Categorical dilemmas: challenges for HIV prevention among men who have sex with men and transgender women in Vietnam

In Vietnam, HIV continues disproportionately to affect men who have sex with men and transgender women, and the increase in HIV prevalence in these populations may be related to a lack of tailoring of current prevention approaches, which often fail to address social diversity within these populations. To effectively respond to HIV in Vietnam, it is imperative to identify sub-populations within the broad category of ‘men who have sex with men’ (MSM), a term which in Vietnam as in many other sites frequently subsumes transgender women. In this paper, we document the different categories used to describe people who engage in same-sex sexual practices and/or non-normative gender performances drawing on data collected via in-depth interviews and focus groups with a total of 79 participants in Hanoi. We identified over 40 different categories used to describe men who have sex with men and/or transgender women. These categories could be described as behaviourally-based, identity-based, or emic, and each carried different meanings, uses (based on age and geography) and levels of stigma. The categories shine light on the complexity of identities among men who have sex with men and transgender women and have utility for future research and programming to more comprehensively address HIV in Vietnam

Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication

Background: Claudication secondary to peripheral artery disease (PAD) is associated with substantial functional impairment. Phosphodiesterase (PDE) inhibitors have been shown to increase walking performance in these patients. K-134 is a selective PDE 3 inhibitor being developed as a potential treatment for claudication. The use of K-134, as with other PDE 3 inhibitors, in patients with PAD raises important safety and tolerability concerns, including the induction of cardiac ischemia, tachycardia, and hypotension. We describe the design, oversight, and implementation of an adaptive, phase II, dose-finding trial evaluating K-134 for the treatment of stable, intermittent claudication. Methods: The study design was a double-blind, multi-dose (25 mg, 50 mg, and 100 mg of K-134), randomized trial with both placebo and active comparator arms conducted in the United States and Russia. The primary objective of the study was to compare the highest tolerable dose of K-134 versus placebo using peak walking time after 26 weeks of therapy as the primary outcome. Study visits with intensive safety assessments were included early in the study period to provide data for adaptive decision making. The trial used an adaptive, dose-finding strategy to efficiently identify the highest dose(s) most likely to be safe and well tolerated, based on the side effect profiles observed within the trial, so that less promising doses could be abandoned. Protocol specified criteria for safety and tolerability endpoints were used and modeled prior to the adaptive decision making. The maximum target sample size was 85 subjects in each of the retained treatment arms. Results: When 199 subjects had been randomized and 28-day data were available from 143, the Data Monitoring Committee (DMC) recommended termination of the lowest dose (25 mg) treatment arm. Safety evaluations performed during 14- and 28-day visits which included in-clinic dosing and assessments at peak drug concentrations provided core data for the DMC review. At the time of review, no subject in any of the five treatment arms (placebo, three K-134-containing arms, and cilostazol) had met pre-specified definitions for resting tachycardia or ischemic changes on exercise ECG. If, instead of dropping the 25-mg K-134 treatment arm, all arms had been continued to full enrollment, then approximately 43 additional research subjects would have been required to complete the trial. Conclusions: In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population

Prevalence of peripheral arterial disease in patients at non-high cardiovascular risk. Rationale and design of the PANDORA study

<p>Abstract</p> <p>Background</p> <p>Lower extremity peripheral arterial disease (PAD) is a marker of widespread atherosclerosis. Individuals with PAD, most of whom do not show typical PAD symptoms ('asymptomatic' patients), are at increased risk of cardiovascular ischaemic events. American College of Cardiology/American Heart Association guidelines recommend that individuals with asymptomatic lower extremity PAD should be identified by measurement of ankle-brachial index (ABI). However, despite its associated risk, PAD remains under-recognised by clinicians and the general population and office-based ABI detection is still poorly-known and under-used in clinical practice. The Prevalence of peripheral Arterial disease in patients with a non-high cardiovascular disease risk, with No overt vascular Diseases nOR diAbetes mellitus (PANDORA) study has a primary aim of assessing the prevalence of lower extremity PAD through ABI measurement, in patients at non-high cardiovascular risk, with no overt cardiovascular diseases (including symptomatic PAD), or diabetes mellitus. Secondary objectives include documenting the prevalence and treatment of cardiovascular risk factors and the characteristics of both patients and physicians as possible determinants for PAD under-diagnosis.</p> <p>Methods/Design</p> <p>PANDORA is a non-interventional, cross-sectional, pan-European study. It includes approximately 1,000 primary care participating sites, across six European countries (Belgium, France, Greece, Italy, The Netherlands, Switzerland). Investigator and patient questionnaires will be used to collect both right and left ABI values at rest, presence of cardiovascular disease risk factors, current pharmacological treatment, and determinants for PAD under-diagnosis.</p> <p>Discussion</p> <p>The PANDORA study will provide important data to estimate the prevalence of asymptomatic PAD in a population otherwise classified at low or intermediate risk on the basis of current risk scores in a primary care setting.</p> <p>Trial registration number</p> <p>Clinical Trials.gov Identifier: NCT00689377.</p