PLoS medicine
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In a Perspective, Julie Garon and Walter Orenstein discuss Lessler and colleagues' modeling study on measles vaccination and the implications for triggered and routine immunization programs.
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Randomized Controlled Trial
Impacts on Breastfeeding Practices of At-Scale Strategies That Combine Intensive Interpersonal Counseling, Mass Media, and Community Mobilization: Results of Cluster-Randomized Program Evaluations in Bangladesh and Viet Nam.
Despite recommendations supporting optimal breastfeeding, the number of women practicing exclusive breastfeeding (EBF) remains low, and few interventions have demonstrated implementation and impact at scale. Alive & Thrive was implemented over a period of 6 y (2009-2014) and aimed to improve breastfeeding practices through intensified interpersonal counseling (IPC), mass media (MM), and community mobilization (CM) intervention components delivered at scale in the context of policy advocacy (PA) in Bangladesh and Viet Nam. In Bangladesh, IPC was delivered through a large non-governmental health program; in Viet Nam, it was integrated into government health facilities. This study evaluated the population-level impact of intensified IPC, MM, CM, and PA (intensive) compared to standard nutrition counseling and less intensive MM, CM, and PA (non-intensive) on breastfeeding practices in these two countries. ⋯ At-scale interventions combining intensive IPC with MM, CM, and PA had greater positive impacts on breastfeeding practices in Bangladesh and Viet Nam than standard counseling with less intensive MM, CM, and PA. To our knowledge, this study is the first to document implementation and impacts of breastfeeding promotion at scale using rigorous evaluation designs. Strategies to design and deliver similar programs could improve breastfeeding practices in other contexts.
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Randomised controlled trials (RCTs) are essential for evidence-based medicine and increasingly rely on front-line clinicians to recruit eligible patients. Clinicians' difficulties with negotiating equipoise is assumed to undermine recruitment, although these issues have not yet been empirically investigated in the context of observable events. We aimed to investigate how clinicians conveyed equipoise during RCT recruitment appointments across six RCTs, with a view to (i) identifying practices that supported or hindered equipoise communication and (ii) exploring how clinicians' reported intentions compared with their actual practices. ⋯ Communicating equipoise is a challenging process that is easily disrupted. Clinicians' personal views about trial treatments encroached on their ability to convey equipoise to patients. Clinicians should be encouraged to reflect on personal biases and be mindful of the common ways in which these can arise in their discussions with patients. Common pitfalls that recurred irrespective of RCT context indicate opportunities for specific training in communication skills that would be broadly applicable to a wide clinical audience.
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Randomized Controlled Trial
Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.
Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. ⋯ The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2-3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%-50%, with the eventual goal of preventing T1D.
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Observational Study
Whole Genome Sequence Analysis of a Large Isoniazid-Resistant Tuberculosis Outbreak in London: A Retrospective Observational Study.
A large isoniazid-resistant tuberculosis outbreak centred on London, United Kingdom, has been ongoing since 1995. The aim of this study was to investigate the power and value of whole genome sequencing (WGS) to resolve the transmission network compared to current molecular strain typing approaches, including analysis of intra-host diversity within a specimen, across body sites, and over time, with identification of genetic factors underlying the epidemiological success of this cluster. ⋯ Our study suggests that (1) certain paradigms need to be revised, such as the 12 SNP distance as the gold standard upper threshold to identify plausible transmissions; (2) WGS technology is helpful to rule out the possibility of direct transmission when isolates are separated by a substantial number of SNPs; (3) the concept of a transmission chain or network may not be useful in institutional or household settings; (4) the practice of isolating single colonies prior to sequencing is likely to lead to an overestimation of the number of SNPs between cases resulting from direct transmission; and (5) despite appreciable genomic diversity within a host, transmission of tuberculosis rarely results in minority variants becoming dominant. Thus, whilst WGS provided some increased resolution over variable number tandem repeat (VNTR)-based clustering, it was insufficient for inferring transmission in the majority of cases.