PLoS Medicine最新文献

{"title":"Cost-effectiveness of leveraging existing HIV primary health systems and community health workers for hypertension screening and treatment in Africa: An individual-based modeling study.","authors":"Matthew D Hickey, James Ayieko, Jane Kabami, Asiphas Owaraganise, Elijah Kakande, Sabina Ogachi, Colette I Aoko, Erick M Wafula, Norton Sang, Helen Sunday, Paul Revill, Loveleen Bansi-Matharu, Starley B Shade, Gabriel Chamie, Laura B Balzer, Maya L Petersen, Diane V Havlir, Moses R Kamya, Andrew N Phillips","doi":"10.1371/journal.pmed.1004531","DOIUrl":"10.1371/journal.pmed.1004531","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) morbidity and mortality is increasing in Africa, largely due to undiagnosed and untreated hypertension. Approaches that leverage existing primary health systems could improve hypertension treatment and reduce CVD, but cost-effectiveness is unknown. We evaluated the cost-effectiveness of population-level hypertension screening and implementation of chronic care clinics across eastern, southern, central, and western Africa.</p><p><strong>Methods and findings: </strong>We conducted a modeling study to simulate hypertension and CVD across 3,000 scenarios representing a range of settings across eastern, southern, central, and western Africa. We evaluated 2 policies compared to current hypertension treatment: (1) expansion of HIV primary care clinics into chronic care clinics that provide hypertension treatment for all persons regardless of HIV status (chronic care clinic or CCC policy); and (2) CCC plus population-level hypertension screening of adults ≥40 years of age by community health workers (CHW policy). For our primary analysis, we used a cost-effectiveness threshold of US $500 per disability-adjusted life-year (DALY) averted, a 3% annual discount rate, and a 50-year time horizon. A strategy was considered cost-effective if it led to the lowest net DALYs, which is a measure of DALY burden that takes account of the DALY implications of the cost for a given cost-effectiveness threshold. Among adults 45 to 64 years, CCC implementation would improve population-level hypertension control (the proportion of people with hypertension whose blood pressure is controlled) from mean 4% (90% range 1% to 7%) to 14% (6% to 26%); additional CHW screening would improve control to 44% (35% to 54%). Among all adults, CCC implementation would reduce ischemic heart disease (IHD) incidence by 10% (3% to 17%), strokes by 13% (5% to 23%), and CVD mortality by 9% (3% to 15%). CCC plus CHW screening would reduce IHD by 28% (19% to 36%), strokes by 36% (25% to 47%), and CVD mortality by 25% (17% to 34%). CHW screening was cost-effective in 62% of scenarios, CCC in 31%, and neither policy was cost-effective in 7% of scenarios. Pooling across setting-scenarios, incremental cost-effectiveness ratios were $69/DALY averted for CCC and $389/DALY averted adding CHW screening to CCC.</p><p><strong>Conclusions: </strong>Leveraging existing healthcare infrastructure to implement population-level hypertension screening by CHWs and hypertension treatment through integrated chronic care clinics is expected to reduce CVD morbidity and mortality and is likely to be cost-effective in most settings across Africa.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004531"},"PeriodicalIF":15.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative cardiometabolic safety and effectiveness of aripiprazole in people with severe mental illness: A target trial emulation.","authors":"Alvin Richards-Belle, Naomi Launders, Sarah Hardoon, Al Richards, Kenneth K C Man, Neil M Davies, Elvira Bramon, Joseph F Hayes, David P J Osborn","doi":"10.1371/journal.pmed.1004520","DOIUrl":"10.1371/journal.pmed.1004520","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;There is limited and conflicting evidence on the comparative cardiometabolic safety and effectiveness of aripiprazole in the management of severe mental illness. We investigated the hypothesis that aripiprazole has a favourable cardiometabolic profile, but similar effectiveness when compared to olanzapine, quetiapine, and risperidone.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We conducted an observational emulation of a head-to-head trial of aripiprazole versus olanzapine, quetiapine, and risperidone in UK primary care using data from the Clinical Practice Research Datalink. We included adults diagnosed with severe mental illness (i.e., bipolar disorder, schizophrenia, and other non-organic psychoses) who were prescribed a new antipsychotic between 2005 and 2017, with a 2-year follow-up to 2019. The primary outcome was total cholesterol at 1 year (cardiometabolic safety). The main secondary outcome was psychiatric hospitalisation (effectiveness). Other outcomes included body weight, blood pressure, all-cause discontinuation, and mortality. Analyses adjusted for baseline confounders, including sociodemographics, diagnoses, concomitant medications, and cardiometabolic parameters. We included 26,537 patients (aripiprazole, n = 3,573, olanzapine, n = 8,554, quetiapine, n = 8,289, risperidone, n = 6,121). Median (IQR) age was 53 (42-67) years, 55.4% were female, 82.3% White, and 18.0% were diagnosed with schizophrenia. Patients prescribed aripiprazole had similar total cholesterol levels after 1 year to those prescribed olanzapine (adjusted mean difference [aMD], -0.03, 95% CI, -0.09 to 0.02, p = 0.261), quetiapine (aMD, -0.03, 95% CI, -0.09 to 0.03, p = 0.324), and risperidone (aMD, -0.01, 95% CI, -0.08 to 0.05, p = 0.707). However, there was evidence that patients prescribed aripiprazole had better outcomes on other cardiometabolic parameters, such as body weight and blood pressure, especially compared to olanzapine. After additional adjustment for prior hospitalisation, patients prescribed aripiprazole had similar rates of psychiatric hospitalisation as those prescribed olanzapine (adjusted hazard ratio [aHR], 0.91, 95% CI, 0.82 to 1.01, p = 0.078), quetiapine (aHR, 0.94, 95% CI, 0.85 to 1.04, p = 0.230), or risperidone (aHR, 1.01, 95% CI, 0.91 to 1.12, p = 0.854).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Data from our large, powered, diverse, real-world target trial emulation sample, followed over 2 years, suggest that adults diagnosed with severe mental illness prescribed aripiprazole have similar total cholesterol 1 year after first prescription compared to those prescribed olanzapine, quetiapine, and risperidone. However, patients prescribed aripiprazole had better outcomes on some other cardiometabolic parameters, and there was little evidence of differences in effectiveness. Our findings inform a common clinical dilemma and contribute to the evidence base for real-world clinical decision-making on antipsychotic c","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004520"},"PeriodicalIF":15.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Child mortality in England after national lockdowns for COVID-19: An analysis of childhood deaths, 2019-2023.","authors":"David Odd, Sylvia Stoianova, Tom Williams, Peter Fleming, Karen Luyt","doi":"10.1371/journal.pmed.1004417","DOIUrl":"10.1371/journal.pmed.1004417","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;During the COVID-19 pandemic children and young people (CYP) mortality in England reduced to the lowest on record, but it is unclear if the mechanisms which facilitated a reduction in mortality had a longer lasting impact, and what impact the pandemic, and its social restrictions, have had on deaths with longer latencies (e.g., malignancies). The aim of this analysis was to quantify the relative rate, and causes, of childhood deaths in England, before, during, and after national lockdowns for COVID-19 and its social changes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;Deaths of all children (occurring before their 18th birthday) occurring from April 2019 until March 2023 in England were identified. Data were collated by the National Child Mortality Database. Study population size and the underlying population profile was derived from 2021 Office of National Statistics census data Mortality for each analysis year was calculated per 1,000,000 person years. Poisson regression was used to test for an overall trend across the time period and tested if trends differed between April 2019 to March 2021 (Period 1)) and April 2021 to March 2023 (Period 2: after lockdown restrictions). This was then repeated for each category of death and demographic group. Twelve thousand eight hundred twenty-eight deaths were included in the analysis. Around 59.4% of deaths occurred under 1 year of age, 57.0% were male, and 63.9% were of white ethnicity. Mortality rate (per 1,000,000 CYP per year) dropped from 274.2 (95% CI 264.8-283.8) in 2019-2020, to 242.2 (95% CI 233.4-251.2) in 2020-2021, increasing to 296.1 (95% CI 286.3-306.1) in 2022-2023. Overall, death rate reduced across Period 1 (Incidence rate ratio (IRR) 0.96 (95% CI 0.92-0.99)) and then increased across Period 2 (IRR 1.12 (95% CI 1.08-1.16)), and this pattern was also seen for death by Infection and Underlying Disease. In contrast, rate of death after Intrapartum events increased across the first period, followed by a decrease in rate in the second (Period 1 IRR 1.15 (95% CI 1.00-1.34)) versus Period 2 (IRR 0.78 (95% CI 0.68-0.91), pdifference = 0.004). Rates of death from preterm birth, trauma and sudden unexpected deaths in infancy and childhood (SUDIC), increased across the entire 4-year-study period (preterm birth, IRR 1.03 (95% CI 1.00-1.07); trauma IRR 1.12 (95% CI 1.06-1.20); SUDIC IRR 1.09 (95% CI 1.04-1.13)), and there was no change in the rate of death from Malignancy (IRR 1.01 (95% CI 0.95-1.06)). Repeating the analysis, split by child characteristics, suggested that mortality initially dropped and subsequently rose for children between 1 and 4 years old (Period 1 RR 0.85 (95% CI 0.76-0.94) versus Period 2 IRR 1.31 (95% CI 1.19-1.43), pdifference &lt; 0.001. For Asian, black and Other ethnic groups, we observed increased rates of deaths in the period 2021-2023, and a significant change in trajectory of death rates between Periods 1 and 2 (Asian (Period 1 IRR 0.93 (95","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004417"},"PeriodicalIF":15.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study.","authors":"Raphael S Peter, Alexandra Nieters, Siri Göpel, Uta Merle, Jürgen M Steinacker, Peter Deibert, Birgit Friedmann-Bette, Andreas Nieß, Barbara Müller, Claudia Schilling, Gunnar Erz, Roland Giesen, Veronika Götz, Karsten Keller, Philipp Maier, Lynn Matits, Sylvia Parthé, Martin Rehm, Jana Schellenberg, Ulrike Schempf, Mengyu Zhu, Hans-Georg Kräusslich, Dietrich Rothenbacher, Winfried V Kern","doi":"10.1371/journal.pmed.1004511","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004511","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance and sleep problems. The long-term prognosis of such post-acute sequelae of COVID-19/post-COVID-19 syndrome (PCS) is unknown, and data finding and correlating organ dysfunction and pathology with self-reported symptoms in patients with non-recovery from PCS is scarce. We wanted to describe clinical characteristics and diagnostic findings among patients with PCS persisting for &gt;1 year and assessed risk factors for PCS persistence versus improvement.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;This nested population-based case-control study included subjects with PCS aged 18-65 years with (n = 982) and age- and sex-matched control subjects without PCS (n = 576) according to an earlier population-based questionnaire study (6-12 months after acute infection, phase 1) consenting to provide follow-up information and to undergo comprehensive outpatient assessment, including neurocognitive, cardiopulmonary exercise, and laboratory testing in four university health centres in southwestern Germany (phase 2, another 8.5 months [median, range 3-14 months] after phase 1). The mean age of the participants was 48 years, and 65% were female. At phase 2, 67.6% of the patients with PCS at phase 1 developed persistent PCS, whereas 78.5% of the recovered participants remained free of health problems related to PCS. Improvement among patients with earlier PCS was associated with mild acute index infection, previous full-time employment, educational status, and no specialist consultation and not attending a rehabilitation programme. The development of new symptoms related to PCS among participants initially recovered was associated with an intercurrent secondary SARS-CoV-2 infection and educational status. Patients with persistent PCS were less frequently never smokers (61.2% versus 75.7%), more often obese (30.2% versus 12.4%) with higher mean values for body mass index (BMI) and body fat, and had lower educational status (university entrance qualification 38.7% versus 61.5%) than participants with continued recovery. Fatigue/exhaustion, neurocognitive disturbance, chest symptoms/breathlessness and anxiety/depression/sleep problems remained the predominant symptom clusters. Exercise intolerance with post-exertional malaise (PEM) for &gt;14 h and symptoms compatible with myalgic encephalomyelitis/chronic fatigue syndrome were reported by 35.6% and 11.6% of participants with persistent PCS patients, respectively. In analyses adjusted for sex-age class combinations, study centre and university entrance qualification, significant differences between participants with persistent PCS versus those with continued recovery were observed for performance in three different neurocognitive tests, scores for","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004511"},"PeriodicalIF":15.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic properties of differing BP thresholds for adverse pregnancy outcomes in standard-risk nulliparous women: A secondary analysis of SCOPE cohort data.","authors":"Laura Slade, Maya Blackman, Hiten D Mistry, Jeffrey N Bone, Milly Wilson, Nuhaat Syeda, Lucilla Poston, Peter von Dadelszen, Laura A Magee","doi":"10.1371/journal.pmed.1004471","DOIUrl":"10.1371/journal.pmed.1004471","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In 2017, the American College of Cardiology and American Heart Association (ACC/AHA) lowered blood pressure (BP) thresholds to define hypertension in adults outside pregnancy. If used in pregnancy, these lower thresholds may identify women at increased risk of adverse outcomes, which would be particularly useful to risk-stratify nulliparous women. In this secondary analysis of the SCOPE cohort, we asked whether, among standard-risk nulliparous women, the ACC/AHA BP categories could identify women at increased risk for adverse outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;Included were pregnancies in the international SCOPE cohort with birth at ≥20 weeks' gestation, 2004 to 2008. Women were mostly of white ethnicity, in their 20s, and of normal-to-overweight body mass index (BMI). Excluded were pregnancies ending in fetal loss at &lt;20 weeks' gestation, and those terminated at any point in pregnancy. Women were categorized by highest BP during pregnancy, using ACC/AHA criteria: normal (BP &lt;120/80 mmHg), \"Elevated BP\" (BP 120 to 129 mmHg/&lt;80 mmHg), \"Stage-1 hypertension\" (systolic BP [sBP] 130 to 139 mmHg or diastolic BP [dBP] 80 to 89 mmHg), and \"Stage-2 hypertension\" that was non-severe (sBP 140 to 159 mmHg or dBP 90 to 109 mmHg) or severe (sBP ≥160 mmHg or dBP ≥110 mmHg). Primary outcomes were preterm birth (PTB), low birthweight, postpartum hemorrhage, and neonatal care admission. Adjusted relative risks (aRRs) and diagnostic test properties were calculated for each outcome, according to: each BP category (versus \"normal\"), and using the lower limit of each BP category as a cut-off. RRs were adjusted for maternal age, BMI, smoking, ethnicity, and alcohol use. Of 5,628 women in SCOPE, 5,597 were included in this analysis. When compared with normotension, severe \"Stage 2 hypertension\" was associated with PTB (24.0% versus 5.3%; aRR 4.88, 95% confidence interval, CI [3.46 to 6.88]), birthweight &lt;10th centile (24.4% versus 8.8%; aRR 2.70 [2.00 to 3.65]), and neonatal unit admission (32.9% versus 8.9%; aRR 3.40 [2.59 to 4.46]). When compared with normotension, non-severe \"Stage 2 hypertension\" was associated with birthweight &lt;10th centile (16.1% versus 8.8%; aRR 1.82 [1.45 to 2.29]) and neonatal unit admission (15.4% versus 8.9%; aRR 1.65 [1.31 to 2.07]), but no association with adverse outcomes was seen with BP categories below \"Stage 2 hypertension.\" When each BP category was assessed as a threshold for diagnosis of abnormal BP (compared with BP values below), only severe \"Stage 2 hypertension\" had a useful (good) likelihood ratio (LR) of 5.09 (95% CI [3.84 to 6.75]) for PTB. No BP threshold could rule-out adverse outcomes (i.e., had a negative LR &lt;0.2). Limitations of our analysis include lack of ethnic diversity and use of values from clinical notes for BP within 2 weeks before birth. This study was limited by: its retrospective nature, not all women having BP recorded at all visits, and the lack of detail ","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004471"},"PeriodicalIF":15.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical health in young males and risk of chronic musculoskeletal, cardiovascular, and respiratory diseases by middle age: A population-based cohort study.","authors":"Aleksandra Turkiewicz, Karin Magnusson, Simon Timpka, Ali Kiadaliri, Andrea Dell'Isola, Martin Englund","doi":"10.1371/journal.pmed.1004517","DOIUrl":"10.1371/journal.pmed.1004517","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cardiovascular, respiratory, and musculoskeletal disease are among the leading causes of disability in middle-aged and older people. Health and lifestyle factors in youth have known associations with cardiovascular or respiratory disease in adulthood, but largely unknown associations with musculoskeletal disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We included approximately 40,000 18-year-old Swedish males, who completed their conscription examination in 1969 to 1970, followed up until age of 60 years. Exposures of interest were physical health: body mass and height, blood pressure, pulse at rest, muscle strength, cardiorespiratory fitness, and hematocrit; self-reported lifestyle: smoking, alcohol, and drug use; self-reported health: overall, headache and gastrointestinal. We followed the participants through the Swedish National Patient Register for incidence of common musculoskeletal (osteoarthritis, back pain, shoulder lesions, joint pain, myalgia), cardiovascular (ischemic heart disease, atrial fibrillation), and respiratory diseases (asthma, chronic obstructive pulmonary disease, bronchitis). We analyzed the associations using general estimating equations Poisson regression with all exposures included in one model and adjusted for parental education and occupation. We found that higher body mass was associated with higher risk of musculoskeletal (risk ratio [RR] per 1 standard deviation [SD] 1.12 [95% confidence interval, CI 1.09, 1.16]), cardiovascular (RR 1.22 [95% CI 1.17, 1.27] per 1 SD) and respiratory diseases (RR 1.14 [95% CI 1.05, 1.23] per 1 SD). Notably, higher muscle strength and cardiorespiratory fitness were associated with higher risk of musculoskeletal disease (RRs 1.08 [95% CI 1.05, 1.11] and 1.06 [95% CI 1.01, 1.12] per 1 SD difference in exposure), while higher cardiorespiratory fitness was protective against both cardiovascular and respiratory diseases (RRs 0.91 [95% CI 0.85, 0.98] and 0.85 [95% CI 0.73, 0.97] per 1 SD exposure, respectively). We confirmed the adverse effects of smoking, with risk ratios when comparing 11+ cigarettes per day to non-smoking of 1.14 (95% CI 1.06, 1.22) for musculoskeletal, 1.58 (95% CI 1.44, 1.74) for cardiovascular, and 1.93 (95% CI 1.60, 2.32) for respiratory diseases. Self-reported headache (category \"often\" compared to \"never\") was associated with musculoskeletal diseases (RR 1.38 [95% CI 1.21, 1.58]) and cardiovascular diseases (RR 1.29 [95% CI 1.07, 1.56]), but had an inconclusive association with respiratory diseases (RR 1.13 [95% CI 0.79, 1.60]). No large consistent associations were found for other exposures. The most notable associations with specific musculoskeletal conditions were for cardiorespiratory fitness and osteoarthritis (RR 1.23 [95% CI 1.15, 1.32] per 1 SD) and for muscle strength and back pain (RR 1.18 [95% CI 1.12, 1.24] per 1 SD) or shoulder diseases (RR 1.27 [95% CI 1.19, 1.36] per 1 SD). The main limitations include lack of ","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004517"},"PeriodicalIF":15.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating the impact of school closures on the COVID-19 dynamics in 74 countries: A modelling analysis.","authors":"Romain Ragonnet, Angus E Hughes, David S Shipman, Michael T Meehan, Alec S Henderson, Guillaume Briffoteaux, Nouredine Melab, Daniel Tuyttens, Emma S McBryde, James M Trauer","doi":"10.1371/journal.pmed.1004512","DOIUrl":"10.1371/journal.pmed.1004512","url":null,"abstract":"<p><strong>Background: </strong>School closures have been a prominent component of the global Coronavirus Disease 2019 (COVID-19) response. However, their effect on viral transmission, COVID-19 mortality and health care system pressure remains incompletely understood, as traditional observational studies fall short in assessing such population-level impacts.</p><p><strong>Methods and findings: </strong>We used a mathematical model to simulate the COVID-19 epidemics of 74 countries, incorporating observed data from 2020 to 2022 and historical school closure timelines. We then simulated a counterfactual scenario, assuming that schools remained open throughout the study period. We compared the simulated epidemics in terms of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections, deaths, and hospital occupancy pressure. We estimated that school closures achieved moderate to significant burden reductions in most settings over the period 2020 to 2022. They reduced peak hospital occupancy pressure in nearly all countries, with 72 out of 74 countries (97%) showing a positive median estimated effect, and median estimated effect ranging from reducing peak hospital occupancy pressure by 89% in Brazil to increasing it by 19% in Indonesia. The median estimated effect of school closures on COVID-19 deaths ranged from a 73% reduction in Thailand to a 7% increase in the United Kingdom. We estimated that school closures may have increased overall COVID-19 mortality (based on median estimates) in 9 countries (12%), including several European nations and Indonesia. This is attributed to changes in population-level immunity dynamics, leading to a concentration of the epidemic during the Delta variant period, alongside an upward shift in the age distribution of infections. While our estimates were associated with significant uncertainty, our sensitivity analyses exploring the impact of social mixing assumptions revealed robustness in our country-specific conclusions. The main study limitations include the fact that analyses were conducted at the national level, whereas school closure policies often varied by region. Furthermore, some regions, including Africa, were underrepresented due to insufficient data informing the model.</p><p><strong>Conclusions: </strong>Our analysis revealed nuanced effects of school closures on COVID-19 dynamics, with reductions in COVID-19 impacts in most countries but negative epidemiological effects in a few others. We identified critical mechanisms for consideration in future policy decisions, highlighting the unpredictable nature of emerging variants and potential shifts in infection demographics associated with school closures.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004512"},"PeriodicalIF":15.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of app-based cognitive behavioral therapy for insomnia on preventing major depressive disorder in youth with insomnia and subclinical depression: A randomized clinical trial.","authors":"Si-Jing Chen, Jian-Yu Que, Ngan Yin Chan, Le Shi, Shirley Xin Li, Joey Wing Yan Chan, Weizhen Huang, Chris Xie Chen, Chi Ching Tsang, Yuen Lam Ho, Charles M Morin, Ji-Hui Zhang, Lin Lu, Yun Kwok Wing","doi":"10.1371/journal.pmed.1004510","DOIUrl":"10.1371/journal.pmed.1004510","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence suggests that insomnia plays an important role in the development of depression, supporting insomnia intervention as a promising approach to prevent depression in youth. This randomized controlled trial evaluated the effectiveness of app-based cognitive behavioral therapy for insomnia (CBT-I) in preventing future onset of major depressive disorder (MDD) in youth.</p><p><strong>Methods and findings: </strong>This was a randomized, assessor-blind, parallel group-controlled trial in Chinese youth (aged 15-25 years) with insomnia disorder and subclinical depressive symptoms. Participants were randomly assigned (1:1) to 6-week app-based CBT-I or 6-week app-based health education (HE) delivered through smartphones. Online assessments and telephone clinical interviews were conducted at baseline, post-intervention, 6- and 12-month follow-ups. The primary outcome was time to onset of MDD. The secondary outcomes included depressive symptoms and insomnia at both symptom and disorder levels. Between September 9, 2019, and November 25, 2022, 708 participants (407 females [57%]; mean age, 22.1 years [SD = 1.9]) were randomly allocated to app-based CBT-I group (n = 354) or app-based HE group (n = 354). Thirty-seven participants (10%) in the intervention group and 62 participants (18%) in the control group developed new-onset MDD throughout the 12-month follow-up, with a hazard ratio of 0.58 (95% confidence interval 0.38-0.87; p = 0.008). The number needed to treat to prevent MDD at 1 year was 10.9 (6.8-26.6). The app-based CBT-I group has higher remission rates of insomnia disorder than the controls at post-intervention (52% versus 28%; relative risk 1.83 [1.49-2.24]; p < 0.001) and throughout 12-month follow-up. In addition, the CBT-I group reported a greater decrease in depressive (adjusted difference -1.0 [-1.6 to -0.5]; Cohen's d = 0.53; p < 0.001) and insomnia symptoms (-2.0 [-2.7 to -1.3], d = 0.78; p < 0.001) than the controls at post-intervention and throughout 6-month follow-up. Insomnia was a mediator of intervention effects on depression. No adverse events related to the interventions were reported.</p><p><strong>Conclusions: </strong>App-based CBT-I is effective in preventing future onset of major depression and improving insomnia outcomes among youth with insomnia and subclinical depression. These findings highlight the importance of targeting insomnia to prevent the onset of MDD and emphasize the need for wider dissemination of digital CBT-I to promote sleep and mental health in the youth population.</p><p><strong>Trial registration: </strong>ClinicalTrials.Gov (NCT04069247).</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004510"},"PeriodicalIF":15.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of nirmatrelvir/ritonavir (Paxlovid) on hospitalization among adults with COVID-19: An electronic health record-based target trial emulation from N3C.","authors":"Abhishek Bhatia, Alexander J Preiss, Xuya Xiao, M Daniel Brannock, G Caleb Alexander, Robert F Chew, Hannah Davis, Megan Fitzgerald, Elaine Hill, Elizabeth P Kelly, Hemalkumar B Mehta, Charisse Madlock-Brown, Kenneth J Wilkins, Christopher G Chute, Melissa Haendel, Richard Moffitt, Emily R Pfaff","doi":"10.1371/journal.pmed.1004493","DOIUrl":"10.1371/journal.pmed.1004493","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Nirmatrelvir with ritonavir (Paxlovid) is indicated for patients with Coronavirus Disease 2019 (COVID-19) who are at risk for progression to severe disease due to the presence of one or more risk factors. Millions of treatment courses have been prescribed in the United States alone. Paxlovid was highly effective at preventing hospitalization and death in clinical trials. Several studies have found a protective association in real-world data, but they variously used less recent study periods, correlational methods, and small, local cohorts. Their estimates also varied widely. The real-world effectiveness of Paxlovid remains uncertain, and it is unknown whether its effect is homogeneous across demographic strata. This study leverages electronic health record data in the National COVID Cohort Collaborative's (N3C) repository to investigate disparities in Paxlovid treatment and to emulate a target trial assessing its effectiveness in reducing severe COVID-19 outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;This target trial emulation used a cohort of 703,647 patients with COVID-19 seen at 34 clinical sites across the United States between April 1, 2022 and August 28, 2023. Treatment was defined as receipt of a Paxlovid prescription within 5 days of the patient's COVID-19 index date (positive test or diagnosis). To emulate randomization, we used the clone-censor-weight technique with inverse probability of censoring weights to balance a set of covariates including sex, age, race and ethnicity, comorbidities, community well-being index (CWBI), prior healthcare utilization, month of COVID-19 index, and site of care provision. The primary outcome was hospitalization; death was a secondary outcome. We estimated that Paxlovid reduced the risk of hospitalization by 39% (95% confidence interval (CI) [36%, 41%]; p &lt; 0.001), with an absolute risk reduction of 0.9 percentage points (95% CI [0.9, 1.0]; p &lt; 0.001), and reduced the risk of death by 61% (95% CI [55%, 67%]; p &lt; 0.001), with an absolute risk reduction of 0.2 percentage points (95% CI [0.1, 0.2]; p &lt; 0.001). We also conducted stratified analyses by vaccination status and age group. Absolute risk reduction for hospitalization was similar among patients that were vaccinated and unvaccinate, but was much greater among patients aged 65+ years than among younger patients. We observed disparities in Paxlovid treatment, with lower rates among black and Hispanic or Latino patients, and within socially vulnerable communities. This study's main limitation is that it estimates causal effects using observational data and could be biased by unmeasured confounding.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this study of Paxlovid's real-world effectiveness, we observed that Paxlovid is effective at preventing hospitalization and death, including among vaccinated patients, and particularly among older patients. This remains true in the era of Severe Acute Respiratory Syndrome Corona","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004493"},"PeriodicalIF":15.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roll out and prospects of the malaria vaccine R21/Matrix-M.","authors":"Lorenz von Seidlein","doi":"10.1371/journal.pmed.1004515","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004515","url":null,"abstract":"<p><p>In this Perspective article, Lorenz von Seidlein outlines the promise of two malaria vaccines, and discusses some of the considerations for their roll out.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 1","pages":"e1004515"},"PeriodicalIF":15.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}