Triple-Antiretroviral Prophylaxis to Prevent Mother-To-Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial

Timothy Thomas and colleagues report the results of the Kisumu breastfeeding study (Kenya), a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy

Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial.

BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. CONCLUSIONS: Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429

Melioidosis diagnostic workshop, 2013.

Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions

Psychological Support for Personality (PSP) versus treatment as usual: study protocol for a feasibility randomized controlled trial of a low intensity intervention for people with personality disorder

Background: Previous research has demonstrated the clinical effectiveness of long-term psychological treatment for people with some types of personality disorder. However, the high intensity and cost of these interventions limit their availability. Lower-intensity interventions are increasingly being offered to people with personality disorder, but their clinical and cost effectiveness have not been properly tested in experimental studies. We therefore set out to develop a low intensity intervention for people with personality disorder and to test the feasibility of conducting a randomized controlled trial to compare the clinical effectiveness of this intervention with that of treatment as usual (TAU). Methods: A two-arm, parallel-group, single-blind, randomized controlled trial of Psychological Support for Personality (PSP) versus TAU for people aged over 18 years, who are using secondary care mental health services and have personality disorder. We will exclude people with co-existing organic or psychotic mental disorders (dementia, bipolar affective disorder, delusional disorder, schizophrenia, schizoaffective disorder, or schizotypal disorder), those with cognitive or language difficulties that would preclude them from providing informed consent or compromise participation in study procedures, and those who are already receiving psychological treatment for personality disorder. Participants will be randomized via a remote system in a ratio of PSP to TAU of 1:1. Randomization will be stratified according to the referring team and gender of the participant. A single follow-up assessment will be conducted by masked researchers 24 weeks after randomization to assess mental health (using the Warwick and Edinburgh Well-Being Schedule), social functioning (using the Work and Social Adjustment Scale), health-related quality of life (EQ-5D-5 L), incidence of suicidal behavior, satisfaction with care (Client Satisfaction Questionnaire), and resource use and costs using a modified version of the Adult Service Use Schedule. In addition to this, each participant will be asked to complete the patient version of the Clinical Global Impression Scale. Feasibility and acceptability will primarily be judged by study recruitment rate and engagement and retention in treatment. The analysis will focus principally on descriptive data on the rate of recruitment, characteristics of participants, attrition, adherence to therapy, and follow-up. We will explore the distribution of study outcomes to investigate assumptions of normality in order to plan the analysis and sample size of a future definitive trial. Discussion: Most people with personality disorder do not currently receive evidence-based interventions. While a number of high intensity psychological treatments have been shown to be effective, there is an urgent need to develop effective low intensity approaches to help people unable to use existing treatments. PSP is a low intensity intervention for individuals, which was developed following extensive consultation with users and providers of services for people with personality disorder. This study aims to examine the feasibility of a randomized trial of PSP compared to TAU for people with personality disorder