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Background The long-term impact of universal home-based testing and treatment as part of universal testing and treatment (UTT) on HIV incidence is unknown. We made projections using a detailed individual-based model of the effect of the intervention delivered in the HPTN 071 (PopART) cluster-randomised trial. Methods In this modelling study, we fitted an individual-based model to the HIV epidemic and HIV care cascade in 21 high prevalence communities in Zambia and South Africa that were part of the PopART cluster-randomised trial (intervention period Nov 1, 2013, to Dec 31, 2017). The model represents coverage of home-based testing and counselling by age and sex, delivered as part of the trial, antiretroviral therapy (ART) uptake, and any changes in national guidelines on ART eligibility. In PopART, communities were randomly assigned to one of three arms: arm A received the full PopART intervention for all individuals who tested positive for HIV, arm B received the intervention with ART provided in accordance with national guidelines, and arm C received standard of care. We fitted the model to trial data twice using Approximate Bayesian Computation, once before data unblinding and then again after data unblinding. We compared projections of intervention impact with observed effects, and for four different scenarios of UTT up to Jan 1, 2030 in the study communities. Findings Compared with standard of care, a 51% (95% credible interval 40–60) reduction in HIV incidence is projected if the trial intervention (arms A and B combined) is continued from 2020 to 2030, over and above a declining trend in HIV incidence under standard of care. Interpretation A widespread and continued commitment to UTT via home-based testing and counselling can have a substantial effect on HIV incidence in high prevalence communities. Funding National Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation, National Institute on Drug Abuse, and National Institute of Mental Health.

PDF file - 72K, S2. A) U87 or LN229 cells were treated with increasing concentration of ABT-263 for 16 h. Subsequently, cells were harvested, stained with Annexin V/Propidium iodide and subjected to flow cytometry. Provided are the percentages of viable cells under the indicated treatment conditions. 2 way ANOVA was performed and three stars "***" indicates a p value of less than 0.001. ABT10/ABT40 - 10/40 μM ABT-263.

PDF file - 1151K, S1. A) Protein lystates from three established glioblastoma cell lines (U87, LN229, U373), two glioblastoma neurosphere cultures (NCH644 and NCH690) as well as one ex-vivo low-passage glioblastoma neurosphere cell line (GS9-6) were harvested and subjected to immunoblotting for ph-Akt Serine 473, Akt, ph-BAD Serine 136, ph-BAD Serine 112 BAD and Mcl-1. B) U373 cells were treated with increasing concentrations of GDC-0941 (μM concentrations) for 7 hours and then subjected to immunoblotting with antibodies against ph-AKT (Serine 473), Akt and Mcl-1. 14-3-3β protein served as a loading control. C) U373 cells were treated with increasing concentrations of ABT-263 (μM concentrations) for 7 hours and subjected to immunoblotting with antibodies against phosphorylated Akt (Serine 473), Akt and Mcl-1. 14-3-3 protein served as loading control. D) LN229 cells were treated with increasing concentrations of ABT-263 (μM concentrations) for 7 hours and subjected to immunoblotting with antibodies against phosphorylated Akt (Serine 473), Akt and Mcl-1. 14-3-3 protein served as loading control. ABT - ABT-263; GDC - GDC-0941.

PDF file - 54K

International audience; High-altitude exposure results in a hyperventilatory-induced respiratory alkalosis followed by renal compensation (bicarbonaturia) to return arterial blood pH (pHa) toward sea-level values. However, acid-base balance has not been comprehensively examined in both lowlanders and indigenous populations-where the latter are thought to be fully adapted to high altitude. The purpose of this investigation was to compare acid-base balance between acclimatizing lowlanders and Andean and Sherpa highlanders at various altitudes (∼3,800, ∼4,300, and ∼5,000 m). We compiled data collected across five independent high-altitude expeditions and report the following novel findings: 1) at 3,800 m, Andeans (n = 7) had elevated pHa compared with Sherpas (n = 12; P < 0.01), but not to lowlanders (n = 16; 9 days acclimatized; P = 0.09); 2) at 4,300 m, lowlanders (n = 16; 21 days acclimatized) had elevated pHa compared with Andeans (n = 32) and Sherpas (n = 11; both P < 0.01), and Andeans had elevated pHa compared with Sherpas (P = 0.01); and 3) at 5,000 m, lowlanders (n = 16; 14 days acclimatized) had higher pHa compared with both Andeans (n = 66) and Sherpas (n = 18; P < 0.01, and P = 0.03, respectively), and Andean and Sherpa highlanders had similar blood pHa (P = 0.65). These novel data characterize acid-base balance acclimatization and adaptation to various altitudes in lowlanders and indigenous highlanders.NEW & NOTEWORTHY Lowlander, Andean, and Sherpa arterial blood data were combined across five independent high-altitude expeditions in the United States, Nepal, and Peru to assess acid-base status at ∼3,800, ∼4,300, and ∼5,000 m. The main finding was that Andean and Sherpa highlander populations have more acidic arterial blood, due to elevated arterial carbon dioxide and similar arterial bicarbonate compared with acclimatizing lowlanders at altitudes ≥4,300 m.

Drought and food security crises heighten risks to lives and livelihoods in East Africa. In recent years, a shift towards acting in advance of such events has gained momentum, notably among the humanitarian and development community. This shift is premised on tools that link climate forecasts with pre-agreed actions and funding, known as Forecast-based Action (FbA), or anticipatory action more widely. While FbA approaches have been developed by a number of humanitarian agencies, the key to scaling-up is mainstreaming these approaches into national risk management systems. This paper addresses this gap in the context of drought risk management in Kenya. We analyse Kenya's current drought management system to assess the potential usability of climate forecast information within the existing system, and outline steps towards improved usability of climate information. Further, we note the critical importance of enabling institutions and reliable financing to ensure that information can be consistently used to trigger early action. We discuss the implications of this for scaling-up FbA into national risk management systems.

The Horn of Africa drylands (HAD) are among the most vulnerable regions to hydroclimatic extremes. The two rainfall seasons — long and short rains — exhibit high intraseasonal and interannual variability. Accurately simulating the long and short rains has proven to be a significant challenge for the current generation of weather forecast and climate models, revealing key gaps in our understanding of the drivers of rainfall in the region. In contrast to existing climate modelling and observation-based studies, here we analyze the HAD rainfall from an observationally-constrained Lagrangian perspective. We quantify and map the major oceanic and terrestrial sources of moisture driving the variability in the long and short rains. Specifically, our results show that the Arabian Sea (through its influence on the northeast monsoon circulation) and the southern Indian Ocean (via the Somali low level jet) contribute ~80% of the HAD rainfall. We see that moisture contributions from land sources are very low at the beginning of each season, but supply up to ~20% from the second month onwards, i.e., when the oceanic-origin rainfall has already increased water availability over land. Further, our findings suggest that the interannual variability in the long and short rains is driven by changes in circulation patterns and regional thermodynamic processes rather than changes in ocean evaporation. Our results can be used to better evaluate, and potentially improve, numerical weather prediction and climate models, which has important implications for (sub-)seasonal forecasts and long-term projections of the HAD rainfall.

Community delivery of Antiretroviral therapy (ART) is a novel innovation to increase sustainable ART coverage for People living with HIV (PLHIV) in resource limited settings. Within a nested cluster-randomised sub-study in two urban communities that participated in the HPTN 071 (PopART) trial in Zambia we investigated individual acceptability and preferences for ART delivery models. Stable PLHIV were enrolled in a cluster-randomized trial of three different models of ART: Facility-based delivery (SoC), Home-based delivery (HBD) and Adherence clubs (AC). Consenting individuals were asked to express their stated preference for ART delivery options. Those assigned to the community models of ART delivery arms could choose (“revealed preference”) between the assigned arm and facility-based delivery. In total 2489 (99.6%) eligible individuals consented to the study and 95.6% chose community models of ART delivery rather than facility-based delivery when offered a choice. When asked to state their preference of model of ART delivery, 67.6% did not state a preference of one model over another, 22.8% stated a preference for HBD, 5.0% and 4.6% stated a preference for AC and SoC, respectively. Offering PLHIV choices of community models of ART delivery is feasible and acceptable with majority expressing HBD as their stated preferred option.

Summary Background There is limited access to eye health services in many low-income and middle-income populations. We aimed to assess the effectiveness in increasing service utilisation of the Peek Community Eye Health (Peek CEH) system, a smartphone-based referral system comprising decision support algorithms (Peek Community Screening app), SMS reminders, and real-time reporting. Methods In this cluster-randomised controlled trial of eye health in Kenya, community unit clusters were defined as one health centre and its catchment population. Clusters were randomly allocated (1:1) to receive Peek CEH and referral (intervention group) or standard care via periodic health centre-based outreach clinics and onward referral (control group). Individuals in the intervention group were assessed at home by screeners and those referred were asked to present for triage assessment in a central location. They received regular SMS reminders. In both groups, community sensitisation was done followed by a triage clinic at the cluster health centre 4 weeks after sensitisation. During triage, individuals in both groups were assessed and treated and, if necessary, referred to a specific hospital. Individuals in the intervention group received further SMS reminders. The primary outcome was the mean attendance rate (the number of people per 10 000 population) at triage of those with confirmed eye conditions, as assessed at 4 weeks after sensitisation in the intention-to-treat population. We estimated the intervention effect using a Student's t-test on cluster-level rates. This trial is registered with Pan African Clinical Trial Registry, number 201807329096632. Findings Between Nov 26, 2018, and June 7, 2019, of the 85 community units in Trans Nzoia County, Kenya, 49 were excluded. We randomly allocated 18 community units each to the intervention group (68 348 individuals) and the control group (60 243 individuals). 9387 individuals from the intervention group and 3070 from the control group attended triage assessment. The mean attendance rate at triage by individuals with eye problems was 1429 (92% CI 1228–1629) in the intervention group and 522 (418–625) in the control group (rate difference 906 per 10 000 [95% CI 689–1124; p Interpretation The Peek CEH system increased primary care attendance by people with eye problems compared with standard approaches, indicating the potential of this mobile health package to increase service uptake and guide appropriate task sharing. Funding The Queen Elizabeth Diamond Jubilee Trust and Wellcome Trust.

Clinically diagnosing fungal keratitis (FK) is challenging; diagnosis can be assisted by investigations including in vivo confocal microscopy (IVCM), smear microscopy, and culture. The aim of this study was to estimate the sensitivity in detecting fungal keratitis (FK) using IVCM, smear microscopy, and culture in a setting with a high prevalence of FK. In this cross-sectional study nested within a prospective cohort study, consecutive microbial keratitis (MK) patients attending a tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. IVCM and corneal scrapes for smear microscopy and culture were performed using a standardised protocol. Smear microscopy was performed using potassium hydroxide (KOH), Gram stain, and calcofluor white. The primary outcomes were sensitivities with 95% confidence intervals [95% CI] for IVCM, smear microscopy and culture, and for each different microscopy stain independently, to detect FK compared to a composite referent. We enrolled 642 patients with MK; 468/642 (72.9%) were filamentous FK, 32/642 (5.0%) were bacterial keratitis and 64/642 (10.0%) were mixed bacterial-filamentous FK, with one yeast infection (0.16%). No organism was identified in 77/642 (12.0%). Smear microscopy had the highest sensitivity (90.7% [87.9–93.1%]), followed by IVCM (89.8% [86.9–92.3%]) and culture (75.7% [71.8–79.3%]). Of the three smear microscopy stains, KOH had the highest sensitivity (85.3% [81.9–88.4%]), followed by Gram stain (83.2% [79.7–86.4%]) and calcofluor white (79.1% [75.4–82.5%]). Smear microscopy and IVCM were the most sensitive tools for identifying FK in our cohort. In low-resource settings we recommend clinicians perform corneal scrapes for microscopy using KOH and Gram staining. Culture remains an important tool to diagnose bacterial infection, identify causative fungi and enable antimicrobial susceptibility testing.

BackgroundThe aim of this study was to describe the health-seeking journey for patients with microbial keratitis (MK) in Nepal and identify factors associated with delay.MethodsProspective cohort study where MK patients attending a large, tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. We collected demographic details, clinical history, and examination findings. Care-seeking journey details were captured including places attended, number of journeys, time from symptom onset, and costs. We compared “direct” with “indirect” presenters, analyzing for predictors of delay.ResultsWe enrolled 643 patients with MK. The majority (96%) self-referred. “Direct” attenders accounted for only 23.6% (152/643) of patients, the majority of “indirect” patients initially presented to a pharmacy (255/491). Over half (328/643) of all cases presented after at least 7 days. The total cost of care increased with increasing numbers of facilities visited (p < 0.001). Those living furthest away were least likely to present directly (p < 0.001). Factors independently associated with delayed presentation included distance >50 km from the eye hospital [aOR 5.760 (95% CI 1.829–18.14, p = 0.003)], previous antifungal use [aOR 4.706 (95% CI 3.139–5.360)], and two or more previous journeys [aOR 1.442 (95% CI 1.111–3.255)].ConclusionsMost patients visited at least one facility prior to our institution, with time to presentation and costs increasing with the number of prior journeys. Distance to the eye hospital is a significant barrier to prompt, direct presentation. Based on these findings, improving access to eye care services, strengthening referral networks and encouraging early appropriate treatment are recommended to reduce delay, ultimately improving clinical outcomes.

Background: A key clinical skill for undergraduate medical students is communication with children, yet it is becoming increasingly difficult for medical schools to provide sufficient experience within a secondary care setting. One potential solution to this is to develop innovative ways of involving local schools.Aim: To demonstrate what was learned from a pilot school visit and show how this was developed into a successful programme.Method: As part of their GP-based Foundations of Primary Care course, medical students were allocated to local primary schools in their tutorial groups led by their GP tutors. They developed and delivered health promotion activities that were appropriate for school pupils. Review of the visit identified areas of improvement which were used to redesign the programme. Surveys were conducted after the subsequent visit to assess the response of medical students, school pupils and teachers.Learning outcomes: Medical students gained experience in communicating and interacting with school-aged children, and developed teaching and team working skills. School pupils reported change in their health-related knowledge and behaviour and the visits introduced them to the medical profession at a young age. The visits were well received by the teachers who valued the medical students' input.Conclusions: Building on the learning from the pilot school visit, a successful programme was developed that was challenging but ultimately enhanced medical student learning and brought significant benefits for the school pupils. Future developments include the potential to expand the topics taught and developing training in teaching for medical students.

PURPOSE: The PopART for Youth (P-ART-Y) study was nested within the HPTN 071 (PopART) trial, a three-arm community randomized trial in 21 communities in Zambia and South Africa. The P-ART-Y study evaluated the acceptability and uptake of a combination HIV prevention package among young people. We report on the HIV care cascade for adolescents aged 10-19 years from 14 communities receiving the full HIV prevention package in Zambia and South Africa. METHODS: Adolescents were offered participation in the PopART intervention, which included universal home-based HIV testing, linkage to care, antiretroviral therapy (ART) adherence, and other services. Data were collected from September 2016 to December 2017, covering the third round (R3) of the intervention. RESULTS: We enumerated (listed) 128,241 adolescents (Zambia: 95,295 and South Africa: 32,946). Of the adolescents offered HIV testing, 81.9% accepted in Zambia and 70.3% in South Africa. Knowledge of HIV status was higher among older adolescents and increased from 31.4% before R3 to 88.3% at the end of R3 in Zambia and from 28.3% to 79.5% in South Africa. Overall, there were 1,710 (1.9%) adolescents identified as living with HIV by the end of R3 (515 new diagnoses and 1,195 self-reported). Of the new diagnoses, 335 (65.0%) were girls aged 15-19 years. The median time to initiate ART was 5 months. ART coverage before and after R3 increased from 61.3% to 78.7% in Zambia and from 65.6% to 87.8% in South Africa, with boys having higher uptake than girls in both countries. CONCLUSIONS: The PopART intervention substantially increased coverage toward the first and second UNAIDS 90-90-90 targets in adolescents.

The joint WWRP–WCRP Subseasonal to Seasonal Prediction Project (e.g., Robertson et al. 2014) created a global repository of experimental or operational near-real-time S2S forecasts and reforecasts (hindcasts) from 11 international meteorological institutions, cohosted by ECMWF and CMA (Vitart et al. 2017). These data are publicly accessible by researchers and users (https://apps.ecmwf.int/datasets/data/s2s and http://s2s.cma.cn/index). With the exception of the fourth case study, which uses GloSea5 forecasts (MacLachlan et al. 2015), all case studies use selected S2S forecasts and reforecasts that are available from this repository, providing a consistent basis for S2S forecast skill assessment and evaluation of their utility. The subseasonal-to-seasonal (S2S) predictive time scale, encompassing lead times ranging from 2 weeks to a season, is at the frontier of forecasting science. Forecasts on this time scale provide opportunities for enhanced application-focused capabilities to complement existing weather and climate services and products. There is, however, a “knowledge–value” gap, where a lack of evidence and awareness of the potential socioeconomic benefits of S2S forecasts limits their wider uptake. To address this gap, here we present the first global community effort at summarizing relevant applications of S2S forecasts to guide further decision-making and support the continued development of S2S forecasts and related services. Focusing on 12 sectoral case studies spanning public health, agriculture, water resource management, renewable energy and utilities, and emergency management and response, we draw on recent advancements to explore their application and utility. These case studies mark a significant step forward in moving from potential to actual S2S forecasting applications. We show that by placing user needs at the forefront of S2S forecast development—demonstrating both skill and utility across sectors—this dialogue can be used to help promote and accelerate the awareness, value, and cogeneration of S2S forecasts. We also highlight that while S2S forecasts are increasingly gaining interest among users, incorporating probabilistic S2S forecasts into existing decision-making operations is not trivial. Nevertheless, S2S forecasting represents a significant opportunity to generate useful, usable, and actionable forecast applications for and with users that will increasingly unlock the potential of this forecasting time scale. DD gratefully acknowledges support from the Swiss National Science Foundation through project PP00P2_170523. For case study 1, ACP and WTKH were funded by the U.K. Climate Resilience Programme, supported by the UKRI Strategic Priorities Fund. RWL was funded by NERC Grant NE/P00678/1 and by the BER DOE Office of Science Federal Award DE-SC0020324. TS was funded by NERC Independent Research Fellowship (NE/P018637/1). CMG and DB were funded by the Helmholtz Young Investigator Group “SPREADOUT” Grant VH-NG-1243. Case study 2 was supported by the U.K. Global Challenges Research Fund NE/P021077/1 (GCRF African SWIFT) and the Tertiary Education Trust Fund (TETFUND) of Nigeria TETFund/DR&D/CE/NRF/STI/73/VOL.1. EO thanks Adrian Tomkins of ICTP, Italy, for his contribution. Case study 3 was undertaken as part of the Columbia World Project, ACToday, Columbia University (https://iri.columbia.edu/actoday/). Case study 4 was supported by the ForPAc (Towards Forecast-based Preparedness Action) project within the NERC/FCDO SHEAR Programme NE/P000428/1, NE/P000673/1, and NE/P000568/1. Case study 5 was undertaken as part of the International Research Applications Project, funded by the U.S. National Oceanic and Atmospheric Administration. EO thanks IRAP project colleagues at The University of Arizona, Indian Meteorological Department, Regional Integrated Multi-Hazard Early Warning System for Africa and Asia, and two of Bihar’s State Agricultural Universities for their contributions. For case study 6, CASC thanks Conselho Nacional de Desenvolvimento Científico e Tecnológico Process 305206/2019-2 and Fundação de Amparo à Pesquisa do Estado de São Paulo Process 2015/50687-8 (CLIMAX Project) for their support. For case study 7, DW’s contributions were carried out under contract with the National Aeronautics and Space Administration. Case study 8 was funded by the EU Horizon 2020 Research and Innovation Programme Grant 7767874 (S2S4E). We also acknowledge the Subseasonal-to-Seasonal Project’s Real-Time Pilot Initiative for providing access to real-time forecasts. For case study 9, TIC-LCPE Hydro-04 was funded by the University of Strathclyde’s Low Carbon Power and Energy program. JB was supported by EPSRC Innovation Fellowship EP/R023484/1. We thank Andrew Low and Richard Hearnden from SSE Renewables for their input. Case study 10 was supported by the Earth Systems and Climate Change Hub under the Australian Government’s National Environmental Science Program, and the Decadal Climate Forecasting Project (CSIRO). Case study 11 was funded by the Technologies for Sustainable Built Environments Centre, Reading University, in conjunction with the EPSRC Grant EP/G037787/1 and BT PLC. Case study 12 was funded through the framework service contract for operating the EFAS Computational Center Contract 198702 and the Copernicus Fire Danger Computations Contract 389730 295 in support of the Copernicus Emergency Management Service and Early Warning Systems between the Joint Research Centre and ECMWF. Peer Reviewed "Article signat per 60 autors/es: Christopher J. White, Daniela I. V. Domeisen, Nachiketa Acharya, Elijah A. Adefisan, Michael L. Anderson, Stella Aura, Ahmed A. Balogun, Douglas Bertram, Sonia Bluhm, David J. Brayshaw, Jethro Browell, Dominik Büeler, Andrew Charlton-Perez, Xandre Chourio, Isadora Christel, Caio A. S. Coelho, Michael J. DeFlorio, Luca Delle Monache, Francesca Di Giuseppe, Ana María García-Solórzano, Peter B. Gibson, Lisa Goddard, Carmen González Romero, Richard J. Graham, Robert M. Graham, Christian M. Grams, Alan Halford, W. T. Katty Huang, Kjeld Jensen, Mary Kilavi, Kamoru A. Lawal, Robert W. Lee, David MacLeod, Andrea Manrique-Suñén, Eduardo S. P. R. Martins, Carolyn J. Maxwell, William J. Merryfield, Ángel G. Muñoz, Eniola Olaniyan, George Otieno, John A. Oyedepo, Lluís Palma, Ilias G. Pechlivanidis, Diego Pons, F. Martin Ralph, Dirceu S. Reis Jr., Tomas A. Remenyi, James S. Risbey, Donald J. C. Robertson, Andrew W. Robertson, Stefan Smith, Albert Soret, Ting Sun, Martin C. Todd, Carly R. Tozer, Francisco C. Vasconcelos Jr., Ilaria Vigo, Duane E. Waliser, Fredrik Wetterhall, and Robert G. Wilson"

Background Good diabetes mellitus (diabetes) and diabetic retinopathy (DR) management depends on the strength of the health system, prompting us to conduct a health system assessment for diabetes and DR in Kenya. We used diabetes and DR as tracer conditions to assess the strengths and weaknesses in the health system, and potential interventions to strengthen the health system. In this paper, we report on the need and relevance of integration to strengthen diabetes and DR care. This theme emerged from the health system assessment. Methods Using a mixed methods study design, we collected data from service providers in diabetes clinics and eye clinics in three counties, from key informants at national and county level, and from documents review. Results There is interest in integration of diabetes and DR services to address discontinuity of care. We report the findings describing the context of integration, why integration is a goal and how these services can be integrated. We use the results to develop a conceptual framework for implementation. Conclusions The principal rationale for integrated service provision is to address service gaps and to prevent complications of diabetes and DR. The stakeholder interest and the existing infrastructure can be leveraged to improve these health outcomes.

Potential evapotranspiration (PET) represents the evaporative demand in the atmosphere for the removal of water from the land and is an essential variable for understanding and modelling land–atmosphere interactions. Weather generators are often used to generate stochastic rainfall time series; however, no such model exists for the generation of a stochastically plausible PET time series. Here we develop a stochastic PET generator, stoPET, by leveraging a recently published global dataset of hourly PET at 0.1∘ resolution (hPET). stoPET is designed to simulate realistic time series of PET that capture the diurnal and seasonal variability in hPET and to support the simulation of various scenarios of climate change. The parsimonious model is based on a sine function fitted to the monthly average diurnal cycle of hPET, producing parameters that are then used to generate any number of synthetic series of randomised hourly PET for a specific climate scenario at any point of the global land surface between 55∘ N and 55∘ S. In addition to supporting a stochastic analysis of historical PET, stoPET also incorporates three methods to account for potential future changes in atmospheric evaporative demand to rising global temperature. These include (1) a user-defined percentage increase in annual PET, (2) a step change in PET based on a unit increase in temperature, and (3) the extrapolation of the historical trend in hPET into the future. We evaluated stoPET at a regional scale and at 12 locations spanning arid and humid climatic regions around the globe. stoPET generates PET distributions that are statistically similar to hPET and an independent PET dataset from CRU, thereby capturing their diurnal/seasonal dynamics, indicating that stoPET produces physically plausible diurnal and seasonal PET variability. We provide examples of how stoPET can generate large ensembles of PET for future climate scenario analysis in sectors like agriculture and water resources with minimal computational demand.

Background: Attendance rates for eye clinics are low across low- and middle-income countries (LMICs) and exhibit marked sociodemographic (SD) inequalities. We aimed to quantify the association between a range of SD domains and attendance rates from vision screening in programmes launching in Botswana, Kenya and Nepal. Methods: We will develop a set of sociodemographic questions and introduce them into routine community-based eye screening programmes in Kenya, Botswana and Nepal, targeting children aged 5-18 years and adults. Our study design is a rolling survey, embedded within the Peek screening programme. The sociodemographic questions will be asked of 10% of all those presenting to be screened, and 100% of those identified with an eye problem. We will also collect data on whether people referred to ophthalmic clinic for treatment or further assessment attended, and we will use logistic regression to report odds ratios for this outcome attendance) for each socioeconomic domain in each country. We hypothesise that attendance rates will be lowest among marginalised sociodemographic groups such as older, less educated, less wealthy women. To identify the most appropriate sociodemographic items we will perform a literature review, and then hold workshops with researchers, academics, programme implementers, and programme designers in each country to tailor the domains and response options to the national context. We will report outcome data at 6 and 12 months, identifying the groups facing the highest barriers to access. Discussion: This low-risk, embedded, pragmatic, observational data collection will enable eye screening programme managers to accurately identify which sociodemographic groups are facing the highest systematic barriers to accessing care at any point in time. This information will be used to inform the development of service improvements to improve equity.

IntroductionGathering data on socioeconomic status (SES) is a prerequisite for any health programme that aims to assess and improve the equitable distribution of its outcomes. Many different modalities can be used to collect SES data, ranging from (1) face-to-face elicitation, to (2) telephone-administered questionnaires, to (3) automated text message-based systems. The relative costs and perceived benefits to patients and providers of these different data collection approaches is unknown. This protocol is for a systematic review that aims to compare the resource requirements, performance characteristics, and acceptability to participants and service providers of these three approaches to collect SES data from those enrolled in health programmes.Methods and analysisAn information specialist will conduct searches on the Cochrane Library, MEDLINE, Embase, Global Health, ClinicalTrials.gov, the WHO ICTRP and OpenGrey. All databases will be searched from 1999 to present with no language limits used. We will also search Google Scholar and check the reference lists of relevant articles for further potentially eligible studies. Any empirical study design will be eligible if it compares two or more modalities to elicit SES data from the following three; in-person, voice call, or automated phone-based systems. Two reviewers will independently screen titles, abstracts and full-text articles; and complete data extraction. For each study, we will extract data on the modality characteristics, primary outcomes (response rate and equivalence) and secondary outcomes (time, costs and acceptability to patients and providers). We will synthesise findings thematically without meta-analysis.Ethics and disseminationEthical approval is not required, as our review will include published and publicly accessible data. This review is part of a project to improve equitable access to eye care services in low-ioncome and middle-income countries. However, the findings will be useful to policy-makers and programme managers in a range of health settings and non-health settings. We will publish our findings in a peer-reviewed journal and develop an accessible summary of results for website posting and stakeholder meetings.PROSPERO registration numberCRD42021251959.

Global warming has increased the frequency of extreme weather events, including heatwaves, over recent decades. Heat early warning systems are being set up in many regions as a tool to mitigate their effects. Such systems are not yet implemented in the West African Sahel, partly because of insufficient knowledge on the skill of models to predict them. The present study addresses this gap by examining the skill of the ECMWF ENS extended-range forecasting system (ENS-ext) to predict Sahelian heatwaves out to subseasonal lead-times. It also assesses the importance of tropical modes of variability, which were previously identified as important large-scale drivers of heatwave occurrence in the Sahel. The results show that ENS-ext is able to predict Sahelian heatwaves with significant skill out to lead-week 2–3. With increasing lead-time, heatwaves are more predictable at nighttime than at daytime. Likewise, the pre-monsoon season heatwaves have a longer predictability than those occurring in late winter. The model is also able to relatively well simulate the observed relationship between heatwave occurrence and tropical mode activity. Furthermore, the prediction skill is better during the active phases of the modes, suggesting that they are good sources of heatwave predictability. Therefore, improving the representation of tropical modes in models will positively impact heatwave prediction at the subseasonal scale in the Sahel, and gain more time and precision for anticipatory actions.

Background/AimGlaucoma accounts for 8% of global blindness and surgery remains an important treatment. We aimed to determine the impact of adding simulation-based surgical education for glaucoma.MethodsWe designed a randomised controlled, parallel-group trial. Those assessing outcomes were masked to group assignment. Fifty-one trainee ophthalmologists from six university training institutions in sub-Saharan Africa were enrolled by inclusion criteria of having performed no surgical trabeculectomies and were randomised. Those randomised to the control group received no placebo intervention, but received the training intervention after the initial 12-month follow-up period. The intervention was an intense simulation-based surgical training course over 1 week. The primary outcome measure was overall simulation surgical competency at 3 months.ResultsTwenty-five were assigned to the intervention group and 26 to the control group, with 2 dropouts from the intervention group. Forty-nine were included in the final intention-to-treat analysis. Surgical competence at baseline was comparable between the arms. This increased to 30.4 (76.1%) and 9.8 (24.4%) for the intervention and the control group, respectively, 3 months after the training intervention for the intervention group, a difference of 20.6 points (95% CI 18.3 to 22.9, pConclusionThese results support the pursuit of financial, advocacy and research investments to establish simulation surgery training units and courses including instruction, feedback, deliberate practice and reflection with outcome measurement to enable trainee glaucoma surgeons to engage in intense simulation training for glaucoma surgery.Trial registration numberPACTR201803002159198.

Background Following the World Health Organization’s (WHO) 2015 guidelines recommending initiation of antiretroviral therapy (ART) irrespective of CD4 count for all people living with HIV (PLHIV), many countries in sub-Saharan Africa have adopted this strategy to reach epidemic control. As the number of PLHIV on ART rises, maintenance of viral suppression on ART for over 90% of PLHIV remains a challenge to government health systems in resource-limited high HIV burden settings. Non facility-based antiretroviral therapy (ART) delivery for stable HIV+ patients may increase sustainable ART coverage in resource-limited settings. Within the HPTN 071 (PopART) trial, two models, home-based delivery (HBD) or adherence clubs (AC), were offered to assess whether they achieved similar viral load suppression (VLS) to standard of care (SoC). In this paper, we describe the trial design and discuss the methodological issues and challenges. Methods A three-arm cluster randomized non-inferiority trial, nested in two urban HPTN 071 trial communities in Zambia, randomly allocated 104 zones to SoC (35), HBD (35), or AC (34). ART and adherence support were delivered 3-monthly at home (HBD), adherence clubs (AC), or clinic (SoC). Adult HIV+ patients defined as “stable” on ART were eligible for inclusion. The primary endpoint was the proportion of PLHIV with virological suppression (≤ 1000 copies HIV RNA/ml) at 12 months (± 3months) after study entry across all three arms. Viral load measurement was done at the routine government laboratories in accordance with national guidelines, annually. The study was powered to determine if either of the community-based interventions would yield a viral suppression rate drop compared to SoC of no more than 5% in its absolute value. Both community-based interventions were delivered by community HIV providers (CHiPs). An additional qualitative study using observations, interviews with PLHIV, and FGDs with community HIV providers was nested in this study to complement the quantitative data. Discussion This trial was designed to provide rigorous randomized evidence of safety and efficacy of non-facility-based delivery of ART for stable PLHIV in high-burden resource-limited settings. This trial will inform policy regarding best practices and what is needed to strengthen scale-up of differentiated models of ART delivery in resource-limited settings. Trial registration ClinicalTrials.gov NCT03025165. Registered on 19 January 2017

Preparedness saves lives. Forecasts can help improve preparedness by triggering early actions as part of pre-defined protocols under the Forecast-based Financing (FbF) approach; however it is essential to understand the skill of a forecast before using it as a trigger. In order to support the development of early-action protocols over Kenya, we evaluate the 33 heavy rainfall advisories (HRAs) issued by the Kenya Meteorological Department (KMD) during 2015–2019. The majority of HRAs warn counties which subsequently receive heavy rainfall within the forecast window. We also find a significant improvement in the advisory ability to anticipate flood events over time, with particularly high levels of skill in recent years. For instance actions with a 2-week lifetime based on advisories issued in 2015 and 2016 would have failed to anticipate nearly all recorded flood events in that period, whilst actions in 2019 would have anticipated over 70 % of the instances of flooding at the county level. When compared against the most significant flood events over the period which led to significant loss of life, all three such periods during 2018 and 2019 were preceded by HRAs, and in these cases the advisories accurately warned the specific counties for which significant impacts were recorded. By contrast none of the four significant flooding events in 2015–2017 were preceded by advisories. This step change in skill may be due to developing forecaster experience with synoptic patterns associated with extremes as well as access to new dynamical prediction tools that specifically address extreme event probability; for example, KMD access to the UK Met Office Global Hazard Map was introduced at the end of 2017. Overall we find that KMD HRAs effectively warn of heavy rainfall and flooding and can be a vital source of information for early preparedness. However a lack of spatial detail on flood impacts and broad probability ranges limit their utility for systematic FbF approaches. We conclude with suggestions for making the HRAs more useful for FbF and outline the developing approach to flood forecasting in Kenya.

Seasonal rainfall forecasts support early preparedness. These forecasts are typically disseminated at Regional Climate Outlook Forums (RCOFs), in the form of seasonal tercile probability categories—above normal, normal, below normal. However, these categories cannot be related directly to impacts on terrestrial water stores within catchments, since they are mediated by non-linear hydrological processes occurring on fine spatiotemporal scales, including rainfall partitioning into infiltration, evapotranspiration, runoff and groundwater recharge. Hydrological models are increasingly capable of capturing these processes, but there is no simple way to drive such models with a specific RCOF seasonal tercile rainfall forecast. Here we demonstrate a new method, “Quantile Bin Resampling” (QBR), for producing seasonal water forecasts for a drainage basin by integrating a tercile seasonal rainfall forecast with a hydrological model. QBR is based on mapping historical quantiles of basin-average rainfall to historical simulations of the water balance, and circumvents challenges associated with using climate model output to drive impact models directly. We evaluate QBR by generating 35 years of seasonal reforecasts for various water balance stores and fluxes for the Upper Ewaso Ng’iro basin in Kenya. Hindcasts indicate that when input tercile rainfall forecasts have skill, QBR provides accurate water forecasts at kilometre-scale resolution, which is relevant for anticipatory action down to village level. Pilot operational experimental water forecasts were produced for this basin using QBR for the 2022 March-May rainfall season, then disseminated to regional stakeholders at the Greater Horn of Africa Climate Outlook Forum (GHACOF). We discuss this initiative, along with limitations, plans and future potential of the method. Beyond the demonstrated application to water-related forecasts, QBR can be easily adapted to work with any rainfall-driven impact model. It can translate objective tercile climate probabilities into impact-relevant water balance forecasts at high spatial resolution in an efficient, transparent and flexible way.

IntroductionThere is evidence for increased resistance against the antimicrobials used to treat keratitis. This review aims to provide global and regional prevalence estimates of antimicrobial resistance in corneal isolates and the range of minimum inhibitory concentrations (MIC) with their associated resistance breakpoints.Methods and analysisWe report this protocol following Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols guidelines. We will conduct an electronic bibliographic search in MEDLINE, EMBASE, Web of Science and the Cochrane Library. Eligible studies will report in any language data for the resistance or MIC for antimicrobials against bacterial, fungal or amoebic organisms isolated from suspected microbial keratitis. Studies that only report on viral keratitis will not be included. There will be no time restrictions on the date of publication. Screening for eligible studies, assessment of risk of bias and data extraction will be conducted by two reviewers independently, using predefined inclusion criteria and prepiloted data extraction forms. We will resolve disagreements between the reviewers by discussion and, if required, a third (senior) reviewer will arbitrate. We will assess the risk of bias using a tool validated in prevalence studies. The certainty of the evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. Pooled proportion estimates will be calculated using a random-effects model. Heterogeneity will be assessed using the I2statistic. We will explore differences between Global Burden of Disease regions and temporal trends.Ethics approval and disseminationEthics approval is not required as this is a protocol for a systematic review of published data. The findings of this review will be published in an open-access, peer-reviewed journal.PROSPERO registration numberCRD42023331126.

BackgroundGlaucoma staging is critical for treatment planning but has rarely been tested in severe/end-stage disease. We compared the performance of the Disc Damage Likelihood Scale (DDLS) and cup:disc ratio (CDR) using a functional glaucoma staging system (GSS) as the reference standard.MethodsPost hoc analysis of a randomised controlled trial at the Eye Department of Kilimanjaro Christian Medical Centre, Tanzania. Eligible participants (aged ≥18 years) with open-angle glaucoma, intraocular pressure (IOP) of >21 mm Hg, were randomised to timolol 0.5% eye drops or selective laser trabeculoplasty. Fundoscopy established vertical and horizontal CDRs and DDLS. Visual acuity and static visual fields were graded (GSS). The study used area under the receiver operating characteristic (AROC) curves and Spearman’s rank correlation coefficients to compare staging systems. Logistic regression with generalised estimating equations determined risk factors of functional severe/end-stage glaucoma.Results382 eyes (201 participants) were evaluated; 195 (51%) had severe or end-stage glaucoma; mean IOP was 26.7 (SD 6.9) mm Hg. DDLS yielded an AROC of 0.90 (95% CI 0.87 to 0.93), vertical cup:disc ratio (vCDR) of 0.88 (95% CI 0.85 to 0.91, p=0.048) for identifying severe/end-stage disease. Correlation coefficients comparing GSS to DDLS and vCDRs were 0.73 and 0.71, respectively. Advanced structural stages, vision impairment, higher IOP and less financial resources were risk factors of functional severe/end-stage glaucoma.ConclusionThis study indicates that both structural staging systems can differentiate severe/end-stage glaucoma from less severe disease, with a moderate advantage of DDLS over CDR. Clinical examination of the optic disc plays an important role in addition to functional assessment when managing severe/end-stage glaucoma.

Dissemination of early warning information and effective preparedness are critical components in flood risk management and shape the dynamics of any successful early response. To enable efficient preparedness and an early response to hazards, early warning information should be simple, usable, and deployed through trusted sources.Successful management of floods are therefore dependent on clear and systematic communication structures which are, in turn, necessary to enable dissemination of such information. However, in many parts of Africa, flood event response is hampered by a lack of information on the inundation and potential exposure, with most large-scale systems limited to river flow forecasting, while local systems may lack coverage.In collaboration with the UK Foreign and Commonwealth Office, we have previously developed a method for fluvial flood inundation and exposure forecasting that combines hydrological forecasts from the Global Flood awareness systems (GLOFAS) with the LISFLOOD-FP global flood model. This was deployed in Mozambique to provide probabilistic inundation maps and exposure estimates to assist humanitarian response for cyclones Idai, Kenneth and Eloise.In this work, the flood models built with globally available datasets, and models augmented with local information, were evaluated for a series of uses and cases. Specifically, the 2020 fluvial flood event in the Nzoia basin in Kenya, the 2019 tropical cyclone flooding in Mozambique from cyclone Idai and recent pluvial flooding in the Zambian city of Lusaka.We discuss the potential and limitations of such information to inform efficient action and build resilient futures via co-production of forecasts in Kenya and the community learning lab component of the FRACTAL+ initiative in Lusaka.

Early warning of drought conditions can help protect lives and livelihoods, especially in dry regions of subsistence agriculture and pastoralism. Regions such as the Horn of Africa Drylands (HAD) may benefit from advance warning of changes to available water supplies, as rural communities make critical decisions about planting and moving livestock at particular points in time. However whilst the regionally-mandated seasonal forecast for HAD provides information on rainfall totals, it does not quantify expected impacts on water balance components such as soil moisture and groundwater storage. This latter information may be more useful to rural communities who rely on groundwater for water resources for humans and livestock, and soil moisture for crop growth. These hydrological quantities can typically be estimated with hydrological models, but in drylands the processes governing water partitioning are complex and largely unrepresented in most existing regional and global hydrological models. Here we leverage the capability of a dryland-specific hydrological model (DRYP) to produce rainfall-driven water security forecasts for HAD. DRYP incorporates spatially varying rainfall and evaporative demand, dynamic surface-groundwater interactions, ephemeral flow through channels and focused groundwater recharge. We employ DRYP in a pilot application to produce seasonal forecasts of soil moisture and groundwater recharge for a large catchment within the HAD. We use the objective seasonal forecasts provided by the IGAD Climate Prediction and Application Centre (ICPAC) and disseminated within the Greater Horn of Africa Climate Outlook Forum (GHACOF). Methodological approaches to integrate DRYP with the regional climate outlook disseminated by ICPAC are described, along with evaluation of potential skill of these new water security forecasts for the regional pilot catchment. Finally, we describe and update on an active forecast pilot activity, where water security forecasts for the current rainfall season (March-May 2022) have been co-produced with ICPAC and disseminated to stakeholders in February 2022 as part of the GHACOF event, now publicly available via the ICPAC East Africa Hazards Watch platform, under the EU H2020-funded DOWN2EARTH project. Co-design activity arising from recent stakeholder workshops will be described.

IntroductionThe HPTN071 (PopART) for Youth (P-ART-Y) study evaluated the acceptability and uptake of a community-level combination HIV prevention package including universal testing and treatment (UTT) among young people in Zambia and South Africa (SA). We determined whether a four-question primary care level screening tool, validated for use in clinical settings, could enhance community (door-to-door) identification of undiagnosed HIV-positive younger adolescents (aged 10-14) who are frequently left out of HIV interventions.MethodCommunity HIV-care Providers (CHiPs) contacted and consented adolescents in their homes and offered them participation in the PopART intervention. CHiPs used a four question-screening tool, which included: history of hospital admission; recurring skin problems; poor health in last 3 months; and death of at least one parent. A “yes” response to one or more questions was classified as being “at risk” of being HIV-positive. The data were captured through an electronic data capturing device from August 2016 to December 2017. Proportions of adolescents who were deemed “at risk” were calculated and the association of screening “at risk” with age, sex and community was tested using a chi-squared test. The adjusted odds ratio (OR) comparing the odds of testing HIV-positive if “at risk” with the odds of testing positive if “not at risk” was estimated using logistic regression.ResultsIn our 14 study sites, 33,283 adolescents aged 10-14 in Zambia and 8,610 in SA participated in the study. About 1.3% (427/33,710) and 1.2% (106/8,610) self-reported to be HIV positive. Excluding the self-reported HIV-positive, we classified 11.3% (3,746/33,283) of adolescents in Zambia and 17.5% (1,491/8,504) in SA as “at risk”. In Zambia and SA, the “at risk” adolescents were 4.6 and nearly 16.7 times more likely to test HIV-positive compared to the “not at risk”, respectively (both pConclusionThe screening tool may be of some value where UTT is not possible and limited resources must be prioritised toward adolescents who are more likely to be living with HIV. Further, the tool is of greater value in settings where there are more adolescents living with HIV who are undiagnosed. However, given our goal is to identify and treat all ALHIV, as well as link all HIV uninfected young people to prevention services, this screening tool should not be a substitute for UTT in community settings.Clinical Trial NumberNCT01900977

BackgroundClinic non-attendance rates are high across the African continent. Emerging evidence suggests that phone-based reminder messages could make a small but important contributing to reducing non-attendance. We used behavioral economics principles to develop an SMS and voice reminder message to improve attendance rates in a school-based eye screening programme in Botswana.MethodsWe will test a new theory-informed SMS and voice reminder message in a national school-based eye screening programme in Botswana. The control will be the standard SMS message used to remind parents/guardians to bring their child for ophthalmic assessment. All messages will be sent three times. The primary outcome is attendance for ophthalmic assessment. We will use an automated adaptive approach, starting with a 1:1:1:1 allocation ratio. Patients will not be blinded,DiscussionAs far as we are aware, only one other study has used behavioral economics to inform the development of reminder messages to be deployed in an African healthcare setting. Our study will will use an adaptive trial design, embedded in a national screening programme. Our approach can be used to trial other forms of reminder message in the future.Trial registrationISRCTN:96528723. Registered 5th January 2022, https://doi.org/10.1186/ISRCTN96528723Administrative informationNote: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modified to group similar items (see http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/).

Steele, Andrew R., Philip N. Ainslie, Rachel Stone, Kaitlyn Tymko, Courtney Tymko, Connor A. Howe, David MacLeod, James D. Anholm, Christopher Gasho, and Michael M. Tymko. Global REACH 2018: characterizing acid-base balance over 21 days at 4,300 m in lowlanders.

Fungal corneal infection (keratitis) is a common clinical problem in South Asia. However, it is often challenging to distinguish this from other aetiologies, such as bacteria or acanthamoeba. In this prospective study, we investigated clinical and epidemiological features that can predict the microbial aetiology of microbial keratitis in Nepal. We recruited patients presenting with keratitis to a tertiary eye hospital in lowland eastern Nepal between June 2019 and November 2020. A structured assessment, including demographics, history, and clinical signs, was carried out. The aetiology was investigated with in vivo confocal microscopy and corneal scrape for microscopy and culture. A predictor score was developed using odds ratios calculated to predict aetiology from features. A fungal cause was identified in 482/642 (75.1%) of cases, which increased to 532/642 (82.9%) when including mixed infections. Unusually, dematiaceous fungi accounted for half of the culture-positive cases (50.6%). Serrated infiltrate margins, patent nasolacrimal duct, raised corneal slough, and organic trauma were independently associated with fungal keratitis (p < 0.01). These four features were combined in a predictor score. The probability of fungal keratitis was 30.1% if one feature was present, increasing to 96.3% if all four were present. Whilst microbiological diagnosis is the “gold standard” to determine the aetiology of an infection, certain clinical signs can help direct the clinician to find a presumptive infectious cause, allowing appropriate treatment to be started without delay. Additionally, this study identified dematiaceous fungi, specifically Curvularia spp., as the main causative agent for fungal keratitis in this region. This novel finding warrants further research to understand potential implications and any trends over time.

The lives and livelihoods of people around the world are increasingly threatened by climate-related risks as climate change increases the frequency and severity of high-impact weather. In turn, the risk of multiple hazards occurring simultaneously grows and compound impacts become more likely. The World Meteorological Organization (WMO) proposed the use of multi-hazard impact-based forecasting (IbF) to better anticipate and reduce the impacts of concurrent hazards, but as yet, there are few operational examples in the humanitarian sector. \ud Drought is particularly susceptible to multi-hazard influences. However, challenges encountered in the development of drought IbF systems – including poor understanding of compound impacts and specific hazard-focused mandates – raise important questions for the feasibility of multi-hazard IbF as envisioned by the WMO. With these challenges in mind, we propose an interim approach in which real-time assessment of dynamic vulnerability provides a context for drought-based IbF. The incorporation of dynamic vulnerability indicators account for the local effects of non-drought hazards, whilst the use of a drought-based system facilitates effective intervention. The proposed approach will improve our understanding of compound events, enhance adoption of IbF in the humanitarian sector, and better mitigate the impacts of concurrent hazards.

Summary Background Non-facility-based antiretroviral therapy (ART) delivery for people with stable HIV might increase sustainable ART coverage in low-income and middle-income countries. Within the HPTN 071 (PopART) trial, two interventions, home-based delivery (HBD) and adherence clubs (AC), which included groups of 15–30 participants who met at a communal venue, were compared with standard of care (SoC). In this trial we looked at the effectiveness and feasibility of these alternative models of care. Specifically, this trial aimed to assess whether these models of care had similar virological suppression to that of SoC 12 months after enrolment. Methods This was a three-arm, cluster-randomised, non-inferiority trial, done in two urban communities in Lusaka, Zambia included in the HPTN 071 trial. The two communities were split into zones, which were randomly assigned (1:1:1) to the three treatment strategies: 35 zones to the SoC group, 35 zones to the HBD group, and 34 zones to the AC group. ART and adherence support were delivered once every 3 months at home for the HBD group, in groups of 15–30 people in the AC group, or in the clinic for the SoC group. Adults with HIV who were receiving first-line ART for at least 6 months, virally suppressed using national HIV guidelines in the last 12 months, had no other health conditions requiring the clinicians attention, live in the study catchment area, and provided written informed consent, were eligible for inclusion. The primary endpoint was viral suppression at 12 months (with a 6 month final measurement window [ie, 9–15 months]), defined as less than 1000 HIV RNA copies per mL, with a non-inferiority margin of 5%. Findings Between May 5 and Dec 19, 2017, 9900 individuals were screened for inclusion, of whom 2489 (25·1%) participants were enrolled into the trial: 781 (31%) in the SoC group, 852 (34%) in the HBD group, and 856 (34%) in the AC group. A higher proportion of participants had viral load measurements in the primary outcome window in the HBD (581 [61%]of 852 participants) and AC (485 [57%] of 856 participants) groups than in the SoC (390 [50%] of 781 patients) group (p=0·0021). Of the 1096 missing observations, 152 (13·8%) were attributable to either deaths (25 [16%] participants), relocations (37 [24%] participants), or lost to follow-up (90 [59%]); 690 (63·0%) participants had viral load results outside the window period; and 254 (23·2%) did not have a viral load result. The prevalence of viral suppression was estimated to be 98·3% (95% CI 96·6 to 99·7) in the SoC group, 98·7% (97·5 to 99·6) in the HBD group, and 99·2% (98·4 to 99·8) in the AC group. This gave an estimated risk difference of 0·3% (95% CI −1·5 to 2·4) for the HBD group compared with the SoC group and 0·9% (−0·8 to 2·8) for the AC group compared with the SoC group. There was strong evidence (p

Funder: Queen Elizabeth Diamond Jubilee Trust [grant code: ITCRZC6813], Background/objectives: Late presentation of congenital cataract in the developing world has led to poor outcomes such that cataract is the leading cause of childhood blindness. Our hypothesis was that, sensitivity of red-reflex testing is greater than sensitivity of torchlight examination. We aimed to compare sensitivity of new red reflex screening tools and assess the feasibility of Arclight red reflex screening in the community. Subject/methods: We compared the diagnostic accuracy of four different screening tools for cataract and retinoblastoma performed by ophthalmic nurses, using a clinic based enriched sample of 41 positives and 60 negatives. We then conducted a separate feasibility study, training non-specialist community nurses. Following the training, community nurses examined 2827 children

The eye-seeking flyWe first conducted a series of phase I laboratory studies to inform our choice of field intervention. We then conducted a phase II randomised controlled trial testing the efficacy of permethrin-treated scarves (PTS) in reducing fly-face contact in Oromia, Ethiopia. Children aged 4-10 years in full health and with no known adverse reactions to permethrin or other insecticides were allocated to either arm using restricted randomisation. Intervention arm children wore Insect Shield® versatile wraps (as PTS) for 28 days. The primary outcomes, fly-eye, -nose and -mouth contact, were assessed on the first day (0/30/60/180 minutes), on day 7 and on day 28. All participants present per timepoint were included in analyses. This trial was registered with ClinicalTrials.gov (NCT03813069).Participants were recruited to the field trial between 29/10/2019 and 01/11/2019, 58 were randomised to test or control arm. More fly (-eye, -nose and -mouth) contacts were observed in the PTS arm at baseline. After adjusting for baseline contact rates, across all timepoints there was a 35% decrease in fly-eye contacts in the PTS relative to control arm (rate ratio [RR] 0.65, 95% CI 0.52-0.83). Similar cross-timepoint reductions were seen for fly-nose and fly-mouth contacts (RR 0.69, 95% CI 0.51-0.92 and RR 0.79, 95% CI 0.62-1.01, respectively). All children were included on day 0. Two in the control arm were absent on day 7, one left the study and four were excluded from analysis at day 28. No adverse events occurred in the trial.Wellcome Trust.

To investigate the association between individual and community-level measures of HIV stigma and HIV incidence within the 21 communities participating in the HPTN (071) PopART trial in Zambia and South Africa.Secondary analysis of data from a population-based cohort followed-up over 36 months between 2013 and 2018. The outcome was rate of incident HIV infection among individuals who were HIV negative at cohort entry. Individual-level exposures, measured in a random sample of all participants, were: (1) perception of stigma in the community, (2) perception of stigma in health settings and (3) fear and judgement towards people living with HIV. Individual-level analyses were conducted with adjusted, individual-level Poisson regression. Community-level HIV stigma exposures drew on data reported by people living with HIV, health workers and community members. We used linear regression to explore the association between HIV stigma and community-level HIV incidence.Among 8172 individuals who were HIV negative and answered individual-level stigma questions at enrolment to the cohort, there was no evidence of a statistically significant association between any domain of HIV stigma and risk of incident HIV infection. Among the full cohort of 26,110 individuals among whom HIV incidence was measured, there was no evidence that community-level HIV incidence was associated with any domain of HIV stigma.HIV stigma is often cited as a barrier to the effectiveness of HIV prevention programming. However, in the setting for the HPTN 071 "PopART trial," measured stigma alone was not associated with the risk of HIV infection.

Summary: Background: Glaucoma is a major cause of sight loss worldwide, with the highest regional prevalence and incidence reported in Africa. The most common low-cost treatment used to control glaucoma is long-term timolol eye drops. However, low adherence is a major challenge. We aimed to investigate whether selective laser trabeculoplasty (SLT) was superior to timolol eye drops for controlling intraocular pressure (IOP) in patients with open-angle glaucoma. Methods: We did a two-arm, parallel-group, single-masked randomised controlled trial at the Eye Department of Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Eligible participants (aged ≥18 years) had open-angle glaucoma and an IOP above 21 mm Hg, and did not have asthma or a history of glaucoma surgery or laser. Participants were randomly assigned (1:1) to receive 0·5% timolol eye drops to administer twice daily or to receive SLT. The primary outcome was the proportion of eyes from both groups with treatment success, defined as an IOP below or equal to target pressure according to glaucoma severity, at 12 months following randomisation. Re-explanation of eye drop application or a repeat SLT was permitted once. The primary analysis was by modified intention-to-treat, excluding participants lost to follow-up, using logistic regression; generalised estimating equations were used to adjust for the correlation between eyes. This trial was registered with the Pan African Clinical Trials Registry, number PACTR201508001235339. Findings: 840 patients were screened for eligibility, of whom 201 (24%) participants (382 eligible eyes) were enrolled between Aug 31, 2015, and May 12, 2017. 100 (50%) participants (191 eyes) were randomly assigned to the timolol group and 101 (50%; 191 eyes) to the SLT group. After 1 year, 339 (89%) of 382 eyes were analysed. Treatment was successful in 55 (31%) of 176 eyes in the timolol group (16 [29%] of 55 eyes required repeat administration counselling) and in 99 (61%) of 163 eyes in the SLT group (33 [33%] of 99 eyes required repeat SLT; odds ratio 3·37 [95% CI 1·96–5·80]; p

To investigate if topical chlorhexidine 0.2%, which is low cost and easy to formulate, is noninferior to topical natamycin 5% for the treatment of filamentous fungal keratitis.Randomized controlled, single-masked, noninferiority clinical trial.Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection confirmed on smear or confocal microscopy.Participants were randomly allocated to receive topical chlorhexidine 0.2% or topical natamycin 5%. Primary analysis (intention-to-treat) was by linear regression, using baseline logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity (BSCVA) and treatment arm as prespecified covariates. Mixed fungal-bacterial infections were excluded from the primary analysis but included in secondary analyses and secondary safety-related outcomes. The noninferiority margin was 0.15 logMAR. This trial was registered with ISRCTN, number ISRCTN14332621.The primary outcome measure was BSCVA at 3 months. Secondary outcome measures included perforation or therapeutic penetrating keratoplasty by 90 days.Between June 3, 2019, and November 9, 2020, 354 eligible participants were enrolled and randomly assigned: 178 to chlorhexidine and 176 to natamycin. Primary outcome data were available for 153 and 151 of the chlorhexidine and natamycin groups, respectively. Of these, mixed bacterial-fungal infections were found in 20 cases (12/153 chlorhexidine, 8/151 natamycin) and excluded from the primary analysis. Therefore, 284 patients were assessed for the primary outcome (141 chlorhexidine, 143 natamycin). We did not find evidence to suggest chlorhexidine was noninferior to natamycin and in fact found strong evidence to suggest that natamycin-treated participants had significantly better 3-month BSCVA than chlorhexidine-treated participants, after adjusting for baseline BSCVA (regression coefficient, -0.30; 95% confidence interval [CI], -0.42 to -0.18; P0.001). There were more perforations and emergency corneal grafts in the chlorhexidine arm (24/175, 13.7%) than in the natamycin arm (10/173, 5.8%; P = 0.018, mixed infections included), whereas natamycin-treated cases were less likely to perforate or require an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34; 95% CI, 0.15-0.79; P = 0.013).Treatment with natamycin is associated with significantly better visual acuity, with fewer adverse events, compared with treatment with chlorhexidine. Natamycin remains the preferred first-line monotherapy treatment for filamentous fungal keratitis.

Within the humanitarian sector, there is a pressing need to scale up anticipatory action as climate change-related disasters increase. This article evaluates forecasts relating to extreme weather events – extreme rainfall, tropical cyclones, river flooding and storm surge – in Myanmar and the Philippines to assess the feasibility of using such forecasts to develop early warning systems and responses. To make best use of limited extant data, a variety of methods (reliability diagrams, hit rates, false alarm ratios, correlations) are employed. We review the skill of the European Centre for Medium-Range Weather Forecasts (ECMWF) tropical cyclone forecasts and find that whilst errors in cyclone position are relatively small, forecasting intensity is more difficult. When a tropical cyclone has formed, the probabilities provided in the ECMWF track forecast are highly reliable and only slightly overconfident. A tropical cyclone activity product is relatively reliable for forecasts less than a week ahead for North Indian Ocean cyclones affecting Myanmar, but becomes very overconfident beyond this. Looking at flood forecasting models, a comparison of the Global Flood Awareness System (GloFAS, produced by the ECMWF and the European Commission as part of the Copernicus Emergency Management Services) with the Global Flood Forecasting Information System (GLOFFIS, produced by Deltares) demonstrates that both GloFAS and GLOFFIS have difficulty simulating 1 in 2 year return period flows or higher, although GloFAS performance is better than GLOFFIS. GloFAS reforecasts show significantly overconfident probabilities over Myanmar where discharge observations are availabel, whilst the lack of a GLOFFIS reforecast prevents evaluation of this forecast system directly. Evaluation of the ten-day operational storm surge forecast (the Global Storm Surge Information System, GLOSSIS) produced by Deltares was attempted but lack of any data prevented assessment. These findings present valuable insights into how well forecasts perform, which is crucial information for establishing effective humanitarian action mechanisms.

Challenges exist for assessing the impacts of climate and climate change on the hydrological cycle on local and regional scales, and in turn on water resources, food, energy, and natural hazards. Potential evapotranspiration (PET) represents atmospheric demand for water, which is required at high spatial and temporal resolutions to compute actual evapotranspiration and thus close the water balance near the land surface for many such applications, but there are currently no available high-resolution datasets of PET. Here we develop an hourly PET dataset (hPET) for the global land surface at 0.1° spatial resolution, based on output from the recently developed ERA5-Land reanalysis dataset, over the period 1981 to present. We show how hPET compares to other available global PET datasets, over common spatiotemporal resolutions and time frames, with respect to spatial patterns of climatology and seasonal variations for selected humid and arid locations across the globe. We provide the data for users to employ for multiple applications to explore diurnal and seasonal variations in evaporative demand for water., Measurement(s)evapotranspirationTechnology Type(s)computational modeling techniqueFactor Type(s)temporal intervalSample Characteristic - Environmentclimate system • hydrological processSample Characteristic - Locationglobal Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.15060387

In 2014, UNAIDS set the target that 90% of individuals on antiretroviral therapy (ART) be virally suppressed. Here, we use data from the HPTN 071 (PopART) trial to report whether the introduction of universal testing and treatment has affected viral suppression or treatment adherence among individuals who self-reported they were taking ART, and identify risk factors for these outcomes.This was a cross-sectional study nested within the randomly selected population cohort of the PopART trial. The trial took place in 21 communities in Zambia and South Africa. Analyses included 3570 HIV-positive participants who were seen at the second follow-up visit in 2016-17 and who self-reported that they were currently taking ART. Viral suppression was defined as HIV RNA of less than 400 copies per mL from a blood sample collected during the cohort visit, and ART adherence was measured using self-reporting (reported as no missed pills in last 7 days). Prevalences of these outcomes were compared across three trial arms using a two-stage approach suitable for clustered data. Each arm consisted of seven communities, with one arm receiving a combination HIV prevention package including immediate ART initiation, one receiving a combination HIV prevention package excluding immediate ART initiation and one arm receving standard of care. Risk factors for each of the outcomes were assessed using logistic regression.Among the 3570 participants who self-reported that they were currently on ART, 416 (11·7%) of 3554 were not virally suppressed (16 were missing viral suppression status) and 345 (9·7%) of 3566 reported being non-adherent to ART (four were missing adherence status). The proportion not virally suppressed was higher in communities in South Africa (195 [16·4%] of 1191) than in Zambia (221 [9·4%] of 2363). There was no evidence that the prevalence of the outcomes differed between trial arms. There was evidence that men, younger individuals, individuals who reported participating in harmful alcohol use, and those who reported internalised stigma were more likely to be non-adherent, and not virally suppressed.The results assuaged concerns that early ART initiation in a universal testing and treatment setting could lead to reduced adherence and viral suppression.US National Institute of Allergy and Infectious Diseases (which is a part of the National Institutes of Health), the International Initiative for Impact Evaluation with support from the Billamp; Melinda Gates Foundation, US President's Emergency Plan for AIDS Relief, and Medical Research Council UK.