Search

Background: TB is a leading infectious cause of death worldwide. The COVID-19 pandemic raised concerns that the burden of TB disease and death would increase due to the synergy between the two conditions., Methods: We used individual-level data submitted to the WHO Global Clinical Platform for COVID-19 on hospitalised patients to explore associations of TB with mortality using multivariable logistic regression., Results: Data were available from 453,233 persons with COVID-19 and known TB status and mortality outcomes from 62 countries (96% SARS-CoV-2 test-positive). Of these, 48% were male, and the median age was 53 years (IQR 38-67). There were 8,214 cases with current TB reported by 46 countries, mainly from Africa. Of people with current TB, 31.4% were admitted with severe illness, and 24.5% died. Current TB was independently associated with higher mortality when adjusted for age, sex, HIV status, illness severity at hospital admission, and underlying conditions (adjusted RR 1.47, 95% CI 1.35-1.61)., Conclusion: Current or past TB were independent risk factors for in-hospital mortality regardless of illness severity at admission. Caveats for interpretation include changes during the data collection period (viral variation, vaccination coverage) and opportunistic sampling. However, the platform exemplifies how timely, coordinated global reporting can inform our understanding of health emergencies and the vulnerable populations affected., (© 2024 The Authors.)

Introduction: There is limited evidence on effective health systems interventions for preventing female genital mutilation (FGM). This study tested a two-level intervention package at primary care applying person-centred communication (PCC) for FGM prevention., Methods: A cluster randomised trial was conducted in 2020-2021 in 180 antenatal care (ANC) clinics in Guinea, Kenya and Somalia. At baseline, all clinics received guidance and materials on FGM prevention and care; at month 3, ANC providers at intervention sites received PCC training. Data were collected from clinic managers, ANC providers and clients at baseline, month 3 and month 6 on primary outcomes, including delivery of PCC counselling, utilisation of level one materials, health facility preparedness for FGM prevention and care services and secondary outcomes related to clients' and providers' knowledge and attitudes. Data were analysed using multilevel and single-level logistic regression models., Results: Providers in the intervention arm were more likely to deliver PCC for FGM prevention compared with those in the control arm, including inquiring about clients' FGM status (adjusted OR (AOR): 8.9, 95% CI: 6.9 to 11.5; p<0.001) and FGM-related beliefs (AOR: 9.7, 95% CI: 7.5 to 12.5; p<0.001) and discussing why (AOR: 9.2, 95% CI: 7.1 to 11.9; p<0.001) or how (AOR: 7.7, 95% CI: 6.0 to 9.9; p<0.001) FGM should be prevented. They were more confident in their FGM-related knowledge (AOR: 7.0, 95% CI: 1.5 to 32.3; p=0.012) and communication skills (AOR: 1.8; 95% CI: 1.0 to 3.2; p=0.035). Intervention clients were less supportive of FGM (AOR: 5.4, 95% CI: 2.4 to 12.4; p<0.001) and had lower intentions of having their daughters undergo FGM (AOR: 0.3, 95% CI: 0.1 to 0.7; p=0.004) or seeking medicalised FGM (AOR: 0.2, 95% CI: 0.1 to 0.5; p<0.001) compared with those in the control arm., Conclusion: This is the first study to provide evidence of an effective FGM prevention intervention that can be delivered in primary care settings in high-prevalence countries., Trial Registration and Date: PACTR201906696419769 (3 June 2019)., Competing Interests: Competing interests: None declared., (© World Health Organization 2024. Licensee BMJ.)

Introduction: In 2016, WHO estimated there were roughly 374 million new infections among adults of the following four curable sexually transmitted infections (STIs): chlamydia (caused by Chlamydia trachomatis (CT)), gonorrhoea ( Neisseria gonorrhoeae (NG)), syphilis ( Treponema pallidum ) and trichomoniasis ( Trichomonas vaginalis (TV)). Accurate point-of-care tests (POCTs) for screening of genital and extragenital CT, NG and TV infections are of great value and have been developed during recent decade. Several tests are commercially available and have shown encouraging performance compared with 'gold-standard' reference tests in laboratory-based studies. However, there is limited data on their clinical performance, including at the POC. Key populations, such as men who have sex with men (MSM), are at higher risk of these STIs at genital and extragenital sites and these STIs are often asymptomatic, especially in extragenital sites and in women. We will conduct a clinical-based evaluation to assess the performance characteristics and acceptability to end-users of molecular-based diagnostic technology for POC/near patient use of the Xpert CT/NG (Cepheid, Sunnyvale, California, USA) test for screening of genital, anorectal and pharyngeal CT and NG infections in MSM and the Xpert CT/NG and Xpert TV (Cepheid, Sunnyvale, California, USA) for screening of genital CT, NG and TV among women at risk for these STIs compared with gold-standard reference nucleic acid amplification tests. This master protocol outlines the overall research approach that will be used in seven countries., Method and Analyses: Consecutive MSM and women at risk presenting at the clinical sites in high, and low- and middle-income countries will be enrolled. The POCTs to be evaluated are Xpert CT/NG and Xpert TV. All procedures will be carried out by trained healthcare staff and tests performed in strict accordance with the manufacturer's instructions. The sensitivity, specificity, positive and negative predictive values for each POCT will be calculated. The study is ongoing with recruitment expected to be completed in all countries by mid-2022 to late-2022., Ethics and Dissemination: Prior to enrolment, this core protocol was independently peer-reviewed and approved by the research project review panel (RP2) of the WHO Department of Sexual and Reproductive Health and Research and by the WHO Ethics Review Committee (ERC). The core protocol has been slightly adapted accordingly to individual countries and adaptations approved by both RP2 and ERC, as well as all relevant institutional review boards at each participating site. Results will be disseminated through peer-reviewed journals and presented at relevant national/international conferences., Competing Interests: Competing interests: The POCT manufacturer discloses and furnishes free of charge to WHO the information and sufficient quantities of the product(s) in order to enable this evaluation as part of the WHO/RHR STI POC initiative. WHO is entitled to evaluate and publish the trial results, and to exclusively control this evaluation and the content of the aforesaid publication. WHO shall submit any proposed publication to the POCT manufacturer for review, comments received will be considered in good faith, but the decision to publish rests with WHO., (© World Health Organization 2024. Licensee BMJ.)

Background: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa., Methods: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs)., Results: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV., Conclusion: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV., Trial Registration: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries., (© 2024. The Author(s).)

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections have increased globally. Asymptomatic infections represent a significant risk of long-term complications. Men who have sex with men (MSM) are disproportionally affected, underscoring the need to offer screening programmes to this population. CT/NG Point of Care Testing (POCT) constitutes a strategic tool to improve the continuum of STI care, however extensive real-life evaluations amongst at risk populations are lacking. The aim of this study is to estimate the GeneXpert CT/NG assay performance and usability for CT and NG at genital and extragenital sites for screening amongst MSM., Methods: This study was a multi-site sexual health clinic-based evaluation (Italy, Malta and Peru) with consecutive enrolment. A first void urine sample (divided in two aliquots), two oropharyngeal and two anorectal swabs were collected for each study participant. One specimen set (one for each anatomical site) was tested with the dual index test (Cepheid) at the clinics by the healthcare staff, the other set with FDA/CE approved Nucleic Acid Amplification Tests (NAATs) at the laboratory. Clinical sites and reference laboratories participated in an internal and external quality control programme. Sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values for each anatomical site were estimated using a meta-analytic approach., Results: One thousand seven hundred two MSM were recruited across all clinical sites for a total of 5049 biological specimens. NG and CT were respectively detected in 274 and 287 of samples. Overall, the NG POCT sensitivity and specificity was 91.43% and 99.75% in urine (LR + 372.80, LR- 0.09), 89.68% and 99.55% in rectal specimens (LR + 197.30, LR- 0.10) and 75.87% and 98.77% at the pharynx respectively (LR + 61.94, LR- 0.24). The CT component of the POCT sensitivity was 84.82% and specificity 99.63% in urine (LR + 228.68, LR- 0.15), 78.07% and 99.19% respectively on rectal site (LR + 96.23, LR-0.22), 67.79% and 99.88% respectively at pharyngeal site (LR + 554.89, LR- 0.32). 95.95% of MSM reported to be willing to wait for POCT results and no provider reported difficulties in terms of performance or interpretation of the results of the Xpert CT/NG., Conclusion: Rapid turnaround time, ease of use and high acceptability make the Xpert CT/NG testing system a strategic tool for increasing testing frequency, reaching those not yet tested and offering the possibility of immediate treatment if needed. The assay showed good negative likelihood ratios and confirms its use to rule out CT/NG infections. Sensitivity varied across sites and pathogens. Periodic staff training at the testing sites should be mandatory., (© 2024. The Author(s).)

Introduction: Globally, the incidence of HIV and syphilis can be reduced by the use of validated point of care tests (POCTs). As part of the WHO PRoSPeRo Network, we aimed to evaluate the performance, acceptability, and operational characteristics of two dual HIV/syphilis POCTs (Bioline HIV/Syphilis Duo (Abbott) and DPP® HIV-Syphilis assay (Chembio) for the screening of HIV and syphilis amongst men who have sex with men (MSM)., Method and Analyses: A cross sectional study of 2,577 MSM in Italy, Malta, Peru, and the United Kingdom (UK) presenting to seven clinic sites, were enrolled. Finger prick blood was collected to perform POCTs and results compared with standard laboratory investigations on venepuncture blood. Acceptability and operational characteristics were assessed using questionnaires. Diagnostic meta-analysis was used to combine data from the evaluation sites., Results: Based on laboratory tests, 23.46% (n = 598/2549) of participants were confirmed HIV positive, and 35.88% of participants (n = 901/2511) were positive on treponemal reference testing. Of all participants showing evidence of antibodies to Treponema pallidum, 50.56% (n = 455/900) were Rapid Plasma Reagin (RPR) test reactive. Of HIV positive individuals, 60.62% (n = 354/584) had evidence of antibodies to T. pallidum, and of these 60.45% (n = 214/354) exhibited reactive RPR tests indicating probable (co)infection. For Bioline POCT, pooled sensitivities and specificities for HIV were 98.95% and 99.89% respectively, and for syphilis were 73.79% and 99.57%. For Chembio pooled sensitivities and specificities for HIV were 98.66% and 99.55%, and for syphilis were 78.60% and 99.48%. Both tests can detect greater than 90% of probable active syphilis cases, as defined by reactive RPR and treponemal test results. These dual POCTs were preferred by 74.77% (n = 1,926) of participants, due to their convenience, and the operational characteristics made them acceptable to health care providers (HCPs)., Conclusions: Both the Bioline and the Chembio dual POCT for syphilis and HIV had acceptable performance, acceptability and operational characteristics amongst MSM in the PRoSPeRo network. These dual POCTs could serve as a strategic, more cost effective, patient and healthcare provider (HCP) friendly alternative to conventional testing; in clinical and other field settings, especially those in resource-limited settings., (© 2024. The Author(s).)

Background: Dual point-of-care tests (POCTs) for the simultaneous detection of antibodies to HIV and syphilis have been developed. Since community-based organisations (CBO) are effective providers of HIV and syphilis testing among men who have sex with men (MSM), evaluation of the utility of these dual tests at CBO testing services is a high priority. The aim of this study is to determine the feasibility of performing dual HIV-syphilis POCT testing among both users and providers at these non-clinical sites., Methods: This evaluation assessed the utility of two lateral flow immunochromatographic antibody technologies for dual screening for HIV/syphilis among MSM seeking testing in four CBO testing services in Spain, Slovenia, Latvia, and Ukraine. The study's conceptual framework divides the concept of feasibility into two inter-related domains, acceptability, and usability and further breaks it down into six subdomains: learnability, willingness, suitability, satisfaction, efficacy, and effectiveness. The feasibility analysis was performed by calculating the median score in 3 stages (for individual questions, subdomains, and domains), using a summated scores method., Results: The final sample included 844 participants, 60 of which were found to be HIV test positive (7.1%) and 61 (7.2%) positive on testing for syphilis. There was a small difference (1.1%) when comparing the results of the two dual POCTs under evaluation to the tests routinely used at each site. The inter-rater agreement showed a high concordance between two independent readings. The analysis of the feasibility for the users of the services indicated good satisfaction, suitability, and willingness. In addition, among 18 providers the total mean score showed good acceptability and usability, good willingness, easy learnability, high suitability, and good efficacy, but lower satisfaction and effectiveness. The operational characteristics of both dual study POCTs were well evaluated by providers., Conclusions: The introduction of dual HIV and syphilis  POCTs in CBO testing services for screening of MSM is feasible, with a high acceptability and usability both for users and providers. Implementation of dual POCTs for HIV and syphilis in CBO testing services is an opportunity for scaling up integrated HIV/syphilis testing for MSM., (© 2024. The Author(s).)

Objective: To identify and summarise the evidence on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection and persistence in body fluids associated with sexual activity (saliva, semen, vaginal secretion, urine and faeces/rectal secretion)., Eligibility: All studies that reported detection of SARS-CoV-2 in saliva, semen, vaginal secretion, urine and faeces/rectal swabs., Information Sources: The WHO COVID-19 database from inception to 20 April 2022., Risk of Bias Assessment: The National Institutes of Health tools., Synthesis of Results: The proportion of patients with positive results for SARS-CoV-2 and the proportion of patients with a viral duration/persistence of at least 14 days in each fluid was calculated using fixed or random effects models., Included Studies: A total of 182 studies with 10 023 participants., Results: The combined proportion of individuals with detection of SARS-CoV-2 was 82.6% (95% CI: 68.8% to 91.0%) in saliva, 1.6% (95% CI: 0.9% to 2.6%) in semen, 2.7% (95% CI: 1.8% to 4.0%) in vaginal secretion, 3.8% (95% CI: 1.9% to 7.6%) in urine and 31.8% (95% CI: 26.4% to 37.7%) in faeces/rectal swabs. The maximum viral persistence for faeces/rectal secretions was 210 days, followed by semen 121 days, saliva 112 days, urine 77 days and vaginal secretions 13 days. Culturable SARS-CoV-2 was positive for saliva and faeces., Limitations: Scarcity of longitudinal studies with follow-up until negative results., Interpretation: SARS-CoV-2 RNA was detected in all fluids associated with sexual activity but was rare in semen and vaginal secretions. Ongoing droplet precautions and awareness of the potential risk of contact with faecal matter/rectal mucosa are needed., Prospero Registration Number: CRD42020204741., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the association between Colombia's third wave when the Mu variant was predominant epidemiologically (until 75%) in Colombia and COVID-19 all-cause in-hospital mortality., Methods: In this retrospective cohort, we included hospitalized patients ≥18 years with SARS-CoV-2 infection between March 2020 to September 2021 in ten hospitals from three cities in Colombia. Description analysis, survival, and multivariate Cox regression analyses were performed to evaluate the association between the third epidemic wave and in-hospital mortality., Results: A total of 25,371 patients were included. The age-stratified time-to-mortality curves showed differences according to epidemic waves in patients ≥75 years (log-rank test p = 0.012). In the multivariate Cox analysis, the third wave was not associated with increased mortality relative to the first wave (aHR 0.95; 95%CI 0.84-1.08), but there was an interaction between age ≥75 years and the third wave finding a lower HR for mortality (aHR 0.56, 95%CI 0.36-0.86)., Conclusions: We did not find an increase in in-hospital mortality during the third epidemic wave in which the Mu variant was predominant in Colombia. The reduced hazard in mortality in patients ≥75 years hospitalized in the third wave could be explained by the high coverage of SARS-CoV-2 vaccination in this population and patients with underlying conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Undetected and unmonitored hypertension carries substantial mortality and morbidity, especially during pregnancy. We assessed the accuracy of OptiBP TM , a smartphone application for estimating blood pressure (BP), across diverse settings. The study was conducted in community settings: Gaibandha, Bangladesh and Ifakara, Tanzania for general populations, and Kalafong Provincial Tertiary Hospital, South Africa for pregnant populations. Based on guidance from the International Organization for Standardization (ISO) 81,060-2:2018 for non-invasive BP devices and global consensus statement, we compared BP measurements taken by two independent trained nurses on a standard auscultatory cuff to the BP measurements taken by a research version of OptiBP TM called CamBP. For ISO criterion 1, the mean error was 0.5 ± 5.8 mm Hg for the systolic blood pressure (SBP) and 0.1 ± 3.9 mmHg for the diastolic blood pressure (DBP) in South Africa; 0.8 ± 7.0 mmHg for the SBP and -0.4 ± 4.0 mmHg for the DBP in Tanzania; 3.3 ± 7.4 mmHg for the SBP and -0.4 ± 4.3 mmHg for the DBP in Bangladesh. For ISO criterion 2, the average standard deviation of the mean error per subject was 4.9 mmHg for the SBP and 3.4 mmHg for the DBP in South Africa; 6.3 mmHg for the SBP and 3.6 mmHg for the DBP in Tanzania; 6.4 mmHg for the SBP and 3.8 mmHg for the DBP in Bangladesh. OptiBP TM demonstrated accuracy against ISO standards in study populations, including pregnant populations, except in Bangladesh for SBP (criterion 2). Further research is needed to improve performance across different populations and integration within health systems., (© 2023. The Author(s).)

Background: Multi-arm multi-stage trials are an efficient, adaptive approach for testing many treatments simultaneously within one protocol. In settings where numbers of patients available to be entered into trials and resources might be limited, such as primary postpartum haemorrhage, it may be necessary to select a pre-specified subset of arms at interim stages even if they are all showing some promise against the control arm. This will put a limit on the maximum number of patients required and reduce the associated costs. Motivated by the World Health Organization Refractory HaEmorrhage Devices trial in postpartum haemorrhage, we explored the properties of such a selection design in a randomised phase III setting and compared it with other alternatives. The objectives are: (1) to investigate how the timing of treatment selection affects the operating characteristics; (2) to explore the use of an information-rich (continuous) intermediate outcome to select the best-performing arm, out of four treatment arms, compared with using the primary (binary) outcome for selection at the interim stage; and (3) to identify factors that can affect the efficiency of the design., Methods: We conducted simulations based on the refractory haemorrhage devices multi-arm multi-stage selection trial to investigate the impact of the timing of treatment selection and applying an adaptive allocation ratio on the probability of correct selection, overall power and familywise type I error rate. Simulations were also conducted to explore how other design parameters will affect both the maximum sample size and trial timelines., Results: The results indicate that the overall power of the trial is bounded by the probability of 'correct' selection at the selection stage. The results showed that good operating characteristics are achieved if the treatment selection is conducted at around 17% of information time. Our results also showed that although randomising more patients to research arms before selection will increase the probability of selecting correctly, this will not increase the overall efficiency of the (selection) design compared with the fixed allocation ratio of 1:1 to all arms throughout., Conclusions: Multi-arm multi-stage selection designs are efficient and flexible with desirable operating characteristics. We give guidance on many aspects of these designs including selecting the intermediate outcome measure, the timing of treatment selection, and choosing the operating characteristics.

Objective: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes., Data Sources: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020., Study Eligibility Criteria: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area., Methods: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis., Results: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81)., Conclusion: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors., (Copyright © 2022. Published by Elsevier Inc.)

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings., Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries., Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population., Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome., Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford's COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health "Fondi Ricerca corrente-L1P6" to IRCCS Ospedale Sacro Cuore-Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC&#95;PC&#95;19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix., Competing Interests: BG, MH, WJ, VB, CK, AR, JB, LR, AD, JD, BC, MP, US, JB, DA, YA, AR, JC, EH, CF, MM, YC, XW, SB, ST, LS, AR, RR, DO, MH, GC, JD, MK, EW, PH, LM, PO No competing interests declared, SM declares receiving salary support from the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research, MS reports grants from DHSC National Institute of Health Research UK, from the Medical Research Council UK, and from the Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool, supporting the conduct of the study; other interest in Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work, AM declares consulting fees for Gilead and MSD, presentation fees for GILEAD, Pfizer and MSD, support for attending ECCMID from Gilead, and advisory board fees for MSD and Gilead, AA declares support from Italian Ministry of Health - "Fondi Ricerca Corrente" Line1 Project 5 to IRCCS Sacro Cuore - Don Calabria Hospital, FC declares a grant from the Canadian Institute of Health Research, JG declares support by Pfizer, Angelini and MSD to attend meetings (registration to meetings only), JD declares personal fees from lectures from Sunovion and Merck and consulting fees from Pfizer, AS has been an investigator in COVID-19 clinical trials by Algernon Pharmaceuticals, Atea Pharmaceuticals, Regeneron Pharmaceuticals, Diffusion Pharmaceuticals, Celltrion, Inc and Atriva Therapeutics, outside the scope of the submitted work, RF declares a peer reviewed research grant from the Canadian Institutes of Health Research, See Appendix 1 for competing interests for group author members, (© 2022, Gonçalves et al.)

Background: WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors., Methods: Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors., Findings: Of 197 479 patients reporting HIV status, 16 955 (8·6%) were people living with HIV. 16 283 (96.0%) of the 16 955 people living with HIV were from Africa; 10 603 (62·9%) were female and 6271 (37·1%) were male; the mean age was 45·5 years (SD 13·7); 6339 (38·3%) were admitted to hospital with severe illness; and 3913 (24·3%) died in hospital. Of the 10 166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91·5%) were on ART. Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1·15, 95% CI 1·10-1·20) and were 38% more likely to die in hospital (aHR 1·38, 1·34-1·41). Among people living with HIV, male sex, age 45-75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status., Interpretation: In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available., Funding: None., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests RH received funding from the Wellcome Trust, Canadian Institute of Health Research, UK Research and Innovation/Medical Research Council, and International COVID-19 Data Alliance–Health Data Research UK. All other authors declare no competing interests., (© 2022 This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: In 2016, WHO launched the Global Health Sector Strategy on STIs, 2016-2021 (GHSS) to provide guidance and benchmarks for country achievement by 2020 and four global targets for achievement by 2030., Methods: A country survey jointly developed by experienced technical personnel at WHO Headquarters (HQ) and WHO regional offices was reviewed and distributed by WHO regional advisors to 194 WHO Member States in September-March 2020. The survey sought to assess implementation and prioritization of STI policy, surveillance, service delivery, commodity availability, and surveillance based on targets of the GHSS., Results: A majority (58%, 112/194) of countries returned a completed survey reflecting current (2019) STI activities. The regions with the highest survey completion rates were South-East Asia Region (91%, 10/11), Region of the Americas (71%, 25/35) and Western Pacific Region (67%, 18/27). Having a national STI strategy was reported by 64% (72/112) and performing STI surveillance activities by 88% (97/110) of reporting countries. Availability of STI services within primary health clinics was reported by 88% of countries (99/112); within HIV clinics by 92% (103/112), and within reproductive health services by 85% (95/112). Existence of a national strategy to eliminate mother-to-child transmission of HIV and syphilis (EMTCT) was reported by 70% of countries (78/112). Antimicrobial resistance (AMR) monitoring for gonococcal infection (gonorrhoea) was reported by 64% (57/89) of reporting countries with this laboratory capacity. Inclusion of HPV vaccine for young women in the national immunization schedule was reported by 59% (65/110) and availability of cervical cancer screening was reported by 91% (95/104). Stockouts of STI medicines, primarily benzathine penicillin, within the prior four years were reported by 34% (37/110) of countries., Conclusions: Mechanisms to support improvements to STI service delivery through national-level policy, commitment, programming and surveillance are needed to operationalize, accelerate and monitor progress towards achievement of the 2030 global STI strategy targets., Competing Interests: The authors have declared that no competing interests exist.

Importance: Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression., Objective: To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event., Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019., Interventions: Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo., Main Outcomes and Measures: Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide., Results: The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group., Conclusions and Relevance: In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities., Trial Registration: ClinicalTrials.gov Identifier: NCT01928446.

Background: Violence against women is a serious public health concern, and is highly prevalent globally, including in India. Health-care providers [HCPs] can play an important role in addressing and reducing negative consequences of violence against women. We implemented a pre-post intervention study of HCP training in three tertiary care facilities in Maharashtra, India., Methods: The study used a pre-post intervention design with assessment of HCPs' (n = 201) knowledge, attitudes, perceived preparedness and practice at three time points: before training, after training and at 6 months follow- up., Results: Total median score of knowledge about common signs and symptoms of violence (8.89 vs, 10.00), attitudes towards acceptability of violence (9.05 vs. 10.00), individual (6.74 vs. 10.00) and system level preparedness (6.11 vs. 8.14) improved from pre to post- training. The generalized estimating equation [GEE] model, adjusted for age, sex, site and department, showed an improvement in knowledge, attitudes and preparedness post- training. The change from pre to 6 months follow- up was not significant for attitude., Conclusions: This package of interventions, including training of HCPs, improved HCPs' knowledge, attitudes and practices, yet changes in attitudes and preparedness did not sustain over time. This study indicates feasibility and positive influence of a multi-component intervention to improve HCP readiness to respond to violence against women in a low-resource setting. Future phases of intervention development include adapting this intervention package for primary and secondary health facilities in this context, and future research should assess these interventions using a rigorous experimental design. Finally, these results can be used to advocate for multi-layered, systems-based approaches to strengthening health response to violence against women., (© 2021. The Author(s).)