<div><h4>Global, regional, and national estimates of the impact of a maternal Klebsiella pneumoniae vaccine: A Bayesian modeling analysis.</h4><i>Kumar CK, Sands K, Walsh TR, O\'Brien S, ... Srikantiah P, Laxminarayan R</i><br /><b>Background</b><br />Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs) but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases.<br /><b>Methods and findings</b><br />We developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality-with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 1.49% [CrI: 0.33 to 3.51] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 5% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis.<br /><b>Conclusions</b><br />A K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase.<br /><br />Copyright: © 2023 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 22 May 2023; 20:e1004239</small></div>

<div><h4>Evaluating systematic targeted universal testing for tuberculosis in primary care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).</h4><i>Martinson NA, Nonyane BAS, Genade LP, Berhanu RH, ... Lebina L, TUTT Trial team</i><br /><b>Background</b><br />The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing.<br /><b>Methods and findings</b><br />Sixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB.<br /><b>Conclusions</b><br />Our trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence.<br /><b>Trial registration</b><br />South African National Clinical Trials Registry DOH-27-092021-4901.<br /><br />Copyright: © 2023 Martinson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 22 May 2023; 20:e1004237</small></div>

<div><h4>Hepatitis C care cascade among patients with and without tuberculosis: Nationwide observational cohort study in the country of Georgia, 2015-2020.</h4><i>Baliashvili D, Blumberg HM, Gandhi NR, Averhoff F, ... Zarkua J, Kempker RR</i><br /><b>Background</b><br />The Eastern European country of Georgia initiated a nationwide hepatitis C virus (HCV) elimination program in 2015 to address a high burden of infection. Screening for HCV infection through antibody testing was integrated into multiple existing programs, including the National Tuberculosis Program (NTP). We sought to compare the hepatitis C care cascade among patients with and without tuberculosis (TB) diagnosis in Georgia between 2015 and 2019 and to identify factors associated with loss to follow-up (LTFU) in hepatitis C care among patients with TB.<br /><b>Methods and findings</b><br />Using national ID numbers, we merged databases of the HCV elimination program, NTP, and national death registry from January 1, 2015 to September 30, 2020. The study population included 11,985 adults (aged ≥18 years) diagnosed with active TB from January 1, 2015 through December 31, 2019, and 1,849,820 adults tested for HCV antibodies between January 1, 2015 and September 30, 2020, who were not diagnosed with TB during that time. We estimated the proportion of patients with and without TB who were LTFU at each step of the HCV care cascade and explored temporal changes. Among 11,985 patients with active TB, 9,065 (76%) patients without prior hepatitis C treatment were tested for HCV antibodies, of which 1,665 (18%) had a positive result; LTFU from hepatitis C care was common, with 316 of 1,557 (20%) patients with a positive antibody test not undergoing viremia testing and 443 of 1,025 (43%) patients with viremia not starting treatment for hepatitis C. Overall, among persons with confirmed viremic HCV infection, due to LTFU at various stages of the care cascade only 28% of patients with TB had a documented cure from HCV infection, compared to 55% among patients without TB. LTFU after positive antibody testing substantially decreased in the last 3 years, from 32% among patients diagnosed with TB in 2017 to 12% among those diagnosed in 2019. After a positive HCV antibody test, patients without TB had viremia testing sooner than patients with TB (hazards ratio [HR] = 1.46, 95% confidence intervals [CI] [1.39, 1.54], p < 0.001). After a positive viremia test, patients without TB started hepatitis C treatment sooner than patients with TB (HR = 2.05, 95% CI [1.87, 2.25], p < 0.001). In the risk factor analysis adjusted for age, sex, and case definition (new versus previously treated), multidrug-resistant (MDR) TB was associated with an increased risk of LTFU after a positive HCV antibody test (adjusted risk ratio [aRR] = 1.41, 95% CI [1.12, 1.76], p = 0.003). The main limitation of this study was that due to the reliance on existing electronic databases, we were unable to account for the impact of all confounding factors in some of the analyses.<br /><b>Conclusions</b><br />LTFU from hepatitis C care after a positive antibody or viremia test was high and more common among patients with TB than in those without TB. Better integration of TB and hepatitis C care systems can potentially reduce LTFU and improve patient outcomes both in Georgia and other countries that are initiating or scaling up their nationwide hepatitis C control efforts and striving to provide personalized TB treatment.<br /><br />Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.<br /><br /><small>PLoS Med: 04 May 2023; 20:e1004121</small></div>

<div><h4>Effect of milk protein and whey permeate in large quantity lipid-based nutrient supplement on linear growth and body composition among stunted children: A randomized 2 × 2 factorial trial in Uganda.</h4><i>Mbabazi J, Pesu H, Mutumba R, Filteau S, ... Friis H, Grenov B</i><br /><b>Background</b><br />Despite possible benefits for growth, milk is costly to include in foods for undernourished children. Furthermore, the relative effects of different milk components, milk protein (MP), and whey permeate (WP) are unclear. We aimed to assess the effects of MP and WP in lipid-based nutrient supplement (LNS), and of LNS itself, on linear growth and body composition among stunted children.<br /><b>Methods and findings</b><br />We performed a randomized, double-blind, 2 × 2 factorial trial among 12 to 59 months old stunted children in Uganda. Children were randomized to 4 formulations of LNS with MP or soy protein isolate and WP or maltodextrin (100 g/day for 12 weeks) or no supplementation. Investigators and outcome assessors were blinded; however, participants were only blinded to the ingredients in LNS. Data were analyzed based on intention-to-treat (ITT) using linear mixed-effects models adjusted for age, sex, season, and site. Primary outcomes were change in height and knee-heel length, and secondary outcomes included body composition by bioimpedance analysis (ISRCTN13093195). Between February and September 2020, we enrolled 750 children with a median age of 30 (interquartile range 23 to 41) months, with mean (± standard deviation) height-for-age z-score (HAZ) -3.02 ± 0.74 and 12.7% (95) were breastfed. The 750 children were randomized to LNS (n = 600) with or without MP (n = 299 versus n = 301) and WP (n = 301 versus n = 299), or no supplementation (n = 150); 736 (98.1%), evenly distributed between groups, completed 12-week follow-up. Eleven serious adverse events occurred in 10 (1.3%) children, mainly hospitalization with malaria and anemia, all deemed unrelated to the intervention. Unsupplemented children had 0.06 (95% confidence interval, CI [0.02, 0.10]; p = 0.015) decline in HAZ, accompanied by 0.29 (95% CI [0.20, 0.39]; p < 0.001) kg/m2 increase in fat mass index (FMI), but 0.06 (95% CI [-0.002; 0.12]; p = 0.057) kg/m2 decline in fat-free mass index (FFMI). There were no interactions between MP and WP. The main effects of MP were 0.03 (95% CI [-0.10, 0.16]; p = 0.662) cm in height and 0.2 (95% CI [-0.3, 0.7]; p = 0.389) mm in knee-heel length. The main effects of WP were -0.08 (95% CI [-0.21, 0.05]; p = 220) cm and -0.2 (95% CI [-0.7; 0.3]; p = 403) mm, respectively. Interactions were found between WP and breastfeeding with respect to linear growth (p < 0.02), due to positive effects among breastfed and negative effects among non-breastfed children. Overall, LNS resulted in 0.56 (95% CI [0.42, 0.70]; p < 0.001) cm height increase, corresponding to 0.17 (95% CI [0.13, 0.21]; p < 0.001) HAZ increase, and 0.21 (95% CI [0.14, 0.28]; p < 0.001) kg weight increase, of which 76.5% (95% CI [61.9; 91.1]) was fat-free mass. Using height-adjusted indicators, LNS increased FFMI (0.07 kg/m2, 95% CI [0.0001; 0.13]; p = 0.049), but not FMI (0.01 kg/m2, 95% CI [-0.10, 0.12]; p = 0.800). Main limitations were lack of blinding of caregivers and short study duration.<br /><b>Conclusions</b><br />Adding dairy to LNS has no additional effects on linear growth or body composition in stunted children aged 12 to 59 months. However, supplementation with LNS, irrespective of milk, supports linear catch-up growth and accretion of fat-free mass, but not fat mass. If left untreated, children already on a stunting trajectory gain fat at the expense of fat-free mass, thus nutrition programs to treat such children should be considered.<br /><b>Trial registration</b><br />ISRCTN13093195.<br /><br />Copyright: © 2023 Mbabazi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 May 2023; 20:e1004227</small></div>

<div><h4>SARS-CoV-2 transmission with and without mask wearing or air cleaners in schools in Switzerland: A modeling study of epidemiological, environmental, and molecular data.</h4><i>Banholzer N, Zürcher K, Jent P, Bittel P, ... Hascher T, Fenner L</i><br /><b>Background</b><br />Growing evidence suggests an important contribution of airborne transmission to the overall spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), in particular via smaller particles called aerosols. However, the contribution of school children to SARS-CoV-2 transmission remains uncertain. The aim of this study was to assess transmission of airborne respiratory infections and the association with infection control measures in schools using a multiple-measurement approach.<br /><b>Methods and findings</b><br />We collected epidemiological (cases of Coronavirus Disease 2019 (COVID-19)), environmental (CO2, aerosol and particle concentrations), and molecular data (bioaerosol and saliva samples) over 7 weeks from January to March 2022 (Omicron wave) in 2 secondary schools (n = 90, average 18 students/classroom) in Switzerland. We analyzed changes in environmental and molecular characteristics between different study conditions (no intervention, mask wearing, air cleaners). Analyses of environmental changes were adjusted for different ventilation, the number of students in class, school and weekday effects. We modeled disease transmission using a semi-mechanistic Bayesian hierarchical model, adjusting for absent students and community transmission. Molecular analysis of saliva (21/262 positive) and airborne samples (10/130) detected SARS-CoV-2 throughout the study (weekly average viral concentration 0.6 copies/L) and occasionally other respiratory viruses. Overall daily average CO2 levels were 1,064 ± 232 ppm (± standard deviation). Daily average aerosol number concentrations without interventions were 177 ± 109 1/cm3 and decreased by 69% (95% CrI 42% to 86%) with mask mandates and 39% (95% CrI 4% to 69%) with air cleaners. Compared to no intervention, the transmission risk was lower with mask mandates (adjusted odds ratio 0.19, 95% CrI 0.09 to 0.38) and comparable with air cleaners (1.00, 95% CrI 0.15 to 6.51). Study limitations include possible confounding by period as the number of susceptible students declined over time. Furthermore, airborne detection of pathogens document exposure but not necessarily transmission.<br /><b>Conclusions</b><br />Molecular detection of airborne and human SARS-CoV-2 indicated sustained transmission in schools. Mask mandates were associated with greater reductions in aerosol concentrations than air cleaners and with lower transmission. Our multiple-measurement approach could be used to continuously monitor transmission risk of respiratory infections and the effectiveness of infection control measures in schools and other congregate settings.<br /><br />Copyright: © 2023 Banholzer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 May 2023; 20:e1004226</small></div>

<div><h4>Association between antenatal diagnosis of late fetal growth restriction and educational outcomes in mid-childhood: A UK prospective cohort study with long-term data linkage study.</h4><i>Olga L, Sovio U, Wong H, Smith G, Aiken C</i><br /><b>Background</b><br />Fetal growth restriction (FGR) is associated with a suboptimal intrauterine environment, which may adversely impact fetal neurodevelopment. However, analysing neurodevelopmental outcomes by observed birthweight fails to differentiate between true FGR and constitutionally small infants and cannot account for iatrogenic intervention. This study aimed to determine the relationship between antenatal FGR and mid-childhood (age 5 to 7 years) educational outcomes.<br /><b>Methods and findings</b><br />The Pregnancy Outcome Prediction Study (2008-2012) was a prospective birth cohort conducted in a single maternity hospital in Cambridge, United Kingdom. Clinicians were blinded to the antenatal diagnosis of FGR. FGR was defined as estimated fetal weight (EFW) <10th percentile at approximately 36 weeks of gestation, plus one or more indicators of placental dysfunction, including ultrasonic markers and maternal serum levels of placental biomarkers. A total of 2,754 children delivered at term were divided into 4 groups: FGR, appropriate-for-gestational age (AGA) with markers of placental dysfunction, healthy small-for-gestational age (SGA), and healthy AGA (referent). Educational outcomes (assessed at 5 to 7 years using UK national standards) were assessed with respect to FGR status using regression models adjusted for relevant covariates, including maternal, pregnancy, and socioeconomic factors. Compared to healthy AGA (N = 1,429), children with FGR (N = 250) were at higher risk of \"below national standard\" educational performance at 6 years (18% versus 11%; aOR 1.68; 95% CI 1.12 to 2.48, p = 0.01). By age 7, children with FGR were more likely to perform below standard in reading (21% versus 15%; aOR 1.46; 95% CI 0.99 to 2.13, p = 0.05), writing (28% versus 23%; aOR 1.46; 95% CI 1.02 to 2.07, p = 0.04), and mathematics (24% versus 16%; aOR 1.49; 95% CI 1.02 to 2.15, p = 0.03). This was consistent whether FGR was defined by ultrasound or biochemical markers. The educational attainment of healthy SGA children (N = 126) was comparable to healthy AGA, although this comparison may be underpowered. Our study design relied on linkage of routinely collected educational data according to nationally standardised metrics; this design allowed a high percentage of eligible participants to be included in the analysis (75%) but excludes those children educated outside of government-funded schools in the UK. Our focus on pragmatic and validated measures of educational attainment does not exclude more subtle effects of the intrauterine environment on specific aspects of neurodevelopment.<br /><b>Conclusions</b><br />Compared to children with normal fetal growth and no markers of placental dysfunction, FGR is associated with poorer educational attainment in mid-childhood.<br /><br />Copyright: © 2023 Olga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 24 Apr 2023; 20:e1004225</small></div>

<div><h4>The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.</h4><i>Sheppard JP, Koshiaris C, Stevens R, Lay-Flurrie S, ... Usher-Smith JA, McManus RJ</i><br /><b>Background</b><br />Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data.<br /><b>Methods and findings</b><br />This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out.<br /><b>Conclusions</b><br />Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.<br /><br />Copyright: © 2023 Sheppard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 19 Apr 2023; 20:e1004223</small></div>

<div><h4>Prevalence and characteristics of long COVID in elderly patients: An observational cohort study of over 2 million adults in the US.</h4><i>Fung KW, Baye F, Baik SH, Zheng Z, McDonald CJ</i><br /><b>Background</b><br />Incidence of long COVID in the elderly is difficult to estimate and can be underreported. While long COVID is sometimes considered a novel disease, many viral or bacterial infections have been known to cause prolonged illnesses. We postulate that some influenza patients might develop residual symptoms that would satisfy the diagnostic criteria for long COVID, a condition we call \"long Flu.\" In this study, we estimate the incidence of long COVID and long Flu among Medicare patients using the World Health Organization (WHO) consensus definition. We compare the incidence, symptomatology, and healthcare utilization between long COVID and long Flu patients.<br /><b>Methods and findings</b><br />This is a cohort study of Medicare (the US federal health insurance program) beneficiaries over 65. ICD-10-CM codes were used to capture COVID-19, influenza, and residual symptoms. Long COVID was identified by (a) the designated long COVID code B94.8 (code-based definition), or (b) any of 11 symptoms identified in the WHO definition (symptom-based definition), from 1 to 3 months post-infection. A symptom would be excluded if it occurred in the year prior to infection. Long Flu was identified in influenza patients from the combined 2018 and 2019 Flu seasons by the same symptom-based definition for long COVID. Long COVID and long Flu were compared in 4 outcome measures: (a) hospitalization (any cause); (b) hospitalization (for long COVID symptom); (c) emergency department (ED) visit (for long COVID symptom); and (d) number of outpatient encounters (for long COVID symptom), adjusted for age, sex, race, region, Medicare-Medicaid dual eligibility status, prior-year hospitalization, and chronic comorbidities. Among 2,071,532 COVID-19 patients diagnosed between April 2020 and June 2021, symptom-based definition identified long COVID in 16.6% (246,154/1,479,183) and 29.2% (61,631/210,765) of outpatients and inpatients, respectively. The designated code gave much lower estimates (outpatients 0.49% (7,213/1,479,183), inpatients 2.6% (5,521/210,765)). Among 933,877 influenza patients, 17.0% (138,951/817,336) of outpatients and 24.6% (18,824/76,390) of inpatients fit the long Flu definition. Long COVID patients had higher incidence of dyspnea, fatigue, palpitations, loss of taste/smell, and neurocognitive symptoms compared to long Flu. Long COVID outpatients were more likely to have any-cause hospitalization (31.9% (74,854/234,688) versus 26.8% (33,140/123,736), odds ratio 1.06 (95% CI 1.05 to 1.08, p < 0.001)), and more outpatient visits than long Flu outpatients (mean 2.9(SD 3.4) versus 2.5(SD 2.7) visits, incidence rate ratio 1.09 (95% CI 1.08 to 1.10, p < 0.001)). There were less ED visits in long COVID patients, probably because of reduction in ED usage during the pandemic. The main limitation of our study is that the diagnosis of long COVID in is not independently verified.<br /><b>Conclusions</b><br />Relying on specific long COVID diagnostic codes results in significant underreporting. We observed that about 30% of hospitalized COVID-19 patients developed long COVID. In a similar proportion of patients, long COVID-like symptoms (long Flu) can be observed after influenza, but there are notable differences in symptomatology between long COVID and long Flu. The impact of long COVID on healthcare utilization is higher than long Flu.<br /><br />Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.<br /><br /><small>PLoS Med: 17 Apr 2023; 20:e1004194</small></div>

<div><h4>Evaluation of a community health worker home visit intervention to improve child development in South Africa: A cluster-randomized controlled trial.</h4><i>Rockers PC, Leppänen JM, Tarullo A, Coetzee L, ... Yousafzai AK, Evans D</i><br /><b>Background</b><br />Effective integration of home visit interventions focused on early childhood development into existing service platforms is important for expanding access in low- and middle-income countries (LMICs). We designed and evaluated a home visit intervention integrated into community health worker (CHW) operations in South Africa.<br /><b>Methods and findings</b><br />We conducted a cluster-randomized controlled trial in Limpopo Province, South Africa. CHWs operating in ward-based outreach teams (WBOTs; clusters) and caregiver-child dyads they served were randomized to the intervention or control group. Group assignment was masked from all data collectors. Dyads were eligible if they resided within a participating CHW catchment area, the caregiver was at least 18 years old, and the child was born after December 15, 2017. Intervention CHWs were trained on a job aid that included content on child health, nutrition, developmental milestones, and encouragement to engage in developmentally appropriate play-based activities, for use during regular monthly home visits with caregivers of children under 2 years of age. Control CHWs provided the local standard of care. Household surveys were administered to the full study sample at baseline and endline. Data were collected on household demographics and assets; caregiver engagement; and child diet, anthropometry, and development scores. In a subsample of children, electroencephalography (EEG) and eye-tracking measures of neural function were assessed at a lab concurrent with endline and at 2 interim time points. Primary outcomes were as follows: height-for-age z-scores (HAZs) and stunting; child development scores measured using the Malawi Developmental Assessment Tool (MDAT); EEG absolute gamma and total power; relative EEG gamma power; and saccadic reaction time (SRT)-an eye-tracking measure of visual processing speed. In the main analysis, unadjusted and adjusted impacts were estimated using intention-to-treat analysis. Adjusted models included a set of demographic covariates measured at baseline. On September 1, 2017, we randomly assigned 51 clusters to intervention (26 clusters, 607 caregiver-child dyads) or control (25 clusters, 488 caregiver-child dyads). At endline (last assessment June 11, 2021), 432 dyads (71%) in 26 clusters remained in the intervention group, and 332 dyads (68%) in 25 clusters remained in the control group. In total, 316 dyads attended the first lab visit, 316 dyads the second lab visit, and 284 dyads the third lab visit. In adjusted models, the intervention had no significant impact on HAZ (adjusted mean difference (aMD) 0.11 [95% confidence interval (CI): -0.07, 0.30]; p = 0.220) or stunting (adjusted odds ratio (aOR) 0.63 [0.32, 1.25]; p = 0.184), nor did the intervention significantly impact gross motor skills (aMD 0.04 [-0.15, 0.24]; p = 0.656), fine motor skills (aMD -0.04 [-0.19, 0.11]; p = 0.610), language skills (aMD -0.02 [-0.18, 0.14]; p = 0.820), or social-emotional skills (aMD -0.02 [-0.20, 0.16]; p = 0.816). In the lab subsample, the intervention had a significant impact on SRT (aMD -7.13 [-12.69, -1.58]; p = 0.012), absolute EEG gamma power (aMD -0.14 [-0.24, -0.04]; p = 0.005), and total EEG power (aMD -0.15 [-0.23, -0.08]; p < 0.001), and no significant impact on relative gamma power (aMD 0.02 [-0.78, 0.83]; p = 0.959). While the effect on SRT was observed at the first 2 lab visits, it was no longer present at the third visit, which coincided with the overall endline assessment. At the end of the first year of the intervention period, 43% of CHWs adhered to monthly home visits. Due to the COVID-19 pandemic, we were not able to assess outcomes until 1 year after the end of the intervention period.<br /><b>Conclusions</b><br />While the home visit intervention did not significantly impact linear growth or skills, we found significant improvement in SRT. This study contributes to a growing literature documenting the positive effects of home visit interventions on child development in LMICs. This study also demonstrates the feasibility of collecting markers of neural function like EEG power and SRT in low-resource settings.<br /><b>Trial registration</b><br />PACTR 201710002683810; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=2683; South African Clinical Trials Registry, SANCTR 4407.<br /><br />Copyright: © 2023 Rockers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 14 Apr 2023; 20:e1004222</small></div>

<div><h4>Investigating time-dependent COVID-19 pandemic mental health data: Challenges and opportunities of using panel data analysis.</h4><i>Pinto da Costa M, Stewart R</i><br /><AbstractText>Mariana Pinto da Costa and Robert Stewart provide commentary on a large prospective panel survey of mental health during the pandemic and consider the implications of such data science initiatives.</AbstractText><br /><br />Copyright: © 2023 Pinto da Costa, Stewart. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004219</small></div>

<div><h4>Infant feeding method and special educational need in 191,745 Scottish schoolchildren: A national, population cohort study.</h4><i>Adams LJ, Pell JP, Mackay DF, Clark D, King A, Fleming M</i><br /><b>Background</b><br />While special educational needs (SEN) are increasingly recorded among schoolchildren, infant breastfeeding has been associated with reduced incidence of childhood physical and mental health problems. This study investigated relationships between infant feeding method and risk of all-cause and cause-specific SEN.<br /><b>Methods and findings</b><br />A population cohort of schoolchildren in Scotland was constructed by linking together health (maternity, birth, and health visitor records) and education (annual school pupil census) databases. Inclusion was restricted to singleton children, born in Scotland from 2004 onwards with available breastfeeding data and who attended local authority mainstream or special schools between 2009 and 2013. Generalised estimating equation models with a binomial distribution and logit link function investigated associations between infant feeding method at 6 to 8 weeks and all-cause and cause-specific SEN, adjusting for sociodemographic and maternity factors. Of 191,745 children meeting inclusion criteria, 126,907 (66.2%) were formula-fed, 48,473 (25.3%) exclusively breastfed, and 16,365 (8.5%) mixed-fed. Overall, 23,141 (12.1%) children required SEN. Compared with formula feeding, mixed feeding and exclusive breastfeeding, respectively, were associated with decreased all-cause SEN (OR 0.90, 95% CI [0.84,0.95], p < 0.001 and 0.78, [0.75,0.82], p < 0.001), and SEN attributed to learning disabilities (0.75, [0.65,0.87], p < 0.001 and 0.66, [0.59,0.74], p < 0.001), and learning difficulties (0.85, [0.77,0.94], p = 0.001 and 0.75, [0.70,0.81], p < 0.001). Compared with formula feeding, exclusively breastfed children had less communication problems (0.81, [0.74,0.88], p = 0.001), social-emotional-behavioural difficulties (0.77, [0.70,0.84], p = 0.001), sensory impairments (0.79, [0.65,0.95], p = 0.01), physical motor disabilities (0.78, [0.66,0.91], p = 0.002), and physical health conditions (0.74, [0.63,0.87], p = 0.01). There were no significant associations for mixed-fed children (communication problems (0.94, [0.83,1.06], p = 0.312), social-emotional-behavioural difficulties (0.96, [0.85,1.09], p = 0.541), sensory impairments (1.07, [0.84,1.37], p = 0.579), physical motor disabilities (0.97, [0.78,1.19], p = 0.754), and physical health conditions (0.93, [0.74,1.16], p = 0.504)). Feeding method was not significantly associated with mental health conditions (exclusive 0.58 [0.33,1.03], p = 0.061 and mixed 0.74 [0.36,1.53], p = 0.421) or autism (exclusive 0.88 [0.77,1.01], p = 0.074 and mixed 1.01 [0.84,1.22], p = 0.903). Our study was limited since only 6- to 8-week feeding method was available precluding differentiation between never-breastfed infants and those who stopped breastfeeding before 6 weeks. Additionally, we had no data on maternal and paternal factors such as education level, IQ, employment status, race/ethnicity, or mental and physical health.<br /><b>Conclusions</b><br />In this study, we observed that both breastfeeding and mixed feeding at 6 to 8 weeks were associated with lower risk of all-cause SEN, and SEN attributed to learning disabilities and learning difficulty. Many women struggle to exclusively breastfeed for the full 6 months recommended by WHO; however, this study provides evidence that a shorter duration of nonexclusive breastfeeding could nonetheless be beneficial with regard to the development of SEN. Our findings augment the existing evidence base concerning the advantages of breastfeeding and reinforce the importance of breastfeeding education and support.<br /><br />Copyright: © 2023 Adams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004191</small></div>

<div><h4>Long-term psychological distress trajectories and the COVID-19 pandemic in three British birth cohorts: A multi-cohort study.</h4><i>Moreno-Agostino D, Fisher HL, Goodman A, Hatch SL, ... Das-Munshi J, Ploubidis GB</i><br /><b>Background</b><br />Growing evidence suggests that population mental health outcomes have worsened since the pandemic started. The extent that these changes have altered common age-related trends in psychological distress, where distress typically rises until midlife and then falls after midlife in both sexes, is unknown. We aimed to analyse whether long-term pre-pandemic psychological distress trajectories were disrupted during the pandemic, and whether these changes have been different across cohorts and by sex.<br /><b>Methods and findings</b><br />We used data from three nationally representative birth cohorts comprising all people born in Great Britain in a single week of 1946 (National Survey of Health and Development, NSHD), 1958 (National Child Development Study, NCDS), or 1970 (British Cohort Study, BCS70). The follow-up data used spanned 39 years in NSHD (1982 to 2021), 40 years in NCDS (1981 to 2001), and 25 years in BCS70 (1996 to 2021). We used psychological distress factor scores, as measured by validated self-reported questionnaires (NSHD: Present State Examination, Psychiatric Symptoms Frequency, and 28- and 12-item versions of General Health Questionnaire; NCDS and BCS70: Malaise Inventory; all: 2-item versions of Generalized Anxiety Disorder scale and Patient Health Questionnaire). We used a multilevel growth curve modelling approach to model the trajectories of distress across cohorts and sexes and obtained estimates of the differences between the distress levels observed during the pandemic and those observed at the most recent pre-pandemic assessment and at the peak in the cohort-specific pre-pandemic distress trajectory, located at midlife. We further analysed whether pre-existing cohort and sex inequalities had changed with the pandemic onset using a difference-in-differences (DiD) approach. The analytic sample included 16,389 participants. By September/October 2020, distress levels had reached or exceeded the levels of the peak in the pre-pandemic life-course trajectories, with larger increases in younger cohorts (standardised mean differences [SMD] and 95% confidence intervals of SMDNSHD,pre-peak = -0.02 [-0.07, 0.04], SMDNCDS,pre-peak = 0.05 [0.02, 0.07], and SMDBCS70,pre-peak = 0.09 [0.07, 0.12] for the 1946, 1958, and 1970 birth cohorts, respectively). Increases in distress were larger among women than men, widening pre-existing sex inequalities (DiD and 95% confidence intervals of DiDNSHD,sex,pre-peak = 0.17 [0.06, 0.28], DiDNCDS,sex,pre-peak = 0.11 [0.07, 0.16], and DiDBCS70,sex,pre-peak = 0.11 [0.05, 0.16] when comparing sex inequalities in the pre-pandemic peak in midlife to those observed by September/October 2020). As expected in cohort designs, our study suffered from high proportions of attrition with respect to the original samples. Although we used non-response weights to restore sample representativeness to the target populations (those born in the United Kingdom in 1946, 1958, and 1970, alive and residing in the UK), results may not be generalisable to other sections within the UK population (e.g., migrants and ethnic minority groups) and countries different than the UK.<br /><b>Conclusions</b><br />Pre-existing long-term psychological distress trajectories of adults born between 1946 and 1970 were disrupted during the COVID-19 pandemic, particularly among women, who reached the highest levels ever recorded in up to 40 years of follow-up data. This may impact future trends of morbidity, disability, and mortality due to common mental health problems.<br /><br />Copyright: © 2023 Moreno-Agostino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004145</small></div>

<div><h4>Mortality in children under 5 years of age with congenital syphilis in Brazil: A nationwide cohort study.</h4><i>Paixao ES, Ferreira AJ, Dos Santos IO, Rodrigues LC, ... Barreto ML, Ichihara MY</i><br /><b>Background</b><br />Congenital syphilis (CS) is a major and avoidable cause of neonatal death worldwide. In this study, we aimed to estimate excess all-cause mortality in children under 5 years with CS compared to those without CS.<br /><b>Methods and findings</b><br />In this population-based cohort study, we used linked, routinely collected data from Brazil from January 2011 to December 2017. Cox survival models were adjusted for maternal region of residence, maternal age, education, material status, self-declared race and newborn sex, and year of birth and stratified according to maternal treatment status, non-treponemal titers and presence of signs and symptoms at birth. Over 7 years, a total of 20 057 013 live-born children followed up (through linkage) to 5 years of age, 93 525 were registered with CS, and 2 476 died. The all-cause mortality rate in the CS group was 7·84/1 000 person-years compared with 2·92/1 000 person-years in children without CS, crude hazard ratio (HR) = 2·41 (95% CI 2·31 to 2·50). In the fully adjusted model, the highest under-five mortality risk was observed among children with CS from untreated mothers HR = 2·82 (95% CI 2·63 to 3·02), infants with non-treponemal titer higher than 1:64 HR = 8·87 (95% CI 7·70 to 10·22), and children with signs and symptoms at birth HR = 7·10 (95% CI 6·60 to 7·63). Among children registered with CS, CS was recorded as the underlying cause of death in 33% (495/1 496) of neonatal, 11% (85/770) of postneonatal, and 2·9% (6/210) of children 1 year of age. The main limitations of this study were the use of a secondary database without additional clinical information and the potential misclassification of exposure status.<br /><b>Conclusions</b><br />This study showed an increased mortality risk among children with CS that goes beyond the first year of life. It also reinforces the importance of maternal treatment that infant non-treponemal titers and the presence of signs and symptoms of CS at birth are strongly associated with subsequent mortality.<br /><b>Trial registration</b><br />Observational study.<br /><br />Copyright: © 2023 Paixao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004209</small></div>

<div><h4>Estimating health spending associated with chronic multimorbidity in 2018: An observational study among adults in the United States.</h4><i>Chang AY, Bryazka D, Dieleman JL</i><br /><b>Background</b><br />The rise in health spending in the United States and the prevalence of multimorbidity-having more than one chronic condition-are interlinked but not well understood. Multimorbidity is believed to have an impact on an individual\'s health spending, but how having one specific additional condition impacts spending is not well established. Moreover, most studies estimating spending for single diseases rarely adjust for multimorbidity. Having more accurate estimates of spending associated with each disease and different combinations could aid policymakers in designing prevention policies to more effectively reduce national health spending. This study explores the relationship between multimorbidity and spending from two distinct perspectives: (1) quantifying spending on different disease combinations; and (2) assessing how spending on a single diseases changes when we consider the contribution of multimorbidity (i.e., additional/reduced spending that could be attributed in the presence of other chronic conditions).<br /><b>Methods and findings</b><br />We used data on private claims from Truven Health MarketScan Research Database, with 16,288,894 unique enrollees ages 18 to 64 from the US, and their annual inpatient and outpatient diagnoses and spending from 2018. We selected conditions that have an average duration of greater than one year among all Global Burden of Disease causes. We used penalized linear regression with stochastic gradient descent approach to assess relationship between spending and multimorbidity, including all possible disease combinations with two or three different conditions (dyads and triads) and for each condition after multimorbidity adjustment. We decomposed the change in multimorbidity-adjusted spending by the type of combination (single, dyads, and triads) and multimorbidity disease category. We defined 63 chronic conditions and observed that 56.2% of the study population had at least two chronic conditions. Approximately 60.1% of disease combinations had super-additive spending (e.g., spending for the combination was significantly greater than the sum of the individual diseases), 15.7% had additive spending, and 23.6% had sub-additive spending (e.g., spending for the combination was significantly less than the sum of the individual diseases). Relatively frequent disease combinations (higher observed prevalence) with high estimated spending were combinations that included endocrine, metabolic, blood, and immune disorders (EMBI disorders), chronic kidney disease, anemias, and blood cancers. When looking at multimorbidity-adjusted spending for single diseases, the following had the highest spending per treated patient and were among those with high observed prevalence: chronic kidney disease ($14,376 [12,291,16,670]), cirrhosis ($6,465 [6,090,6,930]), ischemic heart disease (IHD)-related heart conditions ($6,029 [5,529,6,529]), and inflammatory bowel disease ($4,697 [4,594,4,813]). Relative to unadjusted single-disease spending estimates, 50 conditions had higher spending after adjusting for multimorbidity, 7 had less than 5% difference, and 6 had lower spending after adjustment.<br /><b>Conclusions</b><br />We consistently found chronic kidney disease and IHD to be associated with high spending per treated case, high observed prevalence, and contributing the most to spending when in combination with other chronic conditions. In the midst of a surging health spending globally, and especially in the US, pinpointing high-prevalence, high-spending conditions and disease combinations, as especially conditions that are associated with larger super-additive spending, could help policymakers, insurers, and providers prioritize and design interventions to improve treatment effectiveness and reduce spending.<br /><br />Copyright: © 2023 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004205</small></div>

<div><h4>COVID-19 and mental health in 8 low- and middle-income countries: A prospective cohort study.</h4><i>Aksunger N, Vernot C, Littman R, Voors M, ... Janssens W, Mobarak AM</i><br /><b>Background</b><br />The Coronavirus Disease 2019 (COVID-19) pandemic and associated mitigation policies created a global economic and health crisis of unprecedented depth and scale, raising the estimated prevalence of depression by more than a quarter in high-income countries. Low- and middle-income countries (LMICs) suffered the negative effects on living standards the most severely. However, the consequences of the pandemic for mental health in LMICs have received less attention. Therefore, this study assesses the association between the COVID-19 crisis and mental health in 8 LMICs.<br /><b>Methods and findings</b><br />We conducted a prospective cohort study to examine the correlation between the COVID-19 pandemic and mental health in 10 populations from 8 LMICs in Asia, Africa, and South America. The analysis included 21,162 individuals (mean age 38.01 years, 64% female) who were interviewed at least once pre- as well as post-pandemic. The total number of survey waves ranged from 2 to 17 (mean 7.1). Our individual-level primary outcome measure was based on validated screening tools for depression and a weighted index of depression questions, dependent on the sample. Sample-specific estimates and 95% confidence intervals (CIs) for the association between COVID-19 periods and mental health were estimated using linear regressions with individual fixed effects, controlling for independent time trends and seasonal variation in mental health where possible. In addition, a regression discontinuity design was used for the samples with multiple surveys conducted just before and after the onset of the pandemic. We aggregated sample-specific coefficients using a random-effects model, distinguishing between estimates for the short (0 to 4 months) and longer term (4+ months). The random-effects aggregation showed that depression symptoms are associated with a increase by 0.29 standard deviations (SDs) (95% CI [-.47, -.11], p-value = 0.002) in the 4 months following the onset of the pandemic. This change was equivalent to moving from the 50th to the 63rd percentile in our median sample. Although aggregate depression is correlated with a decline to 0.21 SD (95% CI [-0.07, -.34], p-value = 0.003) in the period thereafter, the average recovery of 0.07 SD (95% CI [-0.09, .22], p-value = 0.41) was not statistically significant. The observed trends were consistent across countries and robust to alternative specifications. Two limitations of our study are that not all samples are representative of the national population, and the mental health measures differ across samples.<br /><b>Conclusions</b><br />Controlling for seasonality, we documented a large, significant, negative association of the pandemic on mental health, especially during the early months of lockdown. The magnitude is comparable (but opposite) to the effects of cash transfers and multifaceted antipoverty programs on mental health in LMICs. Absent policy interventions, the pandemic could be associated with a lasting legacy of depression, particularly in settings with limited mental health support services, such as in many LMICs. We also demonstrated that mental health fluctuates with agricultural crop cycles, deteriorating during \"lean\", pre-harvest periods and recovering thereafter. Ignoring such seasonal variations in mental health may lead to unreliable inferences about the association between the pandemic and mental health.<br /><br />Copyright: © 2023 Aksunger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004081</small></div>

<div><h4>The impact of community-based, peer-led sexual and reproductive health services on knowledge of HIV status among adolescents and young people aged 15 to 24 in Lusaka, Zambia: The Yathu Yathu cluster-randomised trial.</h4><i>Hensen B, Floyd S, Phiri MM, Schaap A, ... Simwinga M, Ayles H</i><br /><b>Background</b><br />The growing population of adolescents and young people (AYP) aged 15 to 24 in sub-Saharan Africa face a high burden of HIV in many settings. Unintended pregnancies among adolescent girls in the region remain high. Nonetheless, the sexual and reproductive health (SRH) service needs of AYP have remained underserved. We conducted a cluster-randomised trial (CRT) to estimate the impact of community-based, peer-led SRH service provision on knowledge of HIV status and other SRH outcomes, including met need for contraceptives.<br /><b>Methods and findings</b><br />Yathu Yathu was a cluster-randomised trial (CRT) conducted from 2019 to 2021 in 2 urban communities in Lusaka, Zambia. The communities were divided into 20 zones (approximately 2,350 AYP/zone) that were randomly allocated to the Yathu Yathu intervention or control arm. In each intervention zone, a community-based hub, staffed by peer support workers, was established to provide SRH services. In 2019, a census was conducted in all zones; all consenting AYP aged 15 to 24 were given a Yathu Yathu card, which allowed them to accrue points for accessing SRH services at the hub and health facility (intervention arm) or the health facility only (control arm). Points could be exchanged for rewards, thus acting as an incentive to use SRH services in both arms. We conducted a cross-sectional survey in 2021 to estimate the impact of Yathu Yathu on the primary outcome: knowledge of HIV status (self-reporting living with HIV or HIV testing in the last 12 months) and secondary outcomes, including use of pre-exposure prophylaxis (PrEP) in the last 12 months, current use of antiretroviral therapy (ART), and met need for contraceptive services. The sampling was stratified on sex and age group, and we analysed data at cluster-level using a two-stage process recommended for CRTs with <15 clusters/arm. A total of 1,989 AYP consented to participate in the survey (50% male); consent was similar across arms (63% consent/arm). Across zones, knowledge of HIV status ranged from 63.6% to 81.2% in intervention zones and 35.4% to 63.0% in control zones. Adjusting for age, sex, and community, knowledge of HIV status was higher in the intervention arm compared to control (73.3% versus 48.4%, respectively, adjusted prevalence ratio (PR) 1.53 95% CI 1.36, 1.72; p < 0.001). By age and sex, results were similar. There was no evidence for impact on any secondary outcomes, including current use of ART and met need for contraceptives. There were no adverse events reported in either arm. A key limitation of our trial is that approximately 35% of the AYP randomly selected for participation in the endline survey could not be reached.<br /><b>Conclusions</b><br />Delivering community-based, peer-led SRH services increased knowledge of HIV status among AYP, both males and females, compared with the control arm. Scaling up the highly effective Yathu Yathu strategy has the potential to make a substantial contribution to increasing access to HIV prevention and care services for young people. However, additional implementation research is needed to understand how to improve uptake of broader SRH services, beyond uptake of HIV testing.<br /><b>Trial registration</b><br />ISRCTN75609016, clinicaltrials.gov number NCT04060420.<br /><br />Copyright: © 2023 Hensen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004203</small></div>

<div><h4>COVID-19 and common mental health symptoms in the early phase of the pandemic: An umbrella review of the evidence.</h4><i>Witteveen AB, Young SY, Cuijpers P, Ayuso-Mateos JL, ... Wang S, Sijbrandij M</i><br /><b>Background</b><br />There remains uncertainty about the impact of the Coronavirus Disease 2019 (COVID-19) pandemic on mental health. This umbrella review provides a comprehensive overview of the association between the pandemic and common mental disorders. We qualitatively summarized evidence from reviews with meta-analyses of individual study-data in the general population, healthcare workers, and specific at-risk populations.<br /><b>Methods and findings</b><br />A systematic search was carried out in 5 databases for peer-reviewed systematic reviews with meta-analyses of prevalence of depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms during the pandemic published between December 31, 2019 until August 12, 2022. We identified 123 reviews of which 7 provided standardized mean differences (SMDs) either from longitudinal pre- to during pandemic study-data or from cross-sectional study-data compared to matched pre-pandemic data. Methodological quality rated with the Assessment of Multiple Systematic Reviews checklist scores (AMSTAR 2) instrument was generally low to moderate. Small but significant increases of depression, anxiety, and/or general mental health symptoms were reported in the general population, in people with preexisting physical health conditions, and in children (3 reviews; SMDs ranged from 0.11 to 0.28). Mental health and depression symptoms significantly increased during periods of social restrictions (1 review; SMDs of 0.41 and 0.83, respectively) but anxiety symptoms did not (SMD: 0.26). Increases of depression symptoms were generally larger and longer-lasting during the pandemic (3 reviews; SMDs depression ranged from 0.16 to 0.23) than those of anxiety (2 reviews: SMDs 0.12 and 0.18). Females showed a significantly larger increase in anxiety symptoms than males (1 review: SMD 0.15). In healthcare workers, people with preexisting mental disorders, any patient group, children and adolescents, and in students, no significant differences from pre- to during pandemic were found (2 reviews; SMD\'s ranging from -0.16 to 0.48). In 116 reviews pooled cross-sectional prevalence rates of depression, anxiety, and PTSD symptoms ranged from 9% to 48% across populations. Although heterogeneity between studies was high and largely unexplained, assessment tools and cut-offs used, age, sex or gender, and COVID-19 exposure factors were found to be moderators in some reviews. The major limitations are the inability to quantify and explain the high heterogeneity across reviews included and the shortage of within-person data from multiple longitudinal studies.<br /><b>Conclusions</b><br />A small but consistent deterioration of mental health and particularly depression during early pandemic and during social restrictions has been found in the general population and in people with chronic somatic disorders. Also, associations between mental health and the pandemic were stronger in females and younger age groups than in others. Explanatory individual-level, COVID-19 exposure, and time-course factors were scarce and showed inconsistencies across reviews. For policy and research, repeated assessments of mental health in population panels including vulnerable individuals are recommended to respond to current and future health crises.<br /><br />Copyright: © 2023 Witteveen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004206</small></div>

<div><h4>The impact of varying the number and selection of conditions on estimated multimorbidity prevalence: A cross-sectional study using a large, primary care population dataset.</h4><i>MacRae C, McMinn M, Mercer SW, Henderson D, ... Dibben C, Guthrie B</i><br /><b>Background</b><br />Multimorbidity prevalence rates vary considerably depending on the conditions considered in the morbidity count, but there is no standardised approach to the number or selection of conditions to include.<br /><b>Methods and findings</b><br />We conducted a cross-sectional study using English primary care data for 1,168,260 participants who were all people alive and permanently registered with 149 included general practices. Outcome measures of the study were prevalence estimates of multimorbidity (defined as ≥2 conditions) when varying the number and selection of conditions considered for 80 conditions. Included conditions featured in ≥1 of the 9 published lists of conditions examined in the study and/or phenotyping algorithms in the Health Data Research UK (HDR-UK) Phenotype Library. First, multimorbidity prevalence was calculated when considering the individually most common 2 conditions, 3 conditions, etc., up to 80 conditions. Second, prevalence was calculated using 9 condition-lists from published studies. Analyses were stratified by dependent variables age, socioeconomic position, and sex. Prevalence when only the 2 commonest conditions were considered was 4.6% (95% CI [4.6, 4.6] p < 0.001), rising to 29.5% (95% CI [29.5, 29.6] p < 0.001) considering the 10 commonest, 35.2% (95% CI [35.1, 35.3] p < 0.001) considering the 20 commonest, and 40.5% (95% CI [40.4, 40.6] p < 0.001) when considering all 80 conditions. The threshold number of conditions at which multimorbidity prevalence was >99% of that measured when considering all 80 conditions was 52 for the whole population but was lower in older people (29 in >80 years) and higher in younger people (71 in 0- to 9-year-olds). Nine published condition-lists were examined; these were either recommended for measuring multimorbidity, used in previous highly cited studies of multimorbidity prevalence, or widely applied measures of \"comorbidity.\" Multimorbidity prevalence using these lists varied from 11.1% to 36.4%. A limitation of the study is that conditions were not always replicated using the same ascertainment rules as previous studies to improve comparability across condition-lists, but this highlights further variability in prevalence estimates across studies.<br /><b>Conclusions</b><br />In this study, we observed that varying the number and selection of conditions results in very large differences in multimorbidity prevalence, and different numbers of conditions are needed to reach ceiling rates of multimorbidity prevalence in certain groups of people. These findings imply that there is a need for a standardised approach to defining multimorbidity, and to facilitate this, researchers can use existing condition-lists associated with highest multimorbidity prevalence.<br /><br />Copyright: © 2023 MacRae et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004208</small></div>

<div><h4>Correction: Effects of a WHO-guided digital health intervention for depression in Syrian refugees in Lebanon: A randomized controlled trial.</h4><i>Cuijpers P, Heim E, Ramia JA, Burchert S, ... van Ommeren M, El Chammay R</i><br /><AbstractText>[This corrects the article DOI: 10.1371/journal.pmed.1004025.].</AbstractText><br /><br />Copyright: © 2023 Cuijpers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004231</small></div>

<div><h4>Inequalities in provision of hip and knee replacement surgery for osteoarthritis by age, sex, and social deprivation in England between 2007-2017: A population-based cohort study of the National Joint Registry.</h4><i>Lenguerrand E, Ben-Shlomo Y, Rangan A, Beswick A, ... Blom AW, Judge A</i><br /><b>Background</b><br />While the United Kingdom National Health Service aimed to reduce social inequalities in the provision of joint replacement, it is unclear whether these gaps have reduced. We describe secular trends in the provision of primary hip and knee replacement surgery between social deprivation groups.<br /><b>Methods and findings</b><br />We used the National Joint Registry to identify all hip and knee replacements performed for osteoarthritis from 2007 to 2017 in England. The Index of Multiple Deprivation (IMD) 2015 was used to identify the relative level of deprivation of the patient living area. Multilevel negative binomial regression models were used to model the differences in rates of joint replacement. Choropleth maps of hip and knee replacement provision were produced to identify the geographical variation in provision by Clinical Commissioning Groups (CCGs). A total of 675,342 primary hip and 834,146 primary knee replacements were studied. The mean age was 70 years old (standard deviation: 9) with 60% and 56% of women undergoing hip and knee replacements, respectively. The overall rate of hip replacement increased from 27 to 36 per 10,000 person-years and knee replacement from 33 to 46. Inequalities of provision between the most (reference) and least affluent areas have remained constant for both joints (hip: rate ratio (RR) = 0.58, 95% confidence interval [0.56, 0.60] in 2007, RR = 0.59 [0.58, 0.61] in 2017; knee: RR = 0.82 [0.80, 0.85] in 2007, RR = 0.81 [0.80, 0.83] in 2017). For hip replacement, CCGs with the highest concentration of deprived areas had lower overall provision rates, and CCGs with very few deprived areas had higher provision rates. There was no clear pattern of provision inequalities between CCGs and deprivation concentration for knee replacement. Study limitations include the lack of publicly available information to explore these inequalities beyond age, sex, and geographical area. Information on clinical need for surgery or patient willingness to access care were unavailable.<br /><b>Conclusions</b><br />In this study, we found that there were inequalities, which remained constant over time, especially in the provision of hip replacement, by degree of social deprivation. Providers of healthcare need to take action to reduce this unwarranted variation in provision of surgery.<br /><br />Copyright: © 2023 Lenguerrand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004210</small></div>

<div><h4>Home working and social and mental wellbeing at different stages of the COVID-19 pandemic in the UK: Evidence from 7 longitudinal population surveys.</h4><i>Wels J, Wielgoszewska B, Moltrecht B, Booth C, ... Katikireddi SV, Ploubidis GB</i><br /><b>Background</b><br />Home working has increased since the Coronavirus Disease 2019 (COVID-19) pandemic\'s onset with concerns that it may have adverse health implications. We assessed the association between home working and social and mental wellbeing among the employed population aged 16 to 66 through harmonised analyses of 7 UK longitudinal studies.<br /><b>Methods and findings</b><br />We estimated associations between home working and measures of psychological distress, low life satisfaction, poor self-rated health, low social contact, and loneliness across 3 different stages of the pandemic (T1 = April to June 2020 -first lockdown, T2 = July to October 2020 -eased restrictions, T3 = November 2020 to March 2021 -second lockdown) using modified Poisson regression and meta-analyses to pool results across studies. We successively adjusted the model for sociodemographic characteristics (e.g., age, sex), job characteristics (e.g., sector of activity, pre-pandemic home working propensities), and pre-pandemic health. Among respectively 10,367, 11,585, and 12,179 participants at T1, T2, and T3, we found higher rates of home working at T1 and T3 compared with T2, reflecting lockdown periods. Home working was not associated with psychological distress at T1 (RR = 0.92, 95% CI = 0.79 to 1.08) or T2 (RR = 0.99, 95% CI = 0.88 to 1.11), but a detrimental association was found with psychological distress at T3 (RR = 1.17, 95% CI = 1.05 to 1.30). Study limitations include the fact that pre-pandemic home working propensities were derived from external sources, no information was collected on home working dosage and possible reverse association between change in wellbeing and home working likelihood.<br /><b>Conclusions</b><br />No clear evidence of an association between home working and mental wellbeing was found, apart from greater risk of psychological distress during the second lockdown, but differences across subgroups (e.g., by sex or level of education) may exist. Longer term shifts to home working might not have adverse impacts on population wellbeing in the absence of pandemic restrictions but further monitoring of health inequalities is required.<br /><br />Copyright: © 2023 Wels et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004214</small></div>

<div><h4>A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.</h4><i>Sobiecki JG, Imamura F, Davis CR, Sharp SJ, ... Wareham NJ, Forouhi NG</i><br /><b>Background</b><br />Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet.<br /><b>Methods and findings</b><br />We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding.<br /><b>Conclusions</b><br />These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully.<br /><b>Trial registration</b><br />Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.<br /><br />Copyright: © 2023 Sobiecki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004221</small></div>

<div><h4>Reimagining the journey to recovery: The COVID-19 pandemic and global mental health.</h4><i>Patel V, Fancourt D, Furukawa TA, Kola L</i><br /><AbstractText>In this editorial, guest editors Vikram Patel, Daisy Fancourt, Lola Kola, and Toshi Furukawa discuss the contents of the special issue on the pandemic and global mental health, highlighting key themes and providing important context.</AbstractText><br /><br />Copyright: © 2023 Patel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004224</small></div>

<div><h4>COVID-19 and mental health: Building back better or reimagining a new way forward?</h4><i>Tomlinson M, Marlow M</i><br /><AbstractText>In this Perspective, Mark Tomlinson and Marguerite Marlow argue that equitable improvements in mental health outcomes cannot be achieved without first dismantling colonial and paternalistic approaches to global mental health.</AbstractText><br /><br />Copyright: © 2023 Tomlinson, Marlow. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004216</small></div>

<div><h4>The COVID-19 pandemic and health-related quality of life across 13 high- and low-middle-income countries: A cross-sectional analysis.</h4><i>Violato M, Pollard J, Lloyd A, Roope LSJ, ... Becerra MF, Clarke PM</i><br /><b>Background</b><br />Most research on the Coronavirus Disease 2019 (COVID-19) health burden has focused on confirmed cases and deaths, rather than consequences for the general population\'s health-related quality of life (HRQoL). It is also important to consider HRQoL to better understand the potential multifaceted implications of the COVID-19 pandemic in various international contexts. This study aimed to assess the association between the COVID-19 pandemic and changes in HRQoL in 13 diverse countries.<br /><b>Methods and findings</b><br />Adults (18+ years) were surveyed online (24 November to 17 December 2020) in 13 countries spanning 6 continents. Our cross-sectional study used descriptive and regression-based analyses (age adjusted and stratified by gender) to assess the association between the pandemic and changes in the general population\'s HRQoL, measured by the EQ-5D-5L instrument and its domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and how overall health deterioration was associated with individual-level (socioeconomic, clinical, and experiences of COVID-19) and national-level (pandemic severity, government responsiveness, and effectiveness) factors. We also produced country-level quality-adjusted life years (QALYs) associated to COVID-19 pandemic-related morbidity. We found that overall health deteriorated, on average across countries, for more than one-third of the 15,480 participants, mostly in the anxiety/depression health domain, especially for younger people (<35 years old) and females/other gender. This translated overall into a 0.066 mean \"loss\" (95% CI: -0.075, -0.057; p-value < 0.001) in the EQ-5D-5L index, representing a reduction of 8% in overall HRQoL. QALYs lost associated with morbidity were 5 to 11 times greater than QALYs lost based on COVID-19 premature mortality. A limitation of the study is that participants were asked to complete the prepandemic health questionnaire retrospectively, meaning responses may be subject to recall bias.<br /><b>Conclusions</b><br />In this study, we observed that the COVID-19 pandemic was associated with a reduction in perceived HRQoL globally, especially with respect to the anxiety/depression health domain and among younger people. The COVID-19 health burden would therefore be substantially underestimated if based only on mortality. HRQoL measures are important to fully capture morbidity from the pandemic in the general population.<br /><br />Copyright: © 2023 Violato et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004146</small></div>

<div><h4>Mental disorders and COVID-19 deaths: Clinical, public health, and human rights implications.</h4><i>Saxena S, Chwa C</i><br /><AbstractText>Shekhar Saxena and Cindy Chwa discuss the neglect of care for people living with mental disorders during the pandemic, and highlight relevant implications for policy-makers.</AbstractText><br /><br />Copyright: © 2023 Saxena, Chwa. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004220</small></div>

<div><h4>The association between cognitive ability and body mass index: A sibling-comparison analysis in four longitudinal studies.</h4><i>Wright L, Davies NM, Bann D</i><br /><b>Background</b><br />Body mass index (BMI) and obesity rates have increased sharply since the 1980s. While multiple epidemiologic studies have found that higher adolescent cognitive ability is associated with lower adult BMI, residual and unobserved confounding due to family background may explain these associations. We used a sibling design to test this association accounting for confounding factors shared within households.<br /><b>Methods and findings</b><br />We used data from four United States general youth population cohort studies: the National Longitudinal Study of Youth 1979 (NLSY-79), the NLSY-79 Children and Young Adult, the NLSY 1997 (NLSY-97), and the Wisconsin Longitudinal Study (WLS); a total of 12,250 siblings from 5,602 households followed from adolescence up to age 62. We used random effects within-between (REWB) and residualized quantile regression (RQR) models to compare between- and within-family estimates of the association between adolescent cognitive ability and adult BMI (20 to 64 years). In REWB models, moving from the 25th to 75th percentile of adolescent cognitive ability was associated with -0.95 kg/m2 (95% CI = -1.21, -0.69) lower BMI between families. Adjusting for family socioeconomic position reduced the association to -0.61 kg/m2 (-0.90, -0.33). However, within families, the association was just -0.06 kg/m2 (-0.35, 0.23). This pattern of results was found across multiple specifications, including analyses conducted in separate cohorts, models examining age-differences in association, and in RQR models examining the association across the distribution of BMI. Limitations include the possibility that within-family estimates are biased due to measurement error of the exposure, confounding via non-shared factors, and carryover effects.<br /><b>Conclusions</b><br />The association between high adolescent cognitive ability and low adult BMI was substantially smaller in within-family compared with between-family analysis. The well-replicated associations between cognitive ability and subsequent BMI may largely reflect confounding by family background factors.<br /><br />Copyright: © 2023 Wright et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004207</small></div>

<div><h4>Impact on childhood mortality of interventions to improve drinking water, sanitation, and hygiene (WASH) to households: Systematic review and meta-analysis.</h4><i>Sharma Waddington H, Masset E, Bick S, Cairncross S</i><br /><b>Background</b><br />In low- and middle-income countries (L&MICs), the biggest contributing factors to the global burden of disease in childhood are deaths due to respiratory illness and diarrhoea, both of which are closely related to use of water, sanitation, and hygiene (WASH) services by households. However, current estimates of the health impacts of WASH interventions use self-reported morbidity, which may fail to capture longer-term or more severe impacts. Reported mortality is thought to be less prone to bias than other reported measures. This study aimed to answer the question: What are the impacts of WASH interventions on reported childhood mortality in L&MICs?<br /><b>Methods and findings</b><br />We conducted a systematic review and meta-analysis, using a published protocol. Systematic searches of 11 academic databases and trial registries, plus organisational repositories, were undertaken to locate studies of WASH interventions, which were published in peer review journals or other sources (e.g., organisational reports and working papers). Intervention studies of WASH improvements implemented under endemic disease circumstances in L&MICs were eligible, which reported findings at any time until March 2020. We used the participant flow data supplied in response to journal editors\' calls for greater transparency. Data were collected by two authors working independently. We included evidence from 24 randomized and 11 nonrandomized studies of WASH interventions from all global regions, incorporating 2,600 deaths. Effects of 48 WASH treatment arms were included in analysis. We critically appraised and synthesised evidence using meta-analysis to improve statistical power. We found WASH interventions are associated with a significant reduction of 17% in the odds of all-cause mortality in childhood (OR = 0.83, 95% CI = 0.74, 0.92, evidence from 38 interventions), and a significant reduction in diarrhoea mortality of 45% (OR = 0.55, 95% CI = 0.35, 0.84; 10 interventions). Further analysis by WASH technology indicated interventions providing improved water in quantity to households were most consistently associated with reductions in all-cause mortality. Community-wide sanitation was most consistently associated with reductions in diarrhoea mortality. Around one-half of the included studies were assessed as being at \"moderate risk of bias\" in attributing mortality in childhood to the WASH intervention, and no studies were found to be at \"low risk of bias.\" The review should be updated to incorporate additional published and unpublished participant flow data.<br /><b>Conclusions</b><br />The findings are congruent with theories of infectious disease transmission. Washing with water presents a barrier to respiratory illness and diarrhoea, which are the two biggest contributors to all-cause mortality in childhood in L&MICs. Community-wide sanitation halts the spread of diarrhoea. We observed that evidence synthesis can provide new findings, going beyond the underlying data from trials to generate crucial insights for policy. Transparent reporting in trials creates opportunities for research synthesis to answer questions about mortality, which individual studies of interventions cannot be reliably designed to address.<br /><br />Copyright: © 2023 Sharma Waddington et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004215</small></div>

<div><h4>Correction: Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.</h4><i>Vinther JL, Cadman T, Avraam D, Ekstrøm CT, ... Lawlor DA, Nybo Andersen AM</i><br /><AbstractText>[This corrects the article DOI: 10.1371/journal.pmed.1004036.].</AbstractText><br /><br />Copyright: © 2023 Vinther et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004232</small></div>

<div><h4>Depression and anxiety in people with cognitive impairment and dementia during the COVID-19 pandemic: Analysis of the English Longitudinal Study of Ageing.</h4><i>Beach B, Steptoe A, Zaninotto P</i><br /><b>Background</b><br />Some studies have identified declines in mental health during the Coronavirus Disease 2019 (COVID-19) pandemic in different age groups, including older people. As anxiety and depression are common neuropsychiatric symptoms among people with cognitive impairment, the mental health experiences of older people during the pandemic should take cognitive function into consideration, along with assessments made prior to the pandemic. This study addresses evidence gaps to test whether changes in depression and anxiety among older people through the COVID-19 pandemic were associated with cognitive impairment. It also investigates whether associations varied according to key sources of sociodemographic inequality.<br /><b>Methods and findings</b><br />Using data from the English Longitudinal Study of Ageing (ELSA) collected from 2018/2019 to November/December 2020, we estimated changes in depression and anxiety for people aged 50+ in England across 3 cognitive function groups: no impairment, mild cognitive impairment, and dementia. Conditional growth curve models were estimated for continuous measures over 3 time points (N = 5,286), with mixed-effects logistic regression used for binary measures. All models adjusted for demographics (age, gender, ethnicity, and cohabiting partnership), socioeconomics (education, wealth, and employment status), geography (urban/rural and English region), and health (self-rated and the presence of multimorbidity). We found that depression (measured with CES-D score) worsened from 2018/2019 to November/December 2020 for people with mild cognitive impairment (1.39 (95% CI: 1.29 to 1.49) to 2.16 (2.02 to 2.30)) or no impairment (1.17 (95%CI: 1.12 to 1.22) to 2.03 (1.96 to 2.10)). Anxiety, using a single-item rating of 0 to 10 also worsened among those with mild cognitive impairment (2.48 (2.30 to 2.66) to 3.14 (2.95 to 3.33)) or no impairment (2.20 (2.11 to 2.28) to 2.85 (2.77 to 2.95)). No statistically significant increases were found for those with dementia. Using a clinical cutoff for likely depression (CES-D ≥4), we found statistically significant increases in the probability of depression between 2018/2019 and November/December 2020 for those with no impairment (0.110 (0.099 to 0.120) to 0.206 (0.191 to 0.222)) and mild impairment (0.139 (0.120 to 0.159) to 0.234 (0.204 to 0.263)). We also found that differences according to cognitive function that existed before the pandemic were no longer present by June/July 2020, and there were no statistically significant differences in depression or anxiety among cognitive groups in November/December 2020. Wealth and education appeared to be stronger drivers for depression and anxiety, respectively, than cognitive impairment. For example, those with no impairment in the richest two-thirds scored 1.76 (1.69 to 1.82) for depression in June/July, compared to 2.01 (1.91 to 2.12) for those with no impairment in the poorest third and 2.03 (1.87 to 2.19) for those with impairment in the poorest third. Results may be limited by the small number of people with dementia and are generalizable only to people living in the community, not to those in institutional care settings.<br /><b>Conclusions</b><br />Our findings suggest a convergence in mental health across cognitive function groups during the pandemic. This suggests mental health services will need to meet an increased demand from older adults, especially those not living with cognitive impairment. Further, with little significant change among those with dementia, their existing need for support will remain; policymakers and care practitioners should ensure this group continues to have equitable access to mental health support.<br /><br />Copyright: © 2023 Beach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004162</small></div>

<div><h4>Correction: Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.</h4><i>Signorell A, Awor P, Okitawutshu J, Tshefu A, ... Lengeler C, Burri C</i><br /><AbstractText>[This corrects the article DOI: 10.1371/journal.pmed.1004189.].</AbstractText><br /><br />Copyright: © 2023 Signorell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004234</small></div>

<div><h4>Impact of point-of-care ultrasound and routine third trimester ultrasound on undiagnosed breech presentation and perinatal outcomes: An observational multicentre cohort study.</h4><i>Knights S, Prasad S, Kalafat E, Dadali A, ... Harlow F, Khalil A</i><br /><b>Background</b><br />Accurate knowledge of fetal presentation at term is vital for optimal antenatal and intrapartum care. The primary objective was to compare the impact of routine third trimester ultrasound or point-of-care ultrasound (POCUS) with standard antenatal care, on the incidence of overall and proportion of all term breech presentations that were undiagnosed at term, and on the related adverse perinatal outcomes.<br /><b>Methods and findings</b><br />This was a retrospective multicentre cohort study where we included data from St. George\'s (SGH) and Norfolk and Norwich University Hospitals (NNUH). Pregnancies were grouped according to whether they received routine third trimester scan (SGH) or POCUS (NNUH). Women with multiple pregnancy, preterm birth prior to 37 weeks, congenital abnormality, and those undergoing planned cesarean section for breech presentation were excluded. Undiagnosed breech presentation was defined as follows: (a) women presenting in labour or with ruptured membranes at term subsequently discovered to have a breech presentation; and (b) women attending for induction of labour at term found to have a breech presentation before induction. The primary outcome was the proportion of all term breech presentations that were undiagnosed. The secondary outcomes included mode of birth, gestational age at birth, birth weight, incidence of emergency cesarean section, and the following neonatal adverse outcomes: Apgar score <7 at 5 minutes, unexpected neonatal unit (NNU) admission, hypoxic ischemic encephalopathy (HIE), and perinatal mortality (including stillbirths and early neonatal deaths). We employed a Bayesian approach using informative priors from a previous similar study; updating their estimates (prior) with our own data (likelihood). The association of undiagnosed breech presentation at birth with adverse perinatal outcomes was analyzed with Bayesian log-binomial regression models. All analyses were conducted using R for Statistical Software (v.4.2.0). Before and after the implementation of routine third trimester scan or POCUS, there were 16,777 and 7,351 births in SGH and 5,119 and 4,575 in NNUH, respectively. The rate of breech presentation in labour was consistent across all groups (3% to 4%). In the SGH cohort, the percentage of all term breech presentations that were undiagnosed was 14.2% (82/578) before (years 2016 to 2020) and 2.8% (7/251) after (year 2020 to 2021) the implementation of universal screening (p < 0.001). Similarly, in the NNUH cohort, the percentage of all term breech presentations that were undiagnosed was 16.2% (27/167) before (year 2015) and 3.5% (5/142) after (year 2020 to 2021) the implementation of universal POCUS screening (p < 0.001). Bayesian regression analysis with informative priors showed that the rate of undiagnosed breech was 71% lower after the implementation of universal ultrasound (RR, 0.29; 95% CrI 0.20, 0.38) with a posterior probability greater than 99.9%. Among the pregnancies with breech presentation, there was also a very high probability (>99.9%) of reduced rate of low Apgar score (<7) at 5 minutes by 77% (RR, 0.23; 95% CrI 0.14, 0.38). There was moderate to high probability (posterior probability: 89.5% and 85.1%, respectively) of a reduction of HIE (RR, 0.32; 95% CrI 0.0.05, 1.77) and extended perinatal mortality rates (RR, 0.21; 95% CrI 0.01, 3.00). Using informative priors, the proportion of all term breech presentations that were undiagnosed was 69% lower after the initiation of universal POCUS (RR, 0.31; 95% CrI 0.21, 0.45) with a posterior probability greater of 99.9%. There was also a very high probability (99.5%) of a reduced rate of low Apgar score (<7) at 5 minutes by 40% (RR, 0.60; 95% CrI 0.39, 0.88). We do not have reliable data on number of facility-based ultrasound scans via the standard antenatal referral pathway or external cephalic versions (ECVs) performed during the study period.<br /><b>Conclusions</b><br />In our study, we observed that both a policy of routine facility-based third trimester ultrasound or POCUS are associated with a reduction in the proportion of term breech presentations that were undiagnosed, with an improvement in neonatal outcomes. The findings from our study support the policy of third trimester ultrasound scan for fetal presentation. Future studies should focus on exploring the cost-effectiveness of POCUS for fetal presentation.<br /><br />Copyright: © 2023 Knights et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004192</small></div>

<div><h4>Evaluation of the sugar-sweetened beverage tax in Oakland, United States, 2015-2019: A quasi-experimental and cost-effectiveness study.</h4><i>White JS, Basu S, Kaplan S, Madsen KA, Villas-Boas SB, Schillinger D</i><br /><b>Background</b><br />While a 2021 federal commission recommended that the United States government levy a sugar-sweetened beverage (SSB) tax to improve diabetes prevention and control efforts, evidence is limited regarding the longer-term impacts of SSB taxes on SSB purchases, health outcomes, costs, and cost-effectiveness. This study estimates the impact and cost-effectiveness of an SSB tax levied in Oakland, California.<br /><b>Methods and findings</b><br />An SSB tax ($0.01/oz) was implemented on July 1, 2017, in Oakland. The main sample of sales data included 11,627 beverage products, 316 stores, and 172,985,767 product-store-month observations. The main analysis, a longitudinal quasi-experimental difference-in-differences approach, compared changes in beverage purchases at stores in Oakland versus Richmond, California (a nontaxed comparator in the same market area) before and 30 months after tax implementation (through December 31, 2019). Additional estimates used synthetic control methods with comparator stores in Los Angeles, California. Estimates were inputted into a closed-cohort microsimulation model to estimate quality-adjusted life years (QALYs) and societal costs (in Oakland) from 6 SSB-associated disease outcomes. In the main analysis, SSB purchases declined by 26.8% (95% CI -39.0 to -14.7, p < 0.001) in Oakland after tax implementation, compared with Richmond. There were no detectable changes in purchases of untaxed beverages or sweet snacks or purchases in border areas surrounding cities. In the synthetic control analysis, declines in SSB purchases were similar to the main analysis (-22.4%, 95% CI -41.7% to -3.0%, p = 0.04). The estimated changes in SSB purchases, when translated into declines in consumption, would be expected to accrue QALYs (94 per 10,000 residents) and significant societal cost savings (>$100,000 per 10,000 residents) over 10 years, with greater gains over a lifetime horizon. Study limitations include a lack of SSB consumption data and use of sales data primarily from chain stores.<br /><b>Conclusions</b><br />An SSB tax levied in Oakland was associated with a substantial decline in volume of SSBs purchased, an association that was sustained more than 2 years after tax implementation. Our study suggests that SSB taxes are effective policy instruments for improving health and generating significant cost savings for society.<br /><br />Copyright: © 2023 White et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004212</small></div>

<div><h4>Depressive and anxiety symptoms in adults during the COVID-19 pandemic in England: A panel data analysis over 2 years.</h4><i>Bu F, Steptoe A, Fancourt D</i><br /><b>Background</b><br />There has been much research into the mental health impact of the Coronavirus Disease 2019 (COVID-19) pandemic and how it is related to time-invariant individual characteristics. However, there is still a lack of research showing long-term trajectories of mental health across different stages of the pandemic. And little is known regarding the longitudinal association of time-varying factors with mental health outcomes. This study aimed to provide a longitudinal profile of how mental health in adults changed across different stages of the COVID-19 pandemic and to examine their longitudinal associations with time-varying contextual (e.g., COVID-19 policy response and pandemic intensity) and individual level factors.<br /><b>Methods and findings</b><br />This study used data from a large panel study of over 57,000 adults living in England, who were followed up regularly for 2 years between March 2020 and April 2022. Mental health outcomes were depressive and anxiety symptoms. Depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9) and anxiety symptoms by the Generalized Anxiety Disorder assessment (GAD-7). Entropy balancing weights were applied to restore sample representativeness. After weighting, approximately 50% of participants were female, 14% from ethnic minority backgrounds, with a mean age of 48 years. Descriptive analyses showed that mental health changes were largely in line with changes in COVID-19 policy response and pandemic intensity. Further, data were analysed using fixed-effects (FE) models, which controlled for all time-invariant confounders (observed or not). FE models were fitted separately across 3 stages of the COVID-19 pandemic, including the first national lockdown (21/03/2020-23/08/2020), second and third national lockdowns (21/09/2020-11/04/2021), and \"freedom\" period (12/04/2021-14/11/2021). We found that more stringent policy response (measured by stringency index) was associated with increased depressive symptoms, in particular, during lockdown periods (β = 0.23, 95% confidence interval (CI) = [0.18 to 0.28], p < 0.001; β = 0.30, 95% CI = [0.21 to 0.39], p < 0.001; β = 0.04, 95% CI = [-0.03 to 0.12], p = 0.262). Higher COVID-19 deaths were also associated with increased depressive symptoms, but this association weakened over time (β = 0.29, 95% CI = [0.25 to 0.32], p < 0.001; β = 0.09, 95% CI = [0.05 to 0.13], p < 0.001; β = -0.06, 95% CI = [-0.30 to 0.19], p = 0.655). Similar results were also found for anxiety symptoms, for example, stringency index (β = 0.17, 95% CI = [0.12 to 0.21], p < 0.001; β = 0.13, 95% CI = [0.06 to 0.21], p = 0.001; β = 0.10, 95% CI = [0.03 to 0.17], p = 0.005), COVID-19 deaths (β = 0.07, 95% CI = [0.04 to 0.10], p < 0.001; β = 0.04, 95% CI = [0.00 to 0.07], p = 0.03; β = 0.16, 95% CI = [-0.08 to 0.39], p = 0.192). Finally, there was also evidence for the longitudinal association of mental health with individual level factors, including confidence in government/healthcare/essentials, COVID-19 knowledge, COVID-19 stress, COVID-19 infection, and social support. However, it is worth noting that the magnitudes of these longitudinal associations were generally small. The main limitation of the study was its non-probability sample design.<br /><b>Conclusions</b><br />Our results provided empirical evidence on how changes in contextual and individual level factors were related to changes in depressive and anxiety symptoms. While some factors (e.g., confidence in healthcare, social support) clearly acted as consistent predictors of depressive and/or anxiety symptoms, other factors (e.g., stringency index, COVID-19 knowledge) were dependent on the specific situations occurring within society. This could provide important implications for policy making and for a better understanding of mental health of the general public during a national or global health crisis.<br /><br />Copyright: © 2023 Bu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004144</small></div>

<div><h4>Mental health and addiction health service use by physicians compared to non-physicians before and during the COVID-19 pandemic: A population-based cohort study in Ontario, Canada.</h4><i>Myran DT, Roberts R, McArthur E, Jeyakumar N, ... Sood MM, Tanuseputro P</i><br /><b>Background</b><br />The Coronavirus Disease 2019 (COVID-19) pandemic has exacerbated mental health challenges among physicians and non-physicians. However, it is unclear if the worsening mental health among physicians is due to specific occupational stressors, reflective of general societal stressors during the pandemic, or a combination. We evaluated the difference in mental health and addictions health service use between physicians and non-physicians, before and during the COVID-19 pandemic.<br /><b>Methods and findings</b><br />We conducted a population-based cohort study in Ontario, Canada between March 11, 2017 and August 11, 2021 using data collected from Ontario\'s universal health system. Physicians were identified using registrations with the College of Physicians and Surgeons of Ontario between 1990 and 2020. Participants included 41,814 physicians and 12,054,070 non-physicians. We compared the first 18 months of the COVID-19 pandemic (March 11, 2020 to August 11, 2021) to the period before COVID-19 pandemic (March 11, 2017 to February 11, 2020). The primary outcome was mental health and addiction outpatient visits overall and subdivided into virtual versus in-person, psychiatrists versus family medicine and general practice clinicians. We used generalized estimating equations for the analyses. Pre-pandemic, after adjustment for age and sex, physicians had higher rates of psychiatry visits (aIRR 3.91 95% CI 3.55 to 4.30) and lower rates of family medicine visits (aIRR 0.62 95% CI 0.58 to 0.66) compared to non-physicians. During the first 18 months of the COVID-19 pandemic, the rate of outpatient mental health and addiction (MHA) visits increased by 23.2% in physicians (888.4 pre versus 1,094.7 during per 1,000 person-years, aIRR 1.39 95% CI 1.28 to 1.51) and 9.8% in non-physicians (615.5 pre versus 675.9 during per 1,000 person-years, aIRR 1.12 95% CI 1.09 to 1.14). Outpatient MHA and virtual care visits increased more among physicians than non-physicians during the first 18 months of the pandemic. Limitations include residual confounding between physician and non-physicians and challenges differentiating whether observed increases in MHA visits during the pandemic are due to stressors or changes in health care access.<br /><b>Conclusions</b><br />The first 18 months of the COVID-19 pandemic was associated with a larger increase in outpatient MHA visits in physicians than non-physicians. These findings suggest physicians may have had larger negative mental health during COVID-19 than the general population and highlight the need for increased access to mental health services and system level changes to promote physician wellness.<br /><br />Copyright: © 2023 Myran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 01 Apr 2023; 20:e1004187</small></div>

<div><h4>Recording of intellectual disability in general hospitals in England 2006-2019: Cohort study using linked datasets.</h4><i>Sheehan R, Mansour H, Broadbent M, Hassiotis A, ... Strydom A, Sommerlad A</i><br /><b>Background</b><br />Accurate recognition and recording of intellectual disability in those who are admitted to general hospitals is necessary for making reasonable adjustments, ensuring equitable access, and monitoring quality of care. In this study, we determined the rate of recording of intellectual disability in those with the condition who were admitted to hospital and factors associated with the condition being unrecorded.<br /><b>Methods and findings</b><br />Retrospective cohort study using 2 linked datasets of routinely collected clinical data in England. We identified adults with diagnosed intellectual disability in a large secondary mental healthcare database and used general hospital records to investigate recording of intellectual disability when people were admitted to general hospitals between 2006 and 2019. Trends over time and factors associated with intellectual disability being unrecorded were investigated. We obtained data on 2,477 adults with intellectual disability who were admitted to a general hospital in England at least once during the study period (total number of admissions = 27,314; median number of admissions = 5). People with intellectual disability were accurately recorded as having the condition during 2.9% (95% CI 2.7% to 3.1%) of their admissions. Broadening the criteria to include a nonspecific code of learning difficulty increased recording to 27.7% (95% CI 27.2% to 28.3%) of all admissions. In analyses adjusted for age, sex, ethnicity, and socioeconomic deprivation, having a mild intellectual disability and being married were associated with increased odds of the intellectual disability being unrecorded in hospital records. We had no measure of quality of hospital care received and could not relate this to the presence or absence of a record of intellectual disability in the patient record.<br /><b>Conclusions</b><br />Recognition and recording of intellectual disability in adults admitted to English general hospitals needs to be improved. Staff awareness training, screening at the point of admission, and data sharing between health and social care services could improve care for people with intellectual disability.<br /><br />Copyright: © 2023 Sheehan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 20 Mar 2023; 20:e1004117</small></div>

<div><h4>Incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver solid organ transplant recipients with resolved HBV infection: A systematic review and meta-analysis.</h4><i>Yin S, Zhang F, Wu J, Lin T, Wang X</i><br /><b>Background</b><br />Current guidelines do not recommend routine antiviral prophylaxis to prevent hepatitis B virus (HBV) reactivation in non-liver solid organ transplant (SOT) recipients with resolved HBV infection, even in anti-hepatitis B surface antigen (anti-HBs)-negative recipients and those receiving intense immunosuppression. This systematic review and meta-analysis aimed to determine the incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver SOT recipients.<br /><b>Methods and findings</b><br />Three databases (PubMed, Embase, and Cochrane Library) were systematically searched up to December 31, 2022. Clinical studies reporting HBV reactivation in non-liver SOT recipients were included. Case reports, case series, and cohort studies with a sample size of less than 10 patients were excluded. Random-effects analysis was used for all meta-analyses. We included 2,913 non-liver SOT recipients with resolved HBV infection from 16 retrospective cohort studies in the analysis. The overall HBV reactivation rate was 2.5% (76/2,913; 95% confidence interval [95% CI 1.6%, 3.6%]; I2 = 55.0%). Higher rates of reactivation were observed in recipients with negative anti-HBs (34/421; 7.8%; 95% CI [5.2%, 10.9%]; I2 = 36.0%) by pooling 6 studies, experiencing acute rejection (13/266; 5.8%; 95% CI [2.3%, 14.5%]; I2 = 63.2%) by pooling 3 studies, receiving ABO blood type-incompatible transplantation (8/111; 7.0%; 95% CI [2.9%, 12.7%]; I2 = 0%) by pooling 3 studies, receiving rituximab (10/133; 7.3%; 95% CI [3.4%, 12.6%]; I2 = 0%) by pooling 3 studies, and receiving anti-thymocyte immunoglobulin (ATG, 25/504; 4.9%; 95% CI [2.5%, 8.1%]; I2 = 49.0%) by pooling 4 studies. Among recipients with post-transplant HBV reactivation, 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) developed HBV-related hepatic failure, and 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) had HBV-related death. Negative anti-HBs (crude odds ratio [OR] 5.05; 95% CI [2.83, 9.00]; p < 0.001; I2 = 0%), ABO blood type-incompatible transplantation (crude OR 2.62; 95% CI [1.05, 6.04]; p = 0.040; I2 = 0%), history of acute rejection (crude OR 2.37; 95% CI [1.13, 4.97]; p = 0.022; I2 = 0%), ATG use (crude OR 3.19; 95% CI [1.48, 6.87]; p = 0.003; I2 = 0%), and rituximab use (crude OR 3.16; 95% CI [1.24, 8.06]; p = 0.016; I2 = 0%) increased the risk of reactivation. Adjusted analyses reported similar results. Limitations include moderate heterogeneity in the meta-analyses and that most studies were conducted in kidney transplant recipients.<br /><b>Conclusions</b><br />Non-liver SOT recipients with resolved HBV infection have a high risk of HBV-related hepatic failure and HBV-related death if HBV reactivation occurs. Potential risk factors for HBV reactivation include rituximab use, anti-thymocyte immunoglobulin use, anti-HBs negative status, acute rejection history, and ABO blood type-incompatible transplantation. Further research on monitoring and routine antiviral prophylaxis of non-liver SOT recipients at higher risk of HBV reactivation is required.<br /><br />Copyright: © 2023 Yin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 15 Mar 2023; 20:e1004196</small></div>

<div><h4>Association of severe mental illness and septic shock case fatality rate in patients admitted to the intensive care unit: A national population-based cohort study.</h4><i>Lakbar I, Leone M, Pauly V, Orleans V, ... Boyer L, Fond G</i><br /><b>Background</b><br />Patients with severe mental illness (SMI) (i.e., schizophrenia, bipolar disorder, or major depressive disorder) have been reported to have excess mortality rates from infection compared to patients without SMI, but whether SMI is associated with higher or lower case fatality rates (CFRs) among infected patients remains unclear. The primary objective was to compare the 90-day CFR in septic shock patients with and without SMI admitted to the intensive care unit (ICU), after adjusting for social disadvantage and physical health comorbidity.<br /><b>Methods and findings</b><br />We conducted a nationwide, population-based cohort study of all adult patients with septic shock admitted to the ICU in France between January 1, 2014, and December 31, 2018, using the French national hospital database. We matched (within hospitals) in a ratio of 1:up to 4 patients with and without SMI (matched-controls) for age (5 years range), sex, degree of social deprivation, and year of hospitalization. Cox regression models were conducted with adjustment for smoking, alcohol and other substance addiction, overweight or obesity, Charlson comorbidity index, presence of trauma, surgical intervention, Simplified Acute Physiology Score II score, organ failures, source of hospital admission (home, transfer from other hospital ward), and the length of time between hospital admission and ICU admission. The primary outcome was 90-day CFR. Secondary outcomes were 30- and 365-day CFRs, and clinical profiles of patients. A total of 187,587 adult patients with septic shock admitted to the ICU were identified, including 3,812 with schizophrenia, 2,258 with bipolar disorder, and 5,246 with major depressive disorder. Compared to matched controls, the 90-day CFR was significantly lower in patients with schizophrenia (1,052/3,269 = 32.2% versus 5,000/10,894 = 45.5%; adjusted hazard ratio (aHR) = 0.70, 95% confidence interval (CI) 0.65,0.75, p < 0.001), bipolar disorder (632/1,923 = 32.9% versus 2,854/6,303 = 45.3%; aHR = 0.70, 95% CI = 0.63,0.76, p < 0.001), and major depressive disorder (1,834/4,432 = 41.4% versus 6,798/14,452 = 47.1%; aHR = 0.85, 95% CI = 0.81,0.90, p < 0.001). Study limitations include inability to capture deaths occurring outside hospital, lack of data on processes of care, and problems associated with missing data and miscoding in medico-administrative databases.<br /><b>Conclusions</b><br />Our findings suggest that, after adjusting for social disadvantage and physical health comorbidity, there are improved septic shock outcome in patients with SMI compared to patients without. This finding may be the result of different immunological profiles and exposures to psychotropic medications, which should be further explored.<br /><br />Copyright: © 2023 Lakbar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 13 Mar 2023; 20:e1004202</small></div>

<div><h4>Strengthening implementation guidelines for HIV service delivery: Considerations for future evidence generation and synthesis.</h4><i>Eshun-Wilson I, Ford N, Mody A, Beres L, ... Baral S, Geng EH</i><br /><AbstractText>Ingrid Eshun-Wilson and colleagues summarize gaps in primary HIV implementation research methods and reporting, and propose areas for future methodological development.</AbstractText><br /><br />Copyright: © 2023 Eshun-Wilson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 06 Mar 2023; 20:e1004168</small></div>

<div><h4>A multicomponent digital intervention to promote help-seeking for mental health problems and suicide in sexual and gender diverse young adults: A randomized controlled trial.</h4><i>Han M, Wang Y, Zhang Y, Wang Y, ... Han J, Chen R</i><br /><b>Background</b><br />LGBTQ+ community\'s higher susceptibility to worse mental health outcomes and more help-seeking barriers compared to the cis-heterosexual population. Despite the LGBTQ+ population facing higher mental health risks, there has been a dearth of research focusing on developing tailored interventions targeting them. This study aimed to assess the effectiveness of a digital multicomponent intervention in promoting help-seeking for mental health issues in LGBTQ+ young adults.<br /><b>Methods and findings</b><br />We recruited LGBTQ+ young adults aged between 18 and 29 who scored moderate or above on at least 1 dimension of the Depression Anxiety Stress Scale 21 and did not have help-seeking experiences in the past 12 months. Participants (n = 144) were stratified by gender assigned at birth (male/female) and randomly allocated (1:1 ratio) to the intervention or active control parallel condition by generating a random number table, so they were blinded to the intervention condition. All participants received online psychoeducational videos, online facilitator-led group discussions, and electronic brochures in December 2021 and January 2022, with the final follow-up in April 2022. The contents of the video, discussion, and brochure are help-seeking for the intervention group and general mental health knowledge for the control group. The primary outcomes were help-seeking intentions for emotional problems and suicidal ideation and attitudes toward seeking help from mental health professionals at the 1-month follow-up. The analysis was performed by including all participants based on their randomized group regardless of adherence to the protocol. A linear mixed model (LMM) was used for analysis. All models were adjusted for baseline scores. Chinese Clinical Trial Registry: ChiCTR2100053248. A total of 137 (95.1%) participants completed a 3-month follow-up, and 4 participants from the intervention condition and 3 from the control condition did not complete the final survey. Compared with the control group (n = 72), a significant improvement was found in help-seeking intentions for suicidal ideation in the intervention group (n = 70) at post-discussion (mean difference = 0.22, 95% CI [0.09, 0.36], p = 0.005), 1-month (mean difference = 0.19, 95% CI [0.06, 0.33], p = 0.018), and 3-month follow-ups (mean difference = 0.25, 95% CI [0.11, 0.38], p = 0.001). There was also a significant improvement in the intervention condition on the help-seeking intention for emotional problems at 1-month (mean difference = 0.17, 95% CI [0.05, 0.28], p = 0.013) and 3-month follow-ups (mean difference = 0.16, 95% CI [0.04, 0.27], p = 0.022) compared with the control group. Participants\' depression and anxiety literacy and help-seeking encouragement related knowledge in intervention conditions showed significant improvements. There were no significant improvements in actual help-seeking behaviors, self-stigma toward seeking professional assistance, depression, and anxiety symptoms. No adverse events or side effects were observed. However, the follow-up time point was limited to 3 months which might not be long enough for drastic mindset and behavioral changes in help-seeking to occur.<br /><b>Conclusions</b><br />The current intervention was an effective approach in promoting help-seeking intentions, mental health literacy, and help-seeking encouragement-related knowledge. Its brief yet integrated intervention format could also be utilized in treating other imminent concerns confronted by LGBTQ+ young adults.<br /><b>Trial registration</b><br />Chictr.org.cn, ChiCTR2100053248.<br /><br />Copyright: © 2023 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br /><br /><small>PLoS Med: 06 Mar 2023; 20:e1004197</small></div>