Social Protection Interventions for TB-Affected Households: A Scoping Review.

Tuberculosis (TB) and poverty are inextricably linked. Catastrophic costs of TB illness drive TB-affected households into worsening impoverishment and hamper treatment success. The WHO's End TB Strategy recommends social protection for TB-affected households to mitigate financial shock and improve TB outcomes. This scoping review maps the landscape of social protection interventions for people with TB and their households in low- and middle-income countries with high TB burden. A systematic search of Medline, Embase, PubMed, and Web of Science for relevant articles was performed, supplemented with a gray literature search of key databases. Articles were included if they described social protection available to people with TB and TB-affected households in a low- or middle-income country. Data were synthesized in tabular form, and descriptive narrative outlined the successes and challenges of the social protection interventions identified. The search identified 33,360 articles. After abstract screening, 74 articles underwent full text screening, and 49 were included in the final analysis. Forty-three types of social protection were identified, of which 24 were TB specific (i.e., only people with TB were eligible). Varying definitions were used to describe similar social protection interventions, which limited cross-study comparison. Intervention successes included acceptability and increased financial autonomy among recipients. Challenges included delays in intervention delivery and unexpected additional bank transfer fees. A wide range of acceptable social protection interventions are available, with cash transfer schemes predominating. Use of standardized definitions of social protection interventions would facilitate consolidation of evidence and enhance design and implementation in future.

Comparing the use of direct observation, standardized patients and exit interviews in low- and middle-income countries: a systematic review of methods of assessing quality of primary care.

Clinical records in primary healthcare settings in low- and middle-income countries (LMIC) are often lacking or of too poor quality to accurately assess what happens during the patient consultation. We examined the most common methods for assessing healthcare workers' clinical behaviour: direct observation, standardized patients and patient/healthcare worker exit interview. The comparative feasibility, acceptability, reliability, validity and practicalities of using these methods in this setting are unclear. We systematically review and synthesize the evidence to compare and contrast the advantages and disadvantages of each method. We include studies in LMICs where methods have been directly compared and systematic and narrative reviews of each method. We searched several electronic databases and focused on real-life (not educational) primary healthcare encounters. The most recent update to the search for direct comparison studies was November 2019. We updated the search for systematic and narrative reviews on the standardized patient method in March 2020 and expanded it to all methods. Search strategies combined indexed terms and keywords. We searched reference lists of eligible articles and sourced additional references from relevant review articles. Titles and abstracts were independently screened by two reviewers and discrepancies resolved through discussion. Data were iteratively coded according to pre-defined categories and synthesized. We included 12 direct comparison studies and eight systematic and narrative reviews. We found that no method was clearly superior to the others-each has pros and cons and may assess different aspects of quality of care provision by healthcare workers. All methods require careful preparation, though the exact domain of quality assessed and ethics and selection and training of personnel are nuanced and the methods were subject to different biases. The differential strengths suggest that individual methods should be used strategically based on the research question or in combination for comprehensive global assessments of quality.

The optimal surface for delivery of CPR: A systematic review and meta-analysis.

AIM: To determine the effect of CPR delivery surface (e.g. firm mattress, floor, backboard) on patient outcomes and CPR delivery. METHODS: We searched Medline, Cochrane Library and Web of Science for studies published since 2009 that evaluated the effect of CPR delivery surface in adults and children on patient outcomes and quality of CPR. We included randomised controlled trials only. We identified pre-2010 studies from the 2010 ILCOR evaluation of this topic. Two reviewers independently screened titles/ abstracts and full-text papers, extracted data and assessed risk of bias. Evidence certainty for each outcome was evaluated using GRADE methodology. Where appropriate, we pooled data in a meta-analysis, using a random-effects model. RESULTS: Database searches identified 2701 citations. We included seven studies published since 2009. We analysed these studies together with the four studies included in the previous ILCOR review. All included studies were randomised controlled trials in manikins. Certainty of evidence was very low. Increasing mattress stiffness or moving the manikin from the bed to the floor did not improve compression depth. Use of a backboard marginally improved compression depth (mean difference 3 mm (95% CI 1-4). CONCLUSION: The use of a backboard led to a small increase in chest compression depth in manikin trials. Different mattress types or delivery of CPR on the floor did not affect chest compression depth. PROSPERO CRD42019154791.

Hepitopes: A live interactive database of HLA class I epitopes in hepatitis B virus.

Increased clinical and scientific scrutiny is being applied to hepatitis B virus (HBV), with focus on the development of new therapeutic approaches, ultimately aiming for cure. Defining the optimum natural CD8+ T cell immune responses that arise in HBV, mediated by HLA class I epitope presentation, may help to inform novel immunotherapeutic strategies. Therefore, we have set out to develop a comprehensive database of these epitopes in HBV, coined 'Hepitopes'. This undertaking has its foundations in a systematic literature review to identify the sites and sequences of all published class I epitopes in HBV. We also collected information regarding the methods used to define each epitope, and any reported associations between an immune response to this epitope and disease outcome. The results of this search have been collated into a new open-access interactive database that is available at http://www.expmedndm.ox.ac.uk/hepitopes. Over time, we will continue to refine and update this resource, as well as inviting contributions from others in the field to support its development. This unique new database is an important foundation for ongoing investigations into the nature and impact of the CD8+ T cell response to HBV.

53BP1 Integrates DNA Repair and p53-Dependent Cell Fate Decisions via Distinct Mechanisms.

The tumor suppressor protein 53BP1, a pivotal regulator of DNA double-strand break (DSB) repair, was first identified as a p53-interacting protein over two decades ago. However, its direct contributions to p53-dependent cellular activities remain undefined. Here, we reveal that 53BP1 stimulates genome-wide p53-dependent gene transactivation and repression events in response to ionizing radiation (IR) and synthetic p53 activation. 53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain-mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28. Loss of these activities results in inefficient p53-dependent cell-cycle checkpoint and exit responses. Furthermore, we demonstrate 53BP1-USP28 cooperation to be essential for normal p53-promoter element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DSB repair regulation. Collectively, our data provide a mechanistic explanation for 53BP1-p53 cooperation in controlling anti-tumorigenic cell-fate decisions and reveal these activities to be distinct and separable from 53BP1's regulation of DNA double-strand break repair pathway choice.