Patient and Public Involvement and Engagement in the Development of a Platform Clinical Trial for Parkinson's Disease: An Evaluation Protocol.

Background: Patient and public involvement and engagement (PPIE) in the design of trials is important, as participant experience critically impacts delivery. The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative is a UK consortium designing a platform trial for disease modifying therapies in PD. Objective: The integration of PPIE in all aspects of trial design and its evaluation throughout the project. Methods: PwP and care partners were recruited to a PPIE working group (WG) via UK Parkinson's charities, investigator patient groups and participants of a Delphi study on trial design. They are supported by charity representatives, trial delivery experts, researchers and core project team members. PPIE is fully embedded within the consortium's five other WGs and steering group. The group's terms of reference, processes for effective working and PPIE evaluation were co-developed with PPIE contributors. Results: 11 PwP and 4 care partners have supported the PPIE WG and contributed to the development of processes for effective working. A mixed methods research-in-action study is ongoing to evaluate PPIE within the consortium. This includes the Patient Engagement in Research Scale -a quantitative PPIE quality measure; semi-structured interviews -identifying areas for improvement and overall impressions of involvement; process fidelity- recording adherence; project documentation review - identifying impact of PPIE on project outputs. Conclusions: We provide a practical example of PPIE in complex projects. Evaluating feasibility, experiences and impact of PPIE involvement in EJS ACT-PD will inform similar programs on effective strategies. This will help enable future patient-centered research.

Single-step genome engineering in the bee gut symbiont Snodgrassella alvi.

Honey bees are economically relevant pollinators experiencing population declines due to a number of threats. As in humans, the health of bees is influenced by their microbiome. The bacterium Snodgrassella alvi is a key member of the bee gut microbiome and has a role in excluding pathogens. Despite this importance, there are not currently any easy-to-use methods for modifying the S. alvi chromosome to study its genetics. To solve this problem, we developed a one-step procedure that uses electroporation and homologous recombination, which we term SnODIFY (Snodgrassella-specific One-step gene Deletion or Insertion to alter FunctionalitY). We used SnODIFY to create seven single-gene knockout mutants and recovered mutants for all constructs tested. Nearly all transformants had the designed genome modifications, indicating that SnODIFY is highly accurate. Mutant phenotypes were validated through knockout of Type 4 pilus genes, which led to reduced biofilm formation. We also used SnODIFY to insert heterologous sequences into the genome by integrating fluorescent protein-coding genes. Finally, we confirmed that genome modification is dependent on S. alvi's endogenous RecA protein. Because it does not require expression of exogenous recombination machinery, SnODIFY is a straightforward, accurate, and lightweight method for genome editing in S. alvi. This workflow can be used to study the functions of S. alvi genes and to engineer this symbiont for applications including protection of honey bee health.

Building a more resilient haitian state

Ce rapport évalue les plans et politiques passés et actuels visant à améliorer la prestation de services publics en Haïti et, en s'appuyant sur cette évaluation, il fournit des recommandations sur la façon dont ces plans et politiques pourraient être améliorées. Le rapport met l'accent sur l'établissement de priorités pour les années à venir et propose des mesures qui pourraient produire des améliorations palpables dans la fourniture de services publics pendant cette période. Il est destiné au gouvernement d'Haïti pour l'élaboration de plans détaillés pour les réformes politiques et institutionnelles, ainsi qu'à la communauté internationale dans sa détermination de la façon de soutenir les efforts du gouvernement.

Comparing megestrol acetate therapy with oxandrolone therapy for HIV-related weight loss: similar results in 2 months.

Weight loss is known to impact survival among patients infected with human immunodeficiency virus (HIV) even in the era of highly active antiretroviral therapy (HAART). In a randomized trial, we compared the effects of 2 months of treatment with either megestrol acetate (800 mg every day) or oxandrolone (10 mg twice per day) on body weight and composition in patients with weight loss of > or =5 kg who were receiving HAART. The mean weight was 66 kg, and the mean body mass index was 21. Mean weight gain in the megestrol acetate and the oxandrolone arms were 2.8 kg (4.6% of the baseline value) and 2.5 kg (3.9% of the baseline value), respectively (P=.80). Lean body mass accounted for 39% of weight gain in the megestrol acetate arm and 56% in the oxandrolone arm (P=.38). Seven patients in the megestrol acetate arm and 5 patients in the oxandrolone arm reported minor adverse events (P=.74). In conclusion, megestrol acetate therapy and oxandrolone therapy have similar effects on body weight and composition and are safe and well-tolerated during HAART.

Combination megestrol acetate, oxandrolone, and dietary advice restores weight in human immunodeficiency virus.

BACKGROUND: We examined changes in total body weight (TBW) and health-related quality of life (HRQL) during prolonged combination weight-gaining therapy and dietary advice in HIV. DESIGN: This was a cohort study of patients initially randomized to single agent therapy for 2 months, megestrol acetate (800 mg daily), or oxandrolone (10 mg twice daily), followed by both agents and dietary advice for 5 months. METHODS: Two community health clinics and 1 urban infectious disease clinic were included, as were HIV-positive adult patients receiving highly active antiretroviral therapy with documented 5% weight loss. TBW and HRQL were measured after 7 months (7 m). RESULTS: Twenty-nine of 39 participants completed 7 m. The average sample age was 40 years, 75% were male, and 52% were of color at enrollment. Baseline mean TBW and body mass index (BMI) were 62.5 kg and 21 kg/m(2), respectively. Net gains in TBW, lean body mass, and fat during the 7 m were 5.3 kg (8.5% of baseline), 2.1 kg, and 3.1 kg, respectively (p < .01 for each). BMI increased to 23.1 kg/m(2) (p < .01). Dietary intake increased by 467 kcal/day (p = .03). Physical health improved by 5.7 (100-point scale, p < .01), and mental health was unchanged (-4.2, p = .11). In multivariable models, female gender (p < .01), lower baseline HIV viral load (p = .03), and increasing age (p < .01) were associated with TBW gain. Injection drug use (p < .01) and higher baseline HIV viral load (p < .01) were associated with reduction in physical health. CONCLUSIONS: Prolonged combination therapy with megestrol acetate, oxandrolone, and dietary advice could reverse weight loss and low BMI associated with incomplete viral suppression and improve physical health.