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Background\ud The use of accurate prediction tools and early intervention are important for addressing severe coronavirus disease 2019 (COVID-19). However, the prediction models for severe COVID-19 available to date are subject to various biases. This study aimed to construct a nomogram to provide accurate, personalized predictions of the risk of severe COVID-19.\ud \ud Methods\ud This study was based on a large, multicenter retrospective derivation cohort and a validation cohort. The derivation cohort consisted of 496 patients from Jiangsu Province, China, between January 10, 2020, and March 15, 2020, and the validation cohort contained 105 patients from Huangshi, Hunan Province, China, between January 21, 2020, and February 29, 2020. A nomogram was developed with the selected predictors of severe COVID-19, which were identified by univariate and multivariate logistic regression analyses. We evaluated the discrimination of the nomogram with the area under the receiver operating characteristic curve (AUC) and the calibration of the nomogram with calibration plots and Hosmer-Lemeshow tests.\ud \ud Results\ud Three predictors, namely, age, lymphocyte count, and pulmonary opacity score, were selected to develop the nomogram. The nomogram exhibited good discrimination (AUC 0.93, 95% confidence interval [CI] 0.90–0.96 in the derivation cohort; AUC 0.85, 95% CI 0.76–0.93 in the validation cohort) and satisfactory agreement.\ud \ud Conclusions\ud The nomogram was a reliable tool for assessing the probability of severe COVID-19 and may facilitate clinicians stratifying patients and providing early and optimal therapies.

Background Ratios of bacteriologically positive tuberculosis (TB) prevalence to notification rates are used to characterise typical durations of TB disease. However, this ignores the clinical spectrum of tuberculosis disease and potentially long infectious periods with minimal or no symptoms prior to care-seeking. Methods We developed novel statistical models to estimate progression from initial bacteriological positivity including smear conversion, symptom onset and initial care-seeking. Case-detection ratios, TB incidence, durations, and other parameters were estimated by fitting the model to tuberculosis prevalence survey and notification data (one subnational and 11 national datasets) within a Bayesian framework using Markov chain Monte Carlo methods. Results Analysis across 11 national datasets found asymptomatic tuberculosis durations in the range 4–8 months for African countries; three countries in Asia (Cambodia, Lao PDR, and Philippines) showed longer durations of > 1 year. For the six countries with relevant data, care-seeking typically began half-way between symptom onset and notification. For Kenya and Blantyre, Malawi, individual-level data were available. The sex-specific durations of asymptomatic bacteriologically-positive tuberculosis were 9.0 months (95% credible interval [CrI]: 7.2–11.2) for men and 8.1 months (95% CrI: 6.2–10.3) for women in Kenya, and 4.9 months (95% CrI: 2.6–7.9) for men and 3.5 months (95% CrI: 1.3–6.2) for women in Blantyre. Age-stratified analysis of data for Kenya showed no strong age-dependence in durations. For Blantyre, HIV-stratified analysis estimated an asymptomatic duration of 1.3 months (95% CrI: 0.3–3.0) for HIV-positive people, shorter than the 8.5 months (95% CrI: 5.0–12.7) for HIV-negative people. Additionally, case-detection ratios were higher for people living with HIV than HIV-negative people (93% vs 71%). Conclusion Asymptomatic TB disease typically lasts around 6 months. We found no evidence of age-dependence, but much shorter durations among people living with HIV, and longer durations in some Asian settings. To eradicate TB transmission, greater gains may be achieved by proactively screening people without symptoms through active case finding interventions

This publication addresses the limited use of qualitative methods in neglected tropical disease (NTD) programmes. It describes a scoping literature review conducted to inform the development of a guide to inform the use of rapid qualitative assessments to strengthen NTD mass drug administration (MDA) programmes. The review assessed how qualitative methods are currently used by NTD programmes and identified qualitative approaches from other health and development programmes with the potential to strengthen the design of MDA interventions. Systematic review articles were reviewed and searched using key terms conducted on Google Scholar and PubMed. Results show that methods used by NTD programmes rely heavily on focus group discussions and in-depth interviews, often with time-consuming analysis and limited information on how results are applied. Results from other fields offered insight into a wider range of methods, including participatory approaches, and on how to increase programmatic uptake of findings. Recommendations on how to apply these findings to NTD control are made. The topic of human resources for qualitative investigations is explored and a guide to improve MDAs using qualitative methods is introduced. This guide has direct applicability across the spectrum of NTDs as well as other public health programmes.

Background Uropathogenic Escherichia coli (UPEC) are amongst the most frequent causes of urinary tract infections. We report a systematic review and meta-analysis of virulence factors and antimicrobial resistance of UPEC isolated from urinary tract infections. Methods A systematic review and meta-analysis were performed using PRISMA guidelines (Research Registry ref. 5874). Data were extracted from PubMed/MEDLINE and ScienceDirect databases for studies published from January 1, 2000 to December 31, 2019. Studies reporting antimicrobial resistance and virulence factors of UPEC isolated in confirmed urinary tract infections (≥105CFU/ml) were eligible. Prevalence of antimicrobial resistance and virulence factors of UPEC were estimated using random-effects meta-analysis model. Estimates with 95% confidence intervals, I-square (I2) statistic, and Cochran’s Q test were computed using the score statistic and the exact binomial method by incorporating the Freeman-Tukey double arcsine transformation of proportions. Results Our search returned 2504 hits, of which 13 studies were included in the meta-analysis, totalling 1888 UPEC isolates. Highest antimicrobial resistance rates were observed among the antibiotic class of tetracycline in 69.1% (498/721), followed by sulphonamides in 59.3% (1119/1888), quinolones in 49.4% (1956/3956), and beta-lactams in 36.9% (4410/11964). Among beta-lactams, high resistance was observed in aminopenicillins in 74.3% (1157/1557) and first generation cephalosporins in 38.8% (370/953). Meanwhile, virulence factors with highest prevalence were immune suppressors (54.1%) followed by adhesins (45.9%). Taken individually, the most observed virulence genes were shiA (92.1%), CSH (80.0%), fimH/MSHA (75.3%), traT (75.1%), sisA (72.2%), iucD (65.7%), iutA (61.8%), kpsMTII (60.6%), and PAI (55.2%). Conclusions The increased antibiotic resistance of UPEC isolates was demonstrated and suggested a need for reassessment of empirical therapies in urinary tract infections treatment caused by this pathogen. In addition, this pathotype exhibited diverse surface and secreted virulence factors.

Introduction Kenya’s maternal mortality ratio is relatively high at 342/100,000 live births. Confidential enquiry into maternal deaths showed that 90% of the maternal deaths received substandard care with health workforce related factors identified in 75% of 2015/2016 maternal deaths. Competent Skilled Health Personnel (SHP) providing emergency obstetric and newborn care (EmONC) in an enabling environment reduces the risk of adverse maternal and newborn outcomes. The study objective was to identify factors that determine the retention of SHP 1 – 5 years after EmONC training in Kenya. Methods A cross-sectional review of EmONC SHP in five counties (Kilifi, Taita Taveta, Garissa, Vihiga and Uasin Gishu) was conducted between January–February 2020. Data was extracted from a training database. Verification of current health facilities where trained SHP were deployed and reasons for non-retention were collected. Descriptive data analysis, transfer rate by county and logistic regression for SHP retention determinants was performed. Results A total of 927 SHP were trained from 2014–2019. Most SHP trained were nurse/midwives (677, 73%) followed by clinical officers (151, 16%) and doctors (99, 11%). Half (500, 54%) of trained SHP were retained in the same facility. Average trained staff transfer rate was 43%, with Uasin Gishu lowest at 24% and Garissa highest at 50%. Considering a subset of trained staff from level 4/5 facilities with distinct hospital departments, only a third (36%) of them are still working in relevant maternity/newborn/gynaecology departments. There was a statistically significant difference in transfer rate by gender in Garissa, Vihiga and the combined 5 counties (p Conclusion Retention of EmONC trained SHP in the relevant maternity departments was low at 36 percent. SHP were more likely to be retained by 1-year after training compared to the subsequent years and this varied from county to county. County policies and guidelines on SHP deployment, transfers and retention should be strengthened to optimise the benefits of EmONC training.

The global movement to use routine information for managing health systems to achieve the Sustainable Development Goals, relies on administrative data which have inherent biases when used to estimate coverage with health services. Health policies and interventions planned with incorrect information can have detrimental impacts on communities. Statistical inferences using administrative data can be improved when they are combined with random probability survey data. Sometimes, survey data are only available for some districts. We present new methods for extending combined estimation techniques to all districts by combining additional data sources. Our study uses data from a probability survey (n = 1786) conducted during 2015 in 19 of Benin’s 77 communes and administrative count data from all of them for a national immunization day (n = 2,792,803). Communes are equivalent to districts. We extend combined-data estimation from 19 to 77 communes by estimating denominators using the survey data and then building a statistical model using population estimates from different sources to estimate denominators in adjacent districts. By dividing administrative numerators by the model-estimated denominators we obtain extrapolated hybrid prevalence estimates. Framing the problem in the Bayesian paradigm guarantees estimated prevalence rates fall within the appropriate ranges and conveniently incorporates a sensitivity analysis. Our new methodology, estimated Benin’s polio vaccination rates for 77 communes. We leveraged probability survey data from 19 communes to formulate estimates for the 58 communes with administrative data alone; polio vaccination coverage estimates in the 58 communes decreased to ranges consistent with those from the probability surveys (87%, standard deviation = 0.09) and more credible than the administrative estimates. Combining probability survey and administrative data can be extended beyond the districts in which both are collected to estimate coverage in an entire catchment area. These more accurate results will better inform health policy-making and intervention planning to reduce waste and improve health in communities.

Objective: This study investigated emotional distress and associated factors among the general population in the aftermath of the COVID-19 lockdown in China. Design and sample: An online nationwide survey was conducted using a self-designed questionnaire, which included items related to demography, lifestyle, and experience of emotional distress during the previous month of the pandemic period. A total of 10,545 respondents completed the survey. Results: Over 30% of participants reported experiencing one or more symptoms of emotional distress to a moderate or higher degree. Increased emotional distress was associated with COVID-19-related impact on diet (β = −1.106, 95% CI: −1.187 to −1.026, p < 0.001), experiencing food shortage (β = 1.334, 95% CI: 1.117 to 1.551, p < 0.001), lack of physical exercise (β = −0.845, 95% CI: −1.024 to −0.667, p < 0.001), younger age (β = −0.050, 95% CI: −0.062 to −0.039, p < 0.001), being a smoker (β = 0.852, 95% CI: 0.604 to 1.100, p < 0.001), lower education level (β = −0.524, 95% CI: −0.702 to −0.346, p < 0.001), and lack of medical insurance (β = −0.742, 95% CI: −1.012 to −0.473, p < 0.001). Emotional distress was negatively associated time spent sleeping (β = −0.020, 95% CI: −0.027 to −0.013, p < 0.001). Conclusion: The levels of emotional distress are high in the aftermath of the lockdown and associated with a number of demographic and lifestyle factors.

This is the 24th in the ongoing series of articles describing the GRADE approach for assessing the certainty of a body of evidence in systematic reviews and health technology assessments and how to move from evidence to recommendations in guidelines.\ud Guideline developers and authors of systematic reviews and other evidence syntheses use randomized controlled studies (RCTs) and non-randomized studies of interventions (NRSI) as sources of evidence for questions about health interventions. RCTs with low risk of bias are the most trustworthy source of evidence for estimating relative effects of interventions because of protection against confounding and other biases. However, in several instances, NRSI can still provide valuable information as complementary, sequential, or replacement evidence for RCTs. In this article we offer guidance on the decision regarding when to search for and include either or both types of studies in systematic reviews to inform health recommendations. This work aims to help methodologists in review teams, technology assessors, guideline panelists, and anyone conducting evidence syntheses using GRADE.

Background and Objectives\ud Children and pregnant women use 75% of the blood supply in sub-Saharan Africa (SSA) but face widespread blood shortages. To increase safe blood supply, Africa-specific evidence and strengthened capacity for transfusion research are needed. Our study analysed seven years of SSA transfusion publications, compared researched topics against priorities, and enumerated SSA transfusion research collaborations. \ud Materials and Methods\ud Data on research topic, journal type, authors’ institutions and country were extracted from transfusion-related SSA articles published between 2008-14 and used to construct a quantitative, graphic visualisation of collaborations. Research topics were compared to those identified as priorities for SSA blood services in 2008 and 2015. \ud Results\ud 267/2176 articles (average 38/year) met criteria for analysis. They involved 1245 authors, 673 institutions, 59 countries (35 SSA) and 1375 collaborations. 41% were on transfusion-transmitted infections. 34% were published in specialist transfusion journals. Only 7% involved exclusively collaborations within SSA. Two of the top fifteen institutions by publication quantity, were from outside SSA. \ud Conclusion\ud Despite a general paucity of SSA-relevant transfusion research, Francophone SSA was well-represented. Published research topics are not well-matched to SSA research priorities; research on supply, distribution, financing and systems is particularly neglected. The study provides a baseline against which to track any re-focusing of research activity to better meet SSA’s needs. Transfusion research hubs within and beyond SSA have been identified as a springboard network for expanding SSA transfusion research capacity. \ud \ud KEYWORDS\ud Sub-Saharan Africa, blood transfusion, research, collaborations

Hospital accreditation has been transferred from high-income countries (HICs) to many low- and middle-income countries (LMICs), supported by a variety of advocates and donor agencies. This review uses a policy transfer theoretical framework to present a structured analysis of the development of hospital accreditation in LMICs. The framework is used to identify how governments in LMICs adopted accreditation from other settings and what mechanisms facilitated and hindered the transfer of accreditation. The review examines the interaction between national and international actors, and how international organizations influenced accreditation policy transfer. Relevant literature was found by searching databases and selected websites; 78 articles were included in the analysis process. The review concludes that accreditation is increasingly used as a tool to improve the quality of healthcare in LMICs. Many countries have established national hospital accreditation programmes and adapted them to fit their national contexts. However, the implementation and sustainability of these programmes are major challenges if resources are scarce. International actors have a substantial influence on the development of accreditation in LMICs, as sources of expertise and pump-priming funding. There is a need to provide a roadmap for the successful development and implementation of accreditation programmes in low-resource settings. Analysing accreditation policy processes could provide contextually sensitive lessons for LMICs seeking to develop and sustain their national accreditation programmes and for international organizations to exploit their role in supporting the development of accreditation in LMICs.

Objectives: Clear communication of systematic review findings will help readers and decision makers. We built on previous work to develop an approach that improves the clarity of statements to convey findings and that draws on Grading of Recommendations Assessment,\ud Development and Evaluation (GRADE).\ud \ud Study Design and Setting: We conducted workshops including 80 attendants and a survey of 110 producers and users of systematic reviews. We calculated acceptability of statements and\ud revised the wording of those that were unacceptable to ≥40% of participants.\ud \ud Results: Most participants agreed statements should be based on size of effect and certainty of evidence. Statements for low, moderate and high certainty evidence were acceptable to >60%. Key guidance, for example, includes statements for high, moderate and low certainty for a large effect on intervention x as: x results in a large reduction…; x likely results in a large reduction…; x may result in a large reduction…, respectively.\ud \ud Conclusions: Producers and users of systematic reviews found statements to communicate findings combining size and certainty of an effect acceptable. This article provides GRADE guidance and a wording template to formulate statements in systematic reviews and other\ud decision tools.\ud \ud Keywords: review literature as topic, health communication, Evidence-Based Medicine, Surveys and Questionnaires, Language, persuasive communication

Background. The bootComb R package allows researchers to derive confidence intervals with correct target coverage for arbitrary combinations of arbitrary numbers of independently estimated parameters. Previous versions (< 1.1.0) of bootComb used independent bootstrap sampling and required that the parameters themselves are independent - an unrealistic assumption in some real-world applications. Findings. Using Gaussian copulas to define the dependence between parameters, the bootComb package has been extended to allow for dependent parameters. Implications. The updated bootComb package can now handle cases of dependent parameters, with users specifying a correlation matrix defining the dependence structure. While in practice it may be difficult to know the exact dependence structure between parameters, `bootComb` allows running sensitivity analyses to assess the impact of parameter dependence on the resulting confidence interval for the combined parameter. Availability. bootComb is available from the Comprehensive R Archive Network (https://CRAN.R-project.org/package=bootComb)., 9 pages, 2 figures. For associated R package, see https://cran.r-project.org/package=bootComb. For paper describing the main bootComb package, see https://doi.org/10.1093/ije/dyab049

Background and Objectives Rapid reviews provide an efficient alternative to standard systematic reviews in response to a high priority or urgent need. Although rapid reviews of interventions have been extensively evaluated, little is known about the characteristics of rapid reviews of diagnostic evidence. Study Design and Setting We performed a scoping review for rapid reviews of medical tests published from 2013 to 2018. We extracted information on review characteristics and methods used to assess the evidence. Results We identified 191 rapid reviews. All reviews were developed within a short time (less than 12 months) and were relatively concise (less than 10 pages). The reviews involved multiple index tests (44%), multiple outcomes (88%), and several test applications (29%). Well-known methodological tailoring strategies were infrequently used. Although reporting of several key features was limited, we found that, in general, rapid reviews have similar characteristics to broader knowledge syntheses. Conclusion Our scoping review is the first to describe the characteristics and methods of rapid reviews of diagnostic evidence. Future research should identify the most appropriate methods for performing rapid reviews of medical tests. Standards for reporting of rapid reviews are needed.

Community-based active case-finding (ACF) may have important impacts on routine TB case-detection and subsequent patient-initiated diagnosis pathways, contributing “indirectly” to infectious diseases prevention and care. We investigated the impact of ACF beyond directly diagnosed patients for TB, using routine case-notification rate (CNR) ratios as a measure of indirect effect. We systematically searched for publications 01-Jan-1980 to 13-Apr-2020 reporting on community-based ACF interventions compared to a comparison group, together with review of linked manuscripts reporting knowledge, attitudes, and practices (KAP) outcomes or qualitative data on TB testing behaviour. We calculated CNR ratios of routine case-notifications (i.e. excluding cases identified directly through ACF) and compared proxy behavioural outcomes for both ACF and comparator communities. Full text manuscripts from 988 of 23,883 abstracts were screened for inclusion; 36 were eligible. Of these, 12 reported routine notification rates separately from ACF intervention-attributed rates, and one reported any proxy behavioural outcomes. Two further studies were identified from screening 1121 abstracts for linked KAP/qualitative manuscripts. 8/12 case-notification studies were considered at critical or serious risk of bias. 8/11 non-randomised studies reported bacteriologically-confirmed CNR ratios between 0.47 (95% CI:0.41–0.53) and 0.96 (95% CI:0.94–0.97), with 7/11 reporting all-form CNR ratios between 0.96 (95% CI:0.88–1.05) and 1.09 (95% CI:1.02–1.16). One high-quality randomised-controlled trial reported a ratio of 1.14 (95% CI 0.91–1.43). KAP/qualitative manuscripts provided insufficient evidence to establish the impact of ACF on subsequent TB testing behaviour. ACF interventions with routine CNR ratios >1 suggest an indirect effect on wider TB case-detection, potentially due to impact on subsequent TB testing behaviour through follow-up after a negative ACF test or increased TB knowledge. However, data on this type of impact are rarely collected. Evaluation of routine case-notification, testing and proxy behavioural outcomes in intervention and comparator communities should be included as standard methodology in future ACF campaign study designs.

Background\ud Clinical scores for sepsis have been primarily developed for, and applied in High-Income Countries. This systematic review and meta-analysis examined the performance of the quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS), Modified Early Warning Score (MEWS), and Universal Vital Assessment (UVA) scores for diagnosis and prediction of mortality in patients with suspected infection in Low-and-Middle-Income Countries.\ud Methods\ud PubMed, Science Direct, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched until May 18, 2021. Studies reporting the performance of at least one of the above-mentioned scores for predicting mortality in patients of 15 years of age and older with suspected infection or sepsis were eligible. The Quality Assessment of Diagnostic Accuracy Studies tool was used for risk-of-bias assessment. PRISMA guidelines were followed (PROSPERO registration: CRD42020153906). The bivariate random-effects regression model was used to pool the individual sensitivities, specificities and areas-under-the-curve (AUC).\ud Findings\ud Twenty-four articles (of 5669 identified) with 27,237 patients were eligible for inclusion. qSOFA pooled sensitivity was 0·70 (95% confidence interval [CI] 0·60–0·78), specificity 0·73 (95% CI 0·67–0·79), and AUC 0·77 (95% CI 0·72–0·82). SIRS pooled sensitivity, specificity and AUC were 0·88 (95% CI 0·79 -0·93), 0·34 (95% CI 0·25–0·44), and 0·69 (95% CI 0·50–0·83), respectively. MEWS pooled sensitivity, specificity and AUC were 0·70 (95% CI 0·57 -0·81), 0·61 (95% CI 0·42–0·77), and 0·72 (95% CI 0·64–0·77), respectively. UVA pooled sensitivity, specificity and AUC were 0·49 (95% CI 0·33 -0·65), 0·91(95% CI 0·84–0·96), and 0·76 (95% CI 0·44–0·93), respectively. Significant heterogeneity was observed in the pooled analysis.\ud Interpretation\ud Individual score performances ranged from poor to acceptable. Future studies should combine selected or modified elements of different scores.\ud Funding\ud Partially funded by the UK National Institute for Health Research (NIHR) (17/63/42).

Introduction Programmes that merge management of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) aim to improve HIV/TB co-infected patients’ access to comprehensive treatment. However, several reports from sub-Saharan Africa (SSA) indicate suboptimal uptake of antiretroviral therapy (ART) even after integration of HIV and TB treatment. This study assessed ART uptake, its barriers and enablers in programmes integrating TB and HIV treatment in SSA. Method A systematic review was performed. Seven databases were searched for eligible quantitative, qualitative and mixed-methods studies published from March 2004 through July 2019. Random-effects meta-analysis was used to obtain pooled estimates of ART uptake. A thematic approach was used to analyse and synthesise data on barriers and enablers. Results Of 5139 references identified, 27 were included in the review: 23/27 estimated ART uptake and 10/27 assessed barriers to and/or enablers of ART uptake. The pooled ART uptake was 53% (95% CI: 42, 63%) and between-study heterogeneity was high (I2 = 99.71%, p Conclusions In SSA, programmes integrating treatment of TB and HIV do not, in general, achieve high ART uptake but we observe a net improvement in uptake after WHO issued the 2012 guidelines on collaborative TB/HIV activities. The recurrence of specific modifiable system-level and patient-level factors in the literature reveals key intervention points to improve ART uptake in these programmes. Systematic review registration: CRD42019131933.

Background:\ud The novel coronavirus disease (COVID-19) vaccines may help control the current pandemic but would require immunization levels that would achieve herd immunity. This study aimed to quantify current COVID-19 vaccine acceptance rates, as well as characterize the determinants, enablers and barriers to vaccine acceptability across the globe by synthesizing published evidence.\ud \ud Methods:\ud A systematic review and meta-analysis of studies was performed on studies assessing the acceptability of a COVID-19 vaccine published between November 1st, 2019, and November 30th, 2020. PubMed, Embase and Cochrane central were searched for eligible studies. Data extracted from retained studies was analyzed using STATA statistical software. A quantitative and narrative synthesis was produced.\ud \ud Results:\ud A total of 35 eligible articles (38 studies) involving a total of 70,997 participants across 7 regions and 35 countries were included. All studies were cross-sectional survey designs. The pooled vaccine acceptance rate across 32 studies was 71% (95% CI: 66 – 76%, p2= 99.4%, range: 29-97%). The pooled vaccine acceptance rate of parents for their children across 4 studies was 52% (95% CI: 37-67%, p2= 99.1%). Vaccine uptake was significantly higher among males (N=13 studies), older age groups (N=7), and healthcare providers (N=2). Enablers of vaccine uptake included perceived individual susceptibility to COVID-19 infection (N=11), prior influenza vaccination (N=7) and high vaccine effectiveness (N=6). The most common barriers to vaccine uptake were general negative attitudes towards vaccines/vaccine hesitancy (N=8), concerns over vaccine safety and efficacy (N=6), vaccine side effects (N=5), and misinformation or conspiracy beliefs around the experimental COVID-19 vaccines (N=2).\ud \ud Conclusions:\ud There is a good acceptance of COVID-19 vaccines globally despite wide variations across countries. Public health campaigns may benefit from capitalising on identified enablers and dispelling important barriers with regards to vaccine safety.

Background Caesarean section (CS) is an important medical intervention for reducing the risk of poor perinatal outcomes. However, CS trends in sub-Saharan Africa (SSA) continue to increase yet maternal and neonatal mortality and morbidity remain high. Rwanda, like many other countries in SSA, has shown an increasing trend in the use of CS. This study assessed the trends and factors associated with CS delivery in Rwanda over the past two decades. Methods We used nationally representative child datasets from the Rwanda Demographic and Health Survey 2000 to 2019–20. All births in the preceding 3 years to the survey were assessed for the mode of delivery. The participants’ characteristics, trends and the prevalence of CS were analysed using frequencies and percentages. Unadjusted and adjusted logistic regression analyses were used to assess the factors associated with population and hospital-based CS in Rwanda for each of the surveys. Results The population-based rate of CS in Rwanda significantly increased from 2.2% (95% CI 1.8–2.6) in 2000 to 15.6% (95% CI 13.9–16.5) in 2019–20. Despite increasing in all health facilities over time, the rate of CS was about four times higher in private (60.6%) compared to public health facilities (15.4%) in 2019–20. The rates and odds of CS were disproportionately high among women of high socioeconomic groups, those who resided in Kigali city, had multiple pregnancies, and attended at least four antenatal care visits while the odds of CS were significantly lower among multiparous women and those who had female babies. Conclusion Over the past two decades, the rate of CS use in Rwanda increased significantly at health facility and population level with high regional and socio-economic disparities. There is a need to examine the disparities in CS trends and developing tailored policy guidelines to ensure proper use of CS in Rwanda.

Background A systematic review of randomised trials may be conclusive signalling no further research is needed; or identify gaps requiring further research that may then be included in review updates. In qualitative evidence synthesis (QES), the rationale, triggers, and methods for updating are less clear cut. We updated a QES on adherence to anti-retroviral treatment to examine if thematic saturation renders additional research redundant. Methods We adopted the original review search strategy and eligibility criteria to identify studies in the subsequent three years. We assessed studies for conceptual detail, categorised as ‘rich’ or ‘sparse’, coding the rich studies. We sought new codes, and appraised whether findings confirmed, extended, enriched, or refuted existing themes. Finally, we examined if the analysis impacted on the original conceptual model. Results After screening 3895 articles, 301 studies met the inclusion criteria. Rich findings from Africa were available in 82 studies; 146 studies were sparse, contained no additional information on specific populations, and did not contribute to the analysis. New studies enriched our understanding on the relationship between external and internal factors influencing adherence, confirming, extending and enriching the existing themes. Despite careful evaluation of the new literature, we did not identify any new themes, and found no studies that refuted our theory. Conclusions Updating an existing QES using the original question confirmed and sometimes enriched evidence within themes but made little or no substantive difference to the theory and overall findings of the original review. We propose this illustrates thematic saturation. We propose a thoughtful approach before embarking on a QES update, and our work underlines the importance of QES priority areas where further primary research may help, and areas where further studies may be redundant.

Simple Summary A group of insecticides, called pyrethroids, are the main strategy for controlling the mosquito vectors of malaria. Pyrethroids are used in all insecticide-treated bednets, and many indoor residual spray programmes (in which insecticides are sprayed on the interior walls of houses). There are different types of pyrethroids within the class (e.g., deltamethrin and permethrin). Across the world, mosquitoes are showing signs of resistance to the pyrethroids, such as reduced mortality following contact. However, it is unclear if this resistance is uniform across the pyrethroid class (i.e., if a mosquito is resistant to deltamethrin, whether it is resistant to permethrin at the same level). In addition, it is not known if switching between different pyrethroids can be used to effectively maintain mosquito control when resistance to a single pyrethroid has been detected. This review examined the evidence from molecular studies, resistance testing from laboratory and field data, and mosquito behavioural assays to answer these questions. The evidence suggested that in areas where pyrethroid resistance exists, different mortality seen between the pyrethroids is not necessarily indicative of an operationally relevant difference in control performance, and there is no reason to rotate between common pyrethroids (i.e., deltamethrin, permethrin, and alpha-cypermethrin) as an insecticide resistance management strategy. Abstract Pyrethroid resistance is widespread in malaria vectors. However, differential mortality in discriminating dose assays to different pyrethroids is often observed in wild populations. When this occurs, it is unclear if this differential mortality should be interpreted as an indication of differential levels of susceptibility within the pyrethroid class, and if so, if countries should consider selecting one specific pyrethroid for programmatic use over another. A review of evidence from molecular studies, resistance testing with laboratory colonies and wild populations, and mosquito behavioural assays were conducted to answer these questions. Evidence suggested that in areas where pyrethroid resistance exists, different results in insecticide susceptibility assays with specific pyrethroids currently in common use (deltamethrin, permethrin, α-cypermethrin, and λ-cyhalothrin) are not necessarily indicative of an operationally relevant difference in potential performance. Consequently, it is not advisable to use rotation between these pyrethroids as an insecticide-resistance management strategy. Less commonly used pyrethroids (bifenthrin and etofenprox) may have sufficiently different modes of action, though further work is needed to examine how this may apply to insecticide resistance management.

Background Girls and women need effective, safe, and affordable menstrual products. Single-use menstrual pads and tampons are regularly provided by agencies among resource-poor populations. Reusable menstrual pads (RMPs: fabric layers sewn together by an enterprise for manufacture of menstrual products) may be an effective alternative. Methods For this review (PROSPERO CRD42020179545) we searched databases (inception to November 1, 2020) for quantitative and qualitative studies that reported on leakage, acceptability, or safety of RMPs. Findings were summarised or combined using forest plots (random-effects meta-analysis). Potential costs and environmental savings associated with RMPs were estimated. Results A total of 44 studies were eligible (~14,800 participants). Most were conducted in low- and middle-income countries (LMIC, 78%), and 20% in refugee settings. The overall quality of studies was low. RMP uptake in cohort studies ranged from 22–100% (12 studies). One Ugandan trial among schoolgirls found leakage with RMPs was lower (44.4%, n = 72) compared to cloths (78%, n = 111, p Conclusion RMPs are used internationally and are an effective, safe, cheaper, and environmentally friendly option for menstrual product provision by programmes. Good quality studies in this field are needed.

Objectives: Consideration of health status in children and adolescents now includes broader concepts such as health-related\ud quality-of-life (HRQoL). Globally, there is a need for relevant preference-based HRQoL measures (PBMs) for use in children\ud and adolescents, yet measurement of HRQoL in these groups presents particular challenges. This article systematically\ud reviews the available generic childhood PBMs and their application and cross-cultural validation in sub-Saharan African (sSA).\ud Methods: A systematic review of published literature from January 1, 1990, to February 8, 2017, was conducted using MEDLINE\ud (through OvidSP), EMBASE (OvidSP), EconLit (EBSCOhost), PsycINFO, Web of Science, and PubMed.\ud Results: A total of 220 full-text articles were included in a qualitative synthesis. Ten generic childhood PBMs were identified,\ud of which 9 were adapted from adult versions and only 1 was developed specifically for children. None of the measures were\ud originally developed in sSA or other resource-constrained settings. The Health Utilities Index Mark 3 (HUI3) and the EQ-5D-Y\ud were the only measures that had been applied in sSA settings. Further, the HUI3 and the EQ-5D-Y were the only generic\ud childhood PBM that attempted to establish cross-cultural validation in sSA. Five of the 6 of these validation studies were\ud conducted using the EQ-5D-Y in a single country, South Africa.\ud Conclusions: The findings show that application of generic childhood PBMs in sSA settings has hitherto been limited to the\ud HUI3 and EQ-5D-Y. Most adaptations of existing measures take an absolutist approach, which assumes that measures can be\ud used across cultures. Nevertheless, there is also need to ensure linguistic and conceptual equivalence and undertake\ud validation across a range of sSA cultural contexts.

Background Tuberculosis is the primary cause of hospital admission in people living with HIV, and the likelihood of death in the hospital is unacceptably high. The Alere Determine TB LAM Ag test (AlereLAM) is a point‐of‐care test and the only lateral flow lipoarabinomannan assay (LF‐LAM) assay currently commercially available and recommended by the World Health Organization (WHO). A 2019 Cochrane Review summarised the diagnostic accuracy of LF‐LAM for tuberculosis in people living with HIV. This systematic review assesses the impact of the use of LF‐LAM (AlereLAM) on mortality and other patient‐important outcomes. Objectives To assess the impact of the use of LF‐LAM (AlereLAM) on mortality in adults living with HIV in inpatient and outpatient settings. To assess the impact of the use of LF‐LAM (AlereLAM) on other patient‐important outcomes in adults living with HIV, including time to diagnosis of tuberculosis, and time to initiation of tuberculosis treatment. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded (Web of Science), BIOSIS Previews, Scopus, LILACS; ProQuest Dissertations and Theses; ClinicalTrials.gov; and the WHO ICTRP up to 12 March 2021. Selection criteria Randomized controlled trials that compared a diagnostic intervention including LF‐LAM with diagnostic strategies that used smear microscopy, mycobacterial culture, a nucleic acid amplification test such as Xpert MTB/RIF, or a combination of these tests. We included adults (≥ 15 years) living with HIV. Data collection and analysis Two review authors independently assessed trials for eligibility, extracted data, and analysed risk of bias using the Cochrane tool for assessing risk of bias in randomized studies. We contacted study authors for clarification as needed. We used risk ratio (RR) with 95% confidence intervals (CI). We used a fixed‐effect model except in the presence of clinical or statistical heterogeneity, in which case we used a random‐effects model. We assessed the certainty of the evidence using GRADE. Main results We included three trials, two in inpatient settings and one in outpatient settings. All trials were conducted in sub‐Saharan Africa and assessed the impact of diagnostic strategies that included LF‐LAM on mortality when the test was used in conjunction with other tuberculosis diagnostic tests or clinical assessment for clinical decision‐making in adults living with HIV. Inpatient settings In inpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy likely reduces mortality in people living with HIV at eight weeks compared to routine tuberculosis diagnostic testing without LF‐LAM (pooled RR 0.85, 95% CI 0.76 to 0.94; 5102 participants, 2 trials; moderate‐certainty evidence). That is, people living with HIV who received LF‐LAM had 15% lower risk of mortality. The absolute effect was 34 fewer deaths per 1000 (from 14 fewer to 55 fewer). In inpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy probably results in a slight increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF‐LAM (pooled RR 1.26, 95% CI 0.94 to 1.69; 5102 participants, 2 trials; moderate‐certainty evidence). Outpatient settings In outpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy may reduce mortality in people living with HIV at six months compared to routine tuberculosis diagnostic testing without LF‐LAM (RR 0.89, 95% CI 0.71 to 1.11; 2972 participants, 1 trial; low‐certainty evidence). Although this trial did not detect a difference in mortality, the direction of effect was towards a mortality reduction, and the effect size was similar to that in inpatient settings. In outpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy may result in a large increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF‐LAM (RR 5.44, 95% CI 4.70 to 6.29, 3022 participants, 1 trial; low‐certainty evidence). Other patient‐important outcomes Assessment of other patient‐important and implementation outcomes in the trials varied. The included trials demonstrated that a higher proportion of people living with HIV were able to produce urine compared to sputum for tuberculosis diagnostic testing; a higher proportion of people living with HIV were diagnosed with tuberculosis in the group that received LF‐LAM; and the incremental diagnostic yield was higher for LF‐LAM than for urine or sputum Xpert MTB/RIF. Authors' conclusions In inpatient settings, the use of LF‐LAM as part of a tuberculosis diagnostic testing strategy likely reduces mortality and probably results in a slight increase in tuberculosis treatment initiation in people living with HIV. The reduction in mortality may be due to earlier diagnosis, which facilitates prompt treatment initiation. In outpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy may reduce mortality and may result in a large increase in tuberculosis treatment initiation in people living with HIV. Our results support the implementation of LF‐LAM to be used in conjunction with other WHO‐recommended tuberculosis diagnostic tests to assist in the rapid diagnosis of tuberculosis in people living with HIV., Plain language summary Impact of diagnostic strategies for tuberculosis using lateral flow urine lipoarabinomannan test in people living with HIV What was the aim of this review? Tuberculosis is the leading cause of death in people living with HIV. The disease is particularly difficult to diagnose in people living with HIV, in part because it is often challenging to produce sputum for diagnosis. The lateral flow urine lipoarabinomannan test (LF‐LAM) is a World Health Organization (WHO)‐recommended rapid test to assist in the detection of active tuberculosis in people living with HIV. This review is limited to studies that used the Alere Determine TB LAM Ag test (AlereLAM), which is the only LF‐LAM test currently recommended by the WHO; thus LF‐LAM refers only to AlereLAM in this review. Rapid and early tuberculosis diagnosis may allow for prompt treatment and prevent severe illness and death. The aim of this review was to determine whether the use of LF‐LAM testing had an effect on death and other patient‐important outcomes in people living with HIV. Key messages In inpatient settings, the use of LF‐LAM as part of a tuberculosis diagnostic testing strategy likely reduces deaths and probably results in a slight increase in tuberculosis treatment initiation in people living with HIV. In outpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy may reduce deaths and may result in a large increase in tuberculosis treatment initiation in people living with HIV. What was studied in the review? We searched for trials in adults (15 years and older) that evaluated the effect of a tuberculosis diagnostic strategy that included the LF‐LAM test compared to standard care using other WHO‐recommended diagnostic tests in adults living with HIV. What were the main results of the review? We identified three trials, two in inpatient settings and one in outpatient settings. Inpatient settings In inpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy likely reduces mortality in people living with HIV at eight weeks compared to routine tuberculosis diagnostic testing without LF‐LAM (2 trials, 5102 participants, moderate‐certainty evidence). In inpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy probably results in a slight increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF‐LAM (2 trials, 5102 participants moderate‐certainty evidence). Outpatient settings In outpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy may reduce mortality in people living with HIV at six months compared to routine tuberculosis diagnostic testing without LF‐LAM (1 trial, 2972 participants, low‐certainty evidence). In outpatient settings, the use of LF‐LAM testing as part of a tuberculosis diagnostic strategy may result in a large increase in the proportion of people living with HIV who were started on tuberculosis treatment compared to routine tuberculosis diagnostic testing without LF‐LAM (1 trial, 3022 participants, low‐certainty evidence). Other patient‐important outcomes The included studies assessed other patient‐important outcomes in different ways. The studies demonstrated that more people living with HIV were able to produce urine compared to sputum for tuberculosis diagnostic testing, and more people living with HIV were diagnosed with tuberculosis in the group that received LF‐LAM. How up‐to‐date is the review? We searched for relevant trials up to 12 March 2021.

IntroductionAntimicrobial resistance (AMR) is increasing in low resource settings. It complicates the management of infectious diseases and is an increasing cause of death. This is due to, among other things, lack of health resources for appropriate diagnosis and unregulated access to antimicrobials in the public sphere. Developing context-specific interventions that enable judicious use of antimicrobials is important to curb this problem.MethodsWe will conduct a systematic review of antimicrobial stewardship (AMS) approaches in Development Assistance Committee in least developed and low-income countries. The inclusion criteria are antimicrobial stewardship interventions in hospitalised patients of all age groups and exclusion criteria are community-based trials and studies that solely focus on viral, fungal or parasite infections. Antimicrobial stewardship interventions will be classified as structural, enabling, persuasive, restrictive or combined. Outcomes of included studies will be classified as clinical, microbiological or behavioural outcomes. The studies to be included will be randomised controlled trials, controlled before–after studies, interrupted time series trials, cohort and qualitative studies. Data will be extracted using forms adapted from the Cochrane collaboration data collection form. This systematic review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and risk of bias will be done according to the Integrated quality Criteria for Review of Multiple Study Designs.Ethics and disseminationOur findings will be presented to clinicians and policymakers, to support developing AMS protocols for low resource settings. We will publish our results in peer-reviewed journals.Trial registration numberCRD42020210634.

Background: HIV and tuberculosis are frequently diagnosed concurrently. In March 2021, World Health Organization recommended that antiretroviral therapy (ART) should be started within two weeks of tuberculosis treatment start, at any CD4 count. We assessed whether earlier ART improved outcomes in people with newly diagnosed HIV and tuberculosis. Methods: We did a systematic review by searching nine databases for trials that compared earlier ART to later ART initiation in people with HIV and tuberculosis. We included studies published from database inception to 12 March 2021. We compared ART within four weeks versus ART more than four weeks after TB treatment, and ART within two weeks versus ART between two and eight weeks, and stratified analysis by CD4 count. The main outcome was death; secondary outcomes included IRIS and AIDS‐defining events. We pooled effect estimates using random effects meta‐analysis. Results and discussion: We screened 2468 abstracts, and identified nine trials. Among people with all CD4 counts, there was no difference in mortality by earlier ART (≤4 week) versus later ART (>4 week) (risk difference [RD] 0%, 95% confidence interval [CI] −2% to +1%). Among people with CD4 count ≤50 cells/mm3, earlier ART (≤4 weeks) reduced risk of death (RD −6%, −10% to −1%). Among people with all CD4 counts earlier ART (≤4 weeks) increased the risk of IRIS (RD +6%, 95% CI +2% to +10%) and reduced the incidence of AIDS‐defining events (RD −2%, 95% CI −4% to 0%). Results were similar when trials were restricted to the four trials which permitted comparison of ART within two weeks to ART between two and eight weeks. Trials were conducted between 2004 and 2014, before recommendations to treat HIV at any CD4 count or to rapidly start ART in people without TB. No trials included children or pregnant women. No trials included integrase inhibitors in ART regimens. Discussion: Earlier ART did not alter risk of death overall among people living with HIV who had TB disease. For logistical and patient preference reasons, earlier ART initiation for everyone with TB and HIV may be preferred to later ART.

Objective:\ud This paper explores the need for conceptual advances and practical guidance in the application of the GRADE approach within public health contexts.\ud \ud Study Design and Setting:\ud We convened an expert workshop and conducted a scoping review to identify challenges experienced by GRADE users in public health contexts. We developed this concept paper through thematic analysis and an iterative process of consultation and discussion conducted with members electronically and at three GRADE Working Group meetings.\ud \ud Results:\ud Five priority issues can pose challenges for public health guideline developers and systematic reviewers when applying GRADE: (1) incorporating the perspectives of diverse stakeholders; (2) selecting and prioritising health and ‘non-health’ outcomes; (3) interpreting outcomes and identifying a threshold for decision-making; (4) assessing certainty of evidence from diverse sources, including non-randomised studies; and (5) addressing implications for decision-makers, including concerns about conditional recommendations. We illustrate these challenges with examples from public health guidelines and systematic reviews, identifying gaps where conceptual advances may facilitate the consistent application or further development of the methodology, and provide solutions.\ud \ud Conclusion:\ud The GRADE Public Health Group will respond to these challenges with solutions that are coherent with existing guidance and can be consistently implemented across public health decision-making contexts.

Background\ud Community-based active case-finding interventions might identify and treat more people with tuberculosis disease than standard case detection. We aimed to assess whether active case-finding interventions can affect tuberculosis epidemiology in the wider community.\ud Methods\ud We did a systematic review by searching PubMed, Embase, Scopus, and Cochrane Library for studies that compared tuberculosis case notification rates, tuberculosis disease prevalence, or tuberculosis infection prevalence or incidence in children, between populations exposed and unexposed to active case-finding interventions. We included studies published in English between Jan 1, 1980, and April 13, 2020. Studies of active case-finding in the general population, in populations perceived to be at high risk for tuberculosis, and in closed settings were included, whereas studies of tuberculosis screening at health-care facilities, among household contacts, or among children only, and studies that screened fewer than 1000 people were excluded. To estimate effectiveness, we extracted or calculated case notification rates, prevalence of tuberculosis disease, and incidence or prevalence of tuberculosis infection in children, and compared ratios of these outcomes between groups that were exposed or not exposed to active case-finding interventions.\ud Results\ud 27 883 abstracts were screened and 988 articles underwent full text review. 28 studies contributed data for analysis of tuberculosis case notifications, nine for prevalence of tuberculosis disease, and two for incidence or prevalence of tuberculosis infection in children. In one cluster-randomised trial in South Africa and Zambia, an active case-finding intervention based on community mobilisation and sputum drop-off did not affect tuberculosis prevalence, whereas, in a cluster-randomised trial in Vietnam, an active case-finding intervention based on sputum tuberculosis tests for everyone reduced tuberculosis prevalence in the community. We found inconsistent, low-quality evidence that active case-finding might increase the number of cases of tuberculosis notified in populations with structural risk factors for tuberculosis.\ud Interpretation\ud Community-based active case-finding for tuberculosis might be effective in changing tuberculosis epidemiology and thereby improving population health if delivered with high coverage and intensity. If possible, active case-finding projects should incorporate a well designed, robust evaluation to contribute to the evidence base and help elucidate which delivery methods and diagnostic strategies are most effective.\ud Funding\ud WHO Global TB Programme.

Background The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. Methods and findings Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen, Author summary Snakebite is a neglected tropical disease and responsible for an estimated 130,000 deaths per year. Coagulopathy is the commonest clinical manifestation of systemic snakebite envenoming and is indicative of a need for antivenom. The 20WBCT is a simple, cheap and quick bedside clotting test devised to detect coagulopathy after snakebite. The test is used widely and is incorporated in multiple national and WHO guidelines. However, following a publication questioning its diagnostic accuracy, there is a lack of consensus regarding its diagnostic accuracy and utility. In this review, we conclude that the 20WBCT is capable of detecting coagulopathy following snakebite with high specificity and acceptable sensitivity. Diagnostic test accuracy of the 20WBCT is improved when assessing for the presence of severe coagulopathy. Inclusion of data in this analysis from a variety of countries, make the findings widely applicable. However, the heterogeneity in study findings indicates the need for local assessment of external validity. The results of this study support the WHO guidelines that recommend its continued use in the absence of conventional laboratory clotting assays. Urgent efforts are required to identify an optimal method of detecting systemic snakebite envenoming and the response to treatment through pharmacokinetic and pharmacodynamic studies of venom and antivenom.

Background Oral ivermectin is a safe broad spectrum anthelminthic used for treating several neglected tropical diseases (NTDs). Currently, ivermectin use is contraindicated in children weighing less than 15 kg, restricting access to this drug for the treatment of NTDs. Here we provide an updated systematic review of the literature and we conducted an individual-level patient data (IPD) meta-analysis describing the safety of ivermectin in children weighing less than 15 kg. Methodology/Principal findings A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for IPD guidelines by searching MEDLINE via PubMed, Web of Science, Ovid Embase, LILACS, Cochrane Database of Systematic Reviews, TOXLINE for all clinical trials, case series, case reports, and database entries for reports on the use of ivermectin in children weighing less than 15 kg that were published between 1 January 1980 to 25 October 2019. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42017056515. A total of 3,730 publications were identified, 97 were selected for potential inclusion, but only 17 sources describing 15 studies met the minimum criteria which consisted of known weights of children less than 15 kg linked to possible adverse events, and provided comprehensive IPD. A total of 1,088 children weighing less than 15 kg were administered oral ivermectin for one of the following indications: scabies, mass drug administration for scabies control, crusted scabies, cutaneous larva migrans, myiasis, pthiriasis, strongyloidiasis, trichuriasis, and parasitic disease of unknown origin. Overall a total of 1.4% (15/1,088) of children experienced 18 adverse events all of which were mild and self-limiting. No serious adverse events were reported. Conclusions/Significance Existing limited data suggest that oral ivermectin in children weighing less than 15 kilograms is safe. Data from well-designed clinical trials are needed to provide further assurance., Author summary Oral ivermectin is a safe and efficacious drug for the treatment of neglected tropical diseases. To date, ivermectin is not indicated in children weighing less than 15 kg because there have been insufficient safety data to support a change of recommendation. A PRISMA-level systematic review was conducted, and 97 potential sources were identified. All lead investigators were contacted to share individual patient data if they could provide the minimum criteria. These were the known weights of the children less than 15 kg in whom there were possible adverse events. A total of 17 investigators replied, sharing individual-level patient data (IPD) from 15 studies, which represent a database of 1,088 children weighing less than 15 kg treated with oral ivermectin. Overall 18 adverse events were reported in 1.4% (15/1,088) of children, all of which were mild and self-limiting. No serious adverse events were recorded. These data suggest that ivermectin is safe for use in children weighing less than 15 kilograms. Further data from well-designed clinical trials are needed to assess the safety of oral ivermectin at escalating doses in children weighing less than 15 kg.

PurposeTo identify approaches, enablers, barriers and outcomes of facility stillbirth and neonatal death audit in low-income and middle-income countries (LMICs).Data sourcesWe searched MEDLINE, CINAHL Complete, Academic Search Index, Science Citation Index, Complementary index and Global health electronic databases.Study selectionStudies were considered eligible when reporting the approaches, enablers, barriers and outcomes of facility-based stillbirth and neonatal death audit in LMICs.Data extractionTwo authors independently performed the data extraction using predefined templates made before data extraction.Results of data synthesisA total of 10 articles from 7 countries were included in the final analysis. Facility or external multidisciplinary teams performed death audits on a weekly or monthly basis. A total of 1018 stillbirths and neonatal deaths were audited. Of 18 audit enablers identified, nine were at the health provider level while 18 of 23 barriers to audit that were identified occurred at the facility level. The facility-level barriers cited by more than one study included: failure to implement change; inadequate training; limited time; increased workload; too many cases and poor documentation. Six studies reported that death audits resulted in structural improvements in physical structure, training, service organisation, supplies and equipment in the wards. Five studies reported that death audits improved the standard of care, with one study showing a significant improvement in measured standards. One study reported a significant reduction in newborn mortality rate of 29.4% (95% CI 0.6% to 2.4%; p=0.0015) and one study a reduction in perinatal mortality of 4.9% (52.8% in 2007 to 47.9% in 2008) before and after perinatal audit implementation.ConclusionStillbirth and neonatal death audit improves facility structures, processes of care and health outcomes in neonatal care. There is a need to enhance enablers and address barriers identified at both health provider and facility levels to improve the audit process.

Background Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and belongs to the neglected tropical diseases. The disease has been reported in 78 countries, with around 290.8 million people in need of treatment in 2018. Schistosomiasis is predominantly considered a rural disease with a subsequent focus of research and control activities in rural settings. Over the past decades, occurrence and even expansion of schistosomiasis foci in peri-urban and urban settings have increasingly been observed. Rural–urban migration in low- and middle-income countries and subsequent rapid and unplanned urbanization are thought to explain these observations. Fifty-five percent (55%) of the world population is already estimated to live in urban areas, with a projected increase to 68% by 2050. In light of rapid urbanization and the efforts to control morbidity and ultimately achieve elimination of schistosomiasis, it is important to deepen our understanding of the occurrence, prevalence, and transmission of schistosomiasis in urban and peri-urban settings. A systematic literature review looking at urban and peri-urban schistosomiasis was therefore carried out as a first step to address the research and mapping gap. Methodology Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic computer-aided literature review was carried out using PubMed, ScienceDirect, and the World Health Organization Database in November 2019, which was updated in March 2020. Only papers for which at least the abstract was available in English were used. Relevant publications were screened, duplicates were removed, guidelines for eligibility were applied, and eligible studies were reviewed. Studies looking at human Schistosoma infections, prevalence, and intensity of infection in urban and peri-urban settings were included as well as those focusing on the intermediate host snails. Principal findings A total of 248 publications met the inclusion criteria. The selected studies confirm that schistosomiasis is prevalent in peri-urban and urban areas in the countries assessed. Earlier studies report higher prevalence levels in urban settings compared to data extracted from more recent publications, yet the challenge of migration, rapid uncontrolled urbanization, and resulting poor living conditions highlight the potential for continuous or even newly established transmission to take place. Conclusions The review indicates that schistosomiasis has long existed in urban and peri-urban areas and remains a public health problem. There is, however, a challenge of comparability of settings due to the lack of a clear definition of what constitutes urban and peri-urban. There is a pressing need for improved monitoring of schistosomiasis in urban communities and consideration of treatment strategies., Author summary Schistosomiasis is an infectious parasitic disease and one of the 20 diseases considered by the World Health Organization as a neglected tropical disease. It is typically associated with poor environmental and sanitary conditions, primarily affecting rural communities. However, with the currently observed rapid urbanization and predicted two-thirds of the world population living in urban areas by 2050, concerns are raised about a spread of schistosomiasis to urban and peri-urban areas. At the same time, there seems to be little knowledge of the extent of schistososomiasis in urban areas. In light of the efforts to control morbidity and ultimately achieve elimination of schistosomiasis as well as reaching Sustainable Development Goals 3 “achieve health for all” and 11 “make human settlements inclusive, safe, resilient, and sustainable,” this systematic literature review was conducted to address the existing research and mapping gaps and to contribute to the understanding of the burden of schistosomiasis in areas that have not, as yet, been the focus of control efforts and mass drug administration programs. The review suggests that rapid and unorganized urbanization and resulting poor living conditions in urban and peri-urban areas may lead to new disease foci and thereby increase the overall disease burden. Research and policy implications are discussed.

Background Diphtheria is a vaccine-preventable disease that persists as a global health problem. An understanding of the pattern of disease is lacking in low- and middle-income countries such as the Philippines. Methods We conducted a retrospective review of the clinical, microbiological, and epidemiological features of patients admitted with a clinical diagnosis of diphtheria to an infectious disease referral hospital in Metro Manila, the Philippines, between 2006 and 2017. Cases were mapped and the distribution was compared with population density. Corynebacterium diphtheriae isolates from between 2015 and 2017 were examined by multilocus sequence typing (MLST). Results We studied 267 patients (range:12−54 cases/year) admitted between 2006 and 2017. The case fatality rate (CFR) was 43.8% (95% confidence interval, 37.8−50.0%). A higher number of cases and CFR was observed among children, We studied 267 patients with diphtheria hospitalized in Metro Manila over 11 years. Case fatality rate was 43.8%, higher in children

Background Despite being preventable, malaria remains an important public health problem. The World Health Organization (WHO) reports that overall progress in malaria control has plateaued for the first time since the turn of the century. Researchers and policymakers are therefore exploring alternative and supplementary malaria vector control tools. Research in 1900 indicated that modification of houses may be effective in reducing malaria: this is now being revisited, with new research now examining blocking house mosquito entry points or modifying house construction materials to reduce exposure of inhabitants to infectious bites. Objectives To assess the effects of house modifications on malaria disease and transmission. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Centre for Agriculture and Bioscience International (CAB) Abstracts (Web of Science); and the Latin American and Caribbean Health Science Information database (LILACS), up to 1 November 2019. We also searched the WHO International Clinical Trials Registry Platform (www.who.int/ictrp/search/en/), ClinicalTrials.gov (www.clinicaltrials.gov), and the ISRCTN registry (www.isrctn.com/) to identify ongoing trials up to the same date. Selection criteria Randomized controlled trials, including cluster‐randomized controlled trials (cRCTs), cross‐over studies, and stepped‐wedge designs were eligible, as were quasi‐experimental trials, including controlled before‐and‐after studies, controlled interrupted time series, and non‐randomized cross‐over studies. We only considered studies reporting epidemiological outcomes (malaria case incidence, malaria infection incidence or parasite prevalence). We also summarised qualitative studies conducted alongside included studies. Data collection and analysis Two review authors selected eligible studies, extracted data, and assessed the risk of bias. We used risk ratios (RR) to compare the effect of the intervention with the control for dichotomous data. For continuous data, we presented the mean difference; and for count and rate data, we used rate ratios. We presented all results with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. Main results Six cRCTs met our inclusion criteria, all conducted in sub‐Saharan Africa; three randomized by household, two by village, and one at the community level. All trials assessed screening of windows, doors, eaves, ceilings or any combination of these; this was either alone, or in combination with eave closure, roof modification or eave tube installation (a "lure and kill" device that reduces mosquito entry whilst maintaining some airflow). In two trials, the interventions were insecticide‐based. In five trials, the researchers implemented the interventions. The community implemented the interventions in the sixth trial. At the time of writing the review, two of the six trials had published results, both of which compared screened houses (without insecticide) to unscreened houses. One trial in Ethiopia assessed screening of windows and doors. Another trial in the Gambia assessed full screening (screening of eaves, doors and windows), as well as screening of ceilings only. Screening may reduce clinical malaria incidence caused by Plasmodium falciparum (rate ratio 0.38, 95% CI 0.18 to 0.82; 1 trial, 184 participants, 219.3 person‐years; low‐certainty evidence; Ethiopian study). For malaria parasite prevalence, the point estimate, derived from The Gambia study, was smaller (RR 0.84, 95% CI 0.60 to 1.17; 713 participants, 1 trial; low‐certainty evidence), and showed an effect on anaemia (RR 0.61, 95% CI 0.42, 0.89; 705 participants; 1 trial, moderate‐certainty evidence). Screening may reduce the entomological inoculation rate (EIR): both trials showed lower estimates in the intervention arm. In the Gambian trial, there was a mean difference in EIR between the control houses and treatment houses ranging from 0.45 to 1.50 (CIs ranged from ‐0.46 to 2.41; low‐certainty evidence), depending on the study year and treatment arm. The Ethiopian trial reported a mean difference in EIR of 4.57, favouring screening (95% CI 3.81 to 5.33; low‐certainty evidence). Pooled analysis of the trials showed that individuals living in fully screened houses were slightly less likely to sleep under a bed net (RR 0.84, 95% CI 0.65 to 1.09; 2 trials, 203 participants). In one trial, bed net usage was also lower in individuals living in houses with screened ceilings (RR 0.69, 95% CI 0.50 to 0.95; 1 trial, 135 participants). Authors' conclusions Based on the two trials published to date, there is some evidence that screening may reduce malaria transmission and malaria infection in people living in the house. The four trials awaiting publication are likely to enrich the current evidence base, and we will add these to this review when they become available., Plain language summary House modifications for preventing malaria What is the aim of this review? House modifications, such as screening (covering potential house entry points for mosquitoes with netting or mesh), or the use of alternative construction materials, may contribute to reducing the burden of malaria. They work by blocking mosquitoes from entering houses, and reducing the number of bites householders receive indoors. Some of the house modifications under consideration additionally aim to kill any mosquitoes that attempt to enter houses by incorporating insecticide into the modification. Key messages Screening windows, doors, eaves and ceilings to prevent mosquitoes entering the house may reduce malaria transmission and illness in people living in the house, based on evidence from two studies conducted in Africa. Four trials awaiting publication are likely to enrich the current evidence base. What was studied in the review? This review summarized studies investigating the effects of house modifications on human malaria outcomes. If studies additionally reported the effect of the house modifications on mosquitoes (those with potential to carry malaria), or householders' views, we also summarized this data. After searching for relevant studies, we identified six studies conducted in sub‐Saharan Africa, two of which have published data, and four of which are not yet in the public domain. All trials assessed screening (of windows, doors, eaves, ceilings, or any combination of these), either alone or in combination with eave closure, roof modification, or eave tube installation (a "lure and kill" device positioned in eave gaps). What are the main results of the review? The two trials with published data assessed the effect of screening alone on malaria infection. Both trials showed a reduction in malaria in screened houses, to varying degrees of effect. One trial in Ethiopia showed that people living in screened houses were around 62% less likely to experience an episode of clinical malaria (caused by P falciparum). However, the certainty of this evidence was low due to issues with the study design, and the trial did not study enough people for us to be confident about the results. Another trial in The Gambia showed that people living in screened houses were around 16% less likely to have P falciparum malaria parasites in their blood, and were less likely to experience anaemia. Our confidence in this result was low because the trial did not study enough people. How up to date is this review? The review authors searched for studies available up to 1 November 2019.

New malaria control tools and tailoring interventions to local contexts are needed to reduce the malaria burden and meet global goals. The housing modification, screening plus a targeted house-based insecticide delivery system called the In2Care® Eave Tubes, has been shown to reduce clinical malaria in a large cluster randomised controlled trial. However, the widescale suitability of this approach is unknown. We aimed to predict household suitability and define the most appropriate locations for ground-truthing where Screening + Eave Tubes (SET) could be implemented across Côte d'Ivoire. We classified DHS sampled households into suitable for SET based on the walls and roof materials. We fitted a Bayesian beta-binomial logistic model using the integrated nested Laplace approximation (INLA) to predict suitability of SET and to define priority locations for ground-truthing and to calculate the potential population coverage and costs. Based on currently available data on house type and malaria infection rate, 31% of the total population and 17.5% of the population in areas of high malaria transmission live in areas suitable for SET. The estimated cost of implementing SET in suitable high malaria transmission areas would be $46m ($13m -$108m). Ground-truthing and more studies should be conducted to evaluate the efficacy and feasibility of SET in these settings. The study provides an example of implementing strategies to reflect local socio-economic and epidemiological factors, and move beyond blanket, one-size-fits-all strategies.

Background: Perinatal depression is a maternal mental health condition that is associated with various adverse health outcomes both for the mothers and the babies. The study aim was to estimate the prevalence of perinatal depression and its risks and determinants in Mainland China.\ud \ud Methods: Systematic searches were conducted in 10 major databases and random effect meta-analysis was performed to achieve the pooled variance of perinatal depression. Subgroup analyses were conducted based on region, scale, methods of diagnosis and study design. Meta-regression was performed with the variables such as age, quality assessment score and gross domestic product (GDP) of the province.\ud \ud Results: Pooled prevalence of perinatal depression was 16.3% (CI=95%; 14.7% to 18.2%, P < 0.001), with antenatal depression 19.7% (CI=95%; 15.8% to 24.2%, P < 0.001) and postnatal depression 14.8% (CI=95%; 13.1% to 16.6%, P < 0.001). Significant publication bias was found and heterogeneity was I2= 98.13%. Lower socioeconomic status, poor physical health, anxiety about pregnancy and reduced social support were major risk factors while better living conditions and education were protective factors. The prevalence of perinatal depression showed a significant increasing trend in the last decade.\ud \ud Limitations: The review does not include studies with small sample size (n

Background Both pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are major global public health problems. We estimated the global, regional, and national prevalence of diabetes mellitus in a population with PTB. Methods We searched for observational studies of DM in people with PTB using the PubMed and Embase electronic bibliographic databases, focusing on articles published in the English language from database inception until March 31, 2021. We included original research that reported the prevalence of DM in PTB or those that had sufficient data to compute these estimates. Studies were excluded if they did not provide primary data or were case studies or reviews. Two authors independently extracted the articles and collected detailed information using a predefined questionnaire. A country-specific random-effects meta-analysis was used for countries with two or more available studies, and a fractional response regression model was employed to predict the prevalence of DM in PTB for countries with one or no study. The study was registered with the International Prospective Register of Systematic Reviews, using the registration number CRD42018101989. Results We identified 22,658 studies, and 153, across 51 countries, were retained for data extraction. The global prevalence of DM among patients with PTB was estimated to be 13.73% (95% confidence interval [CI] 12.51–14.95). The prevalence rates were 19.32% (95% CI 13.18–25.46) in the region of the Americas, 17.31% (95% CI 12.48–22.14) in the European region, 14.62% (95% CI 12.05–17.18) in Southeast Asia, 13.59% (95% CI 7.24–19.95) in the western Pacific region, 9.61% (95% CI 4.55–14.68) in the eastern Mediterranean region, and 9.30% (95% CI 2.83–15.76) in the African region. The country with the highest estimated prevalence was the Marshall Islands (50.12%; 95% CI 4.28–95.76). Conclusion Comorbid PTB and DM remain prevalent worldwide.

Background\ud There is inconclusive evidence on the association between ambient air pollution and pulmonary tuberculosis-related hospital admission and mortality. This review aims to assess if and to what extent, selected air pollutants are associated to pulmonary tuberculosis (PTB) incidence, hospital admissions and mortality.\ud \ud Methods\ud This will be a systematic review and meta-analysis of studies published in English between January 1st, 1946 and October 31st, 2020, quantitatively assessing the association between air pollutants and PTB incidence, hospital admissions and mortality. A comprehensive search strategy will be used to search the databases: Medline, Embase, Scopus and The Cochrane Library. Retrieved studies will be screened based on the set eligibility criteria and data will be extracted from eligible studies. Extracted data will be analysed on STATA version 14.0 software. Studies included will be assessed for their quality using the respective Study Quality Assessment Tools of the National Health Institute. The quality of the evidence on the study outcomes will be graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The risk of bias will be assessed using Cochrane’s Risk of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Study characteristics, socio-demographic and clinical characteristics across eligible studies will be summarised and presented. Pooled estimates of the measures of association between air pollutants and PTB incidence, hospital admission and mortality will be obtained through random-effect meta-analyses models and the respective I2 test statistics will be reported. Meta-regression analyses will be done in case of significant between-study heterogeneity.

Background Meta-analysis of patients with isoniazid-resistant tuberculosis (TB) given standard first-line anti-TB treatment indicated an increased risk of multidrug-resistant TB (MDR-TB) emerging (8%), compared to drug-sensitive TB (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with preexisting isoniazid-resistant disease with first-line anti-TB therapy risks selecting for rifampicin resistance, and hence MDR-TB. Methods Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug susceptibility testing was performed by microscopic observation drug susceptibility assay, mycobacterial growth indicator tube, and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was 5 or fewer single-nucleotide polymorphisms (SNPs), whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. Results Two hundred thirty-nine patients with isoniazid-resistant pulmonary TB were recruited. Fourteen (14/239 [5.9%]) patients were diagnosed with a second episode of TB that was multidrug resistant. Six (6/239 [2.5%]) were identified as having evolved MDR-TB de novo and 6 as having been reinfected with a different strain. In 2 cases, the genomic distance was between 5 and 10 SNPs and therefore indeterminate. Conclusions In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid-resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment., We investigated the sources of multidrug-resistant (MDR) tuberculosis (TB) in patients with isoniazid-resistant TB treated with first-line anti-TB therapy and show that reinfection with a new MDR-TB strain was just as common as the emergence of rifampicin resistance among these patients.

Objectives The objective of this systematic review was to evaluate the success of endocrown restorations on molars in comparison with endocrown restorations on premolars.\ud \ud Registration number The methodology for this review is registered with the PROSPERO database (CRD42019149543).\ud \ud Data sources Medline, Embase, Dentistry & Oral Sciences Source and Cochrane CENTRAL were searched through January 2020, supplemented with hand searching of additional relevant journals.\ud \ud Data selection and data extraction Two independent reviewers screened studies against predefined inclusion criteria and extracted data.\ud \ud Data analysis Narrative analysis was carried out and random-effects meta-analysis was performed where possible.\ud \ud Results Out of the selected eight studies, reported success rate of endocrown restoration in molars varied from 72.73% to 99.57% and in premolars ranged from 68.75% to 100%, with a follow-up range of 3-19 years. The pooled odds ratio and 95% confidence intervals for failure rates in molars compared to premolars in four studies selected for meta-analysis were 1.096 (95% CI: 0.280, 4.292).\ud \ud Conclusions These findings showed similar success rates and no difference in the rate of endocrown failures between molars and premolars, thus suggesting that premolars may be considered suitable candidates for endocrowns. However, the findings should be interpreted with caution due to methodological limitations of the included studies. Further better quality and specifically designed controlled trials directly comparing the clinical performance of endocrowns on molars and premolars are required.

Background Non-traumatic coma is a common acute childhood presentation to healthcare facilities in Africa and is associated with high morbidity and mortality. Historically, the majority of cases were attributed to cerebral malaria (CM). With the recent drastic reduction in malaria incidence, non-malarial coma is becoming a larger proportion of cases and determining the aetiology is diagnostically challenging, particularly in resource-limited settings. The purpose of this study will be to evaluate the aetiology and prognosis of non-traumatic coma in African children. Methods With no date restrictions, systematic searches of MEDLINE, Embase, and Scopus will identify prospective and retrospective studies (including randomised controlled trials, cluster randomised trials, cohort studies, cross-sectional, and case-control studies) recruiting children (1 month–16 years) with non-traumatic coma (defined by Blantyre Coma Score ≤ 2 or comparable alternative) from any African country. Disease-specific studies will be included if coma is associated and reported. The primary outcome is to determine the aetiology (infectious and non-infectious) of non-traumatic coma in African children, with pooled prevalence estimates of causes (e.g., malaria). Secondary outcomes are to determine overall estimates of morbidity and mortality of all-cause non-traumatic coma and disease-specific states of non-traumatic coma, where available. Random effects meta-analysis will summarise aetiology data and in-hospital and post-discharge mortality. Heterogeneity will be quantified with τ2, I2, and Cochran’s Q test. Discussion This systematic review will provide a summary of the best available evidence on the aetiology and outcome of non-traumatic coma in African children. Systematic review registration PROSPERO CRD42020141937

Background:\ud Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19).\ud \ud Purpose:\ud To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. (PROSPERO registration: CRD42020178187)\ud \ud Data Sources:\ud 21 standard, World Health Organization–specific and COVID-19–specific databases, without language restrictions, until 1 May 2020.\ud \ud Study Selection:\ud Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included.\ud \ud Data Extraction:\ud Independent and duplicate screening, data abstraction, and risk of bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews).\ud \ud Data Synthesis:\ud 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs.\ud \ud Limitation:\ud Direct studies in COVID-19 are limited and poorly reported.\ud \ud Conclusion:\ud Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers.

Asthma, the main inflammatory chronic condition affecting the respiratory system, is characterized by hyperresponsiveness and reversible airway obstruction, recruitment of inflammatory cells and excessive production of mucus. Cytokines as biochemical messengers of immune cells, play an important role in the regulation of allergic inflammatory and infectious airway processes. Essential oils of plant origin are complex mixtures of volatile and semi volatile organic compounds that determine the specific aroma of plants and are categorized by their biological activities.

Background The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. Methods We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. Findings We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per μL (the median for the cohort) was 45% (95% CI 38–52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63–87), increasing to 89% (80–94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05–3·08) but not after 30 days (1·25, 0·84–2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16–8·84). Interpretation In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. Funding This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A .

Background Rapid reviews (RRs) have emerged as an efficient alternative to time-consuming systematic reviews—they can help meet the demand for accelerated evidence synthesis to inform decision-making in healthcare. The synthesis of diagnostic evidence has important methodological challenges. Here, we performed an international survey to identify the current practice of producing RRs for diagnostic tests. Methods We developed and administered an online survey inviting institutions that perform RRs of diagnostic tests from all over the world. Results All participants (N = 25) reported the implementation of one or more methods to define the scope of the RR; however, only one strategy (defining a structured question) was used by ≥90% of participants. All participants used at least one methodological shortcut including the use of a previous review as a starting point (92%) and the use of limits on the search (96%). Parallelization and automation of review tasks were not extensively used (48 and 20%, respectively). Conclusion Our survey indicates a greater use of shortcuts and limits for conducting diagnostic test RRs versus the results of a recent scoping review analyzing published RRs. Several shortcuts are used without knowing how their implementation affects the results of the evidence synthesis in the setting of diagnostic test reviews. Thus, a structured evaluation of the challenges and implications of the adoption of these RR methods is warranted.

BACKGROUND:\ud National-level population size estimates (PSEs) for hidden populations are required for HIV programming and modelling. Various estimation methods are available at the site-level, but it remains unclear which are optimal and how best to obtain national-level estimates.\ud \ud SETTING:\ud Zimbabwe METHODS:: Using 2015-2017 data from respondent-driven sampling surveys (RDS) among female sex workers (FSW) aged 18+ years, mappings, and programme records, we calculated PSEs for each of 20 sites across Zimbabwe, using up to three methods per site (service and unique object multipliers, census, and capture-recapture). We compared estimates from different methods, and calculated site medians. We estimated prevalence of sex work at each site using census data available on the number of 15-49 year-old women, generated a list of all 'hotspot' sites for sex work nationally, and matched sites into strata in which the prevalence of sex work from sites with PSEs was applied to those without. Directly and indirectly estimated PSEs for all hotspot sites were summed to provide a national-level PSE, incorporating an adjustment accounting for sex work outside hotspots.\ud \ud RESULTS:\ud Median site PSEs ranged from 12,863 in Harare to 247 in a rural growth-point. Multiplier methods produced the highest PSEs. We identified 55 hotspots estimated to include 95% of all FSW. FSW nationally were estimated to number 40,491, 1.23% of women aged 15-49 years, (plausibility bounds 28,177-58,797, 0.86-1.79%, those under 18 considered sexually exploited minors).\ud \ud CONCLUSION:\ud There are large numbers of FSW estimated in Zimbabwe. Uncertainty in population size estimation should be reflected in policy-making.

Background: Maternal infections are an important cause of maternal mortality and severe maternal morbidity. We report the main findings of the WHO Global Maternal Sepsis Study, which aimed to assess the frequency of maternal infections in health facilities, according to maternal characteristics and outcomes, and coverage of core practices for early identification and management. Methods: We did a facility-based, prospective, 1-week inception cohort study in 713 health facilities providing obstetric, midwifery, or abortion care, or where women could be admitted because of complications of pregnancy, childbirth, post-partum, or post-abortion, in 52 low-income and middle-income countries (LMICs) and high-income countries (HICs). We obtained data from hospital records for all pregnant or recently pregnant women hospitalised with suspected or confirmed infection. We calculated ratios of infection and infection-related severe maternal outcomes (ie, death or near-miss) per 1000 livebirths and the proportion of intrahospital fatalities across country income groups, as well as the distribution of demographic, obstetric, clinical characteristics and outcomes, and coverage of a set of core practices for identification and management across infection severity groups. Findings: Between Nov 28, 2017, and Dec 4, 2017, of 2965 women assessed for eligibility, 2850 pregnant or recently pregnant women with suspected or confirmed infection were included. 70·4 (95% CI 67·7–73·1) hospitalised women per 1000 livebirths had a maternal infection, and 10·9 (9·8–12·0) women per 1000 livebirths presented with infection-related (underlying or contributing cause) severe maternal outcomes. Highest ratios were observed in LMICs and the lowest in HICs. The proportion of intrahospital fatalities was 6·8% among women with severe maternal outcomes, with the highest proportion in low-income countries. Infection-related maternal deaths represented more than half of the intrahospital deaths. Around two-thirds (63·9%, n=1821) of the women had a complete set of vital signs recorded, or received antimicrobials the day of suspicion or diagnosis of the infection (70·2%, n=1875), without marked differences across severity groups. Interpretation: The frequency of maternal infections requiring management in health facilities is high. Our results suggest that contribution of direct (obstetric) and indirect (non-obstetric) infections to overall maternal deaths is greater than previously thought. Improvement of early identification is urgently needed, as well as prompt management of women with infections in health facilities by implementing effective evidence-based practices. Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Espinoza, Marisa Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Pasquale, Julia. No especifíca; Fil: Hernández Muñoz, Rosalinda. No especifíca; Fil: Carvajal, Javier. No especifíca; Fil: Escobar, María Fernanda. No especifíca; Fil: Cecatti, José Guilherme. No especifíca; Fil: Ribeiro Do Valle, Carolina C.. No especifíca; Fil: Mereci, Wilson. No especifíca; Fil: Vélez, Paola. No especifíca; Fil: Pérez, Aquilino M.. No especifíca; Fil: Vitureira, Gerardo. No especifíca; Fil: Leroy, Charlotte. No especifíca; Fil: Roelens, Kristien. No especifíca; Fil: Vandenberghe, Griet. No especifíca; Fil: Aguemon, Christiane Tshabu. No especifíca; Fil: Cisse, Kadari. No especifíca; Fil: Ouedraogo, Henri Gautier. No especifíca; Fil: Kannitha, Cheang. No especifíca; Fil: Rathavy, Tung. No especifíca; Fil: Tebeu, Pierre Marie. No especifíca; Fil: Bustillo, Carolina. No especifíca; Fil: Bredy, Lara. No especifíca; Fil: Herrera Maldonado, Nazarea. No especifíca; Fil: Abdosh, Abdulfetah Abdulkadir. No especifíca; Fil: Teklu, Alula M.. No especifíca; Fil: Kassa, Dawit Worku. No especifíca; Fil: Kumar, Vijay. No especifíca; Fil: Suri, Vanita. No especifíca; Fil: Trikha, Sonia. No especifíca

High-quality data are essential to monitor and evaluate community health worker (CHW) programmes in low- and middle-income countries striving towards universal health coverage. This mixed-methods study was conducted in two purposively selected districts in Kenya (where volunteers collect data) and two in Malawi (where health surveillance assistants are a paid cadre). We calculated data verification ratios to quantify reporting consistency for selected health indicators over 3 months across 339 registers and 72 summary reports. These indicators are related to antenatal care, skilled delivery, immunization, growth monitoring and nutrition in Kenya; new cases, danger signs, drug stock-outs and under-five mortality in Malawi. We used qualitative methods to explore perceptions of data quality with 52 CHWs in Kenya, 83 CHWs in Malawi and 36 key informants. We analysed these data using a framework approach assisted by NVivo11. We found that only 15% of data were reported consistently between CHWs and their supervisors in both contexts. We found remarkable similarities in our qualitative data in Kenya and Malawi. Barriers to data quality mirrored those previously reported elsewhere including unavailability of data collection and reporting tools; inadequate training and supervision; lack of quality control mechanisms; and inadequate register completion. In addition, we found that CHWs experienced tensions at the interface between the formal health system and the communities they served, mediated by the social and cultural expectations of their role. These issues affected data quality in both contexts with reports of difficulties in negotiating gender norms leading to skipping sensitive questions when completing registers; fabrication of data; lack of trust in the data; and limited use of data for decision-making. While routine systems need strengthening, these more nuanced issues also need addressing. This is backed up by our finding of the high value placed on supportive supervision as an enabler of data quality.

IntroductionGlobal health research involves disciplines within and beyond the health sciences. A cross-disciplinary collaborative research approach enables an interchange of knowledge and experience and stimulates innovative responses to complex health challenges. However, there is little robust evidence to guide the design and implementation of cross-disciplinary research in global health, hampering effective collective action. This review synthesised evidence on practical actions for fostering cross-disciplinary research to provide guidance on the design and implementation of research in global health.MethodsWe searched five electronic databases using key words. The search included original research and research notes articles in English. We used a framework adapted from the socio-ecological model and thematic synthesis for data analysis.ResultsThirty-six original research and 27 research notes articles were included in the review. These were predominantly from high-income countries and indicated that practical actions on fostering cross-disciplinary research are closely linked to leadership and teamwork which should be planned and implemented at research team and institutional levels. The publications also indicated that individual qualities such as being receptive to new ideas and funders’ power and influence have practical implications for conducting cross-disciplinary research. Practical actions that individuals, research team leaders, academic institutions and funders can undertake to foster cross-disciplinary research were identified.ConclusionOur review found evidence from high-income countries, not low-and-middle-income countries, about practices that can improve cross-disciplinary research in global health. Critical knowledge gaps exist around how leadership and teamwork processes can better integrate expertise from different disciplines to make cross-disciplinary research more effective.

Background Domestic violence is a leading cause of social morbidity and may increase during and after pregnancy. In high-income countries screening, referral and management interventions are available as part of standard maternity care. Such practice is not routine in low- and middle-income countries (LMIC) where the burden of social morbidity is high. Methods We systematically reviewed available evidence describing the types of interventions, and/or the effectiveness of such interventions for women who report domestic violence during and/or after pregnancy, living in LMIC. Published and grey literature describing interventions for, and/or effectiveness of such interventions for women who report domestic violence during and/or after pregnancy, living in LMIC was reviewed. Outcomes assessed were (i) reduction in the frequency and/or severity of domestic violence, and/or (ii) improved physical, psychological and/or social health. Narrative analysis was conducted. Results After screening 4818 articles, six studies were identified for inclusion. All included studies assessed women (n = 894) during pregnancy. Five studies reported on supportive counselling; one study implemented an intervention consisting of routine screening for domestic violence and supported referrals for women who required this. Two studies evaluated the effectiveness of the interventions on domestic violence with statistically significant decreases in the occurrence of domestic violence following counselling interventions (488 women included). There was a statistically significant increase in family support following counselling in one study (72 women included). There was some evidence of improvement in quality of life, increased use of safety behaviours, improved family and social support, increased access to community resources, increased use of referral services and reduced maternal depression. Overall evidence was of low to moderate quality. Conclusions Screening, referral and supportive counselling is likely to benefit women living in LMIC who experience domestic violence. Larger-scale, high-quality research is, however, required to provide further evidence for the effectiveness of interventions. Improved availability with evaluation of interventions that are likely to be effective is necessary to inform policy, programme decisions and resource allocation for maternal healthcare in LMIC. Trial registration Systematic review registration number: PROSPERO CRD42018087713.