PLoS Medicine最新文献

{"title":"Deaths with COVID-19 and from all-causes following first-ever SARS-CoV-2 infection in individuals with preexisting mental disorders: A national cohort study from Czechia.","authors":"Tomáš Formánek, Libor Potočár, Katrin Wolfova, Hana Melicharová, Karolína Mladá, Anna Wiedemann, Danni Chen, Pavel Mohr, Petr Winkler, Peter B Jones, Jiří Jarkovský","doi":"10.1371/journal.pmed.1004422","DOIUrl":"10.1371/journal.pmed.1004422","url":null,"abstract":"<p><strong>Background: </strong>Evidence suggests reduced survival rates following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in people with preexisting mental disorders, especially psychotic disorders, before the broad introduction of vaccines. It remains unknown whether this elevated mortality risk persisted at later phases of the pandemic and when accounting for the confounding effect of vaccination uptake and clinically recorded physical comorbidities.</p><p><strong>Methods and findings: </strong>We used data from Czech national health registers to identify first-ever serologically confirmed SARS-CoV-2 infections in 5 epochs related to different phases of the pandemic: 1st March 2020 to 30th September 2020, 1st October 2020 to 26th December 2020, 27th December 2020 to 31st March 2021, 1st April 2021 to 31st October 2021, and 1st November 2021 to 29th February 2022. In these people, we ascertained cases of mental disorders using 2 approaches: (1) per the International Classification of Diseases 10th Revision (ICD-10) diagnostic codes for substance use, psychotic, affective, and anxiety disorders; and (2) per ICD-10 diagnostic codes for the above mental disorders coupled with a prescription for anxiolytics/hypnotics/sedatives, antidepressants, antipsychotics, or stimulants per the Anatomical Therapeutic Chemical (ATC) classification codes. We matched individuals with preexisting mental disorders with counterparts who had no recorded mental disorders on age, sex, month and year of infection, vaccination status, and the Charlson Comorbidity Index (CCI). We assessed deaths with Coronavirus Disease 2019 (COVID-19) and from all-causes in the time period of 28 and 60 days following the infection using stratified Cox proportional hazards models, adjusting for matching variables and additional confounders. The number of individuals in matched-cohorts ranged from 1,328 in epoch 1 to 854,079 in epoch 5. The proportion of females ranged from 34.98% in people diagnosed with substance use disorders in epoch 3 to 71.16% in individuals diagnosed and treated with anxiety disorders in epoch 5. The mean age ranged from 40.97 years (standard deviation [SD] = 15.69 years) in individuals diagnosed with substance use disorders in epoch 5 to 56.04 years (SD = 18.37 years) in people diagnosed with psychotic disorders in epoch 2. People diagnosed with or diagnosed and treated for psychotic disorders had a consistently elevated risk of dying with COVID-19 in epochs 2, 3, 4, and 5, with adjusted hazard ratios (aHRs) ranging from 1.46 [95% confidence intervals (CIs), 1.18, 1.79] to 1.93 [95% CIs, 1.12, 3.32]. This patient group demonstrated also a consistently elevated risk of all-cause mortality in epochs 2, 3, 4, and 5 (aHR from 1.43 [95% CIs, 1.23, 1.66] to 1.99 [95% CIs, 1.25, 3.16]). The models could not be reliably fit for psychotic disorders in epoch 1. People diagnosed with substance use disorders had an increased risk of all-cause mort","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004422"},"PeriodicalIF":15.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621286","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":"The impact of primary health care on AIDS incidence and mortality: A cohort study of 3.4 million Brazilians.","authors":"Priscila F P S Pinto, James Macinko, Andréa F Silva, Iracema Lua, Gabriela Jesus, Laio Magno, Carlos A S Teles Santos, Maria Yury Ichihara, Mauricio L Barreto, Corrina Moucheraud, Luis E Souza, Inês Dourado, Davide Rasella","doi":"10.1371/journal.pmed.1004302","DOIUrl":"10.1371/journal.pmed.1004302","url":null,"abstract":"<p><strong>Background: </strong>Primary Health Care (PHC) is essential for effective, efficient, and more equitable health systems for all people, including those living with HIV/AIDS. This study evaluated the impact of the exposure to one of the largest community-based PHC programs in the world, the Brazilian Family Health Strategy (FHS), on AIDS incidence and mortality.</p><p><strong>Methods and findings: </strong>A retrospective cohort study carried out in Brazil from January 1, 2007 to December 31, 2015. We conducted an impact evaluation using a cohort of 3,435,068 ≥13 years low-income individuals who were members of the 100 Million Brazilians Cohort, linked to AIDS diagnoses and deaths registries. We evaluated the impact of FHS on AIDS incidence and mortality and compared outcomes between residents of municipalities with low or no FHS coverage (unexposed) with those in municipalities with 100% FHS coverage (exposed). We used multivariable Poisson regressions adjusted for all relevant municipal and individual-level demographic, socioeconomic, and contextual variables, and weighted with inverse probability of treatment weighting (IPTW). We also estimated the FHS impact by sex and age and performed a wide range of sensitivity and triangulation analyses; 100% FHS coverage was associated with lower AIDS incidence (rate ratio [RR]: 0.76, 95% CI: 0.68 to 0.84) and mortality (RR: 0.68, 95%CI: 0.56 to 0.82). FHS impact was similar between men and women, but was larger in people aged ≥35 years old both for incidence (RR: 0.62, 95% CI: 0.53 to 0.72) and mortality (RR: 0.56, 95% CI: 0.43 to 0.72). The absence of important confounding variables (e.g., sexual behavior) is a key limitation of this study.</p><p><strong>Conclusions: </strong>AIDS should be an avoidable outcome for most people living with HIV today and our study shows that FHS coverage could significantly reduce AIDS incidence and mortality among low-income populations in Brazil. Universal access to comprehensive healthcare through community-based PHC programs should be promoted to achieve the Sustainable Development Goals of ending AIDS by 2030.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004302"},"PeriodicalIF":15.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591759","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":"Non-diabetes status after diagnosis of impaired glucose tolerance and risk of long-term death and vascular complications: A post hoc analysis of the Da Qing Diabetes Prevention Outcome Study.","authors":"Xin Qian, Jinping Wang, Qiuhong Gong, Yali An, Xinxing Feng, Siyao He, Xiaoping Chen, Wenjuan Wang, Lihong Zhang, Yuanchi Hui, Xiuwei Zhai, Bo Zhang, Yanyan Chen, Guangwei Li","doi":"10.1371/journal.pmed.1004419","DOIUrl":"10.1371/journal.pmed.1004419","url":null,"abstract":"<p><strong>Background: </strong>The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified.</p><p><strong>Methods and findings: </strong>In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population.</p><p><strong>Conclusions: </strong>In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004419"},"PeriodicalIF":15.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564887","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":"Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden: A stepped wedge cluster randomised trial.","authors":"Maryam de Brun, Anders Magnuson, Scott Montgomery, Snehal Patil, David Simmons, Kerstin Berntorp, Stefan Jansson, Ulla-Britt Wennerholm, Anna-Karin Wikström, Helen Strevens, Fredrik Ahlsson, Verena Sengpiel, Erik Schwarcz, Elisabeth Storck-Lindholm, Martina Persson, Kerstin Petersson, Linda Ryen, Carina Ursing, Karin Hildén, Helena Backman","doi":"10.1371/journal.pmed.1004420","DOIUrl":"10.1371/journal.pmed.1004420","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight &gt;90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight &gt;90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pr","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004420"},"PeriodicalIF":15.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560103","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":"Assessing thresholds of resistance prevalence at which empiric treatment of gonorrhea should change among men who have sex with men in the US: A cost-effectiveness analysis.","authors":"Xuecheng Yin, Yunfei Li, Minttu M Rönn, Song Li, Yue Yuan, Thomas L Gift, Katherine Hsu, Joshua A Salomon, Yonatan H Grad, Reza Yaesoubi","doi":"10.1371/journal.pmed.1004424","DOIUrl":"10.1371/journal.pmed.1004424","url":null,"abstract":"<p><strong>Background: </strong>Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea.</p><p><strong>Methods and findings: </strong>We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy.</p><p><strong>Conclusions: </strong>Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004424"},"PeriodicalIF":15.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560102","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":"Association between achieving adequate antenatal care and health-seeking behaviors: A study of Demographic and Health Surveys in 47 low- and middle-income countries.","authors":"Boshen Jiao, Isabelle Iversen, Ryoko Sato, Clint Pecenka, Sadaf Khan, Ranju Baral, Margaret E Kruk, Catherine Arsenault, Stéphane Verguet","doi":"10.1371/journal.pmed.1004421","DOIUrl":"10.1371/journal.pmed.1004421","url":null,"abstract":"<p><strong>Background: </strong>Antenatal care (ANC) is essential for ensuring the well-being of pregnant women and their fetuses. This study models the association between achieving adequate ANC and various health and health-seeking indicators across wealth quintiles in low- and middle-income countries (LMICs).</p><p><strong>Methods and findings: </strong>We analyzed data from 638,265 women across 47 LMICs using available Demographic and Health Surveys from 2010 to 2022. Via multilevel logistic regression analyses adjusted for a series of confounding variables and country and wealth quintile fixed effects, we estimated the projected impact of achieving adequate ANC utilization and quality on a series of health and health care indicators: facility birth, postnatal care, childhood immunizations, and childhood stunting and wasting. Achieving adequate levels of ANC utilization and quality (defined as at least 4 visits, blood pressure monitoring, and blood and urine testing) was positively associated with health-seeking behavior across the majority of countries. The strongest association was observed for facility birth, followed by postnatal care and child immunization. The strength of the associations varied across countries and wealth quintiles, with more significant ones observed in countries with lower baseline ANC utilization levels and among the lower wealth quintiles. The associations of ANC with childhood stunting and wasting were notably less statistically significant compared to other indicators. Despite rigorous adjustments for potential confounders, a limitation to the methodology is that it is possible that unobserved variables may still impact outcomes.</p><p><strong>Conclusions: </strong>Strengthening ANC is associated with improved use of other health care in LMICs. ANC could serve as a critical platform for improving health outcomes for mothers and their children, emphasizing its importance beyond direct impact on maternal and neonatal mortality.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004421"},"PeriodicalIF":15.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538870","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":"Direct factor Xa inhibitors and the risk of cancer and cancer mortality: A Danish population-based cohort study.","authors":"Floris Bosch, Erzsébet Horváth-Puhó, Suzanne C Cannegieter, Nick van Es, Henrik T Sørensen","doi":"10.1371/journal.pmed.1004400","DOIUrl":"10.1371/journal.pmed.1004400","url":null,"abstract":"<p><strong>Background: </strong>Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran.</p><p><strong>Methods and findings: </strong>This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period.</p><p><strong>Conclusions: </strong>In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 7","pages":"e1004400"},"PeriodicalIF":15.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477820","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":"Correction: Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis.","authors":"Aaron G Lim, Nick Scott, Josephine G Walker, Saeed Hamid, Margaret Hellard, Peter Vickerman","doi":"10.1371/journal.pmed.1004423","DOIUrl":"10.1371/journal.pmed.1004423","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pmed.1003818.].</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 6","pages":"e1004423"},"PeriodicalIF":15.8,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11198994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452018","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":"Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: An observational cohort study using the OpenSAFELY platform.","authors":"Miriam Samuel, Robin Y Park, Sophie V Eastwood, Fabiola Eto, Caroline E Morton, Daniel Stow, Sebastian Bacon, Amir Mehrkar, Jessica Morley, Iain Dillingham, Peter Inglesby, William J Hulme, Kamlesh Khunti, Rohini Mathur, Jonathan Valabhji, Brian MacKenna, Sarah Finer","doi":"10.1371/journal.pmed.1004398","DOIUrl":"10.1371/journal.pmed.1004398","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Obesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following Coronavirus Disease 2019 (COVID-19) infection. Restrictions imposed to reduce COVID-19 transmission resulted in profound societal changes that impacted many health behaviours, including physical activity and nutrition, associated with rate of weight gain. We investigated which clinical and sociodemographic characteristics were associated with rapid weight gain and the greatest acceleration in rate of weight gain during the pandemic among adults registered with an English National Health Service (NHS) general practitioner (GP) during the COVID-19 pandemic.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;With the approval of NHS England, we used the OpenSAFELY platform inside TPP to conduct an observational cohort study of routinely collected electronic healthcare records. We investigated changes in body mass index (BMI) values recorded in English primary care between March 2015 and March 2022. We extracted data on 17,742,365 adults aged 18 to 90 years old (50.1% female, 76.1% white British) registered with an English primary care practice. We estimated individual rates of weight gain before (δ-prepandemic) and during (δ-pandemic) the pandemic and identified individuals with rapid weight gain (&gt;0.5 kg/m2/year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period (δ-change = δ-pandemic-δ-prepandemic) and defined extreme accelerators as the 10% of individuals with the greatest increase in their rate of weight gain (δ-change ≥1.84 kg/m2/year) between these periods. We estimated associations with these outcomes using multivariable logistic regression adjusted for age, sex, index of multiple deprivation (IMD), and ethnicity. P-values were generated in regression models. The median BMI of our study population was 27.8 kg/m2, interquartile range (IQR) [24.3, 32.1] in 2019 (March 2019 to February 2020) and 28.0 kg/m2, IQR [24.4, 32.6] in 2021. Rapid pandemic weight gain was associated with sex, age, and IMD. Male sex (male versus female: adjusted odds ratio (aOR) 0.76, 95% confidence interval (95% CI) [0.76, 0.76], p &lt; 0.001), older age (e.g., 50 to 59 years versus 18 to 29 years: aOR 0.60, 95% CI [0.60, 0.61], p &lt; 0.001]); and living in less deprived areas (least-deprived-IMD-quintile versus most-deprived: aOR 0.77, 95% CI [0.77, 0.78] p &lt; 0.001) reduced the odds of rapid weight gain. Compared to white British individuals, all other ethnicities had lower odds of rapid pandemic weight gain (e.g., Indian versus white British: aOR 0.69, 95% CI [0.68, 0.70], p &lt; 0.001). Long-term conditions (LTCs) increased the odds, with mental health conditions having the greatest effect (e.g., depression (aOR 1.18, 95% CI [1.17, 1.18], p &lt; 0.001)). Similar characteristics increased odds of extreme acceleration in the rate of we","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 6","pages":"e1004398"},"PeriodicalIF":15.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447392","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":"Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial.","authors":"Stephen R Walsh, Cynthia L Gay, Shelly T Karuna, Ollivier Hyrien, Timothy Skalland, Kenneth H Mayer, Magdalena E Sobieszczyk, Lindsey R Baden, Paul A Goepfert, Carlos Del Rio, Guiseppe Pantaleo, Philip Andrew, Carissa Karg, Zonglin He, Huiyin Lu, Carmen A Paez, Jane A G Baumblatt, Laura L Polakowski, Wairimu Chege, Maija A Anderson, Sophie Janto, Xue Han, Yunda Huang, Julie Dumond, Margaret E Ackerman, Adrian B McDermott, Britta Flach, Estelle Piwowar-Manning, Kelly Seaton, Georgia D Tomaras, David C Montefiori, Lucio Gama, John R Mascola","doi":"10.1371/journal.pmed.1004329","DOIUrl":"10.1371/journal.pmed.1004329","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions were reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 μg/mL (25.2, 33.4), 58.5 μg/mL (49.4, 69.3), and 257.2 μg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 μg/mL (8.8, 13.3) and 22.8 μg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 μg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 μg/mL (2.5, 4.6), 6.5 μg/mL (5.6, 7.5), and 27.2 μg/mL (23.9, 31.0) with IV dosing; 0.97 μg/mL (0.65, 1.4) and 3.1 μg/mL (2.2, 4.3) with SC dosing, and 2.6 μg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A sing","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 6","pages":"e1004329"},"PeriodicalIF":15.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447391","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}