly pancreatic cancer: a meta-analysis of randomized controlled trials

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Jin JM

2018-03-01

Full Text Available Jiamin Jin, Chunbo Teng, Tao Li College of Life Science, Northeast Forestry University, Harbin, China Purpose: We aimed to compare the efficacy of combination therapy versus gemcitabine monotherapy in the treatment of elderly pancreatic cancer (PC by using a meta-analysis.Materials and methods: Databases were searched to identify relevant clinical trials. Hazard ratios (HRs were used to estimate overall survival (OS and progression-free survival (PFS. Statistical analyses were conducted by using Comprehensive Meta Analysis software (version 2.0.Results: A total of 3,401 elderly PC patients from six randomized controlled trials were included for analysis. In comparison with gemcitabine alone, combination therapy in elderly PC patients did not significantly improve OS (HR 0.93, 95% CI: 0.82–1.06, p=0.29. Sub-group analysis according to treatment regimens showed that combined chemotherapy significantly improved OS in comparison with gemcitabine alone (HR 0.73, 95% CI: 0.56–0.94, p=0.016, while gemcitabine plus targeted agents did not improve OS (HR 1.02, 95% CI: 0.87–1.19, p=0.83. Additionally, gemcitabine plus nab-paclitaxel significantly improved PFS in elderly PC patients (HR 0.69, 95% CI: 0.52–0.91, p=0.009 in comparison with gemcitabine alone. No publication bias was detected by Begg’s and Egger’s tests for OS.Conclusion: The findings of this study suggest that combined chemotherapy, but not for gemcitabine plus targeted agents, could be recommended for elderly PC patients due to its survival benefits. Further studies are still needed to assess the treatment tolerance of combination chemotherapy in these patient populations. Keywords: pancreatic cancer, elderly, randomized controlled trials, meta-analysis, targeted agents

Optimized production of vanillin from green vanilla pods by enzyme-assisted extraction combined with pre-freezing and thawing.

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Zhang, Yanjun; Mo, Limei; Chen, Feng; Lu, Minquan; Dong, Wenjiang; Wang, Qinghuang; Xu, Fei; Gu, Fenglin

2014-02-19

Production of vanillin from natural green vanilla pods was carried out by enzyme-assisted extraction combined with pre-freezing and thawing. In the first step the green vanilla pods were pre-frozen and then thawed to destroy cellular compartmentation. In the second step pectinase from Aspergillus niger was used to hydrolyze the pectin between the glucovanillin substrate and β-glucosidase. Four main variables, including enzyme amount, reaction temperature, time and pH, which were of significance for the vanillin content were studied and a central composite design (CCD) based on the results of a single-factor tests was used. Response surface methodology based on CCD was employed to optimize the combination of enzyme amount, reaction temperature, time, and pH for maximum vanillin production. This resulted in the optimal condition in regards of the enzyme amount, reaction temperature, time, and pH at 84.2 mg, 49.5 °C, 7.1 h, and 4.2, respectively. Under the optimal condition, the experimental yield of vanillin was 4.63% ± 0.11% (dwb), which was in good agreement with the value predicted by the model. Compared to the traditional curing process (1.98%) and viscozyme extract (2.36%), the optimized method for the vanillin production significantly increased the yield by 133.85% and 96%, respectively.

Combination of perindopril/indapamide in secondary prevention of stroke and other vascular events: A combined analysis of ADVANCE, PROGRESS and HYVET trials

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Sougat Sourendra Sarkar

2011-03-01

Full Text Available Perindopril/indapamide combination has been shown to reduce cardiovascular risk in different groups of patients. A total of 18,529 patients (9,272 receiving perindopril/indapamide and 9,257 receiving placebo were included in this meta-analysis involving three large randomized clinical trials-ADVANCE, PROGRESS and HYVET. A non-significant reduction in fatal and non-fatal stroke was seen (Odds ratio 0.73; 95% Confidence Interval 0.49 to 1.09; z=1.52 and p= 0.13. The combination was associated with a significantly reduction of vascular death (Odds ratio 0.79; 95% Confidence Interval 0.69 to 0.90; z=3.48 and p=0.0005 and major cardio-vascular events (Odds ratio 0.72; 95% Confidence Interval 0.53 to 0.97; z=2.15 and p= 0.03. Fixed-combination of Perindopril and indapamide substantially reduced major cardiovascular event and vascular death. However, effect on stroke needs further evaluation.

Combination contraceptives: effects on weight.

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Gallo, Maria F; Lopez, Laureen M; Grimes, David A; Carayon, Florence; Schulz, Kenneth F; Helmerhorst, Frans M

2014-01-29

Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. In November 2013, we searched the computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS for studies of combination contraceptives, as well as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). For the initial review, we also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length. All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan. A second author verified the data entered. For continuous data, we calculated the mean difference and 95% confidence interval (CI) for the mean change in weight between baseline and post-treatment measurements using a fixed-effect model. For categorical data, such as the proportion of women who gained or lost more than a specified amount of weight, the Peto odds ratio with 95% CI was calculated. We found 49 trials that met our inclusion criteria. The trials included 85 weight change comparisons for 52 distinct contraceptive pairs (or placebos). The four trials with a placebo or no intervention group did not find

The effect of pre-travel advice on sexual risk behavior abroad: a systematic review.

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Croughs, Mieke; Remmen, Roy; Van den Ende, Jef

2014-01-01

Travelers often have casual sex abroad and the risk of acquiring a sexually transmitted infection (STI) associated with casual travel sex is considered to be threefold higher compared to the risk of casual sex in the home country. Consequently, international guidelines recommend including STI advice in the pre-travel consultation. We performed a systematic review on the effect of a pre-travel STI intervention on sexual risk behavior abroad. In September 2012, a systematic analysis and meta-analysis of peer reviewed literature were performed on the relation between pre-travel STI advice for travelers and sexual risk behavior abroad. Primary outcome measure consisted of the number of travelers with a new sexual partner abroad; secondary outcome measure entailed the proportion of consistent condom use. Six studies were identified for inclusion in the review, of which three clinical trials on the effect of a motivational intervention compared to standard pre-travel STI advice qualified for the meta-analysis. Two of these trials were performed in US marines deployed abroad and one in visitors of a travel clinic. The extensive motivational training program of the marines led to a reduction in sexual risk behavior, while the brief motivational intervention in the travel clinic was not superior to standard advice. The meta-analysis established no overall effect on risk behavior abroad. No clinical trials on the effect of a standard pre-travel STI discussion were found, but a cohort study reported that no relation was found between the recall of a nonstructured pre-travel STI discussion and sexual risk behavior, while the recall of reading the STI information appeared to be related to more consistent condom use. Motivational pre-travel STI intervention was not found to be superior to standard STI advice, while no clinical trials on the effect of standard pre-travel STI advice were found. © 2013 International Society of Travel Medicine.

Electroacupuncture and Rosiglitazone Combined Therapy as a Means of Treating Insulin Resistance and Type 2 Diabetes Mellitus: A Randomized Controlled Trial

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Rong-Tsung Lin

2013-01-01

Full Text Available Aims. To evaluate the efficacy of rosiglitazone (TZD and electroacupuncture (EA combined therapy as a treatment for type 2 diabetes mellitus (T2DM patients by randomized single-blind placebo controlled clinical trial. Methods. A total of 31 newly diagnostic T2DM patients, who fulfilled the study's eligibility criteria, were recruited. The individuals were randomly assigned into two groups, the control group (TZD, N=15 and the experimental group (TZD + EA, N=16. Changes in their plasma free fatty acid (FFA, glucose, and insulin levels, together with their homeostasis model assessment (HOMA indices, were statistically compared before and after treatment. Hypoglycemic activity (% was also compared between these two groups. Results. There was no significant difference in hypoglycemic activity between the TZD and TZD + EA group. The effectiveness of the combined therapy seems to derive from an improvement in insulin resistance and a significant lowering of the secreted insulin rather than the effect of TZD alone on T2DM. The combined treatment had no significant adverse effects. A lower plasma FFA concentration is likely to be the mechanism that causes this effect. Conclusion. This combined therapy seems to suppress endogenous insulin secretion by improving insulin resistance via a mechanism involving a reduction in plasma FFA. This trial is registered with ClinicalTrials.gov NCT01577095.

A combined group treatment for nightmares and insomnia in combat veterans: a pilot study.

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Swanson, Leslie M; Favorite, Todd K; Horin, Elizabeth; Arnedt, J Todd

2009-12-01

Insomnia and nightmares are hallmarks of posttraumatic stress disorder (PTSD). Sleep disturbances in PTSD negatively impact clinical course and functioning. In this open clinical trial, the preliminary effects of a combined treatment for insomnia and nightmares in combat veterans with PTSD were assessed. Ten combat veterans participated in a 10-session group treatment combining cognitive-behavioral therapy for insomnia with exposure, rescripting, and relaxation therapy. Participants maintained daily sleep and dream diaries and completed self-report measures of sleep quality and PTSD symptoms pre- and posttreatment. Participants reported improvements in sleep and nightmares following treatment. Future research using controlled designs to evaluate this treatment is warranted.

Benefits of combining inspiratory muscle with 'whole muscle' training in children with cystic fibrosis: a randomised controlled trial

NARCIS (Netherlands)

Santana-Sosa, Elena; Gonzalez-Saiz, Laura; Groeneveld, Iris F.; Villa-Asensi, José R.; Barrio Gómez de Aguero, María I.; Fleck, Steven J.; López-Mojares, Luis M.; Pérez, Margarita; Lucia, Alejandro

2014-01-01

The purpose of this study (randomised controlled trial) was to assess the effects of an 8-week combined 'whole muscle' (resistance+aerobic) and inspiratory muscle training (IMT) on lung volume, inspiratory muscle strength (PImax) and cardiorespiratory fitness (VO2 peak) (primary outcomes), and

Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial.

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Garcia, Hector H; Gonzales, Isidro; Lescano, Andres G; Bustos, Javier A; Zimic, Mirko; Escalante, Diego; Saavedra, Herbert; Gavidia, Martin; Rodriguez, Lourdes; Najar, Enrique; Umeres, Hugo; Pretell, E Javier

2014-08-01

Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10-2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87-2·38, p=0·151). No significant differences in adverse

Randomized combined modality trial in small cell carcinoma of the lung

International Nuclear Information System (INIS)

Maurer, L.H.; Tulloh, M.; Weiss, R.B.; Blom, J.; Leone, L.; Glidewell, O.; Pajak, T.F.

1980-01-01

A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR, and high-dose MTX with citrovorum rescue), and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also randomized: (1) to determine the effects of prophylactic whole brain irradiation; (2) to establish the effects of maintenance chemotherapy. Survival, frequency of response, and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum, and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (48% vs 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic whole brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival

Combined metformin-clomiphene in clomiphene-resistant polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.

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Abu Hashim, Hatem; Foda, Osama; Ghayaty, Essam

2015-09-01

Our objective was to compare the effectiveness of metformin plus clomiphene citrate vs. gonadotrophins, laparoscopic ovarian diathermy, aromatase inhibitors, N-acetyl-cysteine and other insulin sensitizers+clomiphene for improving fertility outcomes in women with clomiphene-resistant polycystic ovary syndrome. PubMed, SCOPUS and CENTRAL databases were searched until April 2014 with the key words: PCOS, polycystic ovary syndrome, metformin, clomiphene citrate, ovulation induction and pregnancy. The search was limited to articles conducted with humans and published in English. The PRISMA statement was followed. Twelve randomized controlled trials (n = 1411 women) were included. Ovulation and clinical pregnancy rates per woman randomized. Compared with gonadotrophins, the metformin+clomiphene combination resulted in significantly fewer ovulations (odds ratio 0.25; 95% confidence interval 0.15-0.41; p < 0.00001, 3 trials, I(2) = 85%, n = 323) and pregnancies (odds ratio 0.45; 95% confidence interval 0.27-0.75; p = 0.002, 3 trials, I(2) = 0%, n = 323). No significant differences were found when metformin+clomiphene was compared with laparoscopic ovarian diathermy (odds ratio 0.88; 95% confidence interval 0.53-1.47; p = 0.62, 1 trial, n = 282; odds ratio 0.96; 95% confidence interval 0.60-1.54; p = 0.88, 2 trials, I(2) = 0%, n = 332, for ovulation and pregnancy rates, respectively). Likewise, no differences were observed in comparison with aromatase inhibitors (odds ratio 0.88; 95% confidence interval 0.58-1.34; p = 0.55, 3 trials, I(2) = 3%, n = 409; odds ratio 0.85; 95% confidence interval 0.53-1.36; p = 0.50, 2 trials, n = 309, for ovulation and pregnancy rates, respectively). There is evidence for the superiority of gonadotrophins, but the metformin+clomiphene combination is mainly relevant for clomiphene-resistant polycystic ovary syndrome patients and, if not effective, a next step could be gonadotrophins. More attempts with metformin+clomiphene are only relevant

"Pre-schoolers in the playground" an outdoor physical activity intervention for children aged 18 months to 4 years old: study protocol for a pilot cluster randomised controlled trial.

Science.gov (United States)

Barber, Sally E; Jackson, Cath; Akhtar, Shaheen; Bingham, Daniel D; Ainsworth, Hannah; Hewitt, Catherine; Richardson, Gerry; Summerbell, Carolyn D; Pickett, Kate E; Moore, Helen J; Routen, Ash C; O'Malley, Claire L; Brierley, Shirley; Wright, John

2013-10-09

The pre-school years are considered critical for establishing healthy lifestyle behaviours such as physical activity. Levels of physical activity track through childhood into adulthood, thus establishing habitual physical activity early in life is vital. Time spent outdoors is associated with greater physical activity and playground interventions have been shown to increase physical activity in school aged children. There are few pre-school, playground-based interventions, and evaluations of these have found mixed results. A recent report published by the UK Chief Medical Officer (CMO) highlighted that new interventions to promote movement in the early years (0-5 years old) are needed. The aim of this study is to undertake a pilot cluster randomised controlled trial (RCT) of an outdoor playground-based physical activity intervention for parents and their children aged 18 months to 4 years old ("Pre-schoolers in the Playground"; PiP) and to assess the feasibility of conducting a full scale cluster RCT. The PiP intervention is grounded in behavioural theory (Social Cognitive Theory), and is in accordance with the CMO guidance for physical activity in the early years. It is informed by existing literature and data collected from focus groups with parents. One hundred and fifty pre-school children affiliated to 10 primary schools will be recruited. Schools will be randomised to either the PiP intervention arm or the control arm (usual practice). Children in the intervention arm will be invited to attend three 30 minute outdoor play sessions per week for 30 weeks (3 school terms) at the school. Feasibility will be assessed by examining recruitment rates, attendance, attrition, acceptability of the trial and of the PiP intervention to parents, fidelity of intervention implementation, capability and capacity for schools to deliver the intervention. Health outcomes and the feasibility of outcome measurement tools will be assessed. These include physical activity via

8 CFR 1212.12 - Parole determinations and revocations respecting Mariel Cubans.

Science.gov (United States)

2010-01-01

... recommendation that the detainee be released on parole or scheduled for a personal interview. (ii) Personal interview. If a recommendation to grant parole after only a record review is not accepted or if the detainee is not recommended for release, a Panel shall personally interview the detainee. The scheduling of...

8 CFR 212.12 - Parole determinations and revocations respecting Mariel Cubans.

Science.gov (United States)

2010-01-01

... recommendation that the detainee be released on parole or scheduled for a personal interview. (ii) Personal interview. If a recommendation to grant parole after only a record review is not accepted or if the detainee is not recommended for release, a Panel shall personally interview the detainee. The scheduling of...

Aristotelian pre-Socratics, A glance at Aristotle's Narrative from pre-Socratics

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Mehdi Qavam Safari

2015-02-01

Full Text Available In this article, it's tried to study Aristotle's narrative of  pre-Socratics on the base of Aristotle's texts and mainly using  metaphysics, physics, genesis and decadence books. It is also tried to show how Aristotle has interpreted all the pre-Socratics in one way and on the base of his own philosophy framework. He interprets pre-Socratic Arche as an element that means comprehensive matter which is nothing itself, but everything is combination of it and even considers that as substance and the other things as accident. He interprets the distinction of Arche and other things on the basis of this contrast in his philosophy. Aristotle, also analyzes pre-Socratics' viewpoint to change on the base of his distinction among change, genesis and corruption. All these cases show that Aristotle has interpreted the pre-Socratics on the basis of his thought, as Aristotelians. On this basis, since Aristotle's thoughts are the first and the most important sources of pre-Socratic philosophy, Aristotle's role should be considered in studies.

Passing the Baton: Community-based ethnography to design a randomized clinical trial on the effectiveness of oral pre-exposure prophylaxis for HIV prevention among Black men who have sex with men

OpenAIRE

Garcia, Jonathan; Colson, Paul W.; Parker, Caroline; Hirsch, Jennifer S.

2015-01-01

Although HIV interventions and clinical trials increasingly report the use of mixed methods, studies have not reported on the process through which ethnographic or qualitative findings are incorporated into RCT designs. We conducted a community-based ethnography on social and structural factors that may affect the acceptance of and adherence to oral pre-exposure prophylaxis (PrEP) among Black men who have sex with men (BMSM). We then devised the treatment arm of an adherence clinical trial dr...

Pre- and Post-Trial Equality in Criminal Justice in the Context of the Separation of Powers

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L Wolf

2011-08-01

Full Text Available The previous Westminster criminal justice system entailed a different kind of separation of powers insofar as it concerns the role of state prosecutors. In the Westminster system prosecutors are part of the executive branch, whereas they were a split-off from the judiciary in constitutional states and function like a de facto second organ of the third branch of state power. Currently executive interference in state prosecutions often leads to pre-trial inequality. A further difficulty arises from the unconsidered manner in which the former royal prerogative of pardoning was retained in the Constitution of the Republic of South Africa, 1996. It used to be a royal veto of judicial sentences in the constitutional monarchy of the former Westminster model. Although the corresponding veto of parliamentary legislation by the head of state did not survive into modern times, the pardoning power has not been discontinued. Section 84(2(j thus causes an irreconcilable conflict with section 165(5 of the Constitution which guarantees the legally binding force of judicial decisions. It undermines the rule of law and leads to post-trial inequality in the execution of sentences. The parole system, which dates back to 1959, likewise allows the executive to overrule judicial sentences and is in conflict with section 165(5. The perpetuation of the status quo in criminal justice is in effect leading to a re-Westminstering of the constitutional state.

Optimized Production of Vanillin from Green Vanilla Pods by Enzyme-Assisted Extraction Combined with Pre-Freezing and Thawing

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Yanjun Zhang

2014-02-01

Full Text Available Production of vanillin from natural green vanilla pods was carried out by enzyme-assisted extraction combined with pre-freezing and thawing. In the first step the green vanilla pods were pre-frozen and then thawed to destroy cellular compartmentation. In the second step pectinase from Aspergillus niger was used to hydrolyze the pectin between the glucovanillin substrate and β-glucosidase. Four main variables, including enzyme amount, reaction temperature, time and pH, which were of significance for the vanillin content were studied and a central composite design (CCD based on the results of a single-factor tests was used. Response surface methodology based on CCD was employed to optimize the combination of enzyme amount, reaction temperature, time, and pH for maximum vanillin production. This resulted in the optimal condition in regards of the enzyme amount, reaction temperature, time, and pH at 84.2 mg, 49.5 °C, 7.1 h, and 4.2, respectively. Under the optimal condition, the experimental yield of vanillin was 4.63% ± 0.11% (dwb, which was in good agreement with the value predicted by the model. Compared to the traditional curing process (1.98% and viscozyme extract (2.36%, the optimized method for the vanillin production significantly increased the yield by 133.85% and 96%, respectively.

Serum levels of bupivacaine after pre-peritoneal bolus vs. epidural bolus injection for analgesia in abdominal surgery: A safety study within a randomized controlled trial.

Science.gov (United States)

Mungroop, Timothy H; van Samkar, Ganapathy; Geerts, Bart F; van Dieren, Susan; Besselink, Marc G; Veelo, Denise P; Lirk, Philipp

2017-01-01

Continuous wound infiltration (CWI) has become increasingly popular in recent years as an alternative to epidural analgesia. As catheters are not placed until the end of surgery, more intraoperative opioid analgesics might be needed. We, therefore, added a single pre-peritoneal bolus of bupivacaine at the start of laparotomy, similar to the bolus given with epidural analgesia. This was a comparative study within a randomized controlled trial (NTR4948). Patients undergoing hepato-pancreato-biliary surgery received either a pre-peritoneal bolus of 30ml bupivacaine 0.25%, or an epidural bolus of 10ml bupivacaine 0.25% at the start of laparotomy. In a subgroup of patients, we sampled blood and determined bupivacaine serum levels 20, 40, 60 and 80 minutes after bolus injection. We assumed toxicity of bupivacaine to be >1000 ng/ml. A total of 20 patients participated in this sub-study. All plasma levels measured as well as the upper limit of the predicted 99% confidence intervals per time point were well below the toxicity limit. In a mixed linear-effect model both groups did not differ statistically significant (p = 0.131). The intra-operative use of opioids was higher with CWI as compared to epidural (86 (SD 73) μg sufentanil vs. 50 (SD 32). In this exploratory study, the pre-peritoneal bolus using bupivacaine resulted in serum bupivacaine concentrations well below the commonly accepted toxic threshold. With CWI more additional analgesics are needed intraoperatively as compared to epidural analgesia, although this is compensated by a reduction in use of vasopressors with CWI. Netherlands Trial Register NTR4948.

Pre-Exposure Prophylaxis and Antiretroviral Resistance: HIV Prevention at a Cost?

OpenAIRE

Hurt, Christopher B.; Eron, Joseph J.; Cohen, Myron S.

2011-01-01

Prompted by 3 cases of resistance noted in the Pre-Exposure Prophylaxis Initiative and TDF2 trials, we examined literature on mutations elicited by antiretrovirals used for pre-exposure prophylaxis. We discuss signature mutations, how rapidly these emerge, and individual-level and public health consequences of antiretroviral resistance.

Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda.

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Adoke Yeka

2005-07-01

Full Text Available BACKGROUND: Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. METHODS AND FINDINGS: We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ + sulfadoxine-pyrimethamine (SP; amodiaquine (AQ + SP; or AQ + artesunate (AS. Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84% were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p < 0.01 after AQ + SP or AQ + AS (7%-18% and 4%-12%, respectively. Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, p < 0.003. CONCLUSION: AQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN

Artemisinin versus Nonartemisinin Combination Therapy for Uncomplicated Malaria: Randomized Clinical Trials from Four Sites in Uganda

Science.gov (United States)

Yeka, Adoke; Banek, Kristin; Bakyaita, Nathan; Staedke, Sarah G; Kamya, Moses R; Talisuna, Ambrose; Kironde, Fred; Nsobya, Samuel L; Kilian, Albert; Slater, Madeline; Reingold, Arthur; Rosenthal, Philip J; Wabwire-Mangen, Fred; Dorsey, Grant

2005-01-01

Background Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. Methods and Findings We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ) + sulfadoxine-pyrimethamine (SP); amodiaquine (AQ) + SP; or AQ + artesunate (AS). Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84%) were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p AQ + SP or AQ + AS (7%–18% and 4%–12%, respectively). Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection) was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, pAQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN67520427 (http://www.controlled-trials.com/isrctn/trial

Prevention of vaginal and rectal HIV transmission by antiretroviral combinations in humanized mice.

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Philippe A Gallay

Full Text Available With more than 7,000 new HIV infections daily worldwide, there is an urgent need for non-vaccine biomedical prevention (nBP strategies that are safe, effective, and acceptable. Clinical trials have demonstrated that pre-exposure prophylaxis (PrEP with antiretrovirals (ARVs can be effective at preventing HIV infection. In contrast, other trials using the same ARVs failed to show consistent efficacy. Topical (vaginal and rectal dosing is a promising regimen for HIV PrEP as it leads to low systematic drug exposure. A series of titration studies were carried out in bone marrow/liver/thymus (BLT mice aimed at determining the adequate drug concentrations applied vaginally or rectally that offer protection against rectal or vaginal HIV challenge. The dose-response relationship of these agents was measured and showed that topical tenofovir disoproxil fumarate (TDF and emtricitabine (FTC can offer 100% protection against rectal or vaginal HIV challenges. From the challenge data, EC50 values of 4.6 μM for TDF and 0.6 μM for FTC for HIV vaginal administration and 6.1 μM TDF and 0.18 μM for FTC for rectal administration were obtained. These findings suggest that the BLT mouse model is highly suitable for studying the dose-response relationship in single and combination ARV studies of vaginal or rectal HIV exposure. Application of this sensitive HIV infection model to more complex binary and ternary ARV combinations, particularly where agents have different mechanisms of action, should allow selection of optimal ARV combinations to be advanced into pre-clinical and clinical development as nBP products.

Pre-Harvest Application of a New Biocontrol Formulation Induces Resistance to Post-Harvest Anthracnose and Enhances Fruit Yield in Mango

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R. Vivekananthan

2006-08-01

Full Text Available Pre-harvest application of biocontrol formulations consisting of 1. the two plant growth promoting rhizobacterial strains FP7 and Pf1 of Pseudomonas fluorescens; 2. a strain of Bacillus subtilis Bs-1; and 3. a strain (Sc-1 of the yeast Saccharomyces cerevisiae, given at fortnightly or monthly intervals and with or without a chitin amendment, were evaluated in two trials for their ability to reduce anthracnose in mango caused by Colletotrichum gloeosporioides. Growth of C. gloeosporioides in vitro was significantly reduced by strain FP7 and in both field trials the bacterial strain in combination with chitin significantly reduced infection. Pre-harvest application of these formulations at fortnightly intervals also significantly improved flower initiation, yield parameters (mean number of fruits and fruit yield and fruit quality (total soluble solids, ascorbic acid, free acidity, total, reducing and non- reducing sugar content. The delay in latent symptom expression increased by 15 days under stored conditions. The highest levels of phenolic content, peroxidase and polyphenol oxidase on mango leaves, flowers and fruits were achieved with FP7 +chitin.

Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial

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Wouters Patrick

2011-05-01

Full Text Available Abstract Background Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC. Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF is one of the most common complications after coronary artery bypass graft surgery (CABG, affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome. Methods/design This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1 control, 2 remote ischemic preconditioning, 3 remote ischemic postconditioning, or 4 remote ischemic pre- and postconditioning. Remote conditioning is applied at the arm by 3 cycles of 5 minutes of ischemia and reperfusion. Primary endpoint is the incidence AF in the first 72 hours after surgery, detected using a Holter-monitor. Secondary endpoints include length-of-stay on the intensive care unit and in-hospital, and the occurrence of major adverse cardiovascular events at 30 days, 3 months and 1 year. Based on an expected incidence in the control group of 27%, 195 patients per group are needed to detect with 80% power a reduction by 45% following either pre- or postconditioning, while allowing for a 10% dropout and at an alpha of 0.05. With the combined intervention expected to be stronger, we need 75 patients in this group to detect a reduction in incidence of AF of 60%. Discussion The RICO-trial (the effect of

Efficacy of moxibustion for pre- or stage I hypertension: study protocol for a pilot randomized controlled trial

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Shin Kyung-Min

2012-10-01

Full Text Available Abstract Background Hypertension is a risk factor for cardiovascular disease, and the prevalence of hypertension tends to increase with age. Current treatments for hypertension have adverse side effects and poor adherence. The purpose of this study is to evaluate the effects of moxibustion on blood pressure in individuals with pre- or stage I hypertension. Methods/design Forty-five subjects with pre- or stage I hypertension will be randomized into three groups: treatment group A (2 times/week, treatment group B (3 times/week, and the control group (non-treated group. The inclusion criteria will be as follows: (1 aged between 19 and 65 years; (2 prehypertension or stage I hypertension (JNC 7, Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; (3 the participants are volunteers and written consent obtained. The participants in the treatment group A will undergo indirect moxibustion 2 times per week for 4 weeks, and the participants in the treatment group B will undergo indirect moxibustion 3 times per week for 4 weeks. The participants in the control group (non-treated group will maintain their current lifestyle, including diet and exercise. The use of antihypertensive medication is not permitted. The primary endpoint will be a change in patient blood pressure. The secondary endpoints will be the body mass index, lipid profile, EuroQol and Heart Rate Variability. The data will be analyzed with the Student’s t-test and analysis of variance (ANOVA (p Discussion The results of this study will help to establish the optimal approach for the care of adults with pre- or stage I hypertension. Trial registration Clinical Research Information Service KCT0000469

WITHDRAWN: Day care for pre-school children.

Science.gov (United States)

Zoritch, Bozhena; Roberts, Ian; Oakley, Ann

2016-10-11

The debate about how, where and by whom young children should be looked after is one which has occupied much social policy and media attention in recent years. Mothers undertake most of the care of young children. Internationally, out-of-home day-care provision ranges widely. These different levels of provision are not simply a response to different levels of demand for day-care, but reflect cultural and economic interests concerning the welfare of children, the need to promote mothers' participation in paid work, and the importance of socialising children into society's values. At a time when a decline in family values is held responsible for a range of social problems, the day-care debate has a special prominence. To quantify the effects of out-of-home day-care for preschool children on educational, health and welfare outcomes for children and their families. Randomised controlled trials of day-care for pre-school children were identified using electronic databases, hand searches of relevant literature, and contact with authors. Studies were included in the review if the intervention involved the provision of non-parental day care for children under 5 years of age, and the evaluation design was that of a randomised or quasi-randomised controlled trial. A total of eight trials were identified after examining 920 abstracts and 19 books. The trials were assessed for methodological quality. Day-care increases children's IQ, and has beneficial effects on behavioural development and school achievement. Long-term follow up demonstrates increased employment, lower teenage pregnancy rates, higher socio-economic status and decreased criminal behaviour. There are positive effects on mothers' education, employment and interaction with children. Effects on fathers have not been examined. Few studies look at a range of outcomes spanning the health, education and welfare domains. Most of the trials combined non-parental day-care with some element of parent training or education

Combining walking and relaxation for stress reduction-A randomized cross-over trial in healthy adults.

Science.gov (United States)

Matzer, Franziska; Nagele, Eva; Lerch, Nikolaus; Vajda, Christian; Fazekas, Christian

2018-04-01

Both physical activity and relaxation have stress-relieving potential. This study investigates their combined impact on the relaxation response while considering participants' initial stress level. In a randomized cross-over trial, 81 healthy adults completed 4 types of short-term interventions for stress reduction, each lasting for 1 hr: (1) physical activity (walking) combined with resting, (2) walking combined with balneotherapy, (3) combined resting and balneotherapy, and (4) resting only. Saliva cortisol, blood pressure, state of mood, and relaxation were measured preintervention and postintervention. Stress levels were determined by validated questionnaires. All interventions were associated with relaxation responses in the variables saliva cortisol, blood pressure, state of mood, and subjective relaxation. No significant differences were found regarding the reduction of salivary cortisol (F = 1.30; p = .281). The systolic blood pressure was reduced best when walking was combined with balneotherapy or resting (F = 7.34; p stress levels (n = 25) felt more alert after interventions including balneotherapy, whereas they reported an increase of tiredness when walking was combined with resting (F = 3.20; p = .044). Results suggest that combining physical activity and relaxation (resting or balneotherapy) is an advantageous short-term strategy for stress reduction as systolic blood pressure is reduced best while similar levels of relaxation can be obtained. Copyright © 2017 John Wiley & Sons, Ltd.

Predicting prices of agricultural commodities in Thailand using combined approach emphasizing on data pre-processing technique

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Thoranin Sujjaviriyasup

2018-02-01

Full Text Available In this research, a combined approach emphasizing on data pre-processing technique is developed to forecast prices of agricultural commodities in Thailand. The future prices play significant role in decision making to cultivate crops in next year. The proposed model takes ability of MODWT to decompose original time series data into more stable and explicit subseries, and SVR model to formulate complex function of forecasting. The experimental results indicated that the proposed model outperforms traditional forecasting models based on MAE and MAPE criteria. Furthermore, the proposed model reveals that it is able to be a useful forecasting tool for prices of agricultural commodities in Thailand

Clinical Trials

Medline Plus

Full Text Available ... sponsored a trial of two different combinations of asthma treatments. The trial found that one of the ... much better than the other for moderate persistent asthma. The results provided important treatment information for doctors ...

Interactions between pre- and post-emergence weed harrowing in spring cereals

DEFF Research Database (Denmark)

Brandsæter, L.O.; Mangerud, K.; Rasmussen, Jesper

2012-01-01

that pre- and post-emergence harrowing interact positively, that a combination gives more stable weed control effects than pre- and post-emergence weed harrowing used alone, and that a harrow type with bent tines is more aggressive and suitable on hard-packed soils than a harrow with strait tines...... the average effect of post-emergence harrowing was 47% on weed density and 41% on weed biomass. The combined effect of pre- and post-emergence weed harrowing was 61% on weed density and 54% on weed biomass. The combination did not give more stable weed control effects than pre- and post-emergence weed...... harrowing used alone. Pre-emergence harrowing increased the average crop yield by 6.2%, post-emergence harrowing by 4.0% and the combined effect was 10%. Crop yield was mainly increased on hard-packed soils. Weed and crop responses varied strongly among experiments, but the efficacy of pre- and post...

Pre-admission antibiotics for suspected cases of meningococcal disease.

Science.gov (United States)

Sudarsanam, Thambu D; Rupali, Priscilla; Tharyan, Prathap; Abraham, Ooriapadickal Cherian; Thomas, Kurien

2017-06-14

Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis. To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure, and morbidity in people suspected of meningococcal disease. We searched CENTRAL (6 January 2017), MEDLINE (1966 to 6 January 2017), Embase (1980 to 6 January 2017), Web of Science (1985 to 6 January 2017), LILACS (1982 to 6 January 2017), and prospective trial registries to January 2017. We previously searched CAB Abstracts from 1985 to June 2015, but did not update this search in January 2017. Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis. Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial and so did not perform data synthesis. We assessed the overall quality of the evidence using the GRADE approach. We found no RCTs comparing pre-admission antibiotics versus no pre-admission antibiotics or placebo. We included one open-label, non-inferiority RCT with 510 participants, conducted during an epidemic in Niger, evaluating a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.21, 95% CI 0.57 to 2.56; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.83, 95% CI 0.32 to

The Effect of Calcium Pre-Rinse on Salivary Fluoride After 900 ppm Fluoride Mouthwash: A Randomized Clinical Trial

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Nahid Ramazani

2013-01-01

Full Text Available Objective: Calcium fluoride deposit during fluoride application. Uptake and retention of fluoride by saliva depends generally on the concentration of calcium. In this study, the ef-fect of calcium pre-rinse on salivary fluoride concentration after a 900 ppm fluoride mouthwash was investigated.Materials and Methods: This cross-over double-blind randomized clinical trial was con-ducted in a girls' dormitory in Zahedan University of Medical Sciences, southeast Iran. In this study, 42 female dental students were chosen using simple randomization. During the first phase, 21 subjects (group A used fluoride rinse (F regimen and the remaining (group B used calcium pre-rinse followed immediately by fluoride rinse (Ca + F regi-men. In the second phase, participants rinsed using the mouthwashes not previously used. Prior to each phase prophylaxis was performed and no fluoridated product was used dur-ing a two-week interval between the phases. Salivary samples were taken immediately be-fore (baseline, 1 and 12 hours after rinsing. The salivary fluoride concentration was de-termined using fluoride sensitive electrode. Repeated measures ANOVA was used for sta-tistical analysis and the significance level was set at P<0.05.Results: There was significant difference between fluoride concentrations at different time points (P< 0.001. Significant differences were observed when the different time points of two regimens were examined. In contrast to this, the baseline before using F regimen and the baseline before using Ca + F regimen did not show any significance (P= 0.070.Conclusion: Pre-rinsing with calcium before fluoride is recommended because of signifi-cant increases in salivary fluoride concentration.

Resting state glutamate predicts elevated pre-stimulus alpha during self-relatedness: A combined EEG-MRS study on "rest-self overlap".

Science.gov (United States)

Bai, Yu; Nakao, Takashi; Xu, Jiameng; Qin, Pengmin; Chaves, Pedro; Heinzel, Alexander; Duncan, Niall; Lane, Timothy; Yen, Nai-Shing; Tsai, Shang-Yueh; Northoff, Georg

2016-01-01

Recent studies have demonstrated neural overlap between resting state activity and self-referential processing. This "rest-self" overlap occurs especially in anterior cortical midline structures like the perigenual anterior cingulate cortex (PACC). However, the exact neurotemporal and biochemical mechanisms remain to be identified. Therefore, we conducted a combined electroencephalography (EEG)-magnetic resonance spectroscopy (MRS) study. EEG focused on pre-stimulus (e.g., prior to stimulus presentation or perception) power changes to assess the degree to which those changes can predict subjects' perception (and judgment) of subsequent stimuli as high or low self-related. MRS measured resting state concentration of glutamate, focusing on PACC. High pre-stimulus (e.g., prior to stimulus presentation or perception) alpha power significantly correlated with both perception of stimuli judged to be highly self-related and with resting state glutamate concentrations in the PACC. In sum, our results show (i) pre-stimulus (e.g., prior to stimulus presentation or perception) alpha power and resting state glutamate concentration to mediate rest-self overlap that (ii) dispose or incline subjects to assign high degrees of self-relatedness to perceptual stimuli.

Does a pre-treatment diagnostic interview affect the outcome of internet-based self-help for social anxiety disorder? a randomized controlled trial.

Science.gov (United States)

Boettcher, Johanna; Berger, Thomas; Renneberg, Babette

2012-10-01

Numerous studies suggest that Internet-based self-help treatments are effective in treating anxiety disorders. Trials evaluating such interventions differ in their screening procedures and in the amount of clinician contact in the diagnostic assessment phase. The present study evaluates the impact of a pre-treatment diagnostic interview on the outcome of an Internet-based treatment for Social Anxiety Disorder (SAD). One hundred and nine participants seeking treatment for SAD were randomized to either an interview-group (IG, N = 53) or to a non-interview group (NIG, N = 56). All participants took part in the same 10-week cognitive-behavioural unguided self-help programme. Before receiving access to the programme, participants of the IG underwent a structured diagnostic interview. Participants of the NIG started directly with the programme. Participants in both groups showed significant and substantial improvement on social anxiety measures from pre- to post-assessment (d IG = 1.30-1.63; d NIG = 1.00-1.28) and from pre- to 4-month follow-up assessment (d IG = 1.38-1.87; d NIG = 1.10-1.21). Significant between-groups effects in favour of the IG were found on secondary outcome measures of depression and general distress (d = 0.18-0.42). These findings suggest that Internet-based self-help is effective in treating SAD, whether or not a diagnostic interview is involved. However, the pre-treatment interview seems to facilitate change on secondary outcomes such as depression and general distress.

Flutamide versus a cyproterone acetate-ethinyl estradiol combination in moderate acne: a pilot randomized clinical trial

Directory of Open Access Journals (Sweden)

Adalatkhah H

2011-07-01

Full Text Available Hassan Adalatkhah1, Farhad Pourfarzi2, Homayoun Sadeghi-Bazargani31Department of Dermatology, 2Department of Social Medicine, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil; 3Statistics and Epidemiology Department, Faculty of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz, IranBackground: The use of oral flutamide is rarely investigated in acne therapy. The aim of this study was to compare the efficacy of oral flutamide with that of a cyproterone-estradiol combination in treating acne lesions.Methods: A randomized clinical trial enrolled patients with moderate acne into two equal groups to receive either oral flutamide or the cyproterone-estradiol combination for 6 months. Lesion count, Acne Severity Index, and Global Acne Grading system (GAGS scores were used to assess improvement in acne lesions. The dichotomous measurement scale for primary endpoint assessment was defined as improvement from moderate to mild acne based on GAGS score. Patient satisfaction and dermal fat were also assessed. Intention to treat and per protocol analyses were done, reporting related effect sizes.Results: Both treatments resulted in substantial improvement in acne lesions. Although flutamide seemed to have higher efficacy, an intention to treat analysis did not find the two treatment protocols to be different. The relative risk in intention to treat analysis was 1.8 (95% confidence interval [CI] 0.89–1.6, and was 1.33 (95% CI 1.03–1.72 for the per protocol analysis. The number needed to treat for flutamide compared with the cyproterone-estradiol combination was 7.7 and 4.2 in the intention to treat and per protocol analyses, respectively.Conclusion: Flutamide appears to be more effective than a cyproterone-estradiol combination in some aspects of acne treatment, but this requires confirmation in a larger trial.Keywords: acne vulgaris, flutamide, cyproterone acetate, ethinyl estradiol, androgen antagonists

The CLIMATE schools combined study: a cluster randomised controlled trial of a universal Internet-based prevention program for youth substance misuse, depression and anxiety

Science.gov (United States)

2014-01-01

Background Anxiety, depressive and substance use disorders account for three quarters of the disability attributed to mental disorders and frequently co-occur. While programs for the prevention and reduction of symptoms associated with (i) substance use and (ii) mental health disorders exist, research is yet to determine if a combined approach is more effective. This paper describes the study protocol of a cluster randomised controlled trial to evaluate the effectiveness of the CLIMATE Schools Combined intervention, a universal approach to preventing substance use and mental health problems among adolescents. Methods/design Participants will consist of approximately 8400 students aged 13 to 14-years-old from 84 secondary schools in New South Wales, Western Australia and Queensland, Australia. The schools will be cluster randomised to one of four groups; (i) CLIMATE Schools Combined intervention; (ii) CLIMATE Schools - Substance Use; (iii) CLIMATE Schools - Mental Health, or (iv) Control (Health and Physical Education as usual). The primary outcomes of the trial will be the uptake and harmful use of alcohol and other drugs, mental health symptomatology and anxiety, depression and substance use knowledge. Secondary outcomes include substance use related harms, self-efficacy to resist peer pressure, general disability, and truancy. The link between personality and substance use will also be examined. Discussion Compared to students who receive the universal CLIMATE Schools - Substance Use, or CLIMATE Schools - Mental Health or the Control condition (who received usual Health and Physical Education), we expect students who receive the CLIMATE Schools Combined intervention to show greater delays to the initiation of substance use, reductions in substance use and mental health symptoms, and increased substance use and mental health knowledge. Trial registration This trial is registered with the Australian and New Zealand Clinical Trials registry, ACTRN12613000723785

Effects of dietary nitrate, caffeine, and their combination on 20-km cycling time trial performance.

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Glaister, Mark; Pattison, John R; Muniz-Pumares, Daniel; Patterson, Stephen D; Foley, Paul

2015-01-01

The aim of this study was to examine the acute supplementation effects of dietary nitrate, caffeine, and their combination on 20-km cycling time trial performance. Using a randomized, counterbalanced, double-blind Latin-square design, 14 competitive female cyclists (age: 31 ± 7 years; height: 1.69 ± 0.07 m; body mass: 61.6 ± 6.0 kg) completed four 20-km time trials on a racing bicycle fitted to a turbo trainer. Approximately 2.5 hours before each trial, subjects consumed a 70-ml dose of concentrated beetroot juice containing either 0.45 g of dietary nitrate or with the nitrate content removed (placebo). One hour before each trial, subjects consumed a capsule containing either 5 mg·kg of caffeine or maltodextrin (placebo). There was a significant effect of supplementation on power output (p = 0.001), with post hoc tests revealing higher power outputs in caffeine (205 ± 21 W) vs. nitrate (194 ± 22 W) and placebo (194 ± 25 W) trials only. Caffeine-induced improvements in power output corresponded with significantly higher measures of heart rate (caffeine: 166 ± 12 b·min vs. placebo: 159 ± 15 b·min; p = 0.02), blood lactate (caffeine: 6.54 ± 2.40 mmol·L vs. placebo: 4.50 ± 2.11 mmol·L; p caffeine: 0.95 ± 0.04 vs. placebo: 0.91 ± 0.05; p = 0.03). There were no effects (p ≥ 0.05) of supplementation on cycling cadence, rating of perceived exertion, (Equation is included in full-text article.), or integrated electromyographic activity. The results of this study support the well-established beneficial effects of caffeine supplementation on endurance performance. In contrast, acute supplementation with dietary nitrate seems to have no effect on endurance performance and adds nothing to the benefits afforded by caffeine supplementation.

Custirsen in combination with docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer (SYNERGY trial): a phase 3, multicentre, open-label, randomised trial.

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Chi, Kim N; Higano, Celestia S; Blumenstein, Brent; Ferrero, Jean-Marc; Reeves, James; Feyerabend, Susan; Gravis, Gwenaelle; Merseburger, Axel S; Stenzl, Arnulf; Bergman, Andries M; Mukherjee, Som D; Zalewski, Pawel; Saad, Fred; Jacobs, Cindy; Gleave, Martin; de Bono, Johann S

2017-04-01

Clusterin is a chaperone protein associated with treatment resistance and upregulated by apoptotic stressors such as chemotherapy. Custirsen is a second-generation antisense oligonucleotide that inhibits clusterin production. The aim of the SYNERGY trial was to investigate the effect of custirsen in combination with docetaxel and prednisone on overall survival in patients with metastatic castration-resistant prostate cancer. SYNERGY was a phase 3, multicentre, open-label, randomised trial set at 134 study centres in 12 countries. Patients were eligible for participation if they had: metastatic castration-resistant prostate cancer and had received no previous chemotherapy; prostate-specific antigen greater than 5 ng/mL; and a Karnofsky performance score of 70% or higher. Patients were randomly assigned 1:1 centrally to either the docetaxel, prednisone, and custirsen combination or docetaxel and prednisone alone. Patients were not masked to treatment allocation. Randomisation was stratified by opioid use for cancer-related pain and radiographic evidence of progression. All patients received docetaxel 75 mg/m 2 intravenously with 5 mg of prednisone orally twice daily. Patients assigned docetaxel, prednisone, and custirsen received weekly doses of custirsen 640 mg intravenously after three loading doses of 640 mg. The primary endpoint was overall survival analysed in the intention-to-treat population. Patients who received at least one study dose were included in the safety analysis set. This trial is registered with ClinicalTrials.gov, number NCT01188187. The trial is completed and final analyses are reported here. Between Dec 10, 2010, and Nov 7, 2012, 1022 patients were enrolled to the trial, of whom 510 were assigned docetaxel, prednisone, and custirsen and 512 were allocated docetaxel and prednisone. No difference in overall survival was recorded between the two groups (median survival 23·4 months [95% CI 20·9-24·8] with docetaxel, prednisone, and custirsen vs

Analysis of covariance with pre-treatment measurements in randomized trials: comparison of equal and unequal slopes.

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Funatogawa, Ikuko; Funatogawa, Takashi

2011-09-01

In randomized trials, an analysis of covariance (ANCOVA) is often used to analyze post-treatment measurements with pre-treatment measurements as a covariate to compare two treatment groups. Random allocation guarantees only equal variances of pre-treatment measurements. We hence consider data with unequal covariances and variances of post-treatment measurements without assuming normality. Recently, we showed that the actual type I error rate of the usual ANCOVA assuming equal slopes and equal residual variances is asymptotically at a nominal level under equal sample sizes, and that of the ANCOVA with unequal variances is asymptotically at a nominal level, even under unequal sample sizes. In this paper, we investigated the asymptotic properties of the ANCOVA with unequal slopes for such data. The estimators of the treatment effect at the observed mean are identical between equal and unequal variance assumptions, and these are asymptotically normal estimators for the treatment effect at the true mean. However, the variances of these estimators based on standard formulas are biased, and the actual type I error rates are not at a nominal level, irrespective of variance assumptions. In equal sample sizes, the efficiency of the usual ANCOVA assuming equal slopes and equal variances is asymptotically the same as those of the ANCOVA with unequal slopes and higher than that of the ANCOVA with equal slopes and unequal variances. Therefore, the use of the usual ANCOVA is appropriate in equal sample sizes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The combination of novel targeted molecular agents and radiation in the treatment of pediatric gliomas

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Tina eDasgupta

2013-05-01

Full Text Available Brain tumors are the most common solid pediatric malignancy. For high-grade, recurrent or refractory pediatric brain tumors, radiation therapy (XRT is an integral treatment modality. In the era of personalized cancer therapy, molecularly targeted agents have been designed to inhibit pathways critical to tumorigenesis. Our evolving knowledge of genetic aberrations in low-grade gliomas is being exploited with targeted inhibitors. These agents are also being combined with XRT to increase their efficacy. In this review, we discuss novel agents targeting three different pathways in low-grade gliomas, and their potential combination with XRT. B-Raf is a kinase in the Ras/Raf/MAPK kinase pathway, which is integral to cellular division, survival and metabolism. In low-grade pediatric gliomas, point mutations in BRAF (BRAF V600E or a BRAF fusion mutation (KIAA1549:BRAF causes overactivation of the MEK/MAPK pathway. Pre-clinical data shows cooperation between XRT and tagrgeted inhibitors of BRAF V600E, and MEK and mTOR inhibitors in the gliomas with the BRAF fusion. A second important signaling cascade in pediatric glioma pathogenesis is the PI3 kinase (PI3K/mTOR pathway. Dual PI3K/mTOR inhibitors are poised to enter studies of pediatric tumors. Finally, many brain tumors express potent stimulators of angiogenesis. Several inhibitors of immunomodulators are currently being evaluated in in clinical trials for the treatment of recurrent or refractory pediatric central nervous system (CNS tumors. In summary, combinations of these targeted inhibitors with radiation are currently under investigation in both translational bench research and early clinical trials. We summarize the molecular rationale for, and the pre-clinical data supporting the combinations of these targeted agents with other anti-cancer agents and XRT in pediatric gliomas. Parallels are drawn to adult gliomas, and the molecular mechanisms underlying the efficacy of these agents is discussed

Determinants of Dropout and Nonadherence in a Dementia Prevention Randomized Controlled Trial: The Prevention of Dementia by Intensive Vascular Care Trial

NARCIS (Netherlands)

Beishuizen, Cathrien R. L.; Coley, Nicola; Moll van Charante, Eric P.; van Gool, Willem A.; Richard, Edo; Andrieu, Sandrine

2017-01-01

To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. Secondary analysis.

Determinants of Dropout and Nonadherence in a Dementia Prevention Randomized Controlled Trial: The Prevention of Dementia by Intensive Vascular Care Trial

NARCIS (Netherlands)

Beishuizen, C.R.; Coley, N.; Charante, E.P.M. van; Gool, W.A. van; Richard, E.; Andrieu, S.

2017-01-01

OBJECTIVES: To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. DESIGN:

Jianpi Bushen, a Traditional Chinese Medicine Therapy, Combined with Chemotherapy for Gastric Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials

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Chen, Yunbo; Zhang, Guijuan; Chen, Xiaoping; Jiang, Xuefeng; Yuan, Naijun; Wang, Yurong; Hao, Xiaoqian

2018-01-01

Objective. To investigate the effects of Jianpi Bushen (JPBS), a traditional Chinese medicine that is used to invigorate the spleen and tonify the kidney, combined with chemotherapy for the treatment of gastric cancer. Methods. Literature retrieval was performed in PubMed, EMBASE, Cochrane Library, MEDLINE, CNKI, Wanfang Data Information Site, and VIP from inception to October 2017. Randomized controlled trials to evaluate the effects of JPBS combined with chemotherapy were identified. The primary reported outcomes were KPS (Karnofsky Performance Status), clinical curative efficiency, immune function, blood system, and nonhematologic system. Review Manager 5.3 (RevMan 5.3) was used for data analysis, and the quality of the studies was also appraised. Results. A total of 26 studies were included with 3098 individuals. The results of the meta-analysis indicated that treatment of gastric cancer with the combination of JPBS and chemotherapy resulted in better outcomes compared to chemotherapy alone. Conclusion. Evidence from the meta-analysis suggested that JPBS combined with chemotherapy has a positive effect on gastric cancer treatment. However, additional rigorously designed and large sample randomized controlled trials are required to confirm the efficacy and safety of this treatment. PMID:29675052

Population deworming every 6 months with albendazole in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial

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Awasthi, Shally; Peto, Richard; Read, Simon; Richards, Susan M; Pande, Vinod; Bundy, Donald; the DEVTA (Deworming and Enhanced Vitamin A) team

2013-01-01

Summary Background In north India many pre-school children are underweight, many have intestinal worms, and 2–3% die at ages 1·0–6·0 years. We used the state-wide Integrated Child Development Service (ICDS) infrastructure to help to assess any effects of regular deworming on mortality. Methods Participants in this cluster-randomised study were children in catchment areas of 8338 ICDS-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks were cluster-randomly allocated in Oxford between 6-monthly vitamin A (retinol capsule of 200 000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of albendazole effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6–72 months. Annually, one centre per block was randomly selected and visited by a study team 1–5 months after any trial deworming to sample faeces (for presence of worm eggs, reliably assessed only after mid-study), weigh children, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100 000 visits, 25 000 deaths at age 1·0–6·0 years [the primary outcome]). This trial is registered at ClinicalTrials.gov, NCT00222547. Findings Estimated compliance with 6-monthly albendazole was 86%. Among 2589 versus 2576 children surveyed during the second half of the study, nematode egg prevalence was 16% versus 36%, and most infection was light. After at least 2 years of treatment, weight at ages 3·0–6·0 years (standardised to age 4·0 years, 50% male) was 12·72 kg albendazole versus 12·68 kg control (difference 0·04 kg, 95% CI −0·14 to 0·21, p=0·66). Comparing the 36 albendazole-allocated versus 36 control blocks in analyses of the primary outcome, deaths

Evaluation of the effect of high-dose folic acid on endothelial dysfunction in pre-eclamptic patients: A randomized clinical trial

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Mohammad Hashemi

2016-01-01

Full Text Available Background: Pre-eclampsia as a hypertensive disorder of pregnancy complicates up to 5–10% of pregnancies worldwide. Endothelial dysfunction plays an important role in the pathogenesis of pre-eclampsia. In this study, we aim to evaluate the effect of high-dose folic acid on endothelial dysfunction in pre-eclamptic patients. Materials and Methods: In this triple-blinded randomized clinical trial, the enrolled patients were divided randomly into two groups. Folic acid 5.0 mg or placebo was taken daily by oral administration from the initiation of diagnosis until 2 months after delivery by the participants. Every patient's flow-mediated dilation (FMD was evaluated at the beginning of the study and 2 months after delivery with the same experienced operator at the same period of time (3–5 p.m. by high-resolution B-mode ultrasonography. Potential confounding variables were included in the independent samples t-test. t-test or Mann–Whitney U-test was used in the comparison of means between the intervention and placebo groups. To compare FMD in each group, before and after the intervention, paired t-test was used. Results: Mean value of FMD in intervention (9.64 ± 5.57 and control group (9.30 ± 4.25 has no significant difference before the consumption of drugs (P < 0.05. FMD in intervention group (13.72 ± 7.89 significantly increases after daily consumption of 5 mg folic acid in comparison with control group (10.02 ± 4.81 after daily consumption of placebo (P = 0.002. Conclusion: Increased mean of FMD in intervention group shows that this supplement can improve endothelial function and can be significantly affected by maternal blood pressure during pregnancy and some endothelium-dependent disease such as pre-eclampsia and its associated adverse outcomes.

Analysis of Combined Cycle Power Plants with Chemical Looping Reforming of Natural Gas and Pre-Combustion CO2 Capture

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Shareq Mohd Nazir

2018-01-01

Full Text Available In this paper, a gas-fired combined cycle power plant subjected to a pre-combustion CO2 capture method has been analysed under different design conditions and different heat integration options. The power plant configuration includes the chemical looping reforming (CLR of natural gas (NG, water gas shift (WGS process, CO2 capture and compression, and a hydrogen fuelled combined cycle to produce power. The process is denoted as a CLR-CC process. One of the main parameters that affects the performance of the process is the pressure for the CLR. The process is analysed at different design pressures for the CLR, i.e., 5, 10, 15, 18, 25 and 30 bar. It is observed that the net electrical efficiency increases with an increase in the design pressure in the CLR. Secondly, the type of steam generated from the cooling of process streams also effects the net electrical efficiency of the process. Out of the five different cases including the base case presented in this study, it is observed that the net electrical efficiency of CLR-CCs can be improved to 46.5% (lower heating value of NG basis by producing high-pressure steam through heat recovery from the pre-combustion process streams and sending it to the Heat Recovery Steam Generator in the power plant.

HIV/AIDS knowledge in detention in Hunan province, China

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Chen Xi

2010-04-01

Full Text Available Abstract Background Injection drug use (IDU is one of the major modes of HIV transmission in China. Drug use is illegal in China, all identified drug users are registered by Public Security Bureau, and most were sent to detention; most detainees engaged in high risk behaviours. In order to well understand the HIV/AIDS knowledge among detainees, a survey was conducted in different detention settings in Hunan province in 2008 to assess knowledge and attitudes about HIV among detainees and to provide useful information for HIV prevention and intervention strategies in detention centers. Methods A cross-sectional survey was conducted in 10 detentions in Hunan province, China, and demographic information along with knowledge and attitude of HIV/AIDS was collected through standardized interviews. Descriptive statistics were used to describe HIV knowledge, attitudes, and education services among detainees. Results There were 956 detainees interviewed from 10 detention centers. The male to female ratio was 2.24:1. The majority detainees received nine years of compulsory education, accounting for 51.5%. There were nine questions to assess HIV/AIDS knowledge of detainees, and 35.7% of those surveyed answered all nine questions correctly. There were 92.3% (882/956 who consented to be informed about the HIV antibody test results when tested, and 81% (774/956 elected that their family members were also informed. All detention centers had an organized HIV/AIDS education program. Conclusion This study gives us an overview about HIV/AIDS knowledge in detention in Hunan province, and all detention sites in the study provided HIV/AIDS intervention services among detainees that focused on HIV/AIDS knowledge, attitude, and health behaviors.

A combination of subcuticular suture and sterile Micropore tape compared with conventional interrupted sutures for skin closure. A controlled trial.

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Taube, M.; Porter, R. J.; Lord, P. H.

1983-01-01

We have conducted a controlled trial to compare skin closure using conventional interrupted sutures with a combination of subcuticular suture and sterile Micropore tape in 169 patients undergoing appendicectomy, inguinal herniorrhaphy, or saphenofemoral ligation. We have found that the combination technique consistently gives a better cosmetic result and that the tape acts well as a dressing, is convenient, and is well tolerated by patients. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6344732

Premedication with Oral Alprazolam and Melatonin Combination: A Comparison with Either Alone—A Randomized Controlled Factorial Trial

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Krishna Pokharel

2014-01-01

Full Text Available We assessed if the addition of melatonin to alprazolam has superior premedication effects compared to either drug alone. A prospective, double blind placebo controlled trial randomly assigned 80 adult patients (ASA 1&2 with a Visual Analogue Score (VAS for anxiety ≥3 to receive a tablet containing a combination of alprazolam 0.5 mg and melatonin 3 mg, alprazolam 0.5 mg, melatonin 3 mg, or placebo orally 90 min before a standard anesthetic. Primary end points were change in anxiety and sedation score at 15, 30, and 60 min after premedication, and number of patients with loss of memory for the five pictures shown at various time points when assessed after 24 h. One-way ANOVA, Friedman repeated measures analysis of variance, Kruskal Wallis and chi square tests were used as relevant. Combination drug produced the maximum reduction in anxiety VAS (3 (1.0–4.3 from baseline at 60 min (P<0.05. Sedation scores at various time points and number of patients not recognizing the picture shown at 60 min after premedication were comparable between combination drug and alprazolam alone. Addition of melatonin to alprazolam had superior anxiolysis compared with either drugs alone or placebo. Adding melatonin neither worsened sedation score nor the amnesic effect of alprazolam alone. This study was registered, approved, and released from ClinicalTrials.gov. Identifier number: NCT01486615.

Manipulation of pre-target activity on the right frontal eye field enhances conscious visual perception in humans.

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Lorena Chanes

Full Text Available The right Frontal Eye Field (FEF is a region of the human brain, which has been consistently involved in visuo-spatial attention and access to consciousness. Nonetheless, the extent of this cortical site's ability to influence specific aspects of visual performance remains debated. We hereby manipulated pre-target activity on the right FEF and explored its influence on the detection and categorization of low-contrast near-threshold visual stimuli. Our data show that pre-target frontal neurostimulation has the potential when used alone to induce enhancements of conscious visual detection. More interestingly, when FEF stimulation was combined with visuo-spatial cues, improvements remained present only for trials in which the cue correctly predicted the location of the subsequent target. Our data provide evidence for the causal role of the right FEF pre-target activity in the modulation of human conscious vision and reveal the dependence of such neurostimulatory effects on the state of activity set up by cue validity in the dorsal attentional orienting network.

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial

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McCormack, Sheena; Dunn, David T; Desai, Monica; Dolling, David I; Gafos, Mitzy; Gilson, Richard; Sullivan, Ann K; Clarke, Amanda; Reeves, Iain; Schembri, Gabriel; Mackie, Nicola; Bowman, Christine; Lacey, Charles J; Apea, Vanessa; Brady, Michael; Fox, Julie; Taylor, Stephen; Antonucci, Simone; Khoo, Saye H; Rooney, James; Nardone, Anthony; Fisher, Martin; McOwan, Alan; Phillips, Andrew N; Johnson, Anne M; Gazzard, Brian; Gill, Owen N

2016-01-01

Summary Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23

Alien wavelength modeling tool and field trial

DEFF Research Database (Denmark)

Sambo, N.; Sgambelluri, A.; Secondini, M.

2015-01-01

A modeling tool is presented for pre-FEC BER estimation of PM-QPSK alien wavelength signals. A field trial is demonstrated and used as validation of the tool's correctness. A very close correspondence between the performance of the field trial and the one predicted by the modeling tool has been...

PANSAID-PAracetamol and NSAID in combination

DEFF Research Database (Denmark)

Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel

2017-01-01

BACKGROUND: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary...... publication to prevent outcome reporting bias and data-driven analysis results. METHODS/DESIGN: The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen...... of paracetamol and ibuprofen used in a perioperative setting. TRIAL REGISTRATION: ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015....

SYNERGIC TRIAL (SYNchronizing Exercises, Remedies in Gait and Cognition) a multi-Centre randomized controlled double blind trial to improve gait and cognition in mild cognitive impairment.

Science.gov (United States)

Montero-Odasso, Manuel; Almeida, Quincy J; Burhan, Amer M; Camicioli, Richard; Doyon, Julien; Fraser, Sarah; Li, Karen; Liu-Ambrose, Teresa; Middleton, Laura; Muir-Hunter, Susan; McIlroy, William; Morais, José A; Pieruccini-Faria, Frederico; Shoemaker, Kevin; Speechley, Mark; Vasudev, Akshya; Zou, G Y; Berryman, Nicolas; Lussier, Maxime; Vanderhaeghe, Leanne; Bherer, Louis

2018-04-16

Physical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy. The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 × 10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels. The SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance

Extrafine Beclomethasone/formoterol compared to Fluticasone/salmeterol Combination Therapy in COPD

DEFF Research Database (Denmark)

Singh, D.; Nicolini, G.; Bindi, E.

2014-01-01

Background: The study evaluated the efficacy of beclomethasone dipropionate/formoterol fumarate (BDP/FF) extrafine combination versus fluticasone propionate/salmeterol (FP/S) combination in COPD patients. Methods: The trial was a 12-week multicentre, randomised, double-blind, double dummy study......; 419 patients with moderate/severe COPD were randomised to BDP/FF 200/12 mu g or FP/S 500/50 mu g twice daily. The primary objective was to demonstrate the equivalence between treatments in terms of Transition Dyspnoea Index (TDI) score and the superiority of BDP/FF in terms of change from pre- dose...... in the first 30 minutes in forced expiratory volume in the first second (FEV1). Secondary endpoints included lung function, symptom scores, symptom-free days and use of rescue medication, St. George's Respiratory Questionnaire, six minute walking test and COPD exacerbations. Results: BDP/FF was equivalent...

Six psychotropics for pre-symptomatic & early Alzheimer's (MCI, Parkinson's, and Huntington's disease modification

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Edward C Lauterbach

2016-01-01

Full Text Available The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs, including Alzheimer's disease (AD, Parkinson's disease (PD, and Huntington's disease (HD, has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow. Mild cognitive impairment (MCI phase of AD: salutary human randomized controlled trial findings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD: human epidemiological data indicate that lithium reduces AD risk. Animal model studies (AMS reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD: valproate AMS findings show promise. Pre-symptomatic PD: lithium and valproate AMS findings are encouraging. Early HD: uncontrolled clinical data indicate non-progression with lithium, fluoxetine, donepezil, and memantine. Pre-symptomatic HD: lithium and valproate are auspicious in AMS. Many other promising findings awaiting replication (valproate in MCI; lithium, valproate, fluoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, fluoxetine in pre-symptomatic PD; donepezil in early HD; lithium, fluoxetine, memantine in pre-symptomatic HD are reviewed. Dose- and stage-dependent effects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.

In vitro culture of pre-implanted mouse embryos. A model system for studying combined effects

International Nuclear Information System (INIS)

Streffer, C.; Beuningen, D. van; Molls, M.; Pon, A.; Schulz, S.; Zamboglou, N.

1978-01-01

Studies on combined effects, e.g. interaction between chemical toxicants and ionizing radiation, are difficult to perform, as they are dependent on many factors (substance concentration, radiation dose, sequence of treatments, etc.). In order to obtain data from such studies it is necessary to establish a comparatively simple experimental model system. We have established such a model system by studying combined effects on pre-implanted mouse embryos cultured in vitro. This system has the following advantages: (1) The embryos can be cultivated for several days in vitro; (2) Their physiological intactness can be tested; and (3) Cell proliferation, cell killing and chromosomal damage can be investigated comparatively easily. The embryos are isolated at the 2-cell stage and incubated in a culture medium in vitro. The development of the embryos is followed under the microscope until the development of blastocysts or the hatching of blastocysts is observed. These blastocysts can be transplanted to fostered mice and the development of normal animals determined. The proliferation kinetics can be studied easily, and the methods are described. A method has also been developed to measure the DNA content of individual cells by microscope fluorometry. After treatment of the embryos with ionizing radiation or drugs the release of micronuclei has been observed from the cell nuclei, which is an expression for chromosomal damage. Substances or radionuclides can be added to the culture medium or external irradiation can be performed during the culture period. Also the combined effects of radiation and heating can be studied. The effects of X-rays and tritiated compounds have also been investigated. The combined effects of radiation with antibiotics such as actinomycin D, and environmental toxicants such as lead, have been determined. The system described has been useful to evaluate cytological, teratogenic and cytogenetic effects

Clinical Trials

Medline Plus

Full Text Available ... trial found that one of the combinations worked much better than the other for moderate persistent asthma. The results provided important treatment information for doctors and patients. The results from other clinical trials show what doesn't work or may cause harm. For example, the NHLBI ...

Interpreting clinical trial results by deductive reasoning: In search of improved trial design.

Science.gov (United States)

Kurbel, Sven; Mihaljević, Slobodan

2017-10-01

Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials. © 2017 WILEY Periodicals, Inc.

Betting on the fastest horse: Using computer simulation to design a combination HIV intervention for future projects in Maharashtra, India.

Directory of Open Access Journals (Sweden)

Kelly V Ruggles

Full Text Available To inform the design of a combination intervention strategy targeting HIV-infected unhealthy alcohol users in Maharashtra, India, that could be tested in future randomized control trials.Using probabilistic compartmental simulation modeling we compared intervention strategies targeting HIV-infected unhealthy alcohol users on antiretroviral therapy (ART in Maharashtra, India. We tested interventions targeting four behaviors (unhealthy alcohol consumption, risky sexual behavior, depression and antiretroviral adherence, in three formats (individual, group based, community and two durations (shorter versus longer. A total of 5,386 possible intervention combinations were tested across the population for a 20-year time horizon and intervention bundles were narrowed down based on incremental cost-effectiveness analysis using a two-step probabilistic uncertainty analysis approach.Taking into account uncertainty in transmission variables and intervention cost and effectiveness values, we were able to reduce the number of possible intervention combinations to be used in a randomized control trial from over 5,000 to less than 5. The most robust intervention bundle identified was a combination of three interventions: long individual alcohol counseling; weekly Short Message Service (SMS adherence counseling; and brief sex risk group counseling.In addition to guiding policy design, simulation modeling of HIV transmission can be used as a preparatory step to trial design, offering a method for intervention pre-selection at a reduced cost.

Betting on the fastest horse: Using computer simulation to design a combination HIV intervention for future projects in Maharashtra, India.

Science.gov (United States)

Ruggles, Kelly V; Patel, Anik R; Schensul, Stephen; Schensul, Jean; Nucifora, Kimberly; Zhou, Qinlian; Bryant, Kendall; Braithwaite, R Scott

2017-01-01

To inform the design of a combination intervention strategy targeting HIV-infected unhealthy alcohol users in Maharashtra, India, that could be tested in future randomized control trials. Using probabilistic compartmental simulation modeling we compared intervention strategies targeting HIV-infected unhealthy alcohol users on antiretroviral therapy (ART) in Maharashtra, India. We tested interventions targeting four behaviors (unhealthy alcohol consumption, risky sexual behavior, depression and antiretroviral adherence), in three formats (individual, group based, community) and two durations (shorter versus longer). A total of 5,386 possible intervention combinations were tested across the population for a 20-year time horizon and intervention bundles were narrowed down based on incremental cost-effectiveness analysis using a two-step probabilistic uncertainty analysis approach. Taking into account uncertainty in transmission variables and intervention cost and effectiveness values, we were able to reduce the number of possible intervention combinations to be used in a randomized control trial from over 5,000 to less than 5. The most robust intervention bundle identified was a combination of three interventions: long individual alcohol counseling; weekly Short Message Service (SMS) adherence counseling; and brief sex risk group counseling. In addition to guiding policy design, simulation modeling of HIV transmission can be used as a preparatory step to trial design, offering a method for intervention pre-selection at a reduced cost.

[Pre-trial psychiatric reports on Antillean suspected offenders in the Netherlands and on the Dutch Antilles].

Science.gov (United States)

Vinkers, D J; Heytel, F G M; Matroos, G M; Hermans, K M; Hoek, H W

2010-01-01

The registered criminality among Antilleans living in the Netherlands is much higher than among Antilleans living on the Dutch Antilles (113 offences and 11 offences respectively, per year per 1000 persons, pDutch Antilles (n=199) between 2000 and 2006. A careful study was made of pre-trial psychiatric reports on Antillean suspected offenders (referred to as suspects) in the Netherlands and of comparable reports on Antillean suspects on the Dutch Antilles. There was no significant difference in the prevalence of mental disorders among Antillean suspects in the Netherlands (22.3%) and on the Dutch Antilles (20.3%). Abuse of drugs and cannabis was more prevalent on the Dutch Antilles where treatment for addiction is less frequently available than in the Netherlands. Mental retardation was ascertained more often among Antilleans in the Netherlands (22.4%) than among Antilleans on the Dutch Antilles (15.1%). Antillean suspects on the Dutch Antilles were more often found to be fully responsible for their actions than were Antillean suspects in the Netherlands (65.3% versus 19.1%, pDutch Antilles.

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.

Science.gov (United States)

Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-07-01

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. NCT01178073, post results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Debunking the Myth of the Strategic Corporal

Science.gov (United States)

2015-04-13

19 CHAPTER 4: Case Study 2: Iraq: Abu Ghraib Prison Torture .............................. 23 CHAPTER 5: Case Study 3: Iraq: Blackhearts...Before (New York: Atria Paperback, 2014), 68·73. 13 incidents include, the U.S. Anny’s detainee abuse at Abu Ghraib , the British detainee abuse in...that encourages more crime. Perhaps the first and most widely publicized Broken Window was the Abu Ghraib detainee abuse scandal. First revealed in

Effects of home-based exercise on pre-dialysis chronic kidney disease patients: a randomized pilot and feasibility trial.

Science.gov (United States)

Hiraki, Koji; Shibagaki, Yugo; Izawa, Kazuhiro P; Hotta, Chiharu; Wakamiya, Akiko; Sakurada, Tsutomu; Yasuda, Takashi; Kimura, Kenjiro

2017-06-17

Only a few research is available on the effects of home-based exercise training on pre-dialysis chronic kidney disease (CKD) patients. Therefore, we aimed to elucidate the effect of home-based exercise therapy on kidney function and arm and leg muscle strength in pre-dialysis CKD patients. Thirty-six male stage 3-4 pre-dialysis CKD patients (age, 68.7 ± 6.8 years; estimated glomerular filtration rate (eGFR), 39.0 ± 11.6 ml/min/1.73 m 2 ) who were being treated as outpatients were included. The subjects were randomly assigned to an exercise intervention group (Ex group: 18) and a control group (C group: 18). The Ex group wore accelerometer pedometers and were instructed to perform home-based aerobic and resistance exercises, such as brisk walking for 30 min per day, for 12 months. The C group subjects wore accelerometer pedometers but received no exercise therapy guidance; the number of steps covered during normal daily activities was recorded for the C group. The outcome measures were changes in kidney function and handgrip and knee extension muscle strength. Values at the baseline (T1) and 12 months later (T2) were compared. There were no significant differences in baseline characteristics between the two groups; however, the C group was more physically active than the Ex group. Eight subjects dropped out, and 28 subjects (14 in each group) were included in the final analysis. Physical activity increased significantly only in the Ex group. Grip strength (F = 7.0, p = 0.01) and knee extension muscle strength (F = 14.3, p < 0.01) were found to improve only in the Ex group. Further, the changes in eGFR were not significantly different between the two groups (F = 0.01, p = 0.93). Home-based exercise therapy for pre-dialysis CKD patients was feasible and improved arm and leg muscle strength without affecting kidney function. UMIN Clinical Trials Registry ( UMIN000005091 ). Registered 2/15/2011.

Praten met kinderen: effectief voor ouders van (pre)adolescenten?

NARCIS (Netherlands)

Leijten, P.; Overbeek, G.; Janssens, J.

2013-01-01

This randomized controlled trial examined the effectiveness of the parent training programme: Parents and Children Talking Together (pctt) for parents with (pre)adolescent children who experience parenting difficulties. The programme focuses on reducing child problem behaviour by improving parents’

Piecing Together the US Immigrant Detention Puzzle One Night at a Time: An Analysis of All Persons in DHS-ICE Custody on September 22, 2012

Directory of Open Access Journals (Sweden)

Donald Kerwin

2015-11-01

Full Text Available This paper analyzes a dataset of every person in the custody of the US Department of Homeland Security Immigration and Customs Enforcement (DHS-ICE or ICE on September 22, 2012, and compares this data with an earlier analysis of a similar dataset on detainees in DHS-ICE custody on January 25, 2009. DHS-ICE provided the 2012 and 2009 datasets in response to Freedom of Information Act (FOIA requests from the Boston Globe and Associated Press. The paper sets forth findings related to: (1 the removal adjudication processes to which the detainees were subject; (2 the facilities in which they were held; (3 their length of detention; and (4 their criminal histories, if any. It finds that on September 22, 2012:DHS-ICE held 35,197 people in its custody.18,470 detainees had pending removal cases, 14,674 had been ordered removed, and 2,053 cases included no information on whether or not the detainee had been ordered removed.Thirty-eight percent of detainees were subject to summary, non-court removal processes.Forty percent of detainees were from the Northern Triangle states of Central America and 34 percent from Mexico, compared to 37 percent from Mexico and 28 percent from Central America on January 25, 2009.Detainees were held in 189 facilities, with 77 percent concentrated in nine states and 51 percent in the four states that border Mexico.DHS-ICE held 67 percent of all detainees in facilities owned and/or administered by for-profit prison corporations and 90 percent of detainees in the 21 facilities with the largest detention populations.Forty-seven percent of detainees had been held for less than 30 days, and 4,179 (12 percent had been held for more than six months.Of those ordered removed and continuously detained in the interim, 553 persons had been detained for more than six months after being ordered removed, despite being presumptively eligible for release after six months.Sixty-one percent of detainees had criminal convictions, compared to 42

Global women's health: current clinical trials in low- and middle-income countries.

Science.gov (United States)

Merriel, A; Harb, H M; Williams, H; Lilford, R; Coomarasamy, A

2015-01-01

Clinical trials in low- and middle-income countries (LMICs) are necessary to develop evidence-based approaches to improve women's health. Understanding what research is currently being conducted will allow the identification of research gaps, avoidance of duplication, planning of future studies, collaboration amongst research groups, and geographical targeting for research investments. To provide an overview of active women's health trials in LMICs. The World Health Organization's International Clinical Trials Registry Platform was searched for trials registered between 1 April 2012 and 31 March 2014. Selected trials were randomised, conducted in LMICs, active, and with a women's health intervention or a significant outcome for the woman. Two reviewers extracted data. Analysis included geographical spread, speciality areas, pre-enrolment registration, study size, and funders. Of the 8966 records, 509 were eligible for inclusion. Gynaecology trials made up 57% of the research, whereas the remaining 43% of trials were in obstetrics. Research activity focused on fertility (17%), the antenatal period (15%), benign gynaecology (14%), intrapartum care (9%), and pre-invasive disease and cancers (8%). The majority of trials (84%) took place in middle-income countries (MICs). In low-income countries (LICs) 83% of research investigated obstetrics, and in MICs 60% of research investigated gynaecology. Most trials (80%) had a sample size of 500 or fewer participants. The median size of trials in LICs was 815 compared with 128 in MICs. Pre-enrolment registration occurred in 54% of trials. The majority (62%) of trials were funded locally. Many LMICs are active in women's health research. The majority of registered trials are located in MICs; however, the trials in LICs are often larger. The focus of research in MICs may be driven by local priorities and funding, with fertility being highly researched. In LICs, pregnancy is the focus, perhaps reflecting the international

Enhancing methane production from U. lactuca using combined anaerobically digested sludge (ADS) and rumen fluid pre-treatment and the effect on the solubilization of microbial community structures.

Science.gov (United States)

Zou, Yu; Xu, Xiaochen; Li, Liang; Yang, Fenglin; Zhang, Shushen

2018-04-01

Methane production by the anaerobic digestion of seaweed is restricted by the slow degradation caused by the influence of the rigid algal cell wall. At the present time, there has been no study focusing on the anaerobic digestion of U. lactuca by co-fermentation and pre-treatment with rumen fluid. Rumen fluid can favor methane production from algal biomass by utilizing the diversity and quantity of bacterial and archaeal communities in the rumen fluid. This research presents a novel method based on combined ADS and rumen fluid pre-treatment to improve the production of methane from seaweed. Biochemical methane potential (BMP) tests were performed to investigate the biogas production using combined ADS and rumen fluid pre-treatment at varied inoculum ratios on the performance of methane production from U. lactuca biomass. Compared to the control (no rumen fluid pre-treatment), the highest BMP yields of U. lactuca increased from 3%, 27.5% and 39.5% to 31.1%, 73% and 85.6%, respectively, for three different types of treatment. Microbial community analysis revealed that the Methanobrevibacter species, known to accept electrons to form methane, were only detected when rumen fluid was added. Together with the significant increase in species of Methanoculleus, Methanospirillum and Methanosaeta, rumen fluid improved the fermentation and degradation of the microalgae biomass not only by pre-treatment to foster cell-wall degradation but also by relying on methane production within itself during anaerobic processes. Batch experiments further indicated that rumen fluid applied to the co-fermentation and pre-treatment could increase the economic value and hold promise for enhancing biogas production from different seaweed species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy Study of the COmbination of Edoxaban and Physiotherapy on the PRevention of Venous-Thromboembolism in patients after Total Knee Arthroplasty (ESCORT-TKA Trial: Study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Daisuke Sueta

2016-07-01

Discussion: This study will provide clinical evidence on the combined efficacy and safety of edoxaban and physiotherapy compared with that of physiotherapy alone. This is will be the first prospective trial designed to explore how thrombus formation after TKA can be predicted by the T-TAS™.

Solving the pre-marshalling problem to optimality with A* and IDA*

DEFF Research Database (Denmark)

Tierney, Kevin; Pacino, Dario; Voß, Stefan

2017-01-01

We present a novel solution approach to the container pre-marshalling problem using the A* and IDA* algorithms combined with several novel branching and symmetry breaking rules that significantly increases the number of pre-marshalling instances that can be solved to optimality. A* and IDA......* are graph search algorithms that use heuristics combined with a complete graph search to find optimal solutions to problems. The container pre-marshalling problem is a key problem for container terminals seeking to reduce delays of inter-modal container transports. The goal of the container pre...

Treatment of trauma-affected refugees with Venlafaxine versus Sertraline combined with psychotherapy – a randomised study

DEFF Research Database (Denmark)

Sonne, Charlotte Kærgaard; Carlsson, Jessica; Bech, P

2016-01-01

Background: The prevalence of trauma-related psychiatric disorders is high among refugees. Despite this, little is known about the effect of pharmacological treatment for this patient group. The objective of the present study was therefore to examine differences in the effects of venlafaxine...... and sertraline on Post-Traumatic Stress Disorder (PTSD), depression and functional impairment in trauma-affected refugees. Methods: The study was a randomised pragmatic trial comparing venlafaxine and sertraline in combination with psychotherapy and social counselling. PTSD symptoms were measured on the Harvard......: Two hundred seven adult refugee patients were included in the trial (98 in the venlafaxine and 109 in the sertraline group). Of these, 195 patients were eligible for intention-to-treat analyses. Small but significant pre-treatment to post-treatment differences were found on the Harvard Trauma...

Periodontal disease and pre-eclampsia: a systematic review.

Science.gov (United States)

Kunnen, Alina; van Doormaal, Jasper J; Abbas, Frank; Aarnoudse, Jan G; van Pampus, Maria G; Faas, Marijke M

2010-12-01

This review evaluates the possible relationship between periodontal disease and pre-eclampsia, a major pregnancy complication. A generalized inflammatory response plays an important role in the pathogenesis of pre-eclampsia. Because periodontal disease is a low-grade inflammatory state, periodontal disease might contribute to the pathogenesis of pre-eclampsia. A literature search of PubMed, EMBASE and CINAHL until August 2010 revealed 12 eligible observational studies and three randomized-controlled trials (RCTs). It appeared difficult to compare these studies, due to variations in definitions of periodontal disease and pre-eclampsia, timing of periodontal examination and inadequate control for confounding factors. Eight observational studies reported a positive association, while four studies found no association. None of the RTCs reported reductions in pre-eclamptic rate after periodontal therapy during pregnancy. Therefore, it is questionable whether periodontal disease plays a causal role in the pathogenesis of pre-eclampsia. The observed association in eight observational studies might be the result of induction of periodontal disease due to the pre-eclamptic state or it may be an epiphenomenon of an exaggerated inflammatory response to pregnancy. Larger RCTs with pre-eclampsia as the primary outcome and pathophysiological studies are required to explore causality and to dissect biological mechanisms involved. © 2010 John Wiley & Sons A/S.

Generator of combined logical signals

International Nuclear Information System (INIS)

Laviron, Andre; Berard, Claude.

1982-01-01

The invention concerns a generator of combined logical signals to form combinations of two outputs at logical level 1 and N-2 outputs at logical level 0, among N generator outputs. This generator is characterized in that it includes a set of N means for storing combinations. Means enable the N storage means to be loaded with the logical levels corresponding to a pre-set starting combination, to control the operations for shifting the contents of the storage means and to control, by transfer facilities, the transfers of contents between these storage means. Controls enable the storage means to be actuated in order to obtain combinations of logical levels 1 and 0. The generation of combinations can be stopped after another pre-set combination. Application is for testing of safety circuits for nuclear power stations [fr

A model of population dynamics of TB in a prison system and application to South Africa

OpenAIRE

Witbooi, Peter; Vyambwera, Sibaliwe Maku

2017-01-01

Background Tuberculosis (TB) continues to spread in South African prisons in particular, as prisons are over-capacitated and have poor ventilation. The awaiting trial detainees are not screened on admission and are at high risk of getting infected with TB. Results We propose a compartmental model to describe the population dynamics of TB disease in prisons. Our model considers the inflow of susceptible, exposed and TB infectives into the prison population. Removal of individuals out of the pr...

Comparison of pre-processing methods for multiplex bead-based immunoassays.

Science.gov (United States)

Rausch, Tanja K; Schillert, Arne; Ziegler, Andreas; Lüking, Angelika; Zucht, Hans-Dieter; Schulz-Knappe, Peter

2016-08-11

High throughput protein expression studies can be performed using bead-based protein immunoassays, such as the Luminex® xMAP® technology. Technical variability is inherent to these experiments and may lead to systematic bias and reduced power. To reduce technical variability, data pre-processing is performed. However, no recommendations exist for the pre-processing of Luminex® xMAP® data. We compared 37 different data pre-processing combinations of transformation and normalization methods in 42 samples on 384 analytes obtained from a multiplex immunoassay based on the Luminex® xMAP® technology. We evaluated the performance of each pre-processing approach with 6 different performance criteria. Three performance criteria were plots. All plots were evaluated by 15 independent and blinded readers. Four different combinations of transformation and normalization methods performed well as pre-processing procedure for this bead-based protein immunoassay. The following combinations of transformation and normalization were suitable for pre-processing Luminex® xMAP® data in this study: weighted Box-Cox followed by quantile or robust spline normalization (rsn), asinh transformation followed by loess normalization and Box-Cox followed by rsn.

The CLIMATE schools combined study: a cluster randomised controlled trial of a universal Internet-based prevention program for youth substance misuse, depression and anxiety.

Science.gov (United States)

Teesson, Maree; Newton, Nicola C; Slade, Tim; Chapman, Cath; Allsop, Steve; Hides, Leanne; McBride, Nyanda; Mewton, Louise; Tonks, Zoe; Birrell, Louise; Brownhill, Louise; Andrews, Gavin

2014-02-05

Anxiety, depressive and substance use disorders account for three quarters of the disability attributed to mental disorders and frequently co-occur. While programs for the prevention and reduction of symptoms associated with (i) substance use and (ii) mental health disorders exist, research is yet to determine if a combined approach is more effective. This paper describes the study protocol of a cluster randomised controlled trial to evaluate the effectiveness of the CLIMATE Schools Combined intervention, a universal approach to preventing substance use and mental health problems among adolescents. Participants will consist of approximately 8400 students aged 13 to 14-years-old from 84 secondary schools in New South Wales, Western Australia and Queensland, Australia. The schools will be cluster randomised to one of four groups; (i) CLIMATE Schools Combined intervention; (ii) CLIMATE Schools - Substance Use; (iii) CLIMATE Schools - Mental Health, or (iv) Control (Health and Physical Education as usual). The primary outcomes of the trial will be the uptake and harmful use of alcohol and other drugs, mental health symptomatology and anxiety, depression and substance use knowledge. Secondary outcomes include substance use related harms, self-efficacy to resist peer pressure, general disability, and truancy. The link between personality and substance use will also be examined. Compared to students who receive the universal CLIMATE Schools - Substance Use, or CLIMATE Schools - Mental Health or the Control condition (who received usual Health and Physical Education), we expect students who receive the CLIMATE Schools Combined intervention to show greater delays to the initiation of substance use, reductions in substance use and mental health symptoms, and increased substance use and mental health knowledge. This trial is registered with the Australian and New Zealand Clinical Trials registry, ACTRN12613000723785.

Development of a combined database for meta-epidemiological research

DEFF Research Database (Denmark)

Savović, Jelena; Harris, Ross J; Wood, Lesley

2010-01-01

or review. Unique identifiers were assigned to each reference and used to identify duplicate trials. Sets of meta-analyses with overlapping trials were identified and duplicates removed. Overlapping trials were used to examine agreement between assessments of trial characteristics. The combined database...... database will be used to examine the combined evidence on sources of bias in randomized controlled trials. The strategy used to remove overlap between meta-analyses may be of use for future empirical research. Copyright © 2010 John Wiley & Sons, Ltd.......Collections of meta-analyses assembled in meta-epidemiological studies are used to study associations of trial characteristics with intervention effect estimates. However, methods and findings are not consistent across studies. To combine data from 10 meta-epidemiological studies into a single...

Pre-Exercise Hyperhydration-Induced Bodyweight Gain Does Not Alter Prolonged Treadmill Running Time-Trial Performance in Warm Ambient Conditions

Directory of Open Access Journals (Sweden)

Eric D. B. Goulet

2012-08-01

Full Text Available This study compared the effect of pre-exercise hyperhydration (PEH and pre-exercise euhydration (PEE upon treadmill running time-trial (TT performance in the heat. Six highly trained runners or triathletes underwent two 18 km TT runs (~28 °C, 25%–30% RH on a motorized treadmill, in a randomized, crossover fashion, while being euhydrated or after hyperhydration with 26 mL/kg bodyweight (BW of a 130 mmol/L sodium solution. Subjects then ran four successive 4.5 km blocks alternating between 2.5 km at 1% and 2 km at 6% gradient, while drinking a total of 7 mL/kg BW of a 6% sports drink solution (Gatorade, USA. PEH increased BW by 1.00 ± 0.34 kg (P < 0.01 and, compared with PEE, reduced BW loss from 3.1% ± 0.3% (EUH to 1.4% ± 0.4% (HYP (P < 0.01 during exercise. Running TT time did not differ between groups (PEH: 85.6 ± 11.6 min; PEE: 85.3 ± 9.6 min, P = 0.82. Heart rate (5 ± 1 beats/min and rectal (0.3 ± 0.1 °C and body (0.2 ± 0.1 °C temperatures of PEE were higher than those of PEH (P < 0.05. There was no significant difference in abdominal discomfort and perceived exertion or heat stress between groups. Our results suggest that pre-exercise sodium-induced hyperhydration of a magnitude of 1 L does not alter 80–90 min running TT performance under warm conditions in highly-trained runners drinking ~500 mL sports drink during exercise.

Novel therapeutic strategies in human malignancy: combining immunotherapy and oncolytic virotherapy

Directory of Open Access Journals (Sweden)

Sampath P

2015-06-01

Full Text Available Padma Sampath, Steve H Thorne Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA Abstract: Results from randomized clinical trials over the last several years have finally begun to demonstrate the potential of oncolytic viral therapies to treat a variety of cancers. One reason for these successes has been the realization that this platform is most effective when considered primarily as an immunotherapy. Cancer immunotherapy has also made dramatic strides recently with antibodies capable of blocking immune checkpoint inhibitors and adoptive T-cell therapies, notably CAR T-cells, leading a panel of novel and highly clinically effective therapies. It is clear therefore that an understanding of how and when these complementary approaches can most effectively be combined offers the real hope of moving beyond simply treating the disease and toward starting to talk about curative therapies. In this review we discuss approaches to combining these therapeutic platforms, both through engineering the viral vectors to more beneficially interact with the host immune response during therapy, as well as through the direct combinations of different therapeutics. This primarily, but not exclusively focuses on strains of oncolytic vaccinia virus. Some of the results reported to date, primarily in pre-clinical models but also in early clinical trials, are dramatic and hold great promise for the future development of similar therapies and their translation into cancer therapies. Keywords: oncolytic virus, CAR T-cell, adoptive cell therapy, immune checkpoint inhibitor 

Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis – A systematic review with meta-analysis and trial sequential analysis

DEFF Research Database (Denmark)

Sjövall, Karl Fredrik Lennart; Perner, Anders; Hylander Møller, Morten

2017-01-01

assessment and trial sequential analysis (TSA). We included randomised clinical trials (RCT) assessing empirical mono-antibiotic therapy versus a combination of two or more antibiotics in adult ICU patients with severe sepsis. We exclusively assessed patient-important outcomes, including mortality. Two...... reviewers independently evaluated studies for inclusion, extracted data, and assessed risk of bias. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated and the risk of random errors was assessed by TSA. Results Thirteen RCTs (n = 2633) were included; all were judged as having high risk...... of bias. Carbapenems were the most frequently used mono-antibiotic (8 of 13 trials). There was no difference in mortality (RR 1.11, 95% CI 0.95–1.29; p = 0.19) or in any other patient-important outcomes between mono- vs. combination therapy. In TSA of mortality, the Z-curve reached the futility area...

Blood pressure normalization in a large population of hypertensive patients treated with perindopril/indapamide combination: results of the OPTIMAX trial

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Jean-Jacques Mourad

2007-03-01

Full Text Available Jean-Jacques Mourad1, Viet Nguyen1, Marilucy Lopez-Sublet1, Bernard Waeber21Dept Internal Medicine and Hypertension Unit, Avicenne hospital-APHP and Paris 13 University, Bobigny, France; 2Bernard Waeber, Division de Physiopathologie Clinique, Lausanne, SwitzerlandObjective: To determine if the fixed-dose perindopril/indapamide combination (Per/Ind normalizes blood pressure (BP in the same fraction of hypertensive patients when treated in everyday practice or in controlled trials.Methods: In this prospective trial, 17 938 hypertensive patients were treated with Per 2 mg/Ind 0.625 mg for 3–6 months. In Group 1 Per/Ind was initiated in newly diagnosed patients (n = 7032; in Group 2 Per/Ind replaced previous therapy in patients already treated but having either their BP still uncontrolled or experiencing side-effects (n = 7423; in Group 3 Per/Ind was added to previous treatment in patients with persistently high BP (n = 3483. BP was considered normalized when ≤ 140/90 mm Hg. A multivariate analysis for predictors of BP normalization was performed.Results: Subjects were on average 62 years old and had a baseline BP of 162.3/93.6 mm Hg. After treatment with Per/Ind, BP normalization was reached in 69.6% of patients in the Initiation group, 67.5% in the Replacement Group, and 67.4% in the Add-on Group (where patients were more frequently at risk, diabetic, or with target organ damage. Mean decreases in systolic BP of 22.8 mm Hg and in diastolic BP of 12.4 mm Hg were recorded. Conclusions: This trial was established to reflect everyday clinical practice, and a treatment strategy based on the Per/Ind combination, administered as initial, replacement, or add-on therapy, led to normalization rates that were superior to those observed in Europe in routine practice. These results support recent hypertension guidelines which encourage the use of combination therapy in the management of arterial hypertension.Keywords: perindopril, indapamide, blood

Effectiveness and safety of celecoxib combined with diacerein in the treatment of senile degenerative knee osteoarthritis: study protocol and preliminary results of a randomized controlled trial

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Guo-dong Wang

2017-01-01

Full Text Available Background and objectives: The non-steroidal anti-inflammatory drug celecoxib, used for the treatment of senile degenerative knee osteoarthritis, has a rapid onset of action and few side effects. However, it cannot prevent the occurrence and development of knee osteoarthritis. Celecoxib withdrawal is likely to induce a rebound increase in inflammation that may aggravate symptoms. Diacerein is a drug used to improve articular cartilage metabolism. It can delay the progression of senile degenerative knee osteoarthritis, but has a slow onset of action. Whether combined treatment with celecoxib and diacerein provides complimentary actions to achieve a better therapeutic effect on senile degenerative knee osteoarthritis remains unclear. >Design: A prospective, single-center, randomized controlled trial. Methods: Three hundred patients with senile degenerative knee osteoarthritis who receive treatment at the Department of Orthopedics, Second Affiliated Hospital of Nanjing Medical University, China will be randomly assigned to the celecoxib (200 mg, once a day, orally, diacerein (50 mg, twice a day, orally, and celecoxib + diacerein (celecoxib 200 mg, once a day, orally and diacerein 50 mg, twice a day, orally groups, with 100 patients in each group. Patients in each group will be treated for 12 successive weeks, and a 36-week follow-up will be performed. At 24 weeks after treatment, the VAS score for pain during the 20-meter walk test and osteoarthritis index were significantly decreased in the diacerein and celecoxib + diacerein groups compared to pre-treatment (P Outcome measures and preliminary results: The primary outcome measure of this study is the Visual Analogue Scale (VAS score for pain during the 20-meter walk test before and 1, 4, 12, 24, and 36 weeks after treatment. The secondary outcome measures of this study include osteoarthritis index and X-ray image findings of the knee before and 1, 4, 12, 24, and 36 weeks after treatment, as well

The Role of the Insulin/IGF System in Cancer: Lessons Learned from Clinical Trials and the Energy Balance-Cancer Link

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Bowers, Laura W.; Rossi, Emily L.; O’Flanagan, Ciara H.; deGraffenried, Linda A.; Hursting, Stephen D.

2015-01-01

Numerous epidemiological and pre-clinical studies have demonstrated that the insulin/insulin-like growth factor (IGF) system plays a key role in the development and progression of several types of cancer. Insulin/IGF signaling, in cooperation with chronic low-grade inflammation, is also an important contributor to the cancer-promoting effects of obesity. However, clinical trials for drugs targeting different components of this system have produced largely disappointing results, possibly due to the lack of predictive biomarker use and problems with the design of combination therapy regimens. With careful attention to the identification of likely patient responders and optimal drug combinations, the outcome of future trials may be improved. Given that insulin/IGF signaling is known to contribute to obesity-associated cancer, further investigation regarding the efficacy of drugs targeting this system and its downstream effectors in the obese patient population is warranted. PMID:26029167

The Effects of Combinations of Cognitive Impairment and Pre-frailty on Adverse Outcomes from a Prospective Community-Based Cohort Study of Older Chinese People

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Ruby Yu

2018-03-01

Full Text Available ObjectivesTo examine how various combinations of cognitive impairment (overall performance and specific domains and pre-frailty predict risks of adverse outcomes; and to determine whether cognitive frailty may be defined as the combination of cognitive impairment and the presence of pre-frailty.DesignCommunity-based cohort study.ParticipantsChinese men and women (n = 3,491 aged 65+ without dementia, Parkinson’s disease and/or frailty at baseline.MeasurementsFrailty was characterized using the Cardiovascular Health Study criteria. Overall cognitive impairment was defined by a Cantonese Mini-Mental Status Examination (CMMSE total score (<21/24/27, depending on participants’ educational levels; delayed recall impairment by a CMMSE delayed recall score (<3; and language and praxis impairment by a CMMSE language and praxis score (<9. Adverse outcomes included poor quality of life, physical limitation, increased cumulative hospital stay, and mortality.ResultsCompared to those who were robust and cognitively intact at baseline, those who were robust but cognitively impaired were more likely to develop pre-frailty/frailty after 4 years (P < 0.01. Compared to participants who were robust and cognitively intact at baseline, those who were pre-frail and with overall cognitive impairment had lower grip strength (P < 0.05, lower gait speed (P < 0.01, poorer lower limb strength (P < 0.01, and poorer delayed recall at year 4 [OR, 1.6; 95% confidence interval (CI, 1.2–2.3]. They were also associated with increased risks of poor quality of life (OR, 1.5; 95% CI, 1.1–2.2 and incident physical limitation at year 4 (OR, 1.8; 95% CI, 1.3–2.5, increased cumulative hospital stay at year 7 (OR, 1.5; 95% CI, 1.1–2.1, and mortality over an average of 12 years (OR, 1.5; 95% CI, 1.0–2.1 after adjustment for covariates. There was no significant difference in risks of adverse outcomes between participants who were pre-frail, with

The Impacts of a Scalable Intervention on the Language and Literacy Development of Rural Pre-Kindergartners

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Mashburn, Andrew; Justice, Laura M.; McGinty, Anita; Slocum, Laura

2016-01-01

Read It Again (RIA) is a curriculum for pre-kindergarten (pre-K) classrooms that targets children's development of language and literacy skills. A cluster randomized trial was conducted in which 104 pre-K classrooms in the Appalachian region of the United States were randomly assigned to one of three study conditions: Control (n = 30), RIA only…

Production benefits from pre- and post-lambing anthelmintic treatment of ewes on commercial farms in the southern North Island of New Zealand.

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Miller, C M; Ganesh, S; Garland, C B; Leathwick, D M

2015-07-01

To measure the magnitude and variability in production responses to anthelmintic treatments administered to adult ewes around lambing. Ewes carrying twin lambs, from sheep and beef farms (eight in Year 1 and six in Year 2) in the Wairarapa region of New Zealand, were enrolled in 14 trials (part of an experiment carried out on one farm in one year). Experiment 1 compared ewes treated 2-4 weeks pre-lambing with a controlled release capsule (CRC) containing abamectin, albendazole, Se and Co, to ewes injected pre-lambing with a long-acting Se plus vitamin B12 product, and to untreated ewes. Experiment 2 included these treatments, plus a CRC administered at pregnancy scanning. Experiment 3 included the same treatments as Experiment 1, plus administration of a CRC containing albendazole, Se and Co, injectable moxidectin or oral derquantel plus abamectin, all administered pre-lambing, or oral derquantel plus abamectin administered 4-6 weeks after lambing. Variables compared were ewe liveweight at weaning and pre-mating, lamb liveweight at weaning, total weight of lamb weaned per ewe and ewe dag score at weaning. Ewes treated with a CRC pre-lambing were heavier than untreated ewes (mean 3.2 kg) at weaning in 12/14 trials, and pre-mating (mean 2.8 kg) in 9/14 trials (pewes the mean difference was 2.8 kg pre-lambing (9/14 trials) and 1.7 kg pre-weaning (6/14 trials). Lambs reared by treated ewes were heavier (mean 1.55 kg) at weaning in 6/14 trials (pewe (p=0.507). Variation in weight of lamb weaned per ewe was largely explained by differences in lamb survival from birth to weaning (p0.65). Treatment of ewes with a CRC at pregnancy scanning was neither better nor worse than a pre-lambing treatment (p=0.065). There was no difference in the response from treatment with either of the two CRC or moxidectin. Treatment with short-acting oral anthelmintics resulted in no consistent benefit. Anthelmintic treatments administered to ewes around lambing resulted in variable responses

Comparison of patient comprehension of rapid HIV pre-test fundamentals by information delivery format in an emergency department setting

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Clark Melissa A

2007-09-01

Full Text Available Abstract Background Two trials were conducted to compare emergency department patient comprehension of rapid HIV pre-test information using different methods to deliver this information. Methods Patients were enrolled for these two trials at a US emergency department between February 2005 and January 2006. In Trial One, patients were randomized to a no pre-test information or an in-person discussion arm. In Trial Two, a separate group of patients were randomized to an in-person discussion arm or a Tablet PC-based video arm. The video, "Do you know about rapid HIV testing?", and the in-person discussion contained identical Centers for Disease Control and Prevention-suggested pre-test information components as well as information on rapid HIV testing with OraQuick®. Participants were compared by information arm on their comprehension of the pre-test information by their score on a 26-item questionnaire using the Wilcoxon rank-sum test. Results In Trial One, 38 patients completed the no-information arm and 31 completed the in-person discussion arm. Of these 69 patients, 63.8% had twelve years or fewer of formal education and 66.7% had previously been tested for HIV. The mean score on the questionnaire for the in-person discussion arm was higher than for the no information arm (18.7 vs. 13.3, p ≤ 0.0001. In Trial Two, 59 patients completed the in-person discussion and 55 completed the video arms. Of these 114 patients, 50.9% had twelve years or fewer of formal education and 68.4% had previously been tested for HIV. The mean score on the questionnaire for the video arm was similar to the in-person discussion arm (20.0 vs. 19.2; p ≤ 0.33. Conclusion The video "Do you know about rapid HIV testing?" appears to be an acceptable substitute for an in-person pre-test discussion on rapid HIV testing with OraQuick®. In terms of adequately informing ED patients about rapid HIV testing, either form of pre-test information is preferable than for patients

Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention.

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Andrew Mujugira

Full Text Available Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months.From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758 of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40 and (26-39 respectively]. Most couples (98% were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0 and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8; 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10 copies/mL (IQR 3.31-4.53 and median CD4 count was 496 cells/µL (IQR 375-662; the majority (64% had WHO stage 1 HIV-1 disease.Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245.

Combination of Pre-Treatment DWI-Signal Intensity and S-1 Treatment: A Predictor of Survival in Patients with Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy and Sequential S-1

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Yu Zhang

2018-04-01

Full Text Available OBJECTIVE: To identify whether the combination of pre-treatment radiological and clinical factors can predict the overall survival (OS in patients with locally advanced pancreatic cancer (LAPC treated with stereotactic body radiation and sequential S-1 (a prodrug of 5-FU combined with two modulators therapy with improved accuracy compared with that of established clinical and radiologic risk models. METHODS: Patients admitted with LAPC underwent diffusion weighted imaging (DWI scan at 3.0-T (b = 600 s/mm2. The mean signal intensity (SIb = 600 of region-of-interest (ROI was measured. The Log-rank test was done for tumor location, biliary stent, S-1, and other treatments and the Cox regression analysis was done to identify independent prognostic factors for OS. Prediction error curves (PEC were used to assess potential errors in prediction of survival. The accuracy of prediction was evaluated by Integrated Brier Score (IBS and C index. RESULTS: 41 patients were included in this study. The median OS was 11.7 months (2.8-23.23 months. The 1-year OS was 46%. Multivariate analysis showed that pre-treatment SIb = 600 value and administration of S-1 were independent predictors for OS. The performance of pre-treatment SIb = 600 and S-1 treatment in combination was better than that of SIb = 600 or S-1 treatment alone. CONCLUSION: The combination of pre-treatment SIb = 600 and S-1 treatment could predict the OS in patients with LAPC undergoing SBRT and sequential S-1 therapy with improved accuracy compared with that of established clinical and radiologic risk models.

Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.

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Lee, Keun-Wook; Zang, Dae Young; Ryu, Min-Hee; Kim, Ki Hyang; Kim, Mi-Jung; Han, Hye Sook; Koh, Sung Ae; Park, Jin Hyun; Kim, Jin Won; Nam, Byung-Ho; Choi, In Sil

2017-12-01

The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

The promise of pre-exposure prophylaxis with antiretroviral drugs to prevent HIV transmission: a review

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Hankins, Catherine A.; Dybul, Mark R.

2013-01-01

Public health experts are wrestling with how to translate recent scientific findings from pre-exposure prophylaxis (PrEP) effectiveness trials into real-world programmes. This review summarizes clinical trial findings on oral and topical PrEP, discusses how decision-makers can evaluate the place of

The efficacy of different pre- and post-operative analgesics in the management of pain after orthodontic separator placement: A randomized clinical trial

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V Sudhakar

2014-01-01

Full Text Available Introduction: Pain-free treatment to the patients is considered as an important treatment objective for orthodontic health care providers. However, many orthodontists underestimate the degree of pain experienced by the patients. Hence, this study was conducted as a randomized, double-blinded clinical trial with the following objectives. Objective: To study the pain characteristics after separator placement; to compare the efficacy of various commonly used analgesics in pain management and to determine the efficacy of pre- and post-operative analgesics in pain management. Subjects and Methods: Data were collected from 154 patients (77 males and 77 females, age group of 14-21 years, with mean age of 18.8 years who reported to Department of Orthodontics. Patients were randomly divided in to four groups. Group 1: Paracetamol 650 mg, Group 2: Ibuprofen 400 mg, Group 3: Aspirin 300 mg, Group 4: Placebo and the study were conducted as a randomized, double-blinded clinical trial. The patients were instructed to take two tablets, one tablet 1 h before separator placement, and the other one after 6 h. The pain evaluations were made by the patients, when teeth not touching (TNT, biting back teeth together, chewing food (CF using a 100-mm visual analogue scale for 7 days after separator placement. Patients were advised to record the severity of pain. Results: Group 3 (Aspirin 300 mg showed lowest pain values, followed by Group 2 (ibuprofen 400 mg, and Group 1 (paracetamol 650 mg. All NSAID′s achieved good pain control compared to Group 4 (placebo, where the intensity pain was maximum. Conclusion: Pre- and post-operative analgesics were found to be more effective in controlling orthodontic pain, after separator placement at all-time intervals.

[Relieving pre-exam anxiety syndrome with wrist-ankle acupuncture: a randomized controlled trial].

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Shu, Shi; Li, Tong-ming; Fang, Fan-fu; He, Hou-luo; Zhou, Qing-hui; Gu, Wei; Zhou, Shuang

2011-06-01

Pre-exam anxiety syndrome is a common condition occurring in pre-exam students and directly affects their examination performance and physical state. Wrist-ankle acupuncture has significant therapeutic effects in treating mental disorders and may also relieve the symptoms of pre-exam anxiety syndrome. To assess the therapeutic effect of wrist-ankle acupuncture on pre-exam anxiety syndrome. A total of 60 students who met the inclusion criteria of pre-exam anxiety syndrome were enrolled from a university in Shanghai and they were randomly divided into treatment group and control group. There were 30 cases in each group, and no case failed to follow-up. In the treatment group, wrist-ankle acupuncture was adopted to point upper 1 bilaterally (impression between flexor carpi ulnaris tendon and ulnar margin), and there was no requirement for Deqi (arrival of qi). In the control group, sham acupuncture was adopted. The treatment was applied 3 times totally in both groups one week before the exam, once every other day, each time with the needles retained for 30 min. The therapeutic effects were compared between two groups. Before and after 3 treatments, Sarason Test Anxiety Scale (TAS) and Expectation and Treatment Credibility Scale (ETCS) were measured and evaluated. The therapeutic effect experienced by the treatment group was better than that of the control group (PETCS before treatment between the two groups. The scores of TAS after treatment in two groups were higher than those before treatment (PETCS than those in the control group (P<0.05, P<0.01). No adverse reaction was reported. Wrist-ankle acupuncture can relieve the symptoms of pre-exam anxiety syndrome significantly, and this therapy is highly safe.

Treatment of Battlefield Detainees in the War on Terrorism

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2006-11-14

Unprivileged Belligerency’: Spies, Guerrillas, and Saboteurs,28 BRIT. Y.B. INT’L L. 323, 343 (1951) (explaining that belligerency is not violative of...Power, either as an individual or as an agent of the opposing state. POWs are detained for security purposes only, to remove those soldiers from...for personal gain rather than agents of a state, and they could be summarily shot.93 (Modern rules require a fair criminal trial).94 The first

Enhanced eyeblink conditioning in behaviorally inhibited individuals is disrupted by proactive interference following US alone pre-exposures.

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Michael Todd Allen

2016-03-01

Full Text Available Anxiety vulnerable individuals exhibit enhanced acquisition of conditioned eyeblinks as well as enhanced proactive interference from CS or US alone pre-exposures (Holloway et al., 2012. US alone pre-exposures disrupt subsequent CR acquisition to CS-US paired trials as compared to context pre-exposure controls. While Holloway et al., (2012 reported enhanced acquisition in high trait anxiety individuals in the context condition, anxiety vulnerability effects were not reported for the US alone pre-exposure group. It appears from the published data that there were no differences between high and low anxiety individuals in the US alone condition. In the work reported here, we sought to extend the findings of enhanced proactive interference with US alone pre-exposures to determine if the enhanced conditioning was disrupted by proactive interference procedures. We also were interested in the spontaneous eyeblinks during the pre-exposure phase of training. We categorized individuals as anxiety vulnerability or non-vulnerable individuals based scores on the Adult Measure of Behavioural Inhibition (AMBI. Sixty six participants received 60 trials consisting of 30 US alone or context alone pre-exposures followed by 30 CS-US trials. US alone pre-exposures not only disrupted CR acquisition overall, but behaviorally inhibited (BI individuals exhibited enhanced proactive interference as compared to non-inhibited (NI individuals. In addition, US alone pre-exposures disrupted the enhanced acquisition observed in BI individuals as compared to NI individuals following context alone pre-exposures. Differences were also found in rates of spontaneous eyeblinks between BI and NI individuals during context pre-exposure. Our findings will be discussed in the light of the neural substrates of eyeblink conditioning as well as possible factors such as hypervigilance in the amygdala and hippocampal systems, and possible learned helplessness. Applications of these findings of

Enhanced Eyeblink Conditioning in Behaviorally Inhibited Individuals is Disrupted by Proactive Interference Following US Alone Pre-exposures.

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Allen, Michael Todd; Miller, Daniel P

2016-01-01

Anxiety vulnerable individuals exhibit enhanced acquisition of conditioned eyeblinks as well as enhanced proactive interference from conditioned stimulus (CS) or unconditioned stimulus (US) alone pre-exposures (Holloway et al., 2012). US alone pre-exposures disrupt subsequent conditioned response (CR) acquisition to CS-US paired trials as compared to context pre-exposure controls. While Holloway et al. (2012) reported enhanced acquisition in high trait anxiety individuals in the context condition, anxiety vulnerability effects were not reported for the US alone pre-exposure group. It appears from the published data that there were no differences between high and low anxiety individuals in the US alone condition. In the work reported here, we sought to extend the findings of enhanced proactive interference with US alone pre-exposures to determine if the enhanced conditioning was disrupted by proactive interference procedures. We also were interested in the spontaneous eyeblinks during the pre-exposure phase of training. We categorized individuals as anxiety vulnerability or non-vulnerable individuals based scores on the Adult Measure of Behavioral Inhibition (AMBI). Sixty-six participants received 60 trials consisting of 30 US alone or context alone pre-exposures followed by 30 CS-US trials. US alone pre-exposures not only disrupted CR acquisition overall, but behaviorally inhibited (BI) individuals exhibited enhanced proactive interference as compared to non-inhibited (NI) individuals. In addition, US alone pre-exposures disrupted the enhanced acquisition observed in BI individuals as compared to NI individuals following context alone pre-exposures. Differences were also found in rates of spontaneous eyeblinks between BI and NI individuals during context pre-exposure. Our findings will be discussed in the light of the neural substrates of eyeblink conditioning as well as possible factors such as hypervigilance in the amygdala and hippocampal systems, and possible

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

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

2014-09-01

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

A web delivered intervention for depression combining Behavioural Activation with physical activity promotion: study protocol for a pilot randomised controlled trial

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Jeffrey David Lambert

2015-10-01

Full Text Available Background: Physical activity (PA yields moderate effect sizes for treating depression (Cooney et al., 2013. PA may also help reduce depressive relapse, providing additional psychological benefits such as positive self-regard and a sense of competence (Babyak et al., 2000. Behavioural Activation (BA is an evidence-based psychological therapy for depression, which aims to get people more engaged with activities that provide positive reinforcement for non-depressed behaviours (Hopko, Lejuez, LePage, Hopko, & McNeil, 2003. The structured nature of BA is consistent with the use of good behaviour change techniques (specific goal-setting, self-regulation offering a potential platform for promoting PA alongside depression treatment. BA may also be useful for gradually increasing PA in people who are more sedentary than the general population. Aims: This pilot randomised controlled trial aims to assess the feasibility, acceptability, and fidelity of a web-delivered intervention combining BA and PA (eBAcPAc to enhance mental and physical health, and assess the trial methods. Method: A community sample of 120 people exhibiting symptoms of depression and who are participating in less than 150 minutes of moderate to vigorous physical activity per week will be randomized to receive eBAcPAc or be put on a wait list control group. eBAcPAc is informed by previous work (Farrand et al., 2014; Pentecost et al., 2015 and further developed using the Centre for eHealth Research and Disease management Roadmap (CeHReS (van Gemert-Pijnen et al., 2011 in order to be applied in an web-based setting. A platform hosted by the University of Glasgow which has been used to deliver a wide range of successful web-delivered interventions for mental health, will be used to deliver eBAcPAc. Feasibility measures will include data on recruitment, attrition and acceptability. Pre-post outcome measures will include the PHQ-9, and self-reported and accelerometer measured PA. Process and

Safety of hexaminolevulinate for blue light cystoscopy in bladder cancer. A combined analysis of the trials used for registration and postmarketing data

NARCIS (Netherlands)

Witjes, J.A.; Gomella, L.G.; Stenzl, A.; Chang, S.S.; Zaak, D.; Grossman, H.B.

2014-01-01

OBJECTIVE: To detail and put into perspective, safety of hexaminolevulinate blue light cystoscopy (HAL-BLC), including repeated use, based on combined data of controlled trials used for registration of HAL and postmarketing experience. METHODS: Safety data of 2 randomized comparative studies (group

Effect of Kangaroo care combined with music on the mother–premature neonate attachment: A randomized controlled trial

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Maryam Vahdati

2017-01-01

Full Text Available Background: Premature birth may complicate the development and quality of the mother–infant attachment relationship. Music and kangaroo care are two common complementary cares performed in the neonatal intensive care unit (NICU. The present study investigated the effect of kangaroo care combined with music on the mother–premature neonate attachment. Materials and Methods: In this clinical trial, 64 mothers with premature neonates were selected and assigned to the control and study groups through random allocation. In the control group, kangaroo care, and in the study group, kangaroo care combined with music was adopted. The level of mother–premature neonate attachment was measured and compared before and after the intervention in both the groups using Avant's Maternal Attachment Assessment Scale. Results: There was a significant increase in the mean overall score of attachment in the kangaroo care combined with music group (70.72 (11.46 after the intervention compared to the kangaroo care without music group (53.61 (9.76. Conclusions: The mean overall score of mother–neonate attachment in the kangaroo care combined with music group was higher than the kangaroo care group. This difference can be related to the effectiveness of music combined with kangaroo care.

Adolescent survivors: a secondary analysis of a clinical trial targeting behavior change.

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Cox, Cheryl L; McLaughlin, Rosemary A; Rai, Shesh N; Steen, Brenda D; Hudson, Melissa M

2005-08-01

The late effects of radiation and chemotherapy increase childhood cancer survivors' risk of chronic health problems. Survivors' behavior is important in modifying this risk, yet adolescent and young adult survivors fail to engage in important health-promoting behaviors and frequently practice high-risk behaviors. This secondary analysis re-evaluated a multi-component behavior-change intervention that had previously demonstrated no impact in adolescent survivors of childhood cancer. The parent trial compared 132 adolescent survivors in the intervention arm with 135 in the standard-care arm at baseline and at 1 year for disease and treatment knowledge, perception of late effects risk, and the frequency of health-risk and health-protective behaviors (combined as a single summative measure). In contrast, the secondary analysis examined each of the 14 behaviors separately. Additionally, an analysis of covariance (ANCOVA) was conducted to examine the change in health behaviors while statistically controlling for age, gender, and the wide variation in baseline behaviors. Knowledge (P = 0.038), breast self-examination (BSE) (P junk food consumption decreased (P = 0.052) and smoking abstinence was maintained (P = 0.088). Significant interactions between gender and treatment group were demonstrated. Health-risk and health-protective behaviors cannot be effectively combined in a one-dimensional measure. Gender and age influence the impact of interventions targeting health behavior in survivors. Future trials should include observation of the patient-clinician encounter, more complex sampling methods, and pre-trial knowledge of the distribution of the study behaviors.

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

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Norrie John

2010-04-01

Full Text Available Abstract Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.

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Le Moulec, Sylvestre; Hadoux, Julien; Gontier, Eric; Chargari, Cyrus; Helissey, Carole; Lamand, Virginie; Tanz, Rachid; Farace, Françoise; Vedrine, Lionel; Bonardel, Gérald; Soria, Jean-Charles; Besse, Benjamin

2013-12-01

The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab. Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients. Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab. In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.

An intervention that reduces stress in people who combine work with informal care: randomized controlled trial results.

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Boezeman, Edwin J; Nieuwenhuijsen, Karen; Sluiter, Judith K

2018-06-01

The aim of the research was to examine whether a role-focused self-help course intervention would decrease caregiver stress and distress, and functioning problems, among people who suffer stress because they combine paid work with informal care. A pre-registered (NTR 5528) randomized controlled design was applied (intervention vs. wait list control). Participants (n = 128) were people who had paid work and were suffering stress due to their involvement in informal care activities. Participants allocated to the intervention group (n = 65) received the role-focused self-help course. Control group members (n = 63) received this intervention after all measurements. Prior to the random allocation (pre-test), and 1 month (post-test 1) and 2 months (post-test 2) after allocation, all participants completed a questionnaire that measured their caregiver stress (primary outcome), distress, work functioning, negative care-to-work interference and negative care-to-social and personal life interference. Mixed model ANOVAs were used to test the effectiveness of the intervention. Two months after allocation, the intervention group participants had lower levels of caregiver stress and distress compared with the control group participants. The intervention did not directly resolve impaired work functioning or interference of care with work and social/personal life. The intervention decreases caregiver stress and distress in people who suffer stress because they combine paid work with informal caring. The intervention (Dutch version) can be downloaded at no cost from www.amc.nl/mantelzorgstress.

Implementation, recruitment and baseline characteristics: A randomized trial of combined treatments for smoking cessation and weight control

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Terry Bush

2017-09-01

Full Text Available Background: Two-thirds of treatment-seeking smokers are obese or overweight. Most smokers are concerned about gaining weight after quitting. The average smoker experiences modest post-quit weight gain which discourages many smokers from quitting. Although evidence suggests that combined interventions to help smokers quit smoking and prevent weight gain can be helpful, studies have not been replicated in real world settings. Methods: This paper describes recruitment and participant characteristics of the Best Quit Study, a 3-arm randomized controlled trial testing tobacco cessation treatment alone or combined with simultaneous or sequential weight management. Study participants were recruited via tobacco quitlines from August 5, 2013 to December 15, 2014. Results: Statistical analysis on baseline data was conducted in 2015/2016. Among 5082 potentially eligible callers to a tobacco quitline, 2540 were randomized (50% of eligible. Compared with individuals eligible but not randomized, those randomized were significantly more likely to be female (65.7% vs 54.5%, p < 0.01, overweight or obese (76.3% vs 62.5%, p < 0.01, more confident in quitting (p < 0.01, more addicted (first cigarette within 5 min: 50.0% vs 44.4%, p < 0.01, and have a chronic disease (28.6% vs. 24.4%, p < 0.01. Randomized groups were not statistically significantly different on demographics, tobacco or weight variables. Two-thirds of participants were female and white with a mean age of 43. Conclusions: Adding weight management interventions to tobacco cessation quitlines was feasible and acceptable to smokers. If successful for cessation and weight outcomes, a combined intervention may provide a treatment approach for addressing weight gain with smoking cessation through tobacco quitlines. Trial registration: Clinicaltrials.gov NCT01867983. Keywords: Smoking, Weight gain, Quitlines, Simultaneous, Sequential

The Efficacy of a Pre-Workout Vegan Supplement on High-Intensity Cycling Performance in Healthy College-Aged Males.

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Gallien, Gabrielle; Bellar, David; Davis, Greggory R

2017-11-02

There is a limited supply of sport nutrition supplements currently available for vegan or vegetarian athletes. In addition, the efficacy of a vegan or vegetarian pre-workout supplement that does not contain any processed ingredients or stimulants is currently unknown. The purpose of the current study was to examine the effects of an unprocessed vegan pre-workout supplement on high-intensity cycling performance. Participants completed three separate cycling trials following the consumption of a vegan pre-workout supplement, an isocaloric processed supplement, or a zero-calorie placebo supplement. Each supplement was consumed 30 minutes prior to each trial, and each cycling trial was separated by a minimum of 72 hours. Supplements were administered using a randomized, double-blind cross-over design. Each cycling trial was performed at a workload equal to 80% VO 2peak until exhaustion. The average time in seconds (s) until exhaustion values for the vegan, isocaloric, and zero-calorie supplements were 482 ± 163, 480 ± 157, and 496 ± 238, respectively. Consumption of the vegan supplement did not significantly improve performance compared to an isocaloric and zero-calorie supplement (F = 0.12, p =.89). The results of this study indicate that individuals who choose a vegan pre-workout supplement (over an isocaloric or zero-calorie product) will not experience any acute decrements or ergogenic benefits in cycling performance. Although the present study does not support performance benefits of the tested vegan pre-workout supplement before cycling, additional research examining various exercise intensities and modalities is warranted.

Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists

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Jill J. Leckey

2017-10-01

Full Text Available We investigated the effect of pre- “race” ingestion of a 1,3-butanediol acetoacetate diester on blood ketone concentration, substrate metabolism and performance of a cycling time trial (TT in professional cyclists. In a randomized cross-over design, 10 elite male cyclists completed a ~31 km laboratory-based TT on a cycling ergometer programmed to simulate the 2017 World Road Cycling Championships course. Cyclists consumed a standardized meal [2 g/kg body mass (BM carbohydrate (CHO] the evening prior to a trial day and a CHO breakfast (2 g/kg BM CHO with 200 mg caffeine on the morning of a trial day. Cyclists were randomized to consume either the ketone diester (2 × 250 mg/kg or a placebo drink, followed immediately by 200 mL diet cola, given ~ 30 min before and immediately prior to commencing a 20 min incremental warm-up. Blood samples were collected prior to and during the warm-up, pre- and post- TT and at regular intervals after the TT. Urine samples were collected pre- and post- warm-up, immediately post TT and 60 min post TT. Pre-exercise ingestion of the diester resulted in a 2 ± 1% impairment in TT performance that was associated with gut discomfort and higher perception of effort. Serum β-hydroxybutyrate, serum acetoacetate, and urine ketone concentrations increased from rest following ketone ingestion and were higher than placebo throughout the trial. Ketone ingestion induces hyperketonemia in elite professional cyclists when in a carbohydrate fed state, and impairs performance of a cycling TT lasting ~50 min.

Using simulation to aid trial design: Ring-vaccination trials.

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Matt David Thomas Hitchings

2017-03-01

Full Text Available The 2014-6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination.We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design.Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring vaccination design and on the

A phase I trial of sorafenib combined with cisplatin/etoposide or carboplatin/pemetrexed in refractory solid tumor patients.

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Davies, Janine M; Dhruva, Nirav S; Walko, Christine M; Socinski, Mark A; Bernard, Stephen; Hayes, D Neil; Kim, William Y; Ivanova, Anastasia; Keller, Kimberly; Hilbun, Layla R; Chiu, Michael; Dees, E Claire; Stinchcombe, Thomas E

2011-02-01

Sorafenib has demonstrated single agent activity in non-small cell (NSCLC) and small cell lung cancer (SCLC). Carboplatin/pemetrexed (CbP) and cisplatin/etoposide (PE) are commonly used in the treatment of these diseases. A phase I trial escalating doses of sorafenib in combination with fixed doses of PE (Arm A) or CbP (Arm B) was performed using a 3-patient cohort design to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT); DLT were assessed in the first cycle. The trial was subsequently amended with closure of Arm B and to include Arm C with a reduced dose of carboplatin. Between 9/2007 and 9/2008, 20 pts were treated on the trial; median age 62 (range 42-73), male/female ratio 12/8, PS 0/1 ratio 6/14, and median number of prior therapies 2 (range 1-4). The most common tumor types were NSCLC and SCLC. On Arm A at dose level 0 (sorafenib 200 mg BID), 2 of 4 patients experienced DLT; 2 patients were enrolled at dose level -1 (sorafenib 200 mg QD) without DLT, but this arm was closed due to slow accrual. On Arm B, 2 of 3 patients experienced DLT at dose level 0 (sorafenib 200 mg BID). On Arm C at dose level 0 (sorafenib 200 mg BID), 1 of 6 patients experienced DLT, and at dose level +1 (sorafenib 400 mg BID) 2 of 5 patients experienced a DLT. The MTD of sorafenib was 200 mg BID continuously in combination with carboplatin (AUC of 5) and pemetrexed 500 mg/m² every 3 weeks. However, only 6 patients were treated at this dose level, and the results should be interpreted cautiously. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Prevalence of diabetes treatment effect modifiers: the external validity of trials to older adults.

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Weiss, Carlos O; Boyd, Cynthia M; Wolff, Jennifer L; Leff, Bruce

2012-08-01

Potential treatment effect modifiers (TEMs) are specific diseases or conditions with a well-described mechanism for treatment effect modification. The prevalence of TEMs in older adults with type 2 diabetes mellitus (DM) is unknown. Objectives were to 1) determine the prevalence of pre-specified potential TEMs; 2) demonstrate the potential impact of TEMs in the older adult population using a simulated trial; 3) identify TEM combinations associated with number of hospitalizations to test construct validity. Data are from the nationally-representative United States National Health and Examination Survey, 1999-2004: 8646 Civilian, non-institutionalized adults aged 45-64 or 65+ years, including 1443 with DM. TEMs were anemia, congestive heart failure, liver inflammation, polypharmacy, renal insufficiency, cognitive impairment, dizziness, frequent mental distress, mobility difficulty, and visual impairment. A trial was simulated to examine prevalence of potential TEM impact. The cross-sectional association between TEM patterns and number of hospitalizations was estimated to assess construct validity. The prevalence of TEMs was substantial such that 19.0% (95% CI 14.8-23.2) of middle-aged adults and 38.0% (95% CI 33.4-42.5) of older adults had any two. A simulated trial with modest levels of interaction suggested the prevalence of TEMs could nullify treatment benefit in 3.9-27.2% of older adults with DM. Compared to having DM alone, hospitalization rate was increased by several combinations of TEMs with substantial prevalence. We provide national benchmarks that can be used to evaluate TEM prevalence reported by clinical trials of DM, and correspondingly their external validity to older adults.

Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

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Maria Graziella Catalano

2016-01-01

Full Text Available Anaplastic thyroid cancer (ATC has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly and valproic acid (1,000 mg/day; the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11.

Medical advocacy on behalf of detained immigrants.

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Venters, Homer D; Foote, Mary; Keller, Allen S

2011-06-01

Detention of immigrants by Immigration and Customs Enforcement (ICE) is a rapidly growing form of incarceration in the U.S. with almost 400,000 people detained in 2008 (Schriro in Immigration and Customs Enforcement, 2009, http://www.ice.gov/doclib/091005_ice_detention_report-final.pdf ). ICE detainees are predominantly from Mexico and Latin America and only a small minority of detainees are asylum seekers. Immigrant detainees lack a legal guarantee of medical care (unlike criminal arrestees and prisoners) and face challenges in receiving medical care, particularly those with chronic medical conditions (Venters and Keller in J Health Care Poor Underserved 20:951-957, 2009). Although we and others have long been involved in advocating for detained asylum seekers, few resources are dedicated to medical advocacy for the broader population of ICE detainees. At the NYU Center for Health and Human Rights (CHHR), a program of medical advocacy was initiated in 2007 on behalf of ICE detainees focused on improvement of care in detention and medical parole. Our preliminary efforts reveal a pressing need for more involvement by physicians and other health advocates in this area.

The status of Tsukuba BNCT trial: BPA-based boron neutron capture therapy combined with X-ray irradiation

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Yamamoto, T., E-mail: tetsu_tsukuba@yahoo.co.jp [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan)] [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan); Nakai, K. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan); Nariai, T. [Department of Neurosurgery, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo (Japan); Kumada, H.; Okumura, T.; Mizumoto, M.; Tsuboi, K. [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan); Zaboronok, A.; Ishikawa, E.; Aiyama, H.; Endo, K.; Takada, T.; Yoshida, F.; Shibata, Y.; Matsumura, A. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan)

2011-12-15

The phase II trial has been prepared to assess the effectiveness of BPA (250 mg/kg)-based NCT combined with X-ray irradiation and temozolomide (75 mg/m{sup 2}) for the treatment of newly diagnosed GBM. BPA uptake is determined by {sup 18}F-BPA-PET and/or {sup 11}C-MET-PET, and a tumor with the lesion to normal ratio of 2 or more is indicated for BNCT. The maximum normal brain point dose prescribed was limited to 13.0 Gy or less. Primary end point is overall survival.

Health promotion interventions for community-dwelling older people with mild or pre-frailty: a systematic review and meta-analysis.

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Frost, Rachael; Belk, Celia; Jovicic, Ana; Ricciardi, Federico; Kharicha, Kalpa; Gardner, Benjamin; Iliffe, Steve; Goodman, Claire; Manthorpe, Jill; Drennan, Vari M; Walters, Kate

2017-07-20

Mild or pre-frailty is common and associated with increased risks of hospitalisation, functional decline, moves to long-term care, and death. Little is known about the effectiveness of health promotion in reducing these risks. This systematic review aimed to synthesise randomised controlled trials (RCTs) evaluating home and community-based health promotion interventions for older people with mild/pre-frailty. We searched 20 bibliographic databases and 3 trials registers (January 1990 - May 2016) using mild/pre-frailty and associated terms. We included randomised controlled and crossover trials of health promotion interventions for community-dwelling older people (65+ years) with mild/pre-frailty and excluded studies focussing on populations in hospital, long term care facilities or with a specific condition. Risk of bias was assessed by two reviewers using the Cochrane Risk of Bias tool. We pooled study results using standardised mean differences (SMD) where possible and used narrative synthesis where insufficient outcome data were available. We included 10 articles reporting on seven trials (total n = 506 participants) and included five trials in a meta-analysis. Studies were predominantly small, of limited quality and six studies tested group exercise alone. One study additionally investigated a nutrition and exercise intervention and one evaluated telemonitoring. Interventions of exercise in groups showed mixed effects on functioning (no effects on self-reported functioning SMD 0.19 (95% CI -0.57 to 0.95) n = 3 studies; positive effects on performance-based functioning SMD 0.37 (95% CI 0.07 to 0.68) n = 3 studies). No studies assessed moves to long-term care or hospitalisations. Currently the evidence base is of insufficient size, quality and breadth to recommend specific health promotion interventions for older people with mild or pre- frailty. High quality studies of rigorously developed interventions are needed. CRD42014010370 (Review 2).

Effect of progestin vs. combined oral contraceptive pills on lactation: A double-blind randomized controlled trial

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Espey, Eve; Ogburn, Tony; Leeman, Larry; Singh, Rameet; Schrader, Ronald

2013-01-01

Objective To estimate the effect of progestin-only vs. combined hormonal contraceptive pills on rates of breastfeeding continuation in postpartum women. Secondary outcomes include infant growth parameters, contraceptive method continuation and patient satisfaction with breastfeeding and contraceptive method. Methods In this randomized controlled trial, postpartum breastfeeding women who desired oral contraceptives were assigned to progestin-only vs. combined hormonal contraceptive pills. At two and eight weeks postpartum, participants completed in-person questionnaires that assessed breastfeeding continuation and contraceptive use. Infant growth parameters including weight, length and head circumference were assessed at eight weeks postpartum. Telephone questionnaires assessing breastfeeding, contraceptive continuation and satisfaction were completed at 3-7 weeks and 4 and 6 months. Breastfeeding continuation was compared between groups using Cox proportional hazards regression. Differences in baseline demographic characteristics and in variables between the two intervention groups were compared using chi-square tests, Fisher’s Exact test, or two-sample t-tests as appropriate. Results Breastfeeding continuation rates, contraceptive continuation, and infant growth parameters did not differ between users of progestin-only and combined hormonal contraceptive pills. Infant formula supplementation and maternal perception of inadequate milk supply were associated with decreased rates of breastfeeding in both groups. Conclusions Choice of combined or progestin-only birth control pills administered two weeks postpartum did not adversely affect breastfeeding continuation. PMID:22143258

Separate and combined effects of exposure to heat stress and mental fatigue on endurance exercise capacity in the heat.

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Otani, Hidenori; Kaya, Mitsuharu; Tamaki, Akira; Watson, Phillip

2017-01-01

This study investigated the effects of exposure to pre-exercise heat stress and mental fatigue on endurance exercise capacity in a hot environment. Eight volunteers completed four cycle exercise trials at 80% maximum oxygen uptake until exhaustion in an environmental chamber maintained at 30 °C and 50% relative humidity. The four trials required them to complete a 90 min pre-exercise routine of either a seated rest (CON), a prolonged demanding cognitive task to induce mental fatigue (MF), warm water immersion at 40 °C during the last 30 min to induce increasing core temperature (WI), or a prolonged demanding cognitive task and warm water immersion at 40 °C during the last 30 min (MF + WI). Core temperature when starting exercise was higher following warm water immersion (~38 °C; WI and MF + WI) than with no water immersion (~36.8 °C; CON and MF, P fatigue when commencing exercise was higher following cognitive task (MF and MF + WI) than with no cognitive task (CON and WI; P stress or mental fatigue, and this response is synergistically increased during combined exposure to them.

The Effects of Spatial Endogenous Pre-cueing across Eccentricities.

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Feng, Jing; Spence, Ian

2017-01-01

Frequently, we use expectations about likely locations of a target to guide the allocation of our attention. Despite the importance of this attentional process in everyday tasks, examination of pre-cueing effects on attention, particularly endogenous pre-cueing effects, has been relatively little explored outside an eccentricity of 20°. Given the visual field has functional subdivisions that attentional processes can differ significantly among the foveal, perifoveal, and more peripheral areas, how endogenous pre-cues that carry spatial information of targets influence our allocation of attention across a large visual field (especially in the more peripheral areas) remains unclear. We present two experiments examining how the expectation of the location of the target shapes the distribution of attention across eccentricities in the visual field. We measured participants' ability to pick out a target among distractors in the visual field after the presentation of a highly valid cue indicating the size of the area in which the target was likely to occur, or the likely direction of the target (left or right side of the display). Our first experiment showed that participants had a higher target detection rate with faster responses, particularly at eccentricities of 20° and 30°. There was also a marginal advantage of pre-cueing effects when trials of the same size cue were blocked compared to when trials were mixed. Experiment 2 demonstrated a higher target detection rate when the target occurred at the cued direction. This pre-cueing effect was greater at larger eccentricities and with a longer cue-target interval. Our findings on the endogenous pre-cueing effects across a large visual area were summarized using a simple model to assist in conceptualizing the modifications of the distribution of attention over the visual field. We discuss our finding in light of cognitive penetration of perception, and highlight the importance of examining attentional process across

The Effects of Spatial Endogenous Pre-cueing across Eccentricities

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Jing Feng

2017-06-01

Full Text Available Frequently, we use expectations about likely locations of a target to guide the allocation of our attention. Despite the importance of this attentional process in everyday tasks, examination of pre-cueing effects on attention, particularly endogenous pre-cueing effects, has been relatively little explored outside an eccentricity of 20°. Given the visual field has functional subdivisions that attentional processes can differ significantly among the foveal, perifoveal, and more peripheral areas, how endogenous pre-cues that carry spatial information of targets influence our allocation of attention across a large visual field (especially in the more peripheral areas remains unclear. We present two experiments examining how the expectation of the location of the target shapes the distribution of attention across eccentricities in the visual field. We measured participants’ ability to pick out a target among distractors in the visual field after the presentation of a highly valid cue indicating the size of the area in which the target was likely to occur, or the likely direction of the target (left or right side of the display. Our first experiment showed that participants had a higher target detection rate with faster responses, particularly at eccentricities of 20° and 30°. There was also a marginal advantage of pre-cueing effects when trials of the same size cue were blocked compared to when trials were mixed. Experiment 2 demonstrated a higher target detection rate when the target occurred at the cued direction. This pre-cueing effect was greater at larger eccentricities and with a longer cue-target interval. Our findings on the endogenous pre-cueing effects across a large visual area were summarized using a simple model to assist in conceptualizing the modifications of the distribution of attention over the visual field. We discuss our finding in light of cognitive penetration of perception, and highlight the importance of examining

Adolescent pre-exposure prophylaxis for HIV prevention: current perspectives

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Machado DM

2017-11-01

Full Text Available Daisy Maria Machado,1 Alexandre Machado de Sant’Anna Carvalho,2 Rachel Riera3 1Disciplina de Infectologia Pediátrica, Departamento de Pediatria, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2Universidade Federal do Rio de Janeiro, Rio de Janeiro, 3Disciplina de Medicina Baseada em Evidências, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

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Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

Exploring reasons for the observed inconsistent trial reports on intra-articular injections with hyaluronic acid in the treatment of osteoarthritis: Meta-regression analyses of randomized trials.

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Johansen, Mette; Bahrt, Henriette; Altman, Roy D; Bartels, Else M; Juhl, Carsten B; Bliddal, Henning; Lund, Hans; Christensen, Robin

2016-08-01

The aim was to identify factors explaining inconsistent observations concerning the efficacy of intra-articular hyaluronic acid compared to intra-articular sham/control, or non-intervention control, in patients with symptomatic osteoarthritis, based on randomized clinical trials (RCTs). A systematic review and meta-regression analyses of available randomized trials were conducted. The outcome, pain, was assessed according to a pre-specified hierarchy of potentially available outcomes. Hedges׳s standardized mean difference [SMD (95% CI)] served as effect size. REstricted Maximum Likelihood (REML) mixed-effects models were used to combine study results, and heterogeneity was calculated and interpreted as Tau-squared and I-squared, respectively. Overall, 99 studies (14,804 patients) met the inclusion criteria: Of these, only 71 studies (72%), including 85 comparisons (11,216 patients), had adequate data available for inclusion in the primary meta-analysis. Overall, compared with placebo, intra-articular hyaluronic acid reduced pain with an effect size of -0.39 [-0.47 to -0.31; P hyaluronic acid. Based on available trial data, intra-articular hyaluronic acid showed a better effect than intra-articular saline on pain reduction in osteoarthritis. Publication bias and the risk of selective outcome reporting suggest only small clinical effect compared to saline. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparing methods to combine functional loss and mortality in clinical trials for amyotrophic lateral sclerosis

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van Eijk RPA

2018-03-01

Full Text Available Ruben PA van Eijk,1 Marinus JC Eijkemans,2 Dimitris Rizopoulos,3 Leonard H van den Berg,4,* Stavros Nikolakopoulos5,* 1Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands; 2Department of Biostatistics, University Medical Center Utrecht, Utrecht, the Netherlands; 3Department of Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands; 4Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands; 5Department of Biostatistics, University Medical Center Utrecht, Utrecht, the Netherlands *These authors contributed equally to this work Objective: Amyotrophic lateral sclerosis (ALS clinical trials based on single end points only partially capture the full treatment effect when both function and mortality are affected, and may falsely dismiss efficacious drugs as futile. We aimed to investigate the statistical properties of several strategies for the simultaneous analysis of function and mortality in ALS clinical trials. Methods: Based on the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT database, we simulated longitudinal patterns of functional decline, defined by the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R and conditional survival time. Different treatment scenarios with varying effect sizes were simulated with follow-up ranging from 12 to 18 months. We considered the following analytical strategies: 1 Cox model; 2 linear mixed effects (LME model; 3 omnibus test based on Cox and LME models; 4 composite time-to-6-point decrease or death; 5 combined assessment of function and survival (CAFS; and 6 test based on joint modeling framework. For each analytical strategy, we calculated the empirical power and sample size. Results: Both Cox and LME models have increased false-negative rates when treatment exclusively affects either function or survival. The joint model has superior power compared to other strategies. The composite end point

Trial Protocol: Cognitive functional therapy compared with combined manual therapy and motor control exercise for people with non-specific chronic low back pain: protocol for a randomised, controlled trial.

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Belache, Fabiana Terra Cunha; Souza, Cíntia Pereira de; Fernandez, Jessica; Castro, Julia; Ferreira, Paula Dos Santos; Rosa, Elizana Rodrigues de Sousa; Araújo, Nathalia Cristina Gimenez de; Reis, Felipe José Jandre; Almeida, Renato Santos de; Nogueira, Leandro Alberto Calazans; Correia, Luís Cláudio Lemos; Meziat-Filho, Ney

2018-06-11

Chronic low back pain is a public health problem, and there is strong evidence that it is associated with a complex interaction of biopsychosocial factors. Cognitive functional therapy is an intervention that deals with potentially modifiable multidimensional aspects of pain (eg, provocative cognitive, movement and lifestyle behaviours). There is evidence (from a single randomised, controlled trial) that cognitive functional therapy is better than combined manual therapy and motor control exercise. However, this study had significant methodological shortcomings including the failure to carry out an intention-to-treat analysis and a considerable loss of follow-up of participants. It is important to replicate this study in another domain through a randomised clinical trial with similar objectives but correcting these methodological shortcomings. To investigate the efficacy of cognitive functional therapy compared to combined manual therapy and exercise on pain and disability at 3 months in patients with chronic non-specific low back pain. Two-group, randomised, multicentre controlled trial with blinded assessors. One hundred and forty-eight participants with chronic low back pain that has persisted for >3months and no specific spinal pathology will be recruited from the school clinic of the Centro Universitário Augusto Motta and a private clinic in the city of Rio de Janeiro, Brazil. Four to 10 sessions of cognitive functional therapy. The physiotherapists who will treat the participants in the cognitive functional therapy group have previously attended 2 workshops with two different tutors of the method. Such physiotherapists have completed 106 hours of training, including workshops and patient examinations, as well as conducting a pilot study under the supervision of another physiotherapist with>3 years of clinical experience in cognitive functional therapy. Four to 10 sessions of combined manual therapy and motor control exercises. Participants in the combined

Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children

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Falgun Indravadan Vyas

2014-01-01

Full Text Available Objective: Paracetamol and ibuprofen are widely used for fever in children as monotherapy and as combined therapy. None of the treatments is proven clearly superior to others. Hence, the study was planned to compare the efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Materials and Methods: This was an investigator blind, randomized, comparative, parallel clinical trial conducted in 99 febrile children, 6 months to 12 years of age, allocated to three groups. First group received paracetamol 15 mg/kg, second group received ibuprofen 10 mg/kg and third group received both paracetamol and ibuprofen, all as a single dose by the oral route. Patients were followed-up at intervals of 1, 2, 3 and 4 h post dose by tympanic thermometry. Results: Mean tympanic temperature after 4 h of drug administration was significantly lower in the combination group compared with paracetamol group (P < 0.05; however, the difference was not clinically significant (<1΀C. The rate of fall of temperature was highest in the combination group. Number of afebrile children any time post dose until 4 h was highest in the combination group. Difference between combination and paracetamol was significant for the 1 st h (P = 0.04. Highest fall of temperature was noted in the 1 st h of drug administration in all the groups. No serious adverse events were observed in any of the groups. Conclusion: Paracetamol and ibuprofen combination caused quicker temperature reduction than either paracetamol or ibuprofen alone. If quicker reduction of body temperature is the desired goal of therapy, the use of combination of paracetamol + ibuprofen may be advocated.

Magnesium sulphate and other anticonvulsants for women with pre-eclampsia.

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Duley, Lelia; Gülmezoglu, A Metin; Henderson-Smart, David J; Chou, Doris

2010-11-10

Eclampsia, the occurrence of a seizure (fit) in association with pre-eclampsia, is rare but potentially life-threatening. Magnesium sulphate is the drug of choice for treating eclampsia. This review assesses its use for preventing eclampsia. To assess the effects of magnesium sulphate, and other anticonvulsants, for prevention of eclampsia. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (4 June 2010), and the Cochrane Central Register of Controlled Trials Register (The Cochrane Library 2010, Issue 3). Randomised trials comparing anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs, for pre-eclampsia. Two authors assessed trial quality and extracted data independently. We included 15 trials. Six (11,444 women) compared magnesium sulphate with placebo or no anticonvulsant: magnesium sulphate more than a halved the risk of eclampsia (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; number needed to treat for an additional beneficial outcome (NNTB) 100, 95% CI 50 to 100), with a non-significant reduction in maternal death (RR 0.54, 95% CI 0.26 to 1.10) but no clear difference in serious maternal morbidity (RR 1.08, 95% CI 0.89 to 1.32). It reduced the risk of placental abruption (RR 0.64, 95% CI 0.50 to 0.83; NNTB 100, 95% CI 50 to 1000), and increased caesarean section (RR 1.05, 95% CI 1.01 to 1.10). There was no clear difference in stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15). Side effects, primarily flushing, were more common with magnesium sulphate (24% versus 5%; RR 5.26, 95% CI 4.59 to 6.03; number need to treat for an additional harmful outcome (NNTH) 6, 95% CI 5 to 6).Follow-up was reported by one trial comparing magnesium sulphate with placebo: for 3375 women there was no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53) or morbidity potentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26) (median follow-up 26 months); for 3283 children exposed in utero

Rationale, design, methodology and sample characteristics for the Vietnam pre-conceptual micronutrient supplementation trial (PRECONCEPT: a randomized controlled study

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Nguyen Phuong H

2012-10-01

Full Text Available Abstract Background Low birth weight and maternal anemia remain intractable problems in many developing countries. The adequacy of the current strategy of providing iron-folic acid (IFA supplements only during pregnancy has been questioned given many women enter pregnancy with poor iron stores, the substantial micronutrient demand by maternal and fetal tissues, and programmatic issues related to timing and coverage of prenatal care. Weekly IFA supplementation for women of reproductive age (WRA improves iron status and reduces the burden of anemia in the short term, but few studies have evaluated subsequent pregnancy and birth outcomes. The Preconcept trial aims to determine whether pre-pregnancy weekly IFA or multiple micronutrient (MM supplementation will improve birth outcomes and maternal and infant iron status compared to the current practice of prenatal IFA supplementation only. This paper provides an overview of study design, methodology and sample characteristics from baseline survey data and key lessons learned. Methods/design We have recruited 5011 WRA in a double-blind stratified randomized controlled trial in rural Vietnam and randomly assigned them to receive weekly supplements containing either: 1 2800 μg folic acid 2 60 mg iron and 2800 μg folic acid or 3 MM. Women who become pregnant receive daily IFA, and are being followed through pregnancy, delivery, and up to three months post-partum. Study outcomes include birth outcomes and maternal and infant iron status. Data are being collected on household characteristics, maternal diet and mental health, anthropometry, infant feeding practices, morbidity and compliance. Discussion The study is timely and responds to the WHO Global Expert Consultation which identified the need to evaluate the long term benefits of weekly IFA and MM supplementation in WRA. Findings will generate new information to help guide policy and programs designed to reduce the burden of anemia in women and

Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial

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Rawal, Narinder; Macquaire, Valery; Catalá, Elena; Berti, Marco; Costa, Rui; Wietlisbach, Markus

2011-01-01

This randomized, double-blind, double-dummy, multicenter trial compared efficacy and safety of tramadol HCL 37.5 mg/paracetamol 325 mg combination tablet with tramadol HCL 50 mg capsule in the treatment of postoperative pain following ambulatory hand surgery with iv regional anesthesia. Patients received trial medication at admission, immediately after surgery, and every 6 hours after discharge until midnight of the first postoperative day. Analgesic efficacy was assessed by patients (n = 128 in each group, full analysis set) and recorded in a diary on the evening of surgery day and of the first postoperative day. They also documented the occurrence of adverse events. By the end of the first postoperative day, the proportion of treatment responders based on treatment satisfaction (primary efficacy variable) was comparable between the groups (78.1% combination, 71.9% tramadol; P = 0.24) and mean pain intensity (rated on a numerical scale from 0 = no pain to 10 = worst imaginable pain) had been reduced to 1.7 ± 2.0 for both groups. Under both treatments, twice as many patients experienced no pain (score = 0) on the first postoperative day compared to the day of surgery (35.9% vs 16.4% for tramadol/paracetamol and 36.7% vs 18% for tramadol treatment). Rescue medication leading to withdrawal (diclofenac 50 mg) was required by 17.2% patients with tramadol/paracetamol and 13.3% with tramadol. Adverse events (mainly nausea, dizziness, somnolence, vomiting, and increased sweating) occurred less frequently in patients under combination treatment (P = 0.004). Tramadol/paracetamol combination tablets provided comparable analgesic efficacy with a better safety profile to tramadol capsules in patients experiencing postoperative pain following ambulatory hand surgery. PMID:21559356

Ethnic variations in psychotic disorders in the criminal justice system: A systematic review

NARCIS (Netherlands)

Denzel, A.D.; van Esch, A.Y.M.; Harte, J.M.; Scherder, E.J.A.

2016-01-01

Objective To explore the relationship between ethnicity, psychotic disorders and criminal behavior by investigating differences in prevalence rates of psychotic disorders between detainees from Black and minority ethnic (BME) groups and non-BME detainees. Method A systematic review of all empirical

Efficacy of pre-exercise low-level laser therapy on isokinetic muscle performance in individuals with type 2 diabetes mellitus: study protocol for a randomized controlled trial.

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Gomes, Cid André Fidelis de Paula; Leal-Junior, Ernesto Cesar Pinto; Biasotto-Gonzalez, Daniela Aparecida; El-Hage, Yasmin; Politti, Fabiano; Gonzalez, Tabajara de Oliveira; Dibai-Filho, Almir Vieira; de Oliveira, Adriano Rodrigues; Frigero, Marcelo; Antonialli, Fernanda Colella; Vanin, Adriane Aver; de Tarso Camillo de Carvalho, Paulo

2014-04-09

Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes. A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109. The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index - normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2

Wheels, skills and thrills: a social marketing trial to reduce aggressive driving from young men in deprived areas.

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Tapp, Alan; Pressley, Ashley; Baugh, Mike; White, Paul

2013-09-01

Young men from poorer backgrounds are associated with high road traffic collision levels. However, solving this problem has proven very difficult. Hence this paper summarises the findings of a UK government funded two-year trial of a cross-discipline intervention to reduce aggressive driving amongst this group. The intervention reported on here departed from traditional approaches such as fear appeals, stand-alone educational approaches, or punitive measures. Instead, the discipline of social marketing was used to provide overarching direction and structure for the trial, with a key focus on motivation and engagement. The project rested on a strong education and training platform and included a bespoke coaching programme, incentives, and an in-vehicle measurement and feedback device. The project had three development phases leading to the final trial. First, a literature and case study review identified possible design strategies. Second, these strategies were explored using primary research in the form of a qualitative inquiry. Third, a pre-trial design phase sought to introduce key components of the intervention to the trial cohort, retaining some flexibility before committing to the final design. Young males with a history of challenging behaviour (e.g. criminal records, driving convictions) from an economically deprived area within a UK city were recruited. Of 42 recruits, 23 successfully completed the trial. Behaviour changes were measured pre-, during and post-trial through a combination of driver performance data measured by in-vehicle data recorders (IVDRs), assessments of driving undertaken by trained observers, and self-assessment surveys and interviews with trial participants. Results indicate a significant average improvement in driving skills amongst participants who completed the trial. Given the difficulty in engaging and changing behaviour of this specific group, this is regarded as a significant finding. In summary the study provides an indication

Adolescent pre-exposure prophylaxis for HIV prevention: current perspectives

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Machado, Daisy Maria; de Sant’Anna Carvalho, Alexandre Machado; Riera, Rachel

2017-01-01

Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV) drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP) is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no country has yet approved it for use with adolescents. The aim of this review was to identify and summarize the evidence from studies on PrEP for adolescents. We have compiled and reviewed published studies focusing on safety, feasibility, adherence to therapeutics, self-perception, and legal issues related to PrEP in people aged between 10 and 24 years. PMID:29238237

Passing the baton: Community-based ethnography to design a randomized clinical trial on the effectiveness of oral pre-exposure prophylaxis for HIV prevention among Black men who have sex with men.

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Garcia, Jonathan; Colson, Paul W; Parker, Caroline; Hirsch, Jennifer S

2015-11-01

Although HIV interventions and clinical trials increasingly report the use of mixed methods, studies have not reported on the process through which ethnographic or qualitative findings are incorporated into RCT designs. We conducted a community-based ethnography on social and structural factors that may affect the acceptance of and adherence to oral pre-exposure prophylaxis (PrEP) among Black men who have sex with men (BMSM). We then devised the treatment arm of an adherence clinical trial drawing on findings from the community-based ethnography. This article describes how ethnographic findings informed the RCT and identifies distilled themes and findings that could be included as part of an RCT. The enhanced intervention includes in-person support groups, online support groups, peer navigation, and text message reminders. By describing key process-related facilitators and barriers to conducting meaningful mixed methods research, we provide important insights for the practice of designing clinical trials for 'real-world' community settings. Copyright © 2015 Elsevier Inc. All rights reserved.

HIV and incarceration: prisons and detention.

Science.gov (United States)

Jürgens, Ralf; Nowak, Manfred; Day, Marcus

2011-05-19

The high prevalence of HIV infection among prisoners and pre-trial detainees, combined with overcrowding and sub-standard living conditions sometimes amounting to inhuman or degrading treatment in violation of international law, make prisons and other detention centres a high risk environment for the transmission of HIV. Ultimately, this contributes to HIV epidemics in the communities to which prisoners return upon their release. We reviewed the evidence regarding HIV prevalence, risk behaviours and transmission in prisons. We also reviewed evidence of the effectiveness of interventions and approaches to reduce the risk behaviours and, consequently, HIV transmission in prisons. A large number of studies report high levels of risk behaviour in prisons, and HIV transmission has been documented. There is a large body of evidence from countries around the world of what prison systems can do to prevent HIV transmission. In particular, condom distribution programmes, accompanied by measures to prevent the occurrence of rape and other forms of non-consensual sex, needle and syringe programmes and opioid substitution therapies, have proven effective at reducing HIV risk behaviours in a wide range of prison environments without resulting in negative consequences for the health of prison staff or prisoners.The introduction of these programmes in prisons is therefore warranted as part of comprehensive programmes to address HIV in prisons, including HIV education, voluntary HIV testing and counselling, and provision of antiretroviral treatment for HIV-positive prisoners. In addition, however, action to reduce overcrowding and improve conditions in detention is urgently needed.

Combined MRI and MRS improves pre-therapeutic diagnoses of pediatric brain tumors over MRI alone

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Shiroishi, Mark S.; Nelson, Marvin D. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Pediatric Radiology, Pittsburgh, PA (United States); Moore, Kevin R. [Primary Children' s Medical Center, Department of Radiology, Salt Lake City, UT (United States); Gilles, Floyd H. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Pathology, Los Angeles, CA (United States); Gonzalez-Gomez, Ignacio [All Children' s Hospital, Department of Pathology, St. Petersburg, FL (United States); Blueml, Stefan [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States)

2015-09-15

The specific goal of this study was to determine whether the inclusion of MRS had a measureable and positive impact on the accuracy of pre-surgical MR examinations of untreated pediatric brain tumors over that of MRI alone in clinical practice. Final imaging reports of 120 pediatric patients with newly detected brain tumors who underwent combined MRI/MRS examinations were retrospectively reviewed. Final pathology was available in all cases. Group A comprised 60 subjects studied between June 2001 and January 2005, when MRS was considered exploratory and radiologists utilized only conventional MRI to arrive at a diagnosis. For group B, comprising 60 subjects studied between January 2005 and March 2008, the radiologists utilized information from both MRI and MRS. Furthermore, radiologists revisited group A (blind review, time lapse >4 years) to determine whether the additional information from MRS would have altered their interpretation. Sixty-three percent of patients in group A were diagnosed correctly, whereas in 10 % the report was partially correct with the final tumor type mentioned (but not mentioned as most likely tumor), while in 27 % of cases the reports were wrong. For group B, the diagnoses were correct in 87 %, partially correct in 5 %, and incorrect in 8 % of the cases, which is a significant improvement (p < 0.005). Re-review of combined MRI and MRS of group A resulted 87 % correct, 7 % partially correct, and 7 % incorrect diagnoses, which is a significant improvement over the original diagnoses (p < 0.05). Adding MRS to conventional MRI significantly improved diagnostic accuracy in preoperative pediatric patients with untreated brain tumors. (orig.)

Combined MRI and MRS improves pre-therapeutic diagnoses of pediatric brain tumors over MRI alone

International Nuclear Information System (INIS)

Shiroishi, Mark S.; Nelson, Marvin D.; Panigrahy, Ashok; Moore, Kevin R.; Gilles, Floyd H.; Gonzalez-Gomez, Ignacio; Blueml, Stefan

2015-01-01

The specific goal of this study was to determine whether the inclusion of MRS had a measureable and positive impact on the accuracy of pre-surgical MR examinations of untreated pediatric brain tumors over that of MRI alone in clinical practice. Final imaging reports of 120 pediatric patients with newly detected brain tumors who underwent combined MRI/MRS examinations were retrospectively reviewed. Final pathology was available in all cases. Group A comprised 60 subjects studied between June 2001 and January 2005, when MRS was considered exploratory and radiologists utilized only conventional MRI to arrive at a diagnosis. For group B, comprising 60 subjects studied between January 2005 and March 2008, the radiologists utilized information from both MRI and MRS. Furthermore, radiologists revisited group A (blind review, time lapse >4 years) to determine whether the additional information from MRS would have altered their interpretation. Sixty-three percent of patients in group A were diagnosed correctly, whereas in 10 % the report was partially correct with the final tumor type mentioned (but not mentioned as most likely tumor), while in 27 % of cases the reports were wrong. For group B, the diagnoses were correct in 87 %, partially correct in 5 %, and incorrect in 8 % of the cases, which is a significant improvement (p < 0.005). Re-review of combined MRI and MRS of group A resulted 87 % correct, 7 % partially correct, and 7 % incorrect diagnoses, which is a significant improvement over the original diagnoses (p < 0.05). Adding MRS to conventional MRI significantly improved diagnostic accuracy in preoperative pediatric patients with untreated brain tumors. (orig.)

Enhanced phase contrast transfer using ptychography combined with a pre-specimen phase plate in a scanning transmission electron microscope

Energy Technology Data Exchange (ETDEWEB)

Yang, Hao; Ercius, Peter [Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Nellist, Peter D. [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Ophus, Colin, E-mail: clophus@lbl.gov [Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States)

2016-12-15

The ability to image light elements in both crystalline and noncrystalline materials at near atomic resolution with an enhanced contrast is highly advantageous to understand the structure and properties of a wide range of beam sensitive materials including biological specimens and molecular hetero-structures. This requires the imaging system to have an efficient phase contrast transfer at both low and high spatial frequencies. In this work we introduce a new phase contrast imaging method in a scanning transmission electron microscope (STEM) using a pre-specimen phase plate in the probe forming aperture, combined with a fast pixelated detector to record diffraction patterns at every probe position, and phase reconstruction using ptychography. The phase plate significantly enhances the contrast transfer of low spatial frequency information, and ptychography maximizes the extraction of the phase information at all spatial frequencies. In addition, the STEM probe with the presence of the phase plate retains its atomic resolution, allowing simultaneous incoherent Z-contrast imaging to be obtained along with the ptychographic phase image. An experimental image of Au nanoparticles on a carbon support shows high contrast for both materials. Multislice image simulations of a DNA molecule shows the capability of imaging soft matter at low dose conditions, which implies potential applications of low dose imaging of a wide range of beam sensitive materials. - Highlights: • This work demonstrates a phase contrast imaging method by combining a pre-specimen phase plate with ptychogrpahy. • This method is shown to have a high phase contrast transfer efficiency at both low and high spatial frequencies. • Unlike CTEM which uses a heavy defocus to gain contrast, the phase plate gives a linear phase contrast at zero defocus aberrations. • Image simulations of DNA suggest this method is highly attractive for imaging beam sensitive materials at a low dose.

Precooling and Warm-Up Effects on Time Trial Cycling During Heat Stress.

Science.gov (United States)

Al-Horani, Ramzi A; Wingo, Jonathan E; Ng, Jason; Bishop, Phillip; Richardson, Mark

2018-02-01

Heat stress limits endurance exercise performance. Combining precooling and warm-up prior to endurance exercise in the heat may exploit the benefits of both strategies while avoiding the potential negative consequences of each. This study tested the hypothesis that precooling combined with warm-up improves time trial cycling performance in the heat relative to either treatment alone. Nine healthy men completed three 16.1-km time trials in 33°C after: 1) precooling (ice slurry and ice vest) alone (PREC); 2) warm-up alone (WU); or 3) PREC plus WU (COMBO). Tre was lower after PREC compared to WU throughout exercise and lower than COMBO for the first 12 km; COMBO was lower than WU for the first 4 km. Tsk during PREC was lower than COMBO and WU for the first 8 km, and lower in COMBO than WU for the first 4 km. PREC lowered pre-exercise heart rate relative to COMBO and WU (68 ± 10, 106 ± 12, 101 ± 13 bpm, respectively), but it increased similarly during exercise. Local sweat rate (SR) was lower in PREC (0.1 ± 0.1 mg · cm-2 · min-1) than COMBO (0.5 ± 0.2 mg · cm-2 · min-1) and WU (0.6 ± 0.2 mg · cm-2 · min-1) for the first 4 km. Treatments did not differentially affect performance (PREC = 31.9 ± 1.9 min, COMBO = 32.6 ± 2.7 min, WU = 33.1 ± 2.9 min). We conclude precooling alone or with warm-up mitigated thermal strain during exercise, but did not significantly improve 16.1-km cycling time trial performance.Al-horani RA, Wingo JE, Ng J, Bishop P, Richardson M. Precooling and warm-up effects on time trial cycling during heat stress. Aerosp Med Hum Perform. 2018; 89(2):87-93.

Whole-body pre-cooling does not alter human muscle metabolism during sub-maximal exercise in the heat.

Science.gov (United States)

Booth, J; Wilsmore, B R; Macdonald, A D; Zeyl, A; Mcghee, S; Calvert, D; Marino, F E; Storlien, L H; Taylor, N A

2001-06-01

Muscle metabolism was investigated in seven men during two 35 min cycling trials at 60% peak oxygen uptake, at 35 degrees C and 50% relative humidity. On one occasion, exercise was preceded by whole-body cooling achieved by immersion in water during a reduction in temperature from 29 to 24 degrees C, and, for the other trial, by immersion in water at a thermoneutral temperature (control, 34.8 degrees C). Pre-cooling did not alter oxygen uptake during exercise (P > 0.05), whilst the change in cardiac frequency and body mass both tended to be lower following pre-cooling (0.05 whole-body pre-cooling does not alter muscle metabolism during submaximal exercise in the heat. It is more likely that thermoregulatory and cardiovascular strain are reduced, through lower muscle and core temperatures.

EDRN Pre-Validation of Multiplex Biomarker in Urine — EDRN Public Portal

Science.gov (United States)

The goal of this proposal is to begin to establish an EDRN “pre-validation” trial of a multiplex set of transcripts, including the ETS gene fusions, in post-DRE urine sediments. As can be evidenced by our preliminary data, we have established the utility of this multiplex urine test (which includes TMPRSS-ERG, SPINK1, PCA3 and GOLPH2) in a cohort of prospectively collected urine sediments from the University of Michigan EDRN CEVC site (collected by co-I, Dr. John Wei). In this proposal, we will run this multiplex assay on prospectively collected post-DRE urines collected from other EDRN sites. The idea is to couple this “pre-validation” study with an EDRN validation trial under consideration for the Gen-Probe PCA3 urine test (directed by Drs. John Wei and Harry Rittenhouse).

Combined modality treatment with radiotherapy and chemotherapy

International Nuclear Information System (INIS)

Tannock, I.F.; Toronto Univ., ON

1989-01-01

The present paper discusses some of the methodological issues which can confound the interpretation of clinical trials of combined modality treatment. It reviews some of the larger randomized trials which have evaluated combined modality treatment in cancers of the head and neck, lung, gastrointestinal tract and bladder. It concludes that adequate trials have yet to be performed in many of thses sites, but that at present, evidence for long-term benefit from adjunctivechemotherapy is meagre. Finally, it suggests some possible mechanisms which might heve limited the benefit of chemotherapy when added to radiation treatment. (Author). 87 refs.; 4 figs.; 4 tabs

Analysis of covariance with pre-treatment measurements in randomized trials under the cases that covariances and post-treatment variances differ between groups.

Science.gov (United States)

Funatogawa, Takashi; Funatogawa, Ikuko; Shyr, Yu

2011-05-01

When primary endpoints of randomized trials are continuous variables, the analysis of covariance (ANCOVA) with pre-treatment measurements as a covariate is often used to compare two treatment groups. In the ANCOVA, equal slopes (coefficients of pre-treatment measurements) and equal residual variances are commonly assumed. However, random allocation guarantees only equal variances of pre-treatment measurements. Unequal covariances and variances of post-treatment measurements indicate unequal slopes and, usually, unequal residual variances. For non-normal data with unequal covariances and variances of post-treatment measurements, it is known that the ANCOVA with equal slopes and equal variances using an ordinary least-squares method provides an asymptotically normal estimator for the treatment effect. However, the asymptotic variance of the estimator differs from the variance estimated from a standard formula, and its property is unclear. Furthermore, the asymptotic properties of the ANCOVA with equal slopes and unequal variances using a generalized least-squares method are unclear. In this paper, we consider non-normal data with unequal covariances and variances of post-treatment measurements, and examine the asymptotic properties of the ANCOVA with equal slopes using the variance estimated from a standard formula. Analytically, we show that the actual type I error rate, thus the coverage, of the ANCOVA with equal variances is asymptotically at a nominal level under equal sample sizes. That of the ANCOVA with unequal variances using a generalized least-squares method is asymptotically at a nominal level, even under unequal sample sizes. In conclusion, the ANCOVA with equal slopes can be asymptotically justified under random allocation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhancing Pre-Service Special Educator Preparation through Combined Use of Virtual Simulation and Instructional Coaching

Science.gov (United States)

Peterson-Ahmad, Maria

2018-01-01

To meet the ever-increasing teaching standards, pre-service special educators need extensive and advanced opportunities for pedagogical preparation prior to entering the classroom. Providing opportunities for pre-service special educators to practice such strategies within a virtual simulation environment offers teacher preparation programs a way…

Recruitment strategies and challenges in a large intervention trial: Systolic Blood Pressure Intervention Trial.

Science.gov (United States)

Ramsey, Thomas M; Snyder, Joni K; Lovato, Laura C; Roumie, Christianne L; Glasser, Steven P; Cosgrove, Nora M; Olney, Christine M; Tang, Rocky H; Johnson, Karen C; Still, Carolyn H; Gren, Lisa H; Childs, Jeffery C; Crago, Osa L; Summerson, John H; Walsh, Sandy M; Perdue, Letitia H; Bankowski, Denise M; Goff, David C

2016-06-01

The Systolic Blood Pressure Intervention Trial is a multicenter, randomized clinical trial of 9361 participants with hypertension who are ≥50 years old. The trial is designed to evaluate the effect of intensive systolic blood pressure control (systolic blood pressure goal recruitment strategies and lessons learned during recruitment of the Systolic Blood Pressure Intervention Trial cohort and five targeted participant subgroups: pre-existing cardiovascular disease, pre-existing chronic kidney disease, age ≥75 years, women, and minorities. In collaboration with the National Institutes of Health Project Office and Systolic Blood Pressure Intervention Trial Coordinating Center, five Clinical Center Networks oversaw clinical site selection, recruitment, and trial activities. Recruitment began on 8 November 2010 and ended on 15 March 2013 (about 28 months). Various recruitment strategies were used, including mass mailing, brochures, referrals from healthcare providers or friends, posters, newspaper ads, radio ads, and electronic medical record searches. Recruitment was scheduled to last 24 months to enroll a target of 9250 participants; in just over 28 months, the trial enrolled 9361 participants. The trial screened 14,692 volunteers, with 33% of initial screens originating from the use of mass mailing lists. Screening results show that participants also responded to recruitment efforts through referral by Systolic Blood Pressure Intervention Trial staff, healthcare providers, or friends (45%); brochures or posters placed in clinic waiting areas (15%); and television, radio, newspaper, Internet ads, or toll-free numbers (8%). The overall recruitment yield (number randomized/number screened) was 64% (9361 randomized/14,692 screened), 77% for those with cardiovascular disease, 79% for those with chronic kidney disease, 70% for those aged ≥75 years, 55% for women, and 61% for minorities. As recruitment was observed to lag behind expectations, additional

Microbicide clinical trial adherence: insights for introduction.

Science.gov (United States)

Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena

2013-04-08

After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.

The Magpie Trial follow up study: outcome after discharge from hospital for women and children recruited to a trial comparing magnesium sulphate with placebo for pre-eclampsia [ISRCTN86938761

Directory of Open Access Journals (Sweden)

2004-03-01

Full Text Available Abstract Background The Magpie Trial compared magnesium sulphate with placebo for women with pre-eclampsia. 10,141 women were recruited, 8804 before delivery. Overall, 9024 children were included in the analysis of outcome at discharge from hospital. Magnesium sulphate more than halved the risk of eclampsia, and probably reduced the risk of maternal death. There did not appear to be any substantive harmful effects on the baby, in the short term. It is now important to assess whether these benefits persist, and to provide adequate reassurance about longer term safety. The main objective of the Magpie Trial Follow Up Study is to assess whether in utero exposure to magnesium sulphate has a clinically important effect on the child's chance of surviving without major neurosensory disability. Other objectives are to assess long term outcome for the mother, and to develop and assess appropriate strategies for following up large numbers of children in perinatal trials. Study design Follow up is only feasible in selected centres. We therefore anticipate contacting 2800–3350 families, for 2435–2915 of whom the woman was randomised before delivery. A further 280–335 children would have been eligible for follow up if they had survived. The total sample size for the children is therefore 3080–3685, 2680–3210 of whom will have been born to women randomised before delivery. Families eligible for the follow up will be contacted, and surviving children screened using the Ages and Stages Questionnaires. Children who screen positive, and a sample of those who screen negative, will whenever possible have a paediatric and neurodevelopmental assessment. When women are contacted to ask how their child is, they will also be asked about their own health. The primary outcome is a composite measure of death or neurosensory disability for the child at 18 months. Discussion The Follow Up Study began in 2002, and now involves collaborators in 19 countries. Data

An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism.

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Nieschlag, Eberhard; Bouloux, Pierre-Marc G; Stegmann, Barbara J; Shankar, R Ravi; Guan, Yanfen; Tzontcheva, Anjela; McCrary Sisk, Christine; Behre, Hermann M

2017-03-07

Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH. This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 10 6 /mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 10 6 /mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated. Corifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .

Parallel combinations of pre-ionized low jitter spark gaps

International Nuclear Information System (INIS)

Fitzsimmons, W.A.; Rosocha, L.A.

1979-01-01

The properties of 10 to 30 kV four electrode field emission pre-ionized triggered spark gaps have been studied. A mid-plane off-axis trigger electrode is biased at +V 0 /2, and a field emission point is located adjacent to and biased at the grounded cathode potential. Simultaneous application of a -V 0 trigger rapid pulse to both the electrodes results in the rapid sequential closing of the anode-trigger and trigger-cathode gaps. The observed jitter is about 1.5 ns. Parallel operation of these gaps (up to 10 so far) connected to a common capacitive load has been studied. A simple theory that predicts the number of gaps that may be expected to operate in parallel is discussed

Effect of β-alanine supplementation on 20 km cycling time trial performance

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Ruth Margaret JAMES

2014-09-01

Full Text Available The effects of β-alanine supplementation on high-intensity cycling performance and capacity have been evaluated, although the effects on longer duration cycling performance are unclear. Nineteen UK category 1 male cyclists completed four 20 km cycling time trials, two before and two after supplementation with either 6.4 g•d-1 β-alanine (n = 10; BA or a matched placebo (n = 9; P. Performance time for the 20 km time trial and 1 km split times were recorded. There was no significant effect of β-alanine supplementation on 20 km time trial performance (BA-pre 1943 ± 129 s; BA-post 1950 ± 147 s; P-pre 1989 ± 106 s; P-post 1986 ± 115 s or on the performance of each 1 km split. The effect of β-alanine on 20 km time trial performance was deemed unclear as determined by magnitude based inferences. Supplementation with 6.4 g•d-1 of β-alanine for 4 weeks did not affect 20 km cycling time trial performance in well trained male cyclists.

Long acting systemic HIV pre-exposure prophylaxis: an examination of the field.

Science.gov (United States)

Lykins, William R; Luecke, Ellen; Johengen, Daniel; van der Straten, Ariane; Desai, Tejal A

2017-12-01

Oral pre-exposure prophylaxis for the prevention of HIV-1 transmission (HIV PrEP) has been widely successful as demonstrated by a number of clinical trials. However, studies have also demonstrated the need for patients to tightly adhere to oral dosing regimens in order to maintain protective plasma and tissue concentrations. This is especially true for women, who experience less forgiveness from dose skipping than men in clinical trials of HIV PrEP. There is increasing interest in long-acting (LA), user-independent forms of HIV PrEP that could overcome this adherence challenge. These technologies have taken multiple forms including LA injectables and implantables. Phase III efficacy trials are ongoing for a LA injectable candidate for HIV PrEP. This review will focus on the design considerations for both LA injectable and implantable platforms for HIV PrEP. Additionally, we have summarized the existing LA technologies currently in clinical and pre-clinical studies for HIV PrEP as well as other technologies that have been applied to HIV PrEP and contraceptives. Our discussion will focus on the potential application of these technologies in low resource areas, and their use in global women's health.

A trial assessing N-3 as treatment for injury-induced cachexia (ATLANTIC trial: does a moderate dose fish oil intervention improve outcomes in older adults recovering from hip fracture?

Directory of Open Access Journals (Sweden)

Cleland Leslie

2010-10-01

Full Text Available Abstract Background Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega-3 fatty acids derived from fish oils have been extensively studied for their anti-inflammatory benefits. Due to their anti-inflammatory properties, the benefit of fish oil combined with individualized nutrition support amongst proximal femoral fracture patients post surgery is an attractive potential therapeutic strategy. The aim of the ATLANTIC trial is to assess the potential benefits of an anti-inflammatory dose of fish oil within the context of a 12 week individualised nutrition program, commencing seven days post proximal femoral fracture surgery. Methods/Design This randomized controlled, double blinded trial, will recruit 150 community dwelling elderly patients aged ≥65 years, within seven days of surgery for proximal femoral fracture. Participants will be randomly allocated to receive either a 12 week individualized nutrition support program complemented with 20 ml/day anti-inflammatory dose fish oil (~3.6 g eicosapentaenoic acid, ~2.4 g docosahexanoic acid; intervention, or, a 12 week individualized nutrition support program complemented with 20 ml/day low dose fish oil (~0.36 g eicosapentaenoic acid, ~0.24 g docosahexanoic acid; control. Discussion The ATLANTIC trial is the first of its kind to provide fish oil combined with individualized nutrition therapy as an intervention to address the inflammatory response experienced post proximal femoral fracture surgery amongst elderly patients. The final outcomes of this trial will assist clinicians in

Concurrent transcranial direct current stimulation and progressive resistance training in Parkinson's disease: study protocol for a randomised controlled trial.

Science.gov (United States)

Hendy, Ashlee M; Tillman, Alex; Rantalainen, Timo; Muthalib, Makii; Johnson, Liam; Kidgell, Dawson J; Wundersitz, Daniel; Enticott, Peter G; Teo, Wei-Peng

2016-07-19

improve lower limb strength, postural sway, gait speed and stride variability compared with PRT with sham tDCS. Further, we hypothesise that pre-frontal cortex activation during dual-task cognitive and gait/balance activities will be reduced, and that M1 excitability and inhibition will be augmented, following the combined PRT and a-tDCS intervention. Australian New Zealand Clinical Trials Registry ACTRN12615001241527 . Registered on 12 November 2015.

A pneumatic Bionic Voice prosthesis-Pre-clinical trials of controlling the voice onset and offset.

Science.gov (United States)

Ahmadi, Farzaneh; Noorian, Farzad; Novakovic, Daniel; van Schaik, André

2018-01-01

Despite emergent progress in many fields of bionics, a functional Bionic Voice prosthesis for laryngectomy patients (larynx amputees) has not yet been achieved, leading to a lifetime of vocal disability for these patients. This study introduces a novel framework of Pneumatic Bionic Voice Prostheses as an electronic adaptation of the Pneumatic Artificial Larynx (PAL) device. The PAL is a non-invasive mechanical voice source, driven exclusively by respiration with an exceptionally high voice quality, comparable to the existing gold standard of Tracheoesophageal (TE) voice prosthesis. Following PAL design closely as the reference, Pneumatic Bionic Voice Prostheses seem to have a strong potential to substitute the existing gold standard by generating a similar voice quality while remaining non-invasive and non-surgical. This paper designs the first Pneumatic Bionic Voice prosthesis and evaluates its onset and offset control against the PAL device through pre-clinical trials on one laryngectomy patient. The evaluation on a database of more than five hours of continuous/isolated speech recordings shows a close match between the onset/offset control of the Pneumatic Bionic Voice and the PAL with an accuracy of 98.45 ±0.54%. When implemented in real-time, the Pneumatic Bionic Voice prosthesis controller has an average onset/offset delay of 10 milliseconds compared to the PAL. Hence it addresses a major disadvantage of previous electronic voice prostheses, including myoelectric Bionic Voice, in meeting the short time-frames of controlling the onset/offset of the voice in continuous speech.

Placebo cohorts in phase-3 MS treatment trials - predictors for on-trial disease activity 1990-2010 based on a meta-analysis and individual case data.

Directory of Open Access Journals (Sweden)

Jan-Patrick Stellmann

Full Text Available BACKGROUND: Annualized relapse rates (ARR in the placebo cohorts of phase-3 randomized controlled trials (RCT of new treatments for relapsing remitting multiple sclerosis (RRMS have decreased substantially during the last two decades. The causes of these changes are not clear. We consider a better understanding of this phenomenon essential for valuing the effects of new drugs and by designing new trials. OBJECTIVES: To identify predictive factors of on-study ARR in early and recent MS trials. METHODS: ARR, rate of relapse-free patients, trial start dates, baseline demographics, relapse definitions and the use of McDonald criteria were retrieved by literature research of the placebo cohorts from RRMS phase-3 trials. Predictors were estimated by univariate and multivariate regression analyses and random-effects meta-regression. In addition, regression models were calculated by the Sylvia Lawry Centre's (SLC, including individual case data from clinical trials performed until 2000. The most reliable meta-analytic results can be gained from pooled individual case data. In lack of this, random-effects meta-analyses are recommended. RESULTS: Data from 12 published and one unpublished trial show a decrease of ARR from 1988 to 2012 (adjR(2 = 0.807, p<0.0001. Regression models identified McDonald criteria followed by baseline mean age and the pre-study relapse rate as predictors of the ARR. The pooled individual case data (n = 505 confirmed a decrease of ARR over time. The pre-study relapse rate was the best predictor for on-study relapses. Lacking individual case data after implementation of the McDonald criteria excludes a direct comparison concerning McDonald criteria. CONCLUSION: Pre-study relapse rate was the best predictor for on-study relapse rate but failed to explain the decrease of the ARR over time alone. Higher age at baseline and the implementation of McDonald criteria were associated as well with a lowered relapse rate in the random

Hypothalamic Obesity following Craniopharyngioma Surgery: Results of a Pilot Trial of Combined Diazoxide and Metformin Therapy

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Ahmet Alexandra

2011-03-01

Full Text Available Objective. To assess the effect of combined diazoxide-metformin therapy in obese adolescents treated for craniopharyngioma. Design. A prospective open-label 6-month pilot treatment trial in 9 obese subjects with craniopharyngioma. Diazoxide (2 mg/kg divided b.i.d., maximum 200 mg/day and metformin (1000 mg b.i.d.. Whole body insulin sensitivity index (WBISI and area-under-the-curve insulin (AUCins were calculated. Results. Seven subjects completed: 4M/3F, mean ± SD age years, weight  kg, BMI  kg/m2, and BMI SDS . Two were withdrawn due to vomiting and peripheral edema. Of participants completing the study, the mean ± SD weight gain, BMI, and BMI SDS during the 6 months were reduced compared to the 6 months prestudy ( versus  kg, ; versus  kg/m2, ; versus , , resp.. AUCins correlated with weight loss (, and BMI decrease (, . Conclusion. Combined diazoxide-metformin therapy was associated with reduced weight gain in patients with hypothalamic obesity. AUCins at study commencement predicted effectiveness of the treatment.

Pre-clinical and clinical development of the first placental malaria vaccine

DEFF Research Database (Denmark)

Pehrson, Caroline; Salanti, Ali; Theander, Thor G

2017-01-01

the condition.  Areas covered: Pub Med was searched using the broad terms 'malaria parasite placenta' to identify studies of interactions between parasite and host, 'prevention of placental malaria' to identify current strategies to prevent placental malaria, and 'placental malaria vaccine' to identify pre-clinical...... vaccine development. However, all papers from these searches were not systematically included.  Expert commentary: The first phase I clinical trials of vaccines are well underway. Trials testing efficacy are more complicated to carry out as only women that are exposed to parasites during pregnancy...

Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial.

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Morris, Jonathan M; Roberts, Christine L; Bowen, Jennifer R; Patterson, Jillian A; Bond, Diana M; Algert, Charles S; Thornton, Jim G; Crowther, Caroline A

2016-01-30

Preterm pre-labour ruptured membranes close to term is associated with increased risk of neonatal infection, but immediate delivery is associated with risks of prematurity. The balance of risks is unclear. We aimed to establish whether immediate birth in singleton pregnancies with ruptured membranes close to term reduces neonatal infection without increasing other morbidity. The PPROMT trial was a multicentre randomised controlled trial done at 65 centres across 11 countries. Women aged over 16 years with singleton pregnancies and ruptured membranes before the onset of labour between 34 weeks and 36 weeks and 6 days weeks who had no signs of infection were included. Women were randomly assigned (1:1) by a computer-generated randomisation schedule with variable block sizes, stratified by centre, to immediate delivery or expectant management. The primary outcome was the incidence of neonatal sepsis. Secondary infant outcomes included a composite neonatal morbidity and mortality indicator (ie, sepsis, mechanical ventilation ≥24 h, stillbirth, or neonatal death); respiratory distress syndrome; any mechanical ventilation; and duration of stay in a neonatal intensive or special care unit. Secondary maternal outcomes included antepartum or intrapartum haemorrhage, intrapartum fever, postpartum treatment with antibiotics, and mode of delivery. Women and caregivers could not be masked, but those adjudicating on the primary outcome were masked to group allocation. Analyses were by intention to treat. This trial is registered with the International Clinical Trials Registry, number ISRCTN44485060. Between May 28, 2004, and June 30, 2013, 1839 women were recruited and randomly assigned: 924 to the immediate birth group and 915 to the expectant management group. One woman in the immediate birth group and three in the expectant group were excluded from the primary analyses. Neonatal sepsis occurred in 23 (2%) of 923 neonates whose mothers were assigned to immediate birth and 29

Fixed-dose combinations in type 2 diabetes – role of the canagliflozin metformin combination

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Fleming JW

2015-06-01

Full Text Available Joshua W Fleming, Laurie W Fleming, Courtney S Davis Department of Pharmacy Practice, The University of Mississippi School of Pharmacy, Jackson, MS, USA Abstract: Canagliflozin–metformin is one of the newest combination therapies available for the treatment of type 2 diabetes mellitus (T2DM. Canagliflozin is an inhibitor of the sodium–glucose co-transporter 2 which causes an increase in the urinary excretion of glucose. In the present article, we review the safety and efficacy of canagliflozin and metformin from data obtained from Phase III metformin add-on therapy clinical trials as there are no studies to date that specifically evaluate the combination of metformin and canagliflozin. Trials included in this review were dual-therapy trials of subjects who were already taking background metformin and were assigned to receive canagliflozin, glimepiride, or sitagliptin. The addition of canagliflozin to metformin resulted in a decrease in HbA1c of 0.73%–0.93%. Canagliflozin 100 mg was considered to be non-inferior to glimepiride and sitagliptin 100 mg with the canagliflozin 300 mg dose being statistically superior to sitagliptin and glimepiride. Other advantages of the use of canagliflozin are reduction in weight (3.3–4.0 kg and systolic blood pressure (3.3–4.7 mmHg. The primary disadvantages are potential genital mycotic infections, hypotension, and gastrointestinal side effects from metformin. All things considered, this combination appears to be safe and effective in clinical trials and represents a promising option for the treatment of T2DM. Keywords: type 2 diabetes, fixed-dose combination (FDC, canagliflozin metformin 

Patient, Provider, and Combined Interventions for Managing Osteoarthritis in Primary Care: A Cluster Randomized Trial.

Science.gov (United States)

Allen, Kelli D; Oddone, Eugene Z; Coffman, Cynthia J; Jeffreys, Amy S; Bosworth, Hayden B; Chatterjee, Ranee; McDuffie, Jennifer; Strauss, Jennifer L; Yancy, William S; Datta, Santanu K; Corsino, Leonor; Dolor, Rowena J

2017-03-21

A single-site study showed that a combined patient and provider intervention improved outcomes for patients with knee osteoarthritis, but it did not assess separate effects of the interventions. To examine whether patient-based, provider-based, and patient-provider interventions improve osteoarthritis outcomes. Cluster randomized trial with assignment to patient, provider, and patient-provider interventions or usual care. (ClinicalTrials.gov: NCT01435109). 10 Duke University Health System community-based primary care clinics. 537 outpatients with symptomatic hip or knee osteoarthritis. The telephone-based patient intervention focused on weight management, physical activity, and cognitive behavioral pain management. The provider intervention involved electronic delivery of patient-specific osteoarthritis treatment recommendations to providers. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months. Secondary outcomes were objective physical function (Short Physical Performance Battery) and depressive symptoms (Patient Health Questionnaire). Linear mixed models assessed the difference in improvement among groups. No difference was observed in WOMAC score changes from baseline to 12 months in the patient (-1.5 [95% CI, -5.1 to 2.0]; P = 0.40), provider (2.5 [CI, -0.9 to 5.9]; P = 0.152), or patient-provider (-0.7 [CI, -4.2 to 2.8]; P = 0.69) intervention groups compared with usual care. All groups had improvements in WOMAC scores at 12 months (range, -3.7 to -7.7). In addition, no differences were seen in objective physical function or depressive symptoms at 12 months in any of the intervention groups compared with usual care. The study involved 1 health care network. Data on provider referrals were not collected. Contrary to a previous study of a combined patient and provider intervention for osteoarthritis in a Department of Veterans Affairs medical center, this study found no statistically

Analysis of longitudinal laboratory data in the presence of common selection mechanisms: a view toward greater emphasis on pre-marketing pharmaceutical safety.

Science.gov (United States)

Schildcrout, Jonathan S; Jenkins, Cathy A; Ostroff, Jack H; Gillen, Daniel L; Harrell, Frank E; Trost, Donald C

2008-05-30

Pharmaceutical safety has received substantial attention in the recent past; however, longitudinal clinical laboratory data routinely collected during clinical trials to derive safety profiles are often used ineffectively. For example, these data are frequently summarized by comparing proportions (between treatment arms) of participants who cross pre-specified threshold values at some time during follow-up. This research is intended, in part, to encourage more effective utilization of these data by avoiding unnecessary dichotomization of continuous data, acknowledging and making use of the longitudinal follow-up, and combining data from multiple clinical trials. However, appropriate analyses require careful consideration of a number of challenges (e.g. selection, comparability of study populations, etc.). We discuss estimation strategies based on estimating equations and maximum likelihood for analyses in the presence of three response history-dependent selection mechanisms: dropout, follow-up frequency, and treatment discontinuation. In addition, because clinical trials' participants usually represent non-random samples from target populations, we describe two sensitivity analysis approaches. All discussions are motivated by an analysis that aims to characterize the dynamic relationship between concentrations of a liver enzyme (alanine aminotransferase) and three distinct doses (no drug, low dose, and high dose) of an nk-1 antagonist across four Phase II clinical trials.

[Clinical Trial of Treatment of Cervicogenic Scapulohumeral Periarthritis by Red-hot Needle Therapy Combined with Cupping].

Science.gov (United States)

Yuan, Tao; Wang, Fen

2015-10-01

To observe the therapeutic effect of red-hot needle therapy combined with cupping for cervicogenic periarthritis of shoulder. Forty-two cases of cervicogenic periarthritis of shoulder were randomized into red-hot needle group and routine acupuncture group (n = 21). For patients of the routine acupuncture group, the filiform needles were applied to Tianzhu (BL 10), Jianjing (GB 21), Jianzhongshu (SI 15), Jianzhen (SI 9), Jianliao (TE 14), Jianyu (LI 15), Jianqian, Tianzong (SI 11) and Ashi-points on the affected side, followed by conducting cupping at the anterior and posterior regions of the affected shoulder, SI 11, GB 21 and SI 15. For patients of the red-hot needle group, the Ashi-points on the affected shoulder were punctured with cauterized filiform needles, following by performing cupping. The treatment was performed once daily and once every other day respectively for two weeks. The shoulder motor function was assessed according to the adjusted Constant-Murley test. After the treatment, the integrated scores of shoulder pain, shoulder-joint activities in daily living and shoulder-joint motion range were significantly increased in both groups compared with pre-treatment in the same one group (P therapy was significantly superior to that of the routine acupuncture (P therapy combined with cupping is effective in relieving cervicogenic shoulder periarthritis and is remarkably superior to routine acupuncture combined with cupping in improving shoulder periarthritis patients' symptoms.

Dry weight assessment by combined ultrasound and bioimpedance monitoring in low cardiovascular risk hemodialysis patients: a randomized controlled trial.

Science.gov (United States)

Siriopol, Dimitrie; Onofriescu, Mihai; Voroneanu, Luminita; Apetrii, Mugurel; Nistor, Ionut; Hogas, Simona; Kanbay, Mehmet; Sascau, Radu; Scripcariu, Dragos; Covic, Adrian

2017-01-01

Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. The precise assessment of hydration status in HD patients remains a major challenge for nephrologists. Our study aimed to explore whether combining two bedside methods, lung ultrasonography (LUS) and bioimpedance, may provide complementary information to guide treatment in specific HD patients. In total, 250 HD patients from two dialysis units were included in this randomized clinical trial. Patients were randomized 1:1 to have a dry weight assessment based on clinical (control) or LUS with bioimpedance in case of clinical hypovolemia (active)-guided protocol. The primary outcome was to assess the difference between the two groups on a composite of all-cause mortality and first cardiovascular event (CVE)-including death, stroke, and myocardial infarction. During a mean follow-up period was 21.3 ± 5.6 months, there were 54 (21.6%) composite events in the entire population. There was a nonsignificant 9% increase in the risk of this outcome in the active arm (HR = 1.09, 95% CI 0.64-1.86, p = 0.75). Similarly, there were no differences between the two groups when analyzing separately the all-cause mortality and CVE outcomes. However, patients in the active arm had a 19% lower relative risk of pre-dialytic dyspnea (rate ratio-0.81, 95% CI 0.68-0.96), but a 26% higher relative risk of intradialytic cramps (rate ratio-1.26, 95% CI 1.16-1.37). This study shows that a LUS-bioimpedance-guided dry weight adjustment protocol, as compared to clinical evaluation, does not reduce all-cause mortality and/or CVE in HD patients. A fluid management protocol based on bioimpedance with LUS on indication might be a better strategy.

Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis : Phase II Randomized Trial

NARCIS (Netherlands)

Wasunna, Monique; Njenga, Simon; Balasegaram, Manica; Alexander, Neal; Omollo, Raymond; Edwards, Tansy; Dorlo, Thomas P C|info:eu-repo/dai/nl/354064053; Musa, Brima; Ali, Mohammed Hassan Sharaf; Elamin, Mohammed Yasein; Kirigi, George; Juma, Rashid; Kip, Anke E.; Schoone, Gerard J.; Hailu, Asrat; Olobo, Joseph; Ellis, Sally; Kimutai, Robert; Wells, Susan; Khalil, Eltahir Awad Gasim; Strub Wourgaft, Nathalie; Alves, Fabiana; Musa, Ahmed

2016-01-01

Background: SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of

Including ethical considerations in models for first-trimester screening for pre-eclampsia

DEFF Research Database (Denmark)

Jørgensen, Jennifer Maureen; Hedley, Paula L.; Gjerris, Mickey

2014-01-01

Recent efforts to develop reliable and efficient early pregnancy screening programmes for pre-eclampsia have focused on com-bining clinical, biochemical and biophysical markers. The same model has been used for first-trimester screening for fetal aneuploidies i.e. prenatal diagnosis (PD), which...... is routinely offered to all pregnant women in many developed countries. Some studies suggest combining PD and pre-eclampsia screening, so women can be offered testing for a number of conditions at the same clinical visit. A combination of these tests may be practical in terms of saving time and resources......; however, the combination raises ethical issues. First-trimester PD and pre-eclampsia screening entail qualitative differences which alter the requirements for disclosure, non-directedness and consent with regard to the informed consent process. This article explores the differences related to the ethical...

Long-term impact of pre-operative physical rehabilitation protocol on the 6-min walk test of patients with adolescent idiopathic scoliosis: A randomized clinical trial

Directory of Open Access Journals (Sweden)

V.L. dos Santos Alves

2015-05-01

Full Text Available Background: Monitored physical activities in patients with adolescent idiopathic scoliosis (AIS have been shown to improve physical performance, endurance and cardiopulmonary function and may be assessed by the 6-min walk test (6MWT. We aimed to evaluate the long-term results of the 6MWT after a rehabilitation protocol employed before surgical correction for AIS. Methods: This prospective randomized clinical trial studied the impact of a 4-month pre-operative physical rehabilitation protocol on post-operative cardiopulmonary function and physical endurance, by using the 6MWT, in patients with AIS submitted to surgical correction, comparing them to matched controls without physical rehabilitation. Studied variables were heart and respiratory rate, systolic and diastolic blood pressure, peripheral blood oxygen saturation, Borg score, and distance walked. Patients were assessed at baseline, after 4 months of rehabilitation, and 3, 6 and 12 months post-operatively. Results: A total of 50 patients with AIS were included in the study and allocated blindly, by simple randomization, into either one of the two groups, with 25 patients each: study group (pre-operative physical rehabilitation and control group. The physical rehabilitation protocol promoted significant progressive improvement in heart and respiratory rate, peripheral blood oxygen saturation, distance walked, and level of effort assessed by the Borg scale after surgery. Conclusions: Post-surgical recovery, evaluated by 6MWT, was significantly better in patients who underwent a 4-month pre-operative physical rehabilitation protocol. Keywords: Scoliosis, Exercise, Exercise movement techniques, Exercise therapy, Exercise test

Pre-sowing irradiation of vegetable seeds

Energy Technology Data Exchange (ETDEWEB)

Stoyanov, S

1975-01-01

Results are reported of trials with radiation stimulation of vegetable crops conducted under farm conditions in different regions. They were based on exact tests accomplished at the IGHB. Pre-sowing irradiation of seed increased the greenhouse yield of Extase tomato variety by 15%; it increased the yield of Triumph tomato variety under field conditions as well. The pepper variety Kourtovska Kapiya and eggplant variety Bulgarski 12, both grown from irradiated seed in open field produced 18% and 5.5% higher yields, respectively. Irradiation of vegetable seeds finds a large application in the farm practice.

Pre-sowing irradiation of vegetable seeds

International Nuclear Information System (INIS)

Stoyanov, S.

1975-01-01

Results are reported of trials with radiation stimulation of vegetable crops conducted under farm conditions in different regions. They were based on exact tests accomplished at the IGHB. Pre-sowing irradiation of seed increased the greenhouse yield of Extase tomato variety by 15%; it increased the yield of Triumph tomato variety under field conditions as well. The pepper variety Kourtovska Kapiya and eggplant variety Bulgarski 12, both grown from irradiated seed in open field produced 18% and 5.5% higher yields, respectively. Irradiation of vegetable seeds finds a large application in the farm practice. (author)

Is hydrotherapy cost-effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis.

Science.gov (United States)

Epps, H; Ginnelly, L; Utley, M; Southwood, T; Gallivan, S; Sculpher, M; Woo, P

2005-10-01

To compare the effects of combined hydrotherapy and land-based physiotherapy (combined) with land-based physiotherapy only (land) on cost, health-related quality of life (HRQoL) and outcome of disease in children with juvenile idiopathic arthritis (JIA). Also to determine the cost-effectiveness of combined hydrotherapy and land-based physiotherapy in JIA. A multicentre randomised controlled, partially blinded trial was designed with 100 patients in a control arm receiving land-based physiotherapy only (land group) and 100 patients in an intervention arm receiving a combination of hydrotherapy and land-based physiotherapy (combined group). Three tertiary centres in the UK. Patients aged 4-19 years diagnosed more than 3 months with idiopathic arthritides, onset before their 16th birthday, stable on medication with at least one active joint. Patients in the combined and land groups received 16 1-hour treatment sessions over 2 weeks followed by local physiotherapy attendances for 2 months. Disease improvement defined as a decrease of > or =30% in any three of six core set variables without there being a 30% increase in more than one of the remaining three variables was used as the primary outcome measure and assessed at 2 months following completion of intervention. Health services resource use (in- and outpatient care, GP visits, drugs, interventions, and investigations) and productivity costs (parents' time away from paid work) were collected at 6 months follow-up. HRQoL was measured at baseline and 2 and 6 months following intervention using the EQ-5D, and quality-adjusted life-years (QALYs) were calculated. Secondary outcome measures at 2 and 6 months included cardiovascular fitness, pain, isometric muscle strength and patient satisfaction. Seventy-eight patients were recruited into the trial and received treatment. Two months after intervention 47% patients in the combined group and 61% patients in the land group had improved disease with 11 and 5% with worsened

How to Evaluate Phase Differences between Trial Groups in Ongoing Electrophysiological Signals

Science.gov (United States)

VanRullen, Rufin

2016-01-01

A growing number of studies endeavor to reveal periodicities in sensory and cognitive functions, by comparing the distribution of ongoing (pre-stimulus) oscillatory phases between two (or more) trial groups reflecting distinct experimental outcomes. A systematic relation between the phase of spontaneous electrophysiological signals, before a stimulus is even presented, and the eventual result of sensory or cognitive processing for that stimulus, would be indicative of an intrinsic periodicity in the underlying neural process. Prior studies of phase-dependent perception have used a variety of analytical methods to measure and evaluate phase differences, and there is currently no established standard practice in this field. The present report intends to remediate this need, by systematically comparing the statistical power of various measures of “phase opposition” between two trial groups, in a number of real and simulated experimental situations. Seven measures were evaluated: one parametric test (circular Watson-Williams test), and three distinct measures of phase opposition (phase bifurcation index, phase opposition sum, and phase opposition product) combined with two procedures for non-parametric statistical testing (permutation, or a combination of z-score and permutation). While these are obviously not the only existing or conceivable measures, they have all been used in recent studies. All tested methods performed adequately on a previously published dataset (Busch et al., 2009). On a variety of artificially constructed datasets, no single measure was found to surpass all others, but instead the suitability of each measure was contingent on several experimental factors: the time, frequency, and depth of oscillatory phase modulation; the absolute and relative amplitudes of post-stimulus event-related potentials for the two trial groups; the absolute and relative trial numbers for the two groups; and the number of permutations used for non-parametric testing

HPV SEROSTATUS PRE- AND POST-VACCINATION IN A RANDOMIZED PHASE II PREPAREDNESS TRIAL AMONG YOUNG WESTERN CAPE, SOUTH AFRICAN WOMEN: THE EVRI TRIAL.

Science.gov (United States)

Sudenga, Staci L; Torres, B Nelson; Botha, Matthys H; Zeier, Michele; Abrahamsen, Martha E; Glashoff, Richard H; Engelbrecht, Susan; Schim Van der Loeff, Maarten F; Van der Laan, Louvina E; Kipping, Siegfried; Taylor, Douglas; Giuliano, Anna R

2017-06-01

HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women. Women aged 16-24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type. Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6. HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut.

Effect of Turkish classical music on prenatal anxiety and satisfaction: A randomized controlled trial in pregnant women with pre-eclampsia.

Science.gov (United States)

Toker, Eylem; Kömürcü, Nuran

2017-02-01

The present study aimed to evaluate the effect of music therapy on anxiety and satisfaction in pregnant women with preeclampsia. A randomized controlled trial was performed on 70 pregnant women with pre-eclampsia hospitalized in the research and application hospital of Kahramanmaras Sütcü İmam University between December 2012 and February 2014. The subjects were allocated to experimental or control groups in a random manner (n=35 each). Pregnant women in the experimental group were subject to a 30min Turkish classical music therapy trial each day for a period of 7days (5days before and 2days after labor) whereas those in the control group received routine care and also were assigned to 30min of bed rest a day. The Personal Information Form, State-Trait Anxiety Inventory, and Newcastle Satisfaction with Nursing Scale were administered to participants. Data were analyzed using descriptive statistics, student t-test, and Mann-Whitney U test where appropriate. Outcome measures were anxiety scale scores, satisfaction scale scores, vital signs, fetal movement and fetal heart rate. The differences between anxiety scores were not statistically significant (p>0.05). On the other hand, Newcastle Satisfaction with Nursing Scale scores of the experiment group were higher than the control group (pusic Therapy had a minimalizing effect on fetal heart rate and a lowering effect on blood pressure (pusic therapy in the care and follow-up of pregnant women with preeclampsia in obstetrics units. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modafinil combined with cognitive training is associated with improved learning in healthy volunteers--a randomised controlled trial.

Science.gov (United States)

Gilleen, J; Michalopoulou, P G; Reichenberg, A; Drake, R; Wykes, T; Lewis, S W; Kapur, S

2014-04-01

Improving cognition in people with neuropsychiatric disorders remains a major clinical target. By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition. In the present study we tested a recently-proposed methodology to combine CT with a 'cognitive-enhancing' drug to improve cognitive test scores and expanded on previous approaches by delivering combination drug and CT, over a long intervention of repeated sessions, and used multiple tasks to reveal the cognitive processes being enhanced. We also aimed to determine whether gains from this combination approach generalised to untrained tests. In this proof of principle randomised-controlled trial thirty-three healthy volunteers were randomised to receive either modafinil or placebo combined with daily cognitive training over two weeks. Volunteers were trained on tasks of new-language learning, working memory and verbal learning following 200 mg modafinil or placebo for ten days. Improvements in trained and untrained tasks were measured. Rate of new-language learning was significantly enhanced with modafinil, and effects were greatest over the first five sessions. Modafinil improved within-day learning rather than between-day retention. No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning. Gains in all tasks were retained post drug-administration, but transfer effects to broad cognitive abilities were not seen. This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Clinical Trials

Medline Plus

Full Text Available ... combination of estrogen and progestin, the risk of breast cancer also increased. As a result, the U.S. Food ... to test new approaches to prevention, diagnosis, or screening. In the past, clinical trial participants often were ...

Trial of Music, Sucrose, and Combination Therapy for Pain Relief during Heel Prick Procedures in Neonates.

Science.gov (United States)

Shah, Swapnil R; Kadage, Shahajahan; Sinn, John

2017-11-01

To compare the effectiveness of music, oral sucrose, and combination therapy for pain relief in neonates undergoing a heel prick procedure. This randomized, controlled, blinded crossover clinical trial included stable neonates >32 weeks of postmenstrual age. Each neonate crossed over to all 3 interventions in random order during consecutive heel pricks. A video camera on mute mode recorded facial expressions, starting 2 minutes before until 7 minutes after the heel prick. The videos were later analyzed using the Premature Infant Pain Profile-Revised (PIPP-R) scale once per minute by 2 independent assessors, blinded to the intervention. The PIPP-R scores were compared between treatment groups using Friedman test. For the 35 participants, the postmenstrual age was 35 weeks (SD, 2.3) with an average weight of 2210 g (SD, 710). The overall median PIPP-R scores following heel prick over 6 minutes were 4 (IQR 0-6), 3 (IQR 0-6), and 1 (IQR 0-3) for the music, sucrose, and combination therapy interventions, respectively. The PIPP-R scores were significantly lower at all time points after combination therapy compared with the groups given music or sucrose alone. There was no difference in PIPP-R scores between the music and sucrose groups. In relatively stable and mature neonates, the combination of music therapy with sucrose provided better pain relief during heel prick than when sucrose or music was used alone. Recorded music in isolation had a similar effect to the current gold standard of oral sucrose. www.anzctr.org.au ACTRN12615000271505. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of osmotic dehydration pre-treatment and combined drying method on physico-chemical and sensory properties of pomegranate arils, cultivar Mollar de Elche.

Science.gov (United States)

Cano-Lamadrid, Marina; Lech, Krzysztof; Michalska, Anna; Wasilewska, Malwina; Figiel, Adam; Wojdyło, Aneta; Carbonell-Barrachina, Ángel A

2017-10-01

"Mollar de Elche" is the most popular Spanish pomegranate cultivar (intense sweetness and easy-to-chew arils); however, arils have pale pink colour and flat sensory profile. "Mollar the Elche" arils first underwent an osmotic dehydration pre-treatment (OD) with concentrated juices: (i) chokeberry, (ii) apple, and/or (iii) pomegranate cultivar "Wonderful", to improve their antioxidant capacity, colour, and sensory profile complexity, and later the arils were dried by a combined method (convective pre-drying+vacuum microwave finish drying). The use of OD provided dried arils with characteristic sweetness, and improved colour and aromatic complexity. The recommended OD methods were those using (i) pomegranate, and (ii) pomegranate with chokeberry juices; they improved the total anthocyanin content (mean of 368mgkg -1 ), red colour (a ∗ coordinate 15.6), and antioxidant capacity (e.g. ABTS mean of 5.7mmolTrolox100g -1 ). However, further research is still needed because freeze-dried arils had the highest anthocyanin content. Copyright © 2017 Elsevier Ltd. All rights reserved.

Single and Combined Effects of Beetroot Crystals and Sodium Bicarbonate on 4-km Cycling Time Trial Performance.

Science.gov (United States)

Callahan, Marcus J; Parr, Evelyn B; Hawley, John A; Burke, Louise M

2017-06-01

When ingested alone, beetroot juice and sodium bicarbonate are ergogenic for high-intensity exercise performance. This study sought to determine the independent and combined effects of these supplements. Eight endurance trained (VO 2 max 65 mL·kg·min -1 ) male cyclists completed four × 4-km time trials (TT) in a doubleblind Latin square design supplementing with beetroot crystals (BC) for 3 days (15 g·day -1 + 15 g 1 h before TT, containing 300 mg nitrate per 15 g), bicarbonate (Bi 0.3 g·kg -1 body mass [BM] in 5 doses every 15 min from 2.5 h before TT); BC+Bi or placebo (PLA). Subjects completed TTs on a Velotron cycle ergometer under standardized laboratory conditions. Plasma nitrite concentrations were significantly elevated only in the BC+Bi trial before the TT (1520 ± 786 nmol·L -1 ) compared with baseline (665 ± 535 nmol·L -1 , p = .02) and the Bi and PLA conditions (Bi: 593 ± 203 nmol·L -1 , p .05). Blood bicarbonate concentrations were increased in the BC+Bi and Bi trials before the TT (BC+Bi: 30.9 ± 2.8 mmol·L -1 ; Bi: 31.7 ± 1.1 mmol·L -1 ). There were no differences in mean power output (386-394 W) or the time taken to complete the TT (335.8-338.1 s) between any conditions. Under the conditions of this study, supplementation was not ergogenic for 4-km TT performance.

PAAPPAS community trial protocol: a randomized study of obesity prevention for adolescents combining school with household intervention

Directory of Open Access Journals (Sweden)

Michele R. Sgambato

2016-08-01

Full Text Available Abstract Background The prevalence of childhood obesity is increasing at a high rate in Brazil, making prevention a health priority. Schools are the central focus of interventions aiming the prevention and treatment of childhood obesity, however, randomized trials and cohort studies have not yet provided clear evidence of strategies to reduce prevalence of obesity. The aim of this study is to present a protocol to evaluate the efficacy of combining school and household level interventions to reduce excessive weight gain among students. Methods The intervention target fifth and sixth graders from 18 public schools (9 interventions and 9 controls in the municipality of Duque de Caxias, metropolitan area of Rio de Janeiro, Brazil. A sample size of 2500 students will be evaluated at school for their weight status and those from the intervention group who are overweight or obese will be followed monthly at home by community health agents. Demographic, socioeconomic, anthropometric, eating behavior and food consumption data will be collected at school using a standardized questionnaire programmed in personal digital assistant. At school, all students from the intervention group will be encouraged to change eating habits and food consumption and to increase physical activity and reducing sedentary behavior. Discussion This study will provide evidence whether integration of school with primary health care can prevent excessive weight gain among adolescents. Positive results will inform a sustainable strategy to be disseminated in the health care system in Brazil. Trial registration ClinicalTrials.gov, NCT02711488 . Date of registration: March 11, 2016.

A randomised trial of preoperative radiotherapy for stage T3 adenocarcinoma of rectum (TROG 01.04): a progress report

International Nuclear Information System (INIS)

Ngan, S.; Fisher, R.; McKay, M.J.; McClure, B.; Burmeister, B.H.; Schache, D.; Joseph, D.; Solomon, M.; Ackland, S.P.; Goldstein, D.; McLachlan, S.; Dhillon, H.; Thompson, P.

2003-01-01

To provide a progress report of the conduct of the randomised trial TROG 01.04. This is a randomised Australian and New Zealand multi-centre trial of preoperative radiotherapy for rectal cancer currently being conducted under the auspices of Trans-Tasman Radiation Oncology Group, Australasian Gastrointestinal Trials Group, Colorectal Surgical Society of Australasia, and Royal Australasian College of Surgeons. The trial comprises two studies, each with its own main objective. These objectives are, in patients with T3 clinically resectable carcinoma of the rectum, to demonstrate that (Study 1) the local recurrence rate in patients treated with a long course (LC) of pre-operative radiotherapy with continuous infusion 5-FU is lower than that in patients treated with a short course (SC) of pre-operative radiotherapy with early surgery; and (Study 2) the local recurrence rate in patients given pre-operative radiotherapy and chemotherapy is lower than that in patients treated with initial surgery. Over 150 patients have been accrued from 21 centres in the first 21 months. All patients were enrolled on Study 1, SC versus LC pre-operative radiotherapy. Study 2 has enrolled no patients in 15 months and has been discontinued. There was no obvious difference in rates of serious adverse events of SC and LC. An Independent Data Monitoring Committee is monitoring these and other aspects of the trial. The trial of SC versus LC is progressing well: such a trial is clearly feasible in Australia and New Zealand. It is however not feasible to compare initial surgery with preoperative radiotherapy

Police custody health care: a review of health morbidity, models of care and innovations within police custody in the UK, with international comparisons

Directory of Open Access Journals (Sweden)

McKinnon IG

2016-09-01

Full Text Available Iain G McKinnon,1,2 Stuart DM Thomas,3–5 Heather L Noga,6 Jane Senior7 1Institute of Health and Society, Newcastle University, Academic Psychiatry, Campus for Ageing and Vitality, 2Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK; 3School of Global, Urban and Social Studies, RMIT University, Melbourne, VIC, 4Legal Intersections Research Centre, University of Wollongong, Wollongong, NSW, 5Southern Clinical School, Monash University, Clayton, VIC, Australia; 6School of Criminology, Simon Fraser University, Burnaby, BC, Canada; 7Offender Health Research Network, University of Manchester, Manchester, UK Abstract: This paper is a scoping review of the available evidence regarding health care issues in police custody. It describes the types and prevalence of health disorders encountered in custody and provides an overview of current practice and recent innovations in police custody health care. In contrast to the health of prisoners, the health of police custody detainees has, until recently, received little academic or clinical attention. Studies on health care in police custody identified for this review are limited to a few geographical jurisdictions, including the UK, continental Europe, North America, and Australia. There are significant health concerns among police detainees including acute injury, chronic physical health problems, mental and cognitive disorders, and the risks associated with drug and alcohol intoxication or withdrawal. There is some evidence that deaths in police custody have reduced where attention has been paid to the latter issue. Police personnel continue to experience difficulties identifying detainees with health issues relevant to their safe detention, but research shows that the use of evidence-based screening tools improves detection of such morbidities. Innovations in police custody health care mainly relate to detainees with mental disorders, including improved identification of illness

Clinical characteristics, risk factors and pre-surgical evaluation of post-infectious epilepsy.

Science.gov (United States)

Sellner, J; Trinka, E

2013-03-01

Epilepsy is a frequent complication of central nervous system (CNS) infections. Post-infectious epilepsy is commonly refractory to medical treatment and plays a pivotal role for the poor long-term outcome of CNS infections. To provide an overview of clinical characteristics and risk factors of seizures associated with CNS infections. In addition, to summarize the state of the art of anticonvulsive treatment and the pre-surgical evaluation process in refractory cases. A comprehensive literature search for articles published between January 1970 and December 2011 was carried out. The occurrence of seizures during the acute course of meningitis, encephalitis and brain abscess is the main risk factor for the development of post-infectious epilepsy. There is a shortage of trials evaluating the efficacy of prophylactic and symptomatic treatment during the course of acute infection. Moreover, there are no randomized-controlled trials studying anticonvulsive drugs and their combinations for the management of post-infectious epilepsy. In a selected group of patients, however, medically refractory focal epilepsy is potentially curable by surgery. Further studies are required to improve the pathogenetic understanding of post-infectious epilepsy in order to develop preventive measures as well as to evaluate additional medical and surgical treatment strategies for the patients currently not considered for surgery. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

An analytical nonlinear magnetoelectric coupling model of laminated composites under combined pre-stress and magnetic bias loadings

International Nuclear Information System (INIS)

Zhou, Hao-Miao; Qu, Shao-Xing; Ou, Xiao-Wei; Xiao, Ying; Wu, Hua-Ping

2013-01-01

Based on the equivalent circuit method, this paper adopts the nonlinear magnetostrictive constitutive relations to establish an analytical nonlinear magnetoelectric coefficient model for magnetostrictive/piezoelectric/magnetostrictive laminated magnetoelectric composites. When the pre-stress is set to zero in the model, the predicted results of the magnetoelectric coefficient coincide well with the available experimental results both qualitatively and quantitatively. Using the model, we can qualitatively predict the influence of the pre-stress, magnetic bias fields and the volume fraction of the magnetostrictive material on the magnetoelectric coefficient. The predicted results show that the influences of the pre-stress on the magnetoelectric coefficient, which varies with the magnetic bias field, before and after reaching the magnetoelectric coefficient maximum, are opposite. That is, the influence of the pre-stress on curves of the magnetoelectric coefficient reverses when the magnetoelectric coefficient reaches its maximum. Therefore, the correct setting of the pre-stress can lower the applied magnetic bias field and improve the magnetoelectric coefficient. The established nonlinear magnetoelectric effect model can provide a theoretical basis for regulating the magnetoelectric coefficient by the pre-stress and magnetic bias field and make it possible to design high-precision miniature magnetoelectric devices. (paper)

76 FR 13275 - Periodic Review of Individuals Detained at Guantánamo Bay Naval Station Pursuant to the...

Science.gov (United States)

2011-03-10

... shall coordinate a process of periodic review of continued law of war detention for each detainee... Detention. The process established under this order does not address the legality of any detainee's law of... by the Constitution and the laws of the United States of America, including the Authorization for Use...

Effect of burst TENS and conventional TENS combined with cryotherapy on pressure pain threshold: randomised, controlled, clinical trial.

Science.gov (United States)

Macedo, L B; Josué, A M; Maia, P H B; Câmara, A E; Brasileiro, J S

2015-06-01

To assess the immediate effect of conventional and burst transcutaneous electrical nerve stimulation (TENS) in combination with cryotherapy on pain threshold and tolerance in healthy individuals. Randomised, controlled trial. University laboratory. One hundred and twelve healthy women. Volunteers were allocated at random to seven groups (n=16): (1) control, (2) placebo TENS, (3) conventional TENS, (4) burst TENS, (5) cryotherapy, (6) cryotherapy in combination with burst TENS, and (7) cryotherapy in combination with conventional TENS. Pain threshold and tolerance were measured by applying a pressure algometer at the lateral epicondyle of the humerus, before and after each intervention. The primary outcome measure was pressure pain threshold. A significant increase in pain threshold and tolerance at the 5% level of significance was recorded as follows: burst TENS {pain threshold: mean difference 1.3 [95% confidence interval (CI) 1.4 to 1.2]; pain tolerance: mean difference 3.8 (95% CI 3.9 to 3.7)}, cryotherapy [pain threshold: mean difference 1.3 (95% CI 1.4 to 1.2); pain tolerance: mean difference 1.9 (95% CI 1.8 to 2.0)] and cryotherapy in combination with burst TENS [pain threshold: mean difference 2.6 (95% CI 2.4 to 2.8); pain tolerance: mean difference 4.9 (95% CI 5.0 to 4.8)]. Cryotherapy in combination with burst TENS provided greater analgesia compared with the other groups (Pcryotherapy in combination with burst TENS to reduce induced pain, and suggest a potentiating effect when these techniques are combined. No such association was found between cryotherapy and conventional TENS. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Phase I clinical trial and pharmacodynamic evaluation of combination hydroxychloroquine and doxorubicin treatment in pet dogs treated for spontaneously occurring lymphoma.

Science.gov (United States)

Barnard, Rebecca A; Wittenburg, Luke A; Amaravadi, Ravi K; Gustafson, Daniel L; Thorburn, Andrew; Thamm, Douglas H

2014-08-01

Autophagy is a lysosomal degradation process that may act as a mechanism of survival in a variety of cancers. While pharmacologic inhibition of autophagy with hydroxychloroquine (HCQ) is currently being explored in human clinical trials, it has never been evaluated in canine cancers. Non-Hodgkin lymphoma (NHL) is one of the most prevalent tumor types in dogs and has similar pathogenesis and response to treatment as human NHL. Clinical trials in canine patients are conducted in the same way as in human patients, thus, to determine a maximum dose of HCQ that can be combined with a standard chemotherapy, a Phase I, single arm, dose escalation trial was conducted in dogs with spontaneous NHL presenting as patients to an academic, tertiary-care veterinary teaching hospital. HCQ was administered daily by mouth throughout the trial, beginning 72 h prior to doxorubicin (DOX), which was given intravenously on a 21-d cycle. Peripheral blood mononuclear cells and biopsies were collected before and 3 d after HCQ treatment and assessed for autophagy inhibition and HCQ concentration. A total of 30 patients were enrolled in the trial. HCQ alone was well tolerated with only mild lethargy and gastrointestinal-related adverse events. The overall response rate (ORR) for dogs with lymphoma was 93.3%, with median progression-free interval (PFI) of 5 mo. Pharmacokinetic analysis revealed a 100-fold increase in HCQ in tumors compared with plasma. There was a trend that supported therapy-induced increase in LC3-II (the cleaved and lipidated form of microtubule-associated protein 1 light chain 3/LC3, which serves as a maker for autophagosomes) and SQSTM1/p62 (sequestosome 1) after treatment. The superior ORR and comparable PFI to single-agent DOX provide strong support for further evaluation via randomized, placebo-controlled trials in canine and human NHL.

A pneumatic Bionic Voice prosthesis-Pre-clinical trials of controlling the voice onset and offset.

Directory of Open Access Journals (Sweden)

Farzaneh Ahmadi

Full Text Available Despite emergent progress in many fields of bionics, a functional Bionic Voice prosthesis for laryngectomy patients (larynx amputees has not yet been achieved, leading to a lifetime of vocal disability for these patients. This study introduces a novel framework of Pneumatic Bionic Voice Prostheses as an electronic adaptation of the Pneumatic Artificial Larynx (PAL device. The PAL is a non-invasive mechanical voice source, driven exclusively by respiration with an exceptionally high voice quality, comparable to the existing gold standard of Tracheoesophageal (TE voice prosthesis. Following PAL design closely as the reference, Pneumatic Bionic Voice Prostheses seem to have a strong potential to substitute the existing gold standard by generating a similar voice quality while remaining non-invasive and non-surgical. This paper designs the first Pneumatic Bionic Voice prosthesis and evaluates its onset and offset control against the PAL device through pre-clinical trials on one laryngectomy patient. The evaluation on a database of more than five hours of continuous/isolated speech recordings shows a close match between the onset/offset control of the Pneumatic Bionic Voice and the PAL with an accuracy of 98.45 ±0.54%. When implemented in real-time, the Pneumatic Bionic Voice prosthesis controller has an average onset/offset delay of 10 milliseconds compared to the PAL. Hence it addresses a major disadvantage of previous electronic voice prostheses, including myoelectric Bionic Voice, in meeting the short time-frames of controlling the onset/offset of the voice in continuous speech.

A pneumatic Bionic Voice prosthesis—Pre-clinical trials of controlling the voice onset and offset

Science.gov (United States)

Noorian, Farzad; Novakovic, Daniel; van Schaik, André

2018-01-01

Despite emergent progress in many fields of bionics, a functional Bionic Voice prosthesis for laryngectomy patients (larynx amputees) has not yet been achieved, leading to a lifetime of vocal disability for these patients. This study introduces a novel framework of Pneumatic Bionic Voice Prostheses as an electronic adaptation of the Pneumatic Artificial Larynx (PAL) device. The PAL is a non-invasive mechanical voice source, driven exclusively by respiration with an exceptionally high voice quality, comparable to the existing gold standard of Tracheoesophageal (TE) voice prosthesis. Following PAL design closely as the reference, Pneumatic Bionic Voice Prostheses seem to have a strong potential to substitute the existing gold standard by generating a similar voice quality while remaining non-invasive and non-surgical. This paper designs the first Pneumatic Bionic Voice prosthesis and evaluates its onset and offset control against the PAL device through pre-clinical trials on one laryngectomy patient. The evaluation on a database of more than five hours of continuous/isolated speech recordings shows a close match between the onset/offset control of the Pneumatic Bionic Voice and the PAL with an accuracy of 98.45 ±0.54%. When implemented in real-time, the Pneumatic Bionic Voice prosthesis controller has an average onset/offset delay of 10 milliseconds compared to the PAL. Hence it addresses a major disadvantage of previous electronic voice prostheses, including myoelectric Bionic Voice, in meeting the short time-frames of controlling the onset/offset of the voice in continuous speech. PMID:29466455

Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial.

Directory of Open Access Journals (Sweden)

Monique Wasunna

2016-09-01

Full Text Available SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa.A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day, 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day and miltefosine alone (2.5 mg/kg/day for 28 days. The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine and pharmacodynamic assessments.In sequential analyses with 49-51 patients per arm, initial cure was 85% (95% CI: 73-92 in all arms. At D210, definitive cure was 87% (95% CI: 77-97 for AmBisome + SSG, 77% (95% CI 64-90 for AmBisome + miltefosine and 72% (95% CI 60-85 for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults.No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated.The study was registered with ClinicalTrials.gov, number NCT01067443.

Cancer-Related Fatigue and Rehabilitation : A Randomized Controlled Multicenter Trial Comparing Physical Training Combined With Cognitive-Behavioral Therapy With Physical Training Only and With No Intervention

NARCIS (Netherlands)

van Weert, E.; May, A.M.; Korstjens, I.; Post, W.J.; van der Schans, C.P.; van den Borne, B.; Mesters, I.; Ros, W.J.G.; Hoekstra-Weebers, J.E.H.M.

2010-01-01

Background. Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial. Objective. This randomized controlled trial compared the effect on cancer-related fatigue of physical training combined with

Cancer-related fatigue and rehabilitation: A randomized controlled multicenter trial comparing physical training combined with cognitive-behavioral therapy with physical training only and with no intervention

NARCIS (Netherlands)

E. van Weert (Ellen); A.M. May (Anne); I. Korstjens (Irene); W.J. Post (Wendy); C.P. van der Schans (Cees); B. van den Borne (Bart); I. Mesters (Ilse); W.J.G. Ros (Wynand); J.E.H.M. Hoekstra-Weebers (Josette)

2010-01-01

textabstractBackground. Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial. Objective. This randomized controlled trial compared the effect on cancerrelated fatigue of physical training combined

Static stretching does not alter pre and post-landing muscle activation

Directory of Open Access Journals (Sweden)

Moss Wesley R

2011-05-01

Full Text Available Abstract Background Static stretching may result in various strength and power deficiencies. Prior research has not determined, however, if static stretching causes a change in muscle activation during a functional task requiring dynamic stability. The purpose of this study was to determine if static stretching has an effect on mean pre and postlanding muscle (vastus medialis VM, vastus lateralis VL, medial hamstring MH, and biceps femoris BF activity. Methods 26 healthy, physically active subjects were recruited, from which 13 completed a 14-day static stretching regimen for the quadriceps and hamstrings. Using the data from the force plate and EMG readings, a mean of EMG amplitude was calculated for 150 msec before and after landing. Each trial was normalized to an isometric reference position. Means were calculated for the VM, VL, MH, and BF from 5 trials in each session. Measures were collected pre, immediately following the 1st stretching session, and following 2 weeks of stretching. Results A 14-day static stretching regimen resulted in no significant differences in pre or postlanding mean EMG amplitude during a drop landing either acutely or over a 14-day period. Conclusions Static stretching, done acutely or over a 14-day period does not result in measurable differences of mean EMG amplitude during a drop landing. Static stretching may not impede dynamic stability of joints about which stretched muscles cross.

Staying well after depression: trial design and protocol

Directory of Open Access Journals (Sweden)

Duggan Danielle S

2010-03-01

Full Text Available Abstract Background Depression is often a chronic relapsing condition, with relapse rates of 50-80% in those who have been depressed before. This is particularly problematic for those who become suicidal when depressed since habitual recurrence of suicidal thoughts increases likelihood of further acute suicidal episodes. Therefore the question how to prevent relapse is of particular urgency in this group. Methods/Design This trial compares Mindfulness-Based Cognitive Therapy (MBCT, a novel form of treatment combining mindfulness meditation and cognitive therapy for depression, with both Cognitive Psycho-Education (CPE, an equally plausible cognitive treatment but without meditation, and treatment as usual (TAU. It will test whether MBCT reduces the risk of relapse in recurrently depressed patients and the incidence of suicidal symptoms in those with a history of suicidality who do relapse. It recruits participants, screens them by telephone for main inclusion and exclusion criteria and, if they are eligible, invites them to a pre-treatment session to assess eligibility in more detail. This trial allocates eligible participants at random between MBCT and TAU, CPE and TAU, and TAU alone in a ratio of 2:2:1, stratified by presence of suicidal ideation or behaviour and current anti-depressant use. We aim to recruit sufficient participants to allow for retention of 300 following attrition. We deliver both active treatments in groups meeting for two hours every week for eight weeks. We shall estimate effects on rates of relapse and suicidal symptoms over 12 months following treatment and assess clinical status immediately after treatment, and three, six, nine and twelve months thereafter. Discussion This will be the first trial of MBCT to investigate whether MCBT is effective in preventing relapse to depression when compared with a control psychological treatment of equal plausibility; and to explore the use of MBCT for the most severe recurrent

Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination.

Science.gov (United States)

Millward, Michael; Price, Timothy; Townsend, Amanda; Sweeney, Christopher; Spencer, Andrew; Sukumaran, Shawgi; Longenecker, Angie; Lee, Lonnie; Lay, Ana; Sharma, Girish; Gemmill, Robert M; Drabkin, Harry A; Lloyd, G Kenneth; Neuteboom, Saskia T C; McConkey, David J; Palladino, Michael A; Spear, Matthew A

2012-12-01

Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested utility in combining it with an HDAC inhibitor such as vorinostat. Thus, in this study in vitro studies assessed the potential utility of combining marizomib and vorinostat, followed by a clinical trial with the objectives of assessing the recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), safety and preliminary anti-tumor activity of the combination in patients. Combinations of marizomib and vorinostat were assessed in vitro. Subsequently, in a Phase 1 clinical trial patients with melanoma, pancreatic carcinoma or Non-small Cell Lung Cancer (NSCLC) were given escalating doses of weekly marizomib in combination with vorinostat 300 mg daily for 16 days in 28 day cycles. In addition to standard safety studies, proteasome inhibition and pharmacokinetics were assayed. Marked synergy of marizomib and vorinostat was seen in tumor cell lines derived from patients with NSCLC, melanoma and pancreatic carcinoma. In the clinical trial, 22 patients were enrolled. Increased toxicity was not seen with the combination. Co-administration did not appear to affect the PK or PD of either drug in comparison to historical data. Although no responses were demonstrated using RECIST criteria, 61% of evaluable patients demonstrated stable disease with 39% having decreases in tumor measurements. Treatment of multiple tumor cell lines with marizomib and vorinostat resulted in a highly synergistic antitumor activity. The combination of full dose marizomib with vorinostat is tolerable in patients with safety findings consistent with either drug alone.

Effect of pre-cooling, with and without thigh cooling, on strain and endurance exercise performance in the heat.

Science.gov (United States)

Cotter, J D; Sleivert, G G; Roberts, W S; Febbraio, M A

2001-04-01

Body cooling before exercise (i.e. pre-cooling) reduces physiological strain in humans during endurance exercise in temperate and warm environments, usually improving performance. This study examined the effectiveness of pre-cooling humans by ice-vest and cold (3 degrees C) air, with (LC) and without (LW) leg cooling, in reducing heat strain and improving endurance performance in the heat (35 degrees C, 60% RH). Nine habitually-active males completed three trials, involving pre-cooling (LC and LW) or no pre-cooling (CON: 34 degrees C air) before 35-min cycle exercise: 20 min at approximately 65% VO2peak then a 15-min work-performance trial. At exercise onset, mean core (Tc, from oesophagus and rectum) and skin temperatures, forearm blood flow (FBF), heart rate (HR), and ratings of exertion, body temperature and thermal discomfort were lower in LW and LC than CON (Pcooling by ice-vest and cold air effectively reduced physiological and psychophysical strain and improved endurance performance in the heat, irrespective of whether thighs were warmed or cooled.

Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial

Directory of Open Access Journals (Sweden)

Rawal N

2011-04-01

Full Text Available Narinder Rawal1, Valery Macquaire2, Elena Catalá3, Marco Berti4, Rui Costa5, Markus Wietlisbach61Department of Anesthesiology and Intensive Care, Örebro University Hospital, Örebro, Sweden; 2Clinique du Parc Leopold, Brussels, Belgium; 3Pain Clinic, Department Anesthesiology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 4Department of Anesthesiology and Reanimation, Parma Hospital, Parma, Italy; 5Garcia de Orta Hospital, Almada, Portugal; 6Department of Anesthesiology, Sursee Hospital, Sursee, SwitzerlandAbstract: This randomized, double-blind, double-dummy, multicenter trial compared efficacy and safety of tramadol HCL 37.5 mg/paracetamol 325 mg combination tablet with tramadol HCL 50 mg capsule in the treatment of postoperative pain following ambulatory hand surgery with iv regional anesthesia. Patients received trial medication at admission, immediately after surgery, and every 6 hours after discharge until midnight of the first postoperative day. Analgesic efficacy was assessed by patients (n = 128 in each group, full analysis set and recorded in a diary on the evening of surgery day and of the first postoperative day. They also documented the occurrence of adverse events. By the end of the first postoperative day, the proportion of treatment responders based on treatment satisfaction (primary efficacy variable was comparable between the groups (78.1% combination, 71.9% tramadol; P = 0.24 and mean pain intensity (rated on a numerical scale from 0 = no pain to 10 = worst imaginable pain had been reduced to 1.7 ± 2.0 for both groups. Under both treatments, twice as many patients experienced no pain (score = 0 on the first postoperative day compared to the day of surgery (35.9% vs 16.4% for tramadol/paracetamol and 36.7% vs 18% for tramadol treatment. Rescue medication leading to withdrawal (diclofenac 50 mg was required by 17.2% patients with tramadol/paracetamol and 13.3% with tramadol. Adverse events (mainly nausea, dizziness

Performance of seeds Crambe exposed to pre-germination treatments

International Nuclear Information System (INIS)

Rocha Cardoso, Rebeca; Costa Nobre, Danubia Aparecida; Santos de Souza David, Andreia Marcia; Ribeiro Amaro, Hugo Tiago; Borghetti, Renato Antonio; Costa, Marcia Regina

2014-01-01

Encouraging the production and use of biodiesel, seeds of crambe today constitute one of the best options for the supply of raw material, is also an excellent alternative for autumn-winter crop rotation order. The aim of this study was to evaluate the efficiency of combined pre-germination treatments on the seed behavior of Crambe. From a seed sample of FMS Brilhante cultivar, an experimental design completely randomized with a 2 x 5 factorial arrangement was performed. it was formed from combination of two structural conditions, seeds with or without pericarp, and treatments with or without giberelic acid, being: control (no treatment); seeds pre-soaked in distilled water for 24 hours as control; and seeds pre-soaked in gibberellic acid at 4 % at different concentrations (400, 500 and 600 mg.L"-1). Water content, first count germination, germination, seedling emergence and emergence rate index were determined. From these results it is concluded that removal of the pericarp in seed of Crambe, cultivar FMS brilhante, accelerated the germination rate, however, decreased your final percentage. The pre-soaking in gibberellic acid (400, 500 and 600 mg L"-1) for 24 hours, increased the germination and seed vigor crambe with pericarp.

Dextromethorphan and Quinidine Combination for Heroin Detoxification

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Akerele, Evaristo; Bisaga, Adam; Sullivan, Maria A.; Garawi, Fatima; Comer, Sandra D.; Thomas, Anil A.; Nunes, Edward V.; Kleber, Herbert D.

2015-01-01

Dextromethorphan (DM) is a low-affinity, non-competitive NMDA receptor antagonist that has shown promise in pre-clinical and preliminary clinical studies for the reduction of opioid withdrawal symptoms, but when used at higher doses, it is associated with deleterious side effects attributed to its metabolite, dextrorphan. A clinical trial was therefore conducted to test the withdrawal-suppressant effect of a combination of dextromethorphan with quinidine (DM/Q). Quinidine inhibits the metabolism of dextromethorphan, reducing dextrorphan levels. Opioid-dependent patients were admitted to an inpatient unit, stabilized for three days on morphine (25 mg, sc, every six hours), and randomly assigned on day 2 to DM/Q (30 mg/30 mg, twice a day) (n = 22) or matching placebo (n = 9) prior to the discontinuation of morphine on day 4. Withdrawal symptoms, measured with the Modified Himmelsbach Opioid Withdrawal Scale (MHOWS), increased significantly on days 4 and 5 (Z = 3.70, p = .0002), and by day 6, 90% of the sample (28/31) had dropped out of the study. There were no differences between treatment groups on either outcome measure. The combination of dextromethorphan and quinidine appears ineffective as a primary treatment for opioid withdrawal. Future studies should examine dextromethorphan as an adjunct to other anti-withdrawal medications and focus more on the relationship between dextrorphan levels and withdrawal suppression. PMID:18463993

Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.

Science.gov (United States)

Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-08-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.

Randomized trial of stopping or continuing ART among postpartum women with pre-ART CD4 ≥ 400 cells/mm3.

Science.gov (United States)

Currier, Judith S; Britto, Paula; Hoffman, Risa M; Brummel, Sean; Masheto, Gaerolwe; Joao, Esau; Santos, Breno; Aurpibul, Linda; Losso, Marcelo; Pierre, Marie F; Weinberg, Adriana; Gnanashanmugam, Devasena; Chakhtoura, Nahida; Klingman, Karin; Browning, Renee; Coletti, Anne; Mofenson, Lynne; Shapiro, David; Pilotto, Jose

2017-01-01

Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen. The sample size was selected to provide 88% power to detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2 and 3 events. All analyses were intent to treat. 1652 women from 52 sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US were enrolled (1/2010-11/2014). Median age was 28 years and major racial categories were Black African (28%), Asian (25%) White (15%). Median entry CD4 count was 696 cells/mm3 (IQR 575-869), median ART exposure prior to delivery was 19 weeks (IQR 13-24) and 94% had entry HIV-1 RNA women randomized to continue ART, 189/827 (23%) had virologic failure; of the 155 with resistance testing, 103 (66%) failed without resistance to their current regimen, suggesting non-adherence. Overall, serious clinical events were rare among young HIV-positive post-partum women with high CD4 cell counts. Continued ART was safe and was associated with a halving of the rate of WHO 2/3 conditions. Virologic failure rates were high, underscoring the urgent need to improve adherence in this population. ClinicalTrials.gov NCT00955968.

Regulatory requirements for marketing fixed dose combinations

Directory of Open Access Journals (Sweden)

B G Jayasheel

2010-01-01

Full Text Available The development of fixed-dose combinations (FDCs is becoming increasingly important from a public health perspective. FDCs have advantages when there is an identifiable patient population for whom treatment with a particular combination of actives in a fixed ratio is safe and effective and when all of the actives contribute to the overall therapeutic effect. Such combinations of drugs are particularly useful in the management of chronic diseases. In addition, there can be real clinical benefits in the form of increased efficacy and/or a reduced incidence of adverse effects. Additional advantages of FDCs are potentially lower costs of manufacturing compared to the costs of producing separate products administered concurrently, simpler logistics of distribution and reduced development of resistance in the case of antimicrobials. Above all, FDC therapy reduces pill burden and improves medication compliance. Although, FDCs seem to be ideal under certain pre-defined circumstances, if a dosing adjustment is warranted, there may not be an FDC available in the most appropriate strength for the patient and if an adverse drug reaction occurs from using an FDC, it may be difficult to identify the active ingredient responsible for causing the reaction. Appendix VI of Schedule Y (Drugs & Cosmetics Rules 1945, India states the requirements for marketing approval of various types of FDCs. The same is further elaborated in this article to provide a detailed guidance including the clinical trial requirements. However, the heterogeneity of the therapeutic field makes it difficult to develop a standard guidance document.

Prediction of black box warning by mining patterns of Convergent Focus Shift in clinical trial study populations using linked public data.

Science.gov (United States)

Ma, Handong; Weng, Chunhua

2016-04-01

To link public data resources for predicting post-marketing drug safety label changes by analyzing the Convergent Focus Shift patterns among drug testing trials. We identified 256 top-selling prescription drugs between 2003 and 2013 and divided them into 83 BBW drugs (drugs with at least one black box warning label) and 173 ROBUST drugs (drugs without any black box warning label) based on their FDA black box warning (BBW) records. We retrieved 7499 clinical trials that each had at least one of these drugs for intervention from the ClinicalTrials.gov. We stratified all the trials by pre-marketing or post-marketing status, study phase, and study start date. For each trial, we retrieved drug and disease concepts from clinical trial summaries to model its study population using medParser and SNOMED-CT. Convergent Focus Shift (CFS) pattern was calculated and used to assess the temporal changes in study populations from pre-marketing to post-marketing trials for each drug. Then we selected 68 candidate drugs, 18 with BBW warning and 50 without, that each had at least nine pre-marketing trials and nine post-marketing trials for predictive modeling. A random forest predictive model was developed to predict BBW acquisition incidents based on CFS patterns among these drugs. Pre- and post-marketing trials of BBW and ROBUST drugs were compared to look for their differences in CFS patterns. Among the 18 BBW drugs, we consistently observed that the post-marketing trials focused more on recruiting patients with medical conditions previously unconsidered in the pre-marketing trials. In contrast, among the 50 ROBUST drugs, the post-marketing trials involved a variety of medications for testing their associations with target intervention(s). We found it feasible to predict BBW acquisitions using different CFS patterns between the two groups of drugs. Our random forest predictor achieved an AUC of 0.77. We also demonstrated the feasibility of the predictor for identifying long

Combined arm stretch positioning and neuromuscular electrical stimulation during rehabilitation does not improve range of motion, shoulder pain or function in patients after stroke : a randomised trial

NARCIS (Netherlands)

de Jong, Lex D.; Dijkstra, Pieter U.; Gerritsen, Johan; Geurts, Alexander C. H.; Postema, Klaas

2013-01-01

Question Does static stretch positioning combined with simultaneous neuromuscular electrical stimulation (NMES) in the subacute phase after stroke have beneficial effects on basic arm body functions and activities? Design Multicentre randomised trial with concealed allocation, assessor blinding, and

Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

Directory of Open Access Journals (Sweden)

Zielinski Stephanie M

2012-01-01

Full Text Available Abstract Background Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures. Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Methods Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Results Median trial start-up ranged from 41 days (P25-P75 10-139 in the Netherlands to 232 days (P25-P75 98-423 in Canada (p = 0.027. The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21 per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28, representing 3.9% of eligible patients (p Conclusions In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. Trial Registration ClinicalTrials.gov: NCT00761813

Stress ulcer prophylaxis in the intensive care unit trial

DEFF Research Database (Denmark)

Krag, M; Perner, A; Wetterslev, J

2017-01-01

BACKGROUND: In this statistical analysis plan, we aim to provide details of the pre-defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. The aim of the SUP-ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump......-year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre-defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables...... comparing the two intervention groups in the intention-to-treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention-to-treat population. CONCLUSION: Stress ulcer...

Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus-the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial

DEFF Research Database (Denmark)

Lundby-Christensen, Louise; Tarnow, Lise; Boesgaard, Trine W

2016-01-01

OBJECTIVE: To assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial...... design conducted at eight hospitals in Denmark. PARTICIPANTS AND INTERVENTIONS: 412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥7.5% (≥58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1...... weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power may therefore have affected our results. TRIAL REGISTRATION NUMBER: NCT00657943; Results....

Bonding effectiveness to different chemically pre-treated dental zirconia.

Science.gov (United States)

Inokoshi, Masanao; Poitevin, André; De Munck, Jan; Minakuchi, Shunsuke; Van Meerbeek, Bart

2014-09-01

The objective of this study was to evaluate the effect of different chemical pre-treatments on the bond durability to dental zirconia. Fully sintered IPS e.max ZirCAD (Ivoclar Vivadent) blocks were subjected to tribochemical silica sandblasting (CoJet, 3M ESPE). The zirconia samples were additionally pre-treated using one of four zirconia primers/adhesives (Clearfil Ceramic Primer, Kuraray Noritake; Monobond Plus, Ivoclar Vivadent; Scotchbond Universal, 3M ESPE; Z-PRIME Plus, Bisco). Finally, two identically pre-treated zirconia blocks were bonded together using composite cement (RelyX Ultimate, 3M ESPE). The specimens were trimmed at the interface to a cylindrical hourglass and stored in distilled water (7 days, 37 °C), after which they were randomly tested as is or subjected to mechanical ageing involving cyclic tensile stress (10 N, 10 Hz, 10,000 cycles). Subsequently, the micro-tensile bond strength was determined, and SEM fractographic analysis performed. Weibull analysis revealed the highest Weibull scale and shape parameters for the 'Clearfil Ceramic Primer/mechanical ageing' combination. Chemical pre-treatment of CoJet (3M ESPE) sandblasted zirconia using Clearfil Ceramic Primer (Kuraray Noritake) and Monobond Plus (Ivoclar Vivadent) revealed a significantly higher bond strength than when Scotchbond Universal (3M ESPE) and Z-PRIME Plus (Bisco) were used. After ageing, Clearfil Ceramic Primer (Kuraray Noritake) revealed the most stable bond durability. Combined mechanical/chemical pre-treatment, the latter with either Clearfil Ceramic Primer (Kuraray Noritake) or Monobond Plus (Ivoclar Vivadent), resulted in the most durable bond to zirconia. As a standard procedure to durably bond zirconia to tooth tissue, the application of a combined 10-methacryloyloxydecyl dihydrogen phosphate/silane ceramic primer to zirconia is clinically highly recommended.

Cancer clinical trials

International Nuclear Information System (INIS)

Scheurlen, A.; Kay, R.; Baum, M.

1988-01-01

This book contains the proceedings on Cancer clinical trials: A critical appraisal. Topics covered include: Scientific fundamentals; Heterogeneous treatment effects; On combining information: Historical controls, overviews, and comprehensive cohort studies; and assessment of quality of life

Effect of exercising at minimum recommendations of the multiple sclerosis exercise guideline combined with structured education or attention control education - secondary results of the step it up randomised controlled trial.

Science.gov (United States)

Coote, Susan; Uszynski, Marcin; Herring, Matthew P; Hayes, Sara; Scarrott, Carl; Newell, John; Gallagher, Stephen; Larkin, Aidan; Motl, Robert W

2017-06-24

Recent exercise guidelines for people with multiple sclerosis (MS) recommend a minimum of 30 min moderate intensity aerobic exercise and resistance exercise twice per week. This trial compared the secondary outcomes of a combined 10-week guideline based intervention and a Social Cognitive Theory (SCT) education programme with the same exercise intervention involving an attention control education. Physically inactive people with MS, scoring 0-3 on Patient Determined Disease Steps Scale, with no MS relapse or change in MS medication, were randomised to 10-week exercise plus SCT education or exercise plus attention control education conditions. Outcomes included fatigue, depression, anxiety, strength, physical activity, SCT constructs and impact of MS and were measured by a blinded assessor pre and post-intervention and 3 and 6 month follow up. One hundred and seventy-four expressed interest, 92 were eligible and 65 enrolled. Using linear mixed effects models, the differences between groups on all secondary measures post-intervention and at follow-up were not significant. Post-hoc, exploratory, within group analysis identified improvements in both groups post intervention in fatigue (mean ∆(95% CI) SCT -4.99(-9.87, -0.21), p = 0.04, Control -7.68(-12.13, -3.23), p = 0.00), strength (SCT -1.51(-2.41, -0.60), p exercise planning (SCT 5.88(3.37, 8.39), p Exercising at the minimum guideline amount has a positive effect on fatigue, strength and PA that is sustained at 3 and 6 months following the cessation of the program. ClinicalTrials.gov, NCT02301442 , retrospectively registered on November 13th 2014.

Use of 3D printed models in medical education: A randomized control trial comparing 3D prints versus cadaveric materials for learning external cardiac anatomy.

Science.gov (United States)

Lim, Kah Heng Alexander; Loo, Zhou Yaw; Goldie, Stephen J; Adams, Justin W; McMenamin, Paul G

2016-05-06

Three-dimensional (3D) printing is an emerging technology capable of readily producing accurate anatomical models, however, evidence for the use of 3D prints in medical education remains limited. A study was performed to assess their effectiveness against cadaveric materials for learning external cardiac anatomy. A double blind randomized controlled trial was undertaken on undergraduate medical students without prior formal cardiac anatomy teaching. Following a pre-test examining baseline external cardiac anatomy knowledge, participants were randomly assigned to three groups who underwent self-directed learning sessions using either cadaveric materials, 3D prints, or a combination of cadaveric materials/3D prints (combined materials). Participants were then subjected to a post-test written by a third party. Fifty-two participants completed the trial; 18 using cadaveric materials, 16 using 3D models, and 18 using combined materials. Age and time since completion of high school were equally distributed between groups. Pre-test scores were not significantly different (P = 0.231), however, post-test scores were significantly higher for 3D prints group compared to the cadaveric materials or combined materials groups (mean of 60.83% vs. 44.81% and 44.62%, P = 0.010, adjusted P = 0.012). A significant improvement in test scores was detected for the 3D prints group (P = 0.003) but not for the other two groups. The finding of this pilot study suggests that use of 3D prints do not disadvantage students relative to cadaveric materials; maximally, results suggest that 3D may confer certain benefits to anatomy learning and supports their use and ongoing evaluation as supplements to cadaver-based curriculums. Anat Sci Educ 9: 213-221. © 2015 American Association of Anatomists. © 2015 American Association of Anatomists.

Managed ventricular pacing vs. conventional dual-chamber pacing for elective replacements: the PreFER MVP study: clinical background, rationale, and design.

Science.gov (United States)

Quesada, Aurelio; Botto, Gianluca; Erdogan, Ali; Kozak, Milan; Lercher, Peter; Nielsen, Jens Cosedis; Piot, Olivier; Ricci, Renato; Weiss, Christian; Becker, Daniel; Wetzels, Gwenn; De Roy, Luc

2008-03-01

Several clinical studies have shown that, in patients with intact atrioventricular (AV) conduction, unnecessary chronic right ventricular (RV) pacing can be detrimental. The managed ventricular pacing (MVP) algorithm is designed to give preference to spontaneous AV conduction, thus minimizing RV pacing. The clinical outcomes of MVP are being studied in several ongoing trials in patients undergoing a first device implantation, but it is unknown to what extent MVP is beneficial in patients with a history of ventricular pacing. The purpose of the Prefer for Elective Replacement MVP (PreFER MVP) study is to assess the superiority of the MVP algorithm to conventional pacemaker and implantable cardioverter-defibrillator programming in terms of freedom from hospitalization for cardiovascular causes in a population of patients exposed to long periods of ventricular pacing. PreFER MVP is a prospective, 1:1 parallel, randomized (MVP ON/MVP OFF), single-blinded multi-centre trial. The study population consists of patients with more than 40% ventricular pacing documented with their previous device. Approximately, 600 patients will be randomized and followed for at least 24 months. The primary endpoint comprises cardiovascular hospitalization. The PreFER MVP trial is the first large prospective randomized clinical trial evaluating the effect of MVP in patients with a history of RV pacing.

Treatment of ’Battlefield Detainees’ in the War on Terrorism

Science.gov (United States)

2007-01-23

that belligerency is not violative of international law, but is merely unprotected by it). 40 See W. Thomas Mallison and Sally V. Mallison, The...as an individual or as an agent of the opposing state. POWs are detained for security purposes only, to remove those soldiers from further...for personal gain rather than agents of a state, and they could be summarily shot.93 (Modern rules require a fair criminal trial).94 The first

Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts.

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Barbara Szymanska

Full Text Available Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL, or for re-induction post relapse, use a combination of vincristine (VCR, a glucocorticoid, and L-asparaginase (ASP with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX and ASP (VXL against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL.

Isotope heterogeneity of Pre-Holocene groundwater in Iceland

DEFF Research Database (Denmark)

Sveinbjörnsdóttir, Á.E.; Arnorsson, S.; Heinemeier, Jan

2007-01-01

In recent years, it has been shown that groundwater with a Pre-Holocene component is more common in the Icelandic bedrock than previously thought. Some of the Pre-Holocene water samples are more depleted in delta H-2 and delta O-18 than any mean annual precipitation in Iceland today due to the cold...... climate at that time. However, most often Pre-Holocene water components cannot be detected based on the water isotopes alone due to mixing with younger and isotopically heavier water. The Cl concentration in relation to the water isotopes in specific areas has proved to be a good indicator of a Pre......-Holocene component in the groundwater. The deuterium excess value may also help to identify water from a different climate regime, if no oxygen shift has occurred. The relative abundance of a Pre-Holocene water component of the Icelandic groundwater has led to the understanding that combined interpretation of water...

Evaluation of internal peer-review to train nurses recruiting to a randomized controlled trial--Internal Peer-review for Recruitment Training in Trials (InterPReTiT).

Science.gov (United States)

Mann, Cindy; Delgado, Debbie; Horwood, Jeremy

2014-04-01

A discussion and qualitative evaluation of the use of peer-review to train nurses and optimize recruitment practice in a randomized controlled trial. Sound recruitment processes are critical to the success of randomized controlled trials. Nurses recruiting to trials must obtain consent for an intervention that is administered for reasons other than anticipated benefit to the patient. This requires not only patients' acquiescence but also evidence that they have weighed the relevant information in reaching their decision. How trial information is explained is vital, but communication and training can be inadequate. A discussion of a new process to train nurses recruiting to a randomized controlled trial. Literature from 1999-2013 about consenting to trials is included. Over 3 months from 2009-2010, recruiting nurses reviewed recruitment interviews recorded during the pilot phase of a single-site randomized controlled trial and noted content, communication style and interactions. They discussed their findings during peer-review meetings, which were audio-recorded and analysed using qualitative methodology. Peer-review can enhance nurses' training in trial recruitment procedures by supporting development of the necessary communication skills, facilitating consistency in information provision and sharing best practice. Nurse-led peer-review can provide a forum to share communication strategies that will elicit and address participant concerns and obtain evidence of participant understanding prior to consent. Comparing practice can improve consistency and accuracy of trial information and facilitate identification of recruitment issues. Internal peer-review was well accepted and promoted team cohesion. Further evaluation is needed. © 2013 John Wiley & Sons Ltd.

Victims’ Rights and the Right to Review: A Corollary of the Victim’s Pre-Trial Rights to Justice

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Tyrone Kirchengast

2016-12-01

Full Text Available In R v Christopher Killick [2011] EWCA Crim 1608, the Criminal Division of the Court of Appeal for England and Wales gave a decision setting out the rights of a crime victim to seek review of a Crown Prosecution Service (CPS decision not to prosecute and concluded that victims have the right to seek review in such circumstances. This included a recommendation that the right to review should be made the subject of clearer procedures and guidance. This paper discusses article 10 of the Proposal for a Directive of the European Parliament and of the Council, (2011 2011/0129 (COD 18 May 2011 establishing minimum standards on the rights, support and protection of victims of crime (see article 11 Final Directive as applied in the Killick case. The paper further discusses the implementation of Killick in prosecution policy, namely in the CPS guideline on the victims’ right to review (Director of Public Prosecutions for England and Wales 2014. The right to review will be canvassed in light the existing framework of victim rights available during the pre-trial phase and, in particular, the right to private prosecution, access to counsel, and adjunctive and extra-curial rights from declarations or charters of victim rights.

Effects of psychological therapies in randomized trials and practice-based studies.

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Barkham, Michael; Stiles, William B; Connell, Janice; Twigg, Elspeth; Leach, Chris; Lucock, Mike; Mellor-Clark, John; Bower, Peter; King, Michael; Shapiro, David A; Hardy, Gillian E; Greenberg, Leslie; Angus, Lynne

2008-11-01

Randomized trials of the effects of psychological therapies seek internal validity via homogeneous samples and standardized treatment protocols. In contrast, practice-based studies aim for clinical realism and external validity via heterogeneous samples of clients treated under routine practice conditions. We compared indices of treatment effects in these two types of studies. Using published transformation formulas, the Beck Depression Inventory (BDI) scores from five randomized trials of depression (N = 477 clients) were transformed into Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) scores and compared with CORE-OM data collected in four practice-based studies (N = 4,196 clients). Conversely, the practice-based studies' CORE-OM scores were transformed into BDI scores and compared with randomized trial data. Randomized trials showed a modest advantage over practice-based studies in amount of pre-post improvement. This difference was compressed or exaggerated depending on the direction of the transformation but averaged about 12%. There was a similarly sized advantage to randomized trials in rates of reliable and clinically significant improvement (RCSI). The largest difference was yielded by comparisons of effect sizes which suggested an advantage more than twice as large, reflecting narrower pre-treatment distributions in the randomized trials. Outcomes of completed treatments for depression in randomized trials appeared to be modestly greater than those in routine care settings. The size of the difference may be distorted depending on the method for calculating degree of change. Transforming BDI scores into CORE-OM scores and vice versa may be a preferable alternative to effect sizes for comparisons of studies using these measures.

Chinese Massage Combined with Herbal Ointment for Athletes with Nonspecific Low Back Pain: A Randomized Controlled Trial

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Ling Jun Kong

2012-01-01

Full Text Available Non-specific low back pain (NLBP is an increasing health problem for athletes. This randomized controlled trial was designed to investigate the effects of Chinese massage combined with herbal ointment for NLBP. 110 athletes with NLBP were randomly assigned to experimental group with Chinese massage combined with herbal ointment or control group with simple massage therapy. The primary outcome was pain by Chinese Short Form McGill Pain Questionnaire (C-SFMPQ. The secondary outcome was local muscle stiffness by Myotonometer. After 4 weeks, the experimental group experienced significant improvements in C-SFMPQ and in local muscle stiffness compared with control group (between-group difference in mean change from baseline, −1.24 points, P=0.005 in sensory scores; −3.14 points, P<0.001 in affective scores; −4.39 points, P<0.001 in total scores; −0.64 points, P=0.002 in VAS; −1.04 points, P=0.005 in local muscle stiffness during relaxation state. The difference remained at one month followup, but it was only significant in affective scores (−2.83 points, P<0.001 at three months followup. No adverse events were observed. These findings suggest that Chinese massage combined with herbal ointment may be a beneficial complementary and alternative therapy for athletes with NLBP.

Recruitment strategies and challenges in a large intervention trial: Systolic Blood Pressure Intervention Trial (SPRINT)

Science.gov (United States)

Ramsey, Thomas M; Snyder, Joni K; Lovato, Laura C; Roumie, Christianne L; Glasser, Steven P; Cosgrove, Nora M; Olney, Christine M; Tang, Rocky H; Johnson, Karen C; Still, Carolyn H; Gren, Lisa H; Childs, Jeffery C; Crago, Osa L; Summerson, John H; Walsh, Sandy M; Perdue, Letitia H; Bankowski, Denise M; Goff, David C

2016-01-01

Background The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter, randomized clinical trial of 9,361 participants with hypertension who are ≥ 50 years old. The trial is designed to evaluate the effect of intensive systolic blood pressure control (systolic blood pressure goal recruitment strategies and lessons learned during recruitment of the SPRINT cohort and five targeted participant subgroups: pre-existing cardiovascular disease, pre-existing chronic kidney disease, age ≥ 75 years, women, and minorities. Methods In collaboration with the National Institutes of Health Project Office and SPRINT Coordinating Center, five Clinical Center Networks oversaw clinical site selection, recruitment, and trial activities. Recruitment began November 8, 2010 and ended March 15, 2013 (about 28 months). Various recruitment strategies were used, including mass mailing, brochures, referrals from healthcare providers or friends, posters, newspaper ads, radio ads, and electronic medical record searches. Results Recruitment was scheduled to last 24 months to enroll a target of 9,250 participants; in just over 28 months, the trial enrolled 9,361 participants. The trial screened 14,692 volunteers, with 33% of initial screens originating from the use of mass mailing lists. Screening results show that participants also responded to recruitment efforts through referral by SPRINT staff, healthcare providers, or friends (45%); brochures or posters placed in clinic waiting areas (15%); and television, radio, newspaper, internet ads, or toll-free numbers (8%). The overall recruitment yield (number randomized /number screened) was 64% (9,361 randomized /14,692 screened), 77% for those with cardiovascular disease, 79% for those with chronic kidney disease, 70% for those age ≥ 75 years, 55% for women, and 61% for minorities. As recruitment was observed to lag behind expectations, additional clinics were included and inclusion criteria were broadened, keeping event rates

Clinical trials of homoeopathy.

Science.gov (United States)

Kleijnen, J; Knipschild, P; ter Riet, G

1991-01-01

OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease.

Science.gov (United States)

Hampson, Lynne; Maranga, Innocent O; Masinde, Millicent S; Oliver, Anthony W; Batman, Gavin; He, Xiaotong; Desai, Minaxi; Okemwa, Parmenas M; Stringfellow, Helen; Martin-Hirsch, Pierre; Mwaniki, Alex M; Gichangi, Peter; Hampson, Ian N

2016-01-01

Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC-ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit

The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials

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Rachel E. Foong

2018-02-01

Full Text Available The lung clearance index (LCI from the multiple-breath washout (MBW test is a promising surveillance tool for pre-school children with cystic fibrosis (CF. Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed. Healthy children and children with CF aged 3–6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan. MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials. This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible.

Inadvertent P-hacking among trials and systematic reviews of the effect of progestogens in pregnancy? A systematic review and meta-analysis.

Science.gov (United States)

Prior, M; Hibberd, R; Asemota, N; Thornton, J G

2017-06-01

Progestogens have been evaluated in numerous trials and meta-analyses, many of which concluded they were effective. However, two large trials PROMISE and OPPTIMUM have recently concluded that progesterone was ineffective. This raises the possibility that earlier studies and reviews had been biased by either selective publication or selective choice of outcomes, so called "P-hacking". To compare the findings all progestogen trials and systematic reviews with those of trials with pre-registered primary outcomes which avoided selective outcome reporting. Search of PubMed, the Cochrane Library and trial registries. Registration PROSPERO CRD42016035303. Systematic reviews of randomised trials comparing progestogen with placebo in pregnancy and the individual trials included in those reviews. The subset of trials reporting a pre-registered primary outcome were compared with the totality of trials and reviews. For reviews all outcomes were included. For individual trials all outcomes reported in the systematic reviews were included. For the comparison group we recorded the registered primary outcome from trials that were either registered before they started, or registered during the recruitment phase and also double blind. Nineteen of twenty-nine meta-analyses concluded that progestogens were effective. Twenty-two trials reported their pre-registered primary outcomes. There was no effect of progesterone on primary registered dichotomous outcome RR 1.00 (95% CI 0.94-1.07). Only one of the 22 showed a nominally statistically significant benefit. When evaluated in registered double-blind trials with analysis restricted to predefined primary outcomes, progestational agents in pregnancy are ineffective. Progestogens to prevent pregnancy loss, an example of P-hacking. © 2017 Royal College of Obstetricians and Gynaecologists.

Return to work after cancer and pre-cancer job dissatisfaction

DEFF Research Database (Denmark)

Heinesen, Eskil; Kolodziejczyk, Christophe; Ladenburg, Jacob

2017-01-01

We investigate the association between pre-cancer job dissatisfaction and return-to-work probability 3 years after a cancer diagnosis. We use a Danish data set combining administrative data and a survey to breast and colon cancer survivors. We find that the return-to-work probability has a negative...... correlation with pre-cancer job dissatisfaction with mental demands (where the correlation is driven by the high-educated) and with physical demands and the superior (where the correlation is driven by the low-educated). Educational gradients in the probability of returning to work after cancer...... are not significantly affected by controlling for pre-cancer job dissatisfaction and pre-cancer ability to work....

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE" study: a double-blind randomised controlled multicenter clinical trial

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Lee Myoungsook

2011-01-01

Full Text Available Abstract Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT: NCT01031667

Strategies for combinational cancer therapies

International Nuclear Information System (INIS)

Khleif, Samir

2014-01-01

The countless pre-clinical studies and many clinical trials that have applied tumor antigen-based therapies for the cancer treatment, and although the necessary tumor-specific immune response may be elicited in tumor-bearing hosts, this was not sufficient for the positive therapeutic outcome since there are multiple mechanisms that tumors develop to escape immune surveillance. The tumor-mediated inhibitory mechanisms involve co-inhibitory receptor-ligand interactions, such as PD-1/ PD-L1, secretion of inhibitory molecules, such as TGFb, and recruitment of suppressive cells, such as regulatory T cells (Treg), myeloid derived suppressor cells (MDSC), etc. Therefore, we hypothesized that successful cancer immunotherapy requires not only induction and enhancement of effector immune response but also simultaneous targeting of suppressor arm of immune system, thus in addition to enhancing antigen-specific immunity using vaccines or radiation therapy, one should also target tumor-mediated immune suppression to improve the overall efficacy of therapy. We developed multiple strategies to target various tumor-mediated immune inhibitory mechanisms that can enhance anti-tumor immunity and restructure tumor microenvironment to allow effector cells generated due to vaccination or radiation therapy to function potently. We evaluated the immune and therapeutic efficacy of multiple combinational therapies, including blocking and agonist antibodies to co-inhibitory/co-stimulatory molecules, such as PD-1, PD-L1, OX40, CTLA-4, GITR, inhibitors and neutralizing antibodies to inhibitory cytokines/molecules, such as IL-10, TGFb, IDO, and small molecules for selective inhibition of Tregs. In addition to evaluation of anti-tumor efficacy we are also investigated cellular and molecular mechanisms of action for these agents when combined with vaccine or radiation therapy and exploring the interactions between compounds within combinational therapies in animal tumor models. We are

Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC): study protocol for a randomised, stepped-wedge cluster trial within the EFFECTS trial.

Science.gov (United States)

Lundström, Erik; Isaksson, Eva; Wester, Per; Laska, Ann-Charlotte; Näsman, Per

2018-01-08

Many randomised controlled trials (RCTs) fail to meet their recruitment goals in time. Trialists are advised to include study recruitment strategies within their trials. EFFECTS is a Swedish, academic-led RCT of fluoxetine for stroke recovery. The trial's primary objective is to investigate whether 20 mg fluoxetine daily compared with placebo for 6 months after an acute stroke improves the patient's functional outcome. The first patient was included on 20 October 2014 and, as of 31 August 2017, EFFECTS has included 810 of planned 1500 individuals. EFFECTS currently has 32 active centres. The primary objective of the ERUTECC (Enhancing Recruitment Using Teleconference and Commitment Contract) study is to investigate whether a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% at 60 days post intervention, compared with 60 days pre-intervention, in an ongoing RCT. ERUTECC is a randomised, stepped-wedge cluster trial embedded in EFFECTS. The plan is to start ERUTECC with a running-in period of September 2017. The first intervention is due in October 2017, and the study will continue for 12 months. We are planning to intervene at all active centres in EFFECTS, except the five top recruiting centres (n = 27). The rationale for not intervening at the top recruiting centres is that we believe they have reached their full potential and the intervention would be too weak for them. The hypothesis of this study is that a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% 60 days post intervention, compared to 60 days pre-intervention, in an ongoing RCT. EFFECTS is a large, pragmatic RCT of stroke in Sweden. Results from the embedded ERUTECC study could probably be generalised to high-income Western countries, and is relevant to trial management and could improve trial management in the

The Effectiveness of a 5% Retinoic Acid Peel Combined with Microdermabrasion for Facial Photoaging: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Science.gov (United States)

Faghihi, Gita; Fatemi-Tabaei, Saghi; Abtahi-Naeini, Bahareh; Siadat, Amir Hossein; Sadeghian, Giti; Ali Nilforoushzadeh, Mohammad; Mohamadian-Shoeili, Hamed

2017-01-01

Background . Tretinoin has been shown to improve photoaged skin. This study was designed to evaluate the efficacy and tolerability of a 5% retinoic acid peel combined with microdermabrasion for facial photoaging. Materials and Methods . Forty-five patients, aged 35-70, affected by moderate-to-severe photodamage were enrolled in this trial. All patients received 3 sessions of full facial microdermabrasion and 3 sessions of either 5% retinoic acid peel or placebo after the microdermabrasion. Efficacy was measured using the Glogau scale. Patients were assessed at 2 weeks and 1, 2, and 6 months after treatment initiation. Results . The mean ± SD age of participants was 49.55 ± 11.61 years, and the majorities (73.3%) were female. Between 1 month and 2 months, participants reported slight but statistically significant improvements for all parameters ( P < 0.001). In terms of adverse effects, there were statistically significant differences reported between the 5% retinoic acid peel groups and the control group ( P < 0.001). The majority of adverse effects reported in the study were described as mild and transient. Conclusion . This study demonstrated that 5% retinoic acid peel cream combined with microdermabrasion was safe and effective in the treatment of photoaging in the Iranian population. This trial is registered with IRCT2015121112782N8.

Butorphanol pre-treatment prevents myoclonus induced by etomidate: a randomised, double-blind, controlled clinical trial.

Science.gov (United States)

He, Liang; Ding, Ying; Chen, Huiyu; Qian, Yanning; Li, Zhong

2014-01-01

Myoclonic movements are common problems during induction of anaesthesia with etomidate. The myoclonus occurring after etomidate administration may represent a form of seizure. Agonistic modulation of the κ opiate receptor may reduce seizures, and butorphanol acts in such a manner. The aim of this randomised, double-blind, placebo-controlled clinical trial was to test our hypothesis that pre-treatment with butorphanol might reduce the incidence and severity of myoclonus induced by etomidate. Patients (108) with American Society of Anaesthesiologists physical status I or II were randomly assigned to one of two groups to receive either 0.015 mg/kg of butorphanol (n = 54) or saline (n = 54) intravenously. At two minutes after infusion of butorphanol or saline, 0.3 mg/kg etomidate was given. The occurrence and severity (observational score of 0-3) of myoclonus was assessed during 2 minutes after administration of etomidate. For each patient, blood pressure (BP), saturation of peripheral oxygen (SpO₂), and heart rate (HR) were measured. The incidence of myoclonus was significantly lower in Group Butorphanol than in Group Saline (13.0% vs 79.6%; RR = 0.163, 95%CI: 0.081-0.329; χ² = 48.265, p <0.0001). The severity levels of myoclonic movement were also significantly lower in Group Butorphanol than in Group Saline (p <0.0001). Throughout the procedure, changes of BP, SpO₂, and HR did not differ between the groups. There were no problems with bradycardia or hypotension. Infusion of 0.015 mg/kg butorphanol 2 minutes before etomidate administration is effective for suppressing myoclonus induced by etomidate during induction of general anaesthesia.

Effectiveness of a pre-procedural mouthwash in reducing bacteria in dental aerosols: randomized clinical trial

Directory of Open Access Journals (Sweden)

Belén RETAMAL-VALDES

2017-03-01

Full Text Available Abstract The aim of this randomized, single blinded clinical trial was to evaluate the effect of a pre-procedural mouthwash containing cetylpyridinium chloride (CPC, zinc lactate (Zn and sodium fluoride (F in the reduction of viable bacteria in oral aerosol after a dental prophylaxis with ultrasonic scaler. Sixty systemically healthy volunteers receiving dental prophylaxis were randomly assigned to one of the following experimental groups (15 per group: (i rinsing with 0.075% CPC, 0.28% Zn and 0.05% F (CPC+Zn+F, (ii water or (iii 0.12% chlorhexidine digluconate (CHX, and (iv no rinsing. Viable bacteria were collected from different locations in the dental office on enriched TSA plates and anaerobically incubated for 72 hours. The colonies were counted and species were then identified by Checkerboard DNA–DNA Hybridization. The total number of colony-forming units (CFUs detected in the aerosols from volunteers who rinsed with CPC+Zn+F or CHX was statistically significantly (p<0.05 lower than of those subjects who did not rinse or who rinsed with water. When all locations were considered together, the aerosols from the CPC+Zn+F and CHX groups showed, respectively, 70% and 77% fewer CFUs than those from the No Rinsing group and 61% and 70% than those from the Water group. The mean proportions of bacterial species from the orange complex were statistically significantly (p<0.05 lower in aerosols from the CPC+Zn+F and CHX groups compared with the others two groups. In conclusion, the mouthwash containing CPC+Zn+F, is effective in reducing viable bacteria in oral aerosol after a dental prophylaxis with ultrasonic scaler.

The Efficacy and Safety of Tamsulosin Combined with Extracorporeal Shockwave Lithotripsy for Urolithiasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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Chen, Kai; Mi, Hua; Xu, Guangyu; Liu, Lin; Sun, Xiubin; Wang, Shiping; Meng, Qingrong; Lv, Tao

2015-10-01

Many studies have been conducted to investigate adjunctive tamsulosin therapy after extracorporeal shockwave lithotripsy (SWL) for urolithiasis. The results from those studies, however, are still inconsistent. Therefore, we performed a meta-analysis to provide an update on the clinical efficacy and safety of tamsulosin combined with SWL for urolithiasis. A systematic search was performed in PubMed, Cochrane Library, and Embase to identify all relevant randomized controlled trials until January 2015. Two reviewers independently assessed trial quality and extracted data. Meta-analysis was conducted with Review Manager (RevMan), version 5.1. Twenty-one studies (2093 subjects in total) were identified in the current meta-analysis. Compared with a control group, the experimental group (tamsulosin combined with SWL) showed an increased overall benefit for stone expulsion, with pooled risk ratio (RR) of 1.20 (95% confidence interval [CI], 1.15-1.26). With respect to the different geographic regions, European and American had a high possibility of improvement in stone expulsion (RR: 1.33, 95% CI, 1.19-1.49). According to the stone locations (renal, upper and lower ureteral) and sizes (4-10 mm and 11-24 mm), tamsulosin is more useful for lower ureteral stone (RR: 1.28; 95% CI, 1.14-1.43) and larger sized stones (RR: 1.49; 95% CI, 1.28-1.75). The effect estimates did not vary markedly when stratified by follow-up durations but varied by dose of tamsulosin. Furthermore, a shorter expulsion time, reduced occurrence of steinstrasse, fewer incidences of colic, and lower analgesic requirements were observed within the experimental group. In addition, tamsulosin is well tolerated, and its adverse events rarely led to dropouts of patients. Overall, evidence suggests that tamsulosin combined with SWL is safe and effective in enhancing stone expulsion for patients with urolithiasis. Furthermore, high-quality, randomized and placebo-controlled trials evaluating the efficacy and

Tracheal intubation in critically ill patients: a comprehensive systematic review of randomized trials.

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Cabrini, Luca; Landoni, Giovanni; Baiardo Radaelli, Martina; Saleh, Omar; Votta, Carmine D; Fominskiy, Evgeny; Putzu, Alessandro; Snak de Souza, Cézar Daniel; Antonelli, Massimo; Bellomo, Rinaldo; Pelosi, Paolo; Zangrillo, Alberto

2018-01-20

We performed a systematic review of randomized controlled studies evaluating any drug, technique or device aimed at improving the success rate or safety of tracheal intubation in the critically ill. We searched PubMed, BioMed Central, Embase and the Cochrane Central Register of Clinical Trials and references of retrieved articles. Finally, pertinent reviews were also scanned to detect further studies until May 2017. The following inclusion criteria were considered: tracheal intubation in adult critically ill patients; randomized controlled trial; study performed in Intensive Care Unit, Emergency Department or ordinary ward; and work published in the last 20 years. Exclusion criteria were pre-hospital or operating theatre settings and simulation-based studies. Two investigators selected studies for the final analysis. Extracted data included first author, publication year, characteristics of patients and clinical settings, intervention details, comparators and relevant outcomes. The risk of bias was assessed with the Cochrane Collaboration's Risk of Bias tool. We identified 22 trials on use of a pre-procedure check-list (1 study), pre-oxygenation or apneic oxygenation (6 studies), sedatives (3 studies), neuromuscular blocking agents (1 study), patient positioning (1 study), video laryngoscopy (9 studies), and post-intubation lung recruitment (1 study). Pre-oxygenation with non-invasive ventilation (NIV) and/or high-flow nasal cannula (HFNC) showed a possible beneficial role. Post-intubation recruitment improved oxygenation , while ramped position increased the number of intubation attempts and thiopental had negative hemodynamic effects. No effect was found for use of a checklist, apneic oxygenation (on oxygenation and hemodynamics), videolaryngoscopy (on number and length of intubation attempts), sedatives and neuromuscular blockers (on hemodynamics). Finally, videolaryngoscopy was associated with severe adverse effects in multiple trials. The limited available

Price discounts significantly enhance fruit and vegetable purchases when combined with nutrition education: a randomized controlled supermarket trial.

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Waterlander, Wilma E; de Boer, Michiel R; Schuit, Albertine J; Seidell, Jacob C; Steenhuis, Ingrid H M

2013-04-01

Reducing fruit and vegetable (F&V) prices is a frequently considered policy to improve dietary habits in the context of health promotion. However, evidence on the effectiveness of this intervention is limited. The objective was to examine the effects of a 50% price discount on F&Vs or nutrition education or a combination of both on supermarket purchases. A 6-mo randomized controlled trial within Dutch supermarkets was conducted. Regular supermarket shoppers were randomly assigned to 1 of 4 conditions: 50% price discounts on F&Vs, nutrition education, 50% price discounts plus nutrition education, or no intervention. A total of 199 participants provided baseline data; 151 (76%) were included in the final analysis. F&V purchases were measured by using supermarket register receipts at baseline, at 1 mo after the start of the intervention, at 3 mo, at 6 mo (end of the intervention period), and 3 mo after the intervention ended (9 mo). Adjusted multilevel models showed significantly higher F&V purchases (per household/2 wk) as a result of the price discount (+3.9 kg; 95% CI: 1.5, 6.3 kg) and the discount plus education intervention (+5.6 kg; 95% CI: 3.2, 7.9 kg) at 6 mo compared with control. Moreover, the percentage of participants who consumed recommended amounts of F&Vs (≥400 g/d) increased from 42.5% at baseline to 61.3% at 6 mo in both discount groups (P = 0.03). Education alone had no significant effect. Discounting F&Vs is a promising intervention strategy because it resulted in substantially higher F&V purchases, and no adverse effects were observed. Therefore, pricing strategies form an important focus for future interventions or policy. However, the long-term effects and the ultimate health outcomes require further investigation. This trial was registered at the ISRCTN Trial Register as number ISRCTN56596945 and at the Dutch Trial Register (http://www.trialregister.nl/trialreg/index.asp) as number NL22568.029.08.

AccuCopy quantification combined with pre-amplification of long-distance PCR for fast analysis of intron 22 inversion in haemophilia A.

Science.gov (United States)

Ding, Qianlan; Wu, Xi; Lu, Yeling; Chen, Changming; Shen, Rui; Zhang, Xi; Jiang, Zhengwen; Wang, Xuefeng

2016-07-01

To develop a digitalized intron 22 inversion (Inv22) detection in patients with severe haemophilia A. The design included two tests: A genotyping test included two multiplex pre-amplification of LD-PCR (PLP) with two combinations of five primers to amplify wild-type and chimeric int22h alleles; a carrier mosaicism test was similar to the genotyping test except only amplification of chimeric int22h alleles by removing one primer from each of two combinations. AccuCopy detection was used to quantify PLP products. PLP product patterns in the genotyping test allowed identifying all known Inv22. Quantitative patterns accurately represented the product patterns. The results of 164 samples detected by the genotyping test were consistent with those obtained by LD-PCR detection. Limit of detection (LOD) of the carrier mosaicism test was at least 2% of heterozygous cells with Inv22. Performing the test in two obligate mothers with negative Inv22 from two sporadic pedigrees mosaic rates of blood and hair root of the mother from pedigree 1 were 8.3% and >20%, respectively and negative results were obtained in pedigree 2. AccuCopy quantification combined with PLP (AQ-PLP) method was confirmed to be rapid and reliable for genotyping Inv22 and highly sensitive to carrier mosaicism detection. Copyright © 2016 Elsevier B.V. All rights reserved.

The adsorption of NO on an oxygen pre-covered Pt(1 1 1) surface: in situ high-resolution XPS combined with molecular beam studies

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Zhu, J. F.; Kinne, M.; Fuhrmann, T.; Tränkenschuh, B.; Denecke, R.; Steinrück, H.-P.

2003-12-01

Adsorption of NO on a Pt(1 1 1) surface pre-covered with a p(2 × 2) atomic oxygen layer has been studied in situ by high-resolution X-ray photoelectron spectroscopy and temperature-programmed XPS using third-generation synchrotron radiation at BESSY II, Berlin, combined with molecular beam techniques and ex situ by low energy electron diffraction and temperature-programmed desorption. O 1s XP spectra reveal that an ordered p(2 × 2)-O layer dramatically changes the adsorption behavior of NO as compared to the clean surface. The atomic oxygen occupies fcc hollow sites, and therefore blocks NO adsorption on these sites, which are energetically preferred on clean Pt(1 1 1). As a consequence, NO populates on-top sites at low coverage. At 110 K for higher coverages, NO can additionally adsorb on hcp hollow sites, thereby inducing a shift of the O 1s binding energy of atomic oxygen towards lower energies by about 0.25 eV. The bond strength of the hcp hollow NO species to the substrate is weakened by the presence of atomic oxygen. A sharp p(2 × 2) LEED pattern is observed for NO adsorption on the oxygen pre-covered surface, up to saturation coverage. The total saturation coverage of NO on Pt(1 1 1) pre-covered with varying amounts of oxygen (below 0.25 ML) decreases linearly with the coverage of oxygen. The initial sticking coefficient of NO is reduced from 0.96 on clean Pt(1 1 1) to 0.88 on a p(2 × 2) oxygen pre-covered surface.

Effects of Combined Physical and Cognitive Exercises on Cognition and Mobility in Patients With Mild Cognitive Impairment: A Randomized Clinical Trial.