PLOS MedicinePLOShttps://journals.plos.org/plosmedicine/webmaster@plos.orgA Peer-Reviewed Open-Access Journalhttps://journals.plos.org/plosmedicine/feed/atomAll PLOS articles are Open Access.https://journals.plos.org/plosmedicine/resource/img/favicon.icohttps://journals.plos.org/plosmedicine/resource/img/favicon.ico2024-03-19T05:43:32ZLong-term HIV care outcomes under universal HIV treatment guidelines: A retrospective cohort study in 25 countriesEllen BrazierOlga TymejczykKara Wools-KaloustianAwachana JiamsakulMarco Tulio Luque TorresJennifer S. LeeLisa AbuogiVohith KholFernando Mejía CorderoKeri N. AlthoffMatthew G. LawDenis Nashon behalf of the International epidemiology Databases to Evaluate AIDS (IeDEA)10.1371/journal.pmed.10043672024-03-18T14:00:00Z2024-03-18T14:00:00Z<p>by Ellen Brazier, Olga Tymejczyk, Kara Wools-Kaloustian, Awachana Jiamsakul, Marco Tulio Luque Torres, Jennifer S. Lee, Lisa Abuogi, Vohith Khol, Fernando Mejía Cordero, Keri N. Althoff, Matthew G. Law, Denis Nash, on behalf of the International epidemiology Databases to Evaluate AIDS (IeDEA) </p>
Background <p>While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation.</p> Methods and findings <p>For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium’s Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change–associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; <i>p</i> = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; <i>p</i> < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], <i>p</i> < .001) compared with enrollment before guideline adoption, with no before–after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis.</p> Conclusions <p>In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality.</p>Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analysesHuijie CuiWenqiang ZhangLi ZhangYang QuZhengxing XuZhixin TanPeijing YanMingshuang TangChao YangYutong WangLin ChenChenghan XiaoYanqiu ZouYunjie LiuLing ZhangYanfang YangYuqin YaoJiayuan LiZhenmi LiuChunxia YangXia JiangBen Zhang10.1371/journal.pmed.10043622024-03-15T14:00:00Z2024-03-15T14:00:00Z<p>by Huijie Cui, Wenqiang Zhang, Li Zhang, Yang Qu, Zhengxing Xu, Zhixin Tan, Peijing Yan, Mingshuang Tang, Chao Yang, Yutong Wang, Lin Chen, Chenghan Xiao, Yanqiu Zou, Yunjie Liu, Ling Zhang, Yanfang Yang, Yuqin Yao, Jiayuan Li, Zhenmi Liu, Chunxia Yang, Xia Jiang, Ben Zhang</p>
Background <p>The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for prostate cancer, but few modifiable factors have been firmly established. The objective of this study was to identify and evaluate various factors modifying the risk of prostate cancer reported in meta-analyses of prospective observational studies and mendelian randomization (MR) analyses.</p> Methods and findings <p>We searched PubMed, Embase, and Web of Science from the inception to January 10, 2022, updated on September 9, 2023, to identify meta-analyses and MR studies on prostate cancer. Eligibility criteria for meta-analyses were (1) meta-analyses including prospective observational studies or studies that declared outcome-free at baseline; (2) evaluating the factors of any category associated with prostate cancer incidence; and (3) providing effect estimates for further data synthesis. Similar criteria were applied to MR studies. Meta-analysis was repeated using the random-effects inverse-variance model with DerSimonian—Laird method. Quality assessment was then conducted for included meta-analyses using AMSTAR-2 tool and for MR studies using STROBE-MR and assumption evaluation. Subsequent evidence grading criteria for significant associations in meta-analyses contained sample size, <i>P</i> values and 95% confidence intervals, 95% prediction intervals, heterogeneity, and publication bias, assigning 4 evidence grades (convincing, highly suggestive, suggestive, or weak). Significant associations in MR studies were graded as robust, probable, suggestive, or insufficient considering <i>P</i> values and concordance of effect directions.Finally, 92 selected from 411 meta-analyses and 64 selected from 118 MR studies were included after excluding the overlapping and outdated studies which were published earlier and contained fewer participants or fewer instrument variables for the same exposure. In total, 123 observational associations (45 significant and 78 null) and 145 causal associations (55 significant and 90 null) were categorized into lifestyle; diet and nutrition; anthropometric indices; biomarkers; clinical variables, diseases, and treatments; and environmental factors. Concerning evidence grading on significant associations, there were 5 highly suggestive, 36 suggestive, and 4 weak associations in meta-analyses, and 10 robust, 24 probable, 4 suggestive, and 17 insufficient causal associations in MR studies. Twenty-six overlapping factors between meta-analyses and MR studies were identified, with consistent significant effects found for physical activity (PA) (occupational PA in meta: OR = 0.87, 95% CI: 0.80, 0.94; accelerator-measured PA in MR: OR = 0.49, 95% CI: 0.33, 0.72), height (meta: OR = 1.09, 95% CI: 1.06, 1.12; MR: OR = 1.07, 95% CI: 1.01, 1.15, for aggressive prostate cancer), and smoking (current smoking in meta: OR = 0.74, 95% CI: 0.68, 0.80; smoking initiation in MR: OR = 0.91, 95% CI: 0.86, 0.97). Methodological limitation is that the evidence grading criteria could be expanded by considering more indices.</p> Conclusions <p>In this large-scale study, we summarized the associations of various factors with prostate cancer risk and provided comparisons between observational associations by meta-analysis and genetically estimated causality by MR analyses. In the absence of convincing overlapping evidence based on the existing literature, no robust associations were identified, but some effects were observed for height, physical activity, and smoking.</p>Antimicrobial resistance prevalence in bloodstream infection in 29 European countries by age and sex: An observational studyNaomi R. WaterlowBen S. CooperJulie V. RobothamGwenan Mary Knight10.1371/journal.pmed.10043012024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Naomi R. Waterlow, Ben S. Cooper, Julie V. Robotham, Gwenan Mary Knight</p>
Background <p>Antibiotic usage, contact with high transmission healthcare settings as well as changes in immune system function all vary by a patient’s age and sex. Yet, most analyses of antimicrobial resistance (AMR) ignore demographic indicators and provide only country-level resistance prevalence values. This study aimed to address this knowledge gap by quantifying how resistance prevalence and incidence of bloodstream infection (BSI) varied by age and sex across bacteria and antibiotics in Europe.</p> Methods and findings <p>We used patient-level data collected as part of routine surveillance between 2015 and 2019 on BSIs in 29 European countries from the European Antimicrobial Resistance Surveillance Network (EARS-Net). A total of 6,862,577 susceptibility results from isolates with age, sex, and spatial information from 944,520 individuals were used to characterise resistance prevalence patterns for 38 different bacterial species and antibiotic combinations, and 47% of these susceptibility results were from females, with a similar age distribution in both sexes (mean of 66 years old). A total of 349,448 isolates from 2019 with age and sex metadata were used to calculate incidence. We fit Bayesian multilevel regression models by country, laboratory code, sex, age, and year of sample to quantify resistant prevalence and provide estimates of country-, bacteria-, and drug-family effect variation. We explore our results in greater depths for 2 of the most clinically important bacteria–antibiotic combinations (aminopenicillin resistance in <i>Escherichia coli</i> and methicillin resistance in <i>Staphylococcus aureus</i>) and present a simplifying indicative index of the difference in predicted resistance between old (aged 100) and young (aged 1). At the European level, we find distinct patterns in resistance prevalence by age. Trends often vary more within an antibiotic family, such as fluroquinolones, than within a bacterial species, such as <i>Pseudomonas aeruginosa</i>. Clear resistance increases by age for methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) contrast with a peak in resistance to several antibiotics at approximately 30 years of age for <i>P</i>. <i>aeruginosa</i>. For most bacterial species, there was a u-shaped pattern of infection incidence with age, which was higher in males. An important exception was <i>E</i>. <i>coli</i>, for which there was an elevated incidence in females between the ages of 15 and 40. At the country-level, subnational differences account for a large amount of resistance variation (approximately 38%), and there are a range of functional forms for the associations between age and resistance prevalence. For MRSA, age trends were mostly positive, with 72% (<i>n</i> = 21) of countries seeing an increased resistance between males aged 1 and 100 years and a greater change in resistance in males. This compares to age trends for aminopenicillin resistance in <i>E</i>. <i>coli</i> which were mostly negative (males: 93% (<i>n</i> = 27) of countries see decreased resistance between those aged 1 and 100 years) with a smaller change in resistance in females. A change in resistance prevalence between those aged 1 and 100 years ranged up to 0.51 (median, 95% quantile of model simulated prevalence using posterior parameter ranges 0.48, 0.55 in males) for MRSA in one country but varied between 0.16 (95% quantile 0.12, 0.21 in females) to −0.27 (95% quantile −0.4, −0.15 in males) across individual countries for aminopenicillin resistance in <i>E</i>. <i>coli</i>. Limitations include potential bias due to the nature of routine surveillance and dependency of results on model structure.</p> Conclusions <p>In this study, we found that the prevalence of resistance in BSIs in Europe varies substantially by bacteria and antibiotic over the age and sex of the patient shedding new light on gaps in our understanding of AMR epidemiology. Future work is needed to determine the drivers of these associations in order to more effectively target transmission and antibiotic stewardship interventions.</p>Short-term impacts of Universal Basic Income on population mental health inequalities in the UK: A microsimulation modelling studyRachel M. ThomsonDaniel KopaskerPatryk BronkaMatteo RichiardiVladimir KhodygoAndrew J. BaxterErik IgelströmAnna PearceAlastair H. LeylandS. Vittal Katikireddi10.1371/journal.pmed.10043582024-03-04T14:00:00Z2024-03-04T14:00:00Z<p>by Rachel M. Thomson, Daniel Kopasker, Patryk Bronka, Matteo Richiardi, Vladimir Khodygo, Andrew J. Baxter, Erik Igelström, Anna Pearce, Alastair H. Leyland, S. Vittal Katikireddi</p>
Background <p>Population mental health in the United Kingdom (UK) has deteriorated, alongside worsening socioeconomic conditions, over the last decade. Policies such as Universal Basic Income (UBI) have been suggested as an alternative economic approach to improve population mental health and reduce health inequalities. UBI may improve mental health (MH), but to our knowledge, no studies have trialled or modelled UBI in whole populations. We aimed to estimate the short-term effects of introducing UBI on mental health in the UK working-age population.</p> Methods and findings <p>Adults aged 25 to 64 years were simulated across a 4-year period from 2022 to 2026 with the SimPaths microsimulation model, which models the effects of UK tax/benefit policies on mental health via income, poverty, and employment transitions. Data from the nationally representative UK Household Longitudinal Study were used to generate the simulated population (<i>n</i> = 25,000) and causal effect estimates. Three counterfactual UBI scenarios were modelled from 2023: “Partial” (value equivalent to existing benefits), “Full” (equivalent to the UK Minimum Income Standard), and “Full+” (retaining means-tested benefits for disability, housing, and childcare). Likely common mental disorder (CMD) was measured using the General Health Questionnaire (GHQ-12, score ≥4). Relative and slope indices of inequality were calculated, and outcomes stratified by gender, age, education, and household structure. Simulations were run 1,000 times to generate 95% uncertainty intervals (UIs). Sensitivity analyses relaxed SimPaths assumptions about reduced employment resulting from Full/Full+ UBI.Partial UBI had little impact on poverty, employment, or mental health. Full UBI scenarios practically eradicated poverty but decreased employment (for Full+ from 78.9% [95% UI 77.9, 79.9] to 74.1% [95% UI 72.6, 75.4]). Full+ UBI increased absolute CMD prevalence by 0.38% (percentage points; 95% UI 0.13, 0.69) in 2023, equivalent to 157,951 additional CMD cases (95% UI 54,036, 286,805); effects were largest for men (0.63% [95% UI 0.31, 1.01]) and those with children (0.64% [95% UI 0.18, 1.14]). In our sensitivity analysis assuming minimal UBI-related employment impacts, CMD prevalence instead fell by 0.27% (95% UI −0.49, −0.05), a reduction of 112,228 cases (95% UI 20,783, 203,673); effects were largest for women (−0.32% [95% UI −0.65, 0.00]), those without children (−0.40% [95% UI −0.68, −0.15]), and those with least education (−0.42% [95% UI −0.97, 0.15]). There was no effect on educational mental health inequalities in any scenario, and effects waned by 2026.The main limitations of our methods are the model’s short time horizon and focus on pathways from UBI to mental health solely via income, poverty, and employment, as well as the inability to integrate macroeconomic consequences of UBI; future iterations of the model will address these limitations.</p> Conclusions <p>UBI has potential to improve short-term population mental health by reducing poverty, particularly for women, but impacts are highly dependent on whether individuals choose to remain in employment following its introduction. Future research modelling additional causal pathways between UBI and mental health would be beneficial.</p>Diagnosis and management of endometrial hyperplasia: A UK national audit of adherence to national guidance 2012–2020Ian HendersonNaomi BlackHajra KhattakUKARCOG Working Group AuthorsJanesh K. GuptaMichael P. Rimmer10.1371/journal.pmed.10043462024-02-29T14:00:00Z2024-02-29T14:00:00Z<p>by Ian Henderson, Naomi Black, Hajra Khattak, UKARCOG Working Group Authors , Janesh K. Gupta, Michael P. Rimmer</p>
Background <p>Endometrial hyperplasia (EH) is a precusor lesion for endometrial cancer (EC), the commonest gynaecological malignancy in high-income countries. EH is a proliferation of glandular tissue, classified as either non-atypical endometrial hyperplasia (NEH) or, if the cytological features are abnormal, atypical endometrial hyperplasia (AEH). The clinical significance of AEH is that patients face both a high risk of having occult EC and a high risk of progression to EC if untreated. Recommendations on the care of women with EH were introduced by United Kingdom–wide guidance (Green-top Guide No. 67, 2016). National adherence to guidance is unknown.We aimed to describe the care of patients with EH; to compare the patterns of care for those with EH with national guidance to identify opportunities for quality improvement; and to compare patterns of care prior to and following the introduction of national guidance to understand its impact.</p> Methods and findings <p>In this UK-wide patient-level clinical audit, we included 3,307 women who received a new histological diagnosis of EH through a gynaecology service between 1 January 2012 and 30 June 2020. We described first-line management, management at 2 years, and surgical characteristics prior to and following national guidance for EH using proportions and 95% confidence intervals (CIs) and compared process measures between time periods using multilevel Poisson regression.Of the 3,307 patients, 1,570 had NEH and 1,511 had AEH between 2012 and 2019. An additional 85 patients had NEH and 141 had AEH during 2020. Prior to national guidance, 9% (95% CI [6%, 15%]) received no initial treatment for NEH compared with 3% (95% CI [1%, 5%]) post-guidance; 31% (95% CI [26%, 36%]) and 48% (95% CI [43% 53%]) received an intrauterine progestogen, respectively, in the same periods. The predominant management of women with AEH did not differ, with 68% (95% CI [61%, 74%]) and 67% (95 CI [63%, 71%]) receiving first-line hysterectomy, respectively. By 2 years, follow-up to histological regression without hysterectomy increased from 38% (95% CI [33%, 43%]) to 52% (95% CI [47%, 58%]) for those with NEH (rate ratio (RR) 1.38, 95% CI [1.18, 1.63] <i>p</i> < 0.001). We observed an increase in the use of total laparoscopic hysterectomy among those with AEH (RR 1.26, 95% CI [1.04, 1.52]). In the later period, 37% (95% CI [29%, 44%]) of women initially diagnosed with AEH who underwent a first-line hysterectomy, received an upgraded diagnosis of EC. Study limitations included retrospective data collection from routine clinical documentation and the inability to comprehensively understand the shared decision-making process where care differed from guidance.</p> Conclusions <p>The care of patients with EH has changed in accordance with national guidance. More women received first-line medical management of NEH and were followed up to histological regression. The follow-up of those with AEH who do not undergo hysterectomy must be improved, given their very high risk of coexistent cancer and high risk of developing cancer.</p>Combining fecal immunochemical testing and questionnaire-based risk assessment in selecting participants for colonoscopy screening in the Chinese National Colorectal Cancer Screening Programs: A population-based cohort studyXuesi DongLingbin DuZilin LuoYongjie XuChenran WangFei WangWei CaoLiang ZhaoYadi ZhengHongting ZhuChangfa XiaJiang LiMulong DuDong HangJiansong RenJufang ShiHongbing ShenWanqing ChenNi LiJie HeCancer Screening Program in Urban China (CanSPUC) Group10.1371/journal.pmed.10043402024-02-22T14:00:00Z2024-02-22T14:00:00Z<p>by Xuesi Dong, Lingbin Du, Zilin Luo, Yongjie Xu, Chenran Wang, Fei Wang, Wei Cao, Liang Zhao, Yadi Zheng, Hongting Zhu, Changfa Xia, Jiang Li, Mulong Du, Dong Hang, Jiansong Ren, Jufang Shi, Hongbing Shen, Wanqing Chen, Ni Li, Jie He, Cancer Screening Program in Urban China (CanSPUC) Group </p>
Background <p>Screening reduces colorectal cancer (CRC) burden by allowing early resection of precancerous and cancerous lesions. An adequate selection of high-risk individuals and a high uptake rate for colonoscopy screening are critical to identifying people more likely to benefit from screening and allocating healthcare resources properly. We evaluated whether combining a questionnaire-based interview for risk factors with fecal immunochemical test (FIT) outcomes for high-risk assessment is more efficient and economical than a questionnaire-based interview-only strategy.</p> Methods and findings <p>In this multicenter, population-based, prospective cohort study, we enrolled community residents aged 40 to 74 years in 29 provinces across China. From 2016 to 2020, a total of 1,526,824 eligible participants were consecutively enrolled in the Cancer Screening Program in Urban China (CanSPUC) cohort, and 940,605 were enrolled in the Whole Life Cycle of Cancer Screening Program (WHOLE) cohort, with follow-up to December 31, 2022. The mean ages were 56.89 and 58.61 years in CanSPUC and WHOLE, respectively. In the WHOLE cohort, high-risk individuals were identified by combining questionnaire-based interviews to collect data on risk factors (demographics, diet history, family history of CRC, etc.) with FIT outcomes (RF–FIT strategy), whereas in the CanSPUC cohort, high-risk individuals were identified using only interview-based data on risk factors (RF strategy). The primary outcomes were participation rate and yield (detection rate of advanced neoplasm, early-stage detection rate of CRCs [stage I/II], screening yield per 10,000 invitees), which were reported for the entire population and for different gender and age groups. The secondary outcome was the cost per case detected.In total, 71,967 (7.65%) and 281,985 (18.47%) individuals were identified as high-risk and were invited to undergo colonoscopy in the RF–FIT group and RF group, respectively. The colonoscopy participation rate in the RF–FIT group was 26.50% (19,071 of 71,967) and in the RF group was 19.54% (55,106 of 281,985; chi-squared test, <i>p</i> < 0.001). A total of 102 (0.53%) CRCs and 2,074 (10.88%) advanced adenomas were detected by the RF–FIT, versus 90 (0.16%) and 3,593 (6.52%) by the RF strategy (chi-squared test, both <i>p</i> < 0.001). The early-stage detection rate using the RF–FIT strategy was significantly higher than that by the RF strategy (67.05% versus 47.95%, Fisher’s exact test, <i>p</i> = 0.016). The cost per CRC detected was $24,849 by the RF–FIT strategy versus $55,846 by the RF strategy. A limitation of the study was lack of balance between groups with regard to family history of CRC (3.5% versus 0.7%).</p> Conclusions <p>Colonoscopy participation and screening yield were better with the RF–FIT strategy. The association with CRC incidence and mortality reduction should be evaluated after long-term follow-up.</p>Correction: Impact of taxes and warning labels on red meat purchases among US consumers: A randomized controlled trialThe PLOS Medicine Staff10.1371/journal.pmed.10043572024-02-21T14:00:00Z2024-02-21T14:00:00Z<p>by The PLOS Medicine Staff </p>Comparison of 3 optimized delivery strategies for completion of isoniazid-rifapentine (3HP) for tuberculosis prevention among people living with HIV in Uganda: A single-center randomized trialFred C. SemitalaJillian L. KadotaAllan MusinguziFred WelisheAnne NakitendeLydia AkelloLynn Kunihira TinkaJane NakimuliJoan Ritar KasidiOpira BishopSuzan NakasendwaYeonsoo BaikDevika PatelAmanda SammannPayam NahidRobert BelknapMoses R. KamyaMargaret A. HandleyPatrick PJ PhillipsAnne KatahoireChristopher A. BergerNoah KiwanukaAchilles KatambaDavid W. DowdyAdithya Cattamanchi10.1371/journal.pmed.10043562024-02-20T14:00:00Z2024-02-20T14:00:00Z<p>by Fred C. Semitala, Jillian L. Kadota, Allan Musinguzi, Fred Welishe, Anne Nakitende, Lydia Akello, Lynn Kunihira Tinka, Jane Nakimuli, Joan Ritar Kasidi, Opira Bishop, Suzan Nakasendwa, Yeonsoo Baik, Devika Patel, Amanda Sammann, Payam Nahid, Robert Belknap, Moses R. Kamya, Margaret A. Handley, Patrick PJ Phillips, Anne Katahoire, Christopher A. Berger, Noah Kiwanuka, Achilles Katamba, David W. Dowdy, Adithya Cattamanchi</p>
Background <p>Expanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies.</p> Methods and findings <p>In a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion (≥11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher’s exact test (two-sided α = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] <i>p</i> < 0.001), SAT (0.92; 97.5% CI [0.89, 0.94] <i>p</i> < 0.001), and Choice (0.93; 97.5% CI [0.91, 0.96] <i>p</i> < 0.001) arms. There was no difference in acceptance and completion between any 2 arms overall or in prespecified subgroup analyses based on sex, age, time on antiretroviral therapy, and history of prior treatment for TB or TB infection. Only 14 (0.8%) participants experienced an adverse event prompting discontinuation of 3HP. The main limitation of the study is that it was conducted in a single center. Multicenter studies are now needed to confirm the feasibility and generalizability of the facilitated 3HP delivery strategies in other settings.</p> Conclusions <p>Short-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers.</p> Trial Registration <p>ClinicalTrials.gov NCT03934931.</p>Estimating the impact of alternative programmatic cotrimoxazole strategies on mortality among children born to mothers with HIV: A modelling studyShrey MathurMelanie SmukCeri EvansCatherine J. WedderburnDiana M. GibbMartina PenazzatoAndrew J. Prendergast10.1371/journal.pmed.10043342024-02-20T14:00:00Z2024-02-20T14:00:00Z<p>by Shrey Mathur, Melanie Smuk, Ceri Evans, Catherine J. Wedderburn, Diana M. Gibb, Martina Penazzato, Andrew J. Prendergast</p>
Background <p>World Health Organization (WHO) guidelines recommend cotrimoxazole prophylaxis for children who are HIV-exposed until infection is excluded and vertical transmission risk has ended. While cotrimoxazole has benefits for children with HIV, there is no mortality benefit for children who are HIV-exposed but uninfected, prompting a review of global guidelines. Here, we model the potential impact of alternative cotrimoxazole strategies on mortality in children who are HIV-exposed.</p> Methods and findings <p>Using a deterministic compartmental model, we estimated mortality in children who are HIV-exposed from 6 weeks to 2 years of age in 4 high-burden countries: Côte d’Ivoire, Mozambique, Uganda, and Zimbabwe. Vertical transmission rates, testing rates, and antiretroviral therapy (ART) uptake were derived from UNAIDS data, trial evidence, and meta-analyses. We explored 6 programmatic strategies: maintaining current recommendations; shorter cotrimoxazole provision for 3, 6, 9, or 12 months; and starting cotrimoxazole only for children diagnosed with HIV.Modelled alternatives to the current strategy increased mortality to varying degrees; countries with high vertical transmission had the greatest mortality. Compared to current recommendations, starting cotrimoxazole only after a positive HIV test had the greatest predicted increase in mortality: Mozambique (961 excess annual deaths; excess mortality 339 per 100,000 HIV-exposed children; risk ratio (RR) 1.06), Uganda (491; 221; RR 1.04), Zimbabwe (352; 260; RR 1.05), and Côte d’Ivoire (125; 322; RR 1.06). Similar effects were observed for 3-, 6-, 9-, and 12-month strategies. Increased mortality persisted but was attenuated when modelling lower cotrimoxazole uptake, smaller mortality benefits, higher testing coverage, and lower vertical transmission rates. The study is limited by uncertain estimates of cotrimoxazole coverage in programmatic settings; an inability to model increases in mortality arising from antimicrobial resistance due to limited surveillance data in sub-Saharan Africa; and lack of a formal health economic analysis.</p> Conclusions <p>Changing current guidelines from universal cotrimoxazole provision for children who are HIV-exposed increased predicted mortality across the 4 modelled high-burden countries, depending on test-to-treat cascade coverage and vertical transmission rates. These findings can help inform policymaker deliberations on cotrimoxazole strategies, recognising that the risks and benefits differ across settings.</p>Risk of long COVID and associated symptoms after acute SARS-COV-2 infection in ethnic minorities: A nationwide register-linked cohort study in DenmarkGeorge Frederick MkomaCharles AgyemangThomas BenfieldMikael RostilaAgneta CederströmJørgen Holm PetersenMarie Norredam10.1371/journal.pmed.10042802024-02-20T14:00:00Z2024-02-20T14:00:00Z<p>by George Frederick Mkoma, Charles Agyemang, Thomas Benfield, Mikael Rostila, Agneta Cederström, Jørgen Holm Petersen, Marie Norredam</p>
Background <p>Ethnic minorities living in high-income countries have been disproportionately affected by Coronavirus Disease 2019 (COVID-19) in terms of infection rates, hospitalisations, and deaths; however, less is known about long COVID in these populations. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities.</p> Methods and findings <p>We used nationwide register-based cohort data on individuals diagnosed with COVID-19 aged ≥18 years (n = 2,287,175) between January 2020 and August 2022 in Denmark. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively.Among individuals who were first time diagnosed with COVID-19 during the study period, 39,876 (1.7%) were hospitalised and 2,247,299 (98.3%) were nonhospitalised individuals. Of the diagnosed COVID-19 cases, 1,952,021 (85.3%) were native Danes and 335,154 (14.7%) were ethnic minorities. After adjustment for age, sex, civil status, education, family income, and Charlson comorbidity index, ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41, 95% confidence interval [CI] [1.12,1.79], <i>p</i> = 0.003), Middle East (aHR 1.38, 95% CI [1.24,1.55], <i>p</i> < 0.001), Eastern Europe (aHR 1.35, 95% CI [1.22,1.49], <i>p</i> < 0.001), and Asia (aHR 1.23, 95% CI [1.09,1.40], <i>p</i> = 0.001) had significantly greater risk of long COVID diagnosis than native Danes. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in people of Iraqi origin (aHR 1.56, 95% CI [1.30,1.88], <i>p</i> < 0.001), people of Turkish origin (aHR 1.42, 95% CI [1.24,1.63], <i>p</i> < 0.001), and people of Somali origin (aHR 1.42, 95% CI [1.07,1.91], <i>p</i> = 0.016). A significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. The risk of long COVID diagnosis among ethnic minorities was more pronounced between January 2020 and June 2021. Furthermore, the odds of reporting cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms were higher among people of North African, Middle Eastern, Eastern European, and Asian origins than among native Danes in both unadjusted and adjusted models. Despite including the nationwide sample of individuals diagnosed with COVID-19, the precision of our estimates on long COVID was limited to the sample of patients with symptoms who had contacted the hospital.</p> Conclusions <p>Belonging to an ethnic minority group was significantly associated with an increased risk of long COVID, indicating the need to better understand long COVID drivers and address care and treatment strategies in these populations.</p>COVID-19 diagnostic testing and vaccinations among First Nations in Manitoba: A nations-based retrospective cohort study using linked administrative data, 2020–2021Nathan C. NickelWanda Phillips-BeckJennifer E. EnnsOkechukwu EkumaCarole TaylorSarah FileatreaultNkiru EzeLeona StarJosée LavoieAlan KatzMarni BrownellAlyson MaharMarcelo UrquiaDan ChateauLisa LixMariette ChartierEmily BrownellMiyosha Tso DehAnita DurksenRazvan Romanescu10.1371/journal.pmed.10043482024-02-16T14:00:00Z2024-02-16T14:00:00Z<p>by Nathan C. Nickel, Wanda Phillips-Beck, Jennifer E. Enns, Okechukwu Ekuma, Carole Taylor, Sarah Fileatreault, Nkiru Eze, Leona Star, Josée Lavoie, Alan Katz, Marni Brownell, Alyson Mahar, Marcelo Urquia, Dan Chateau, Lisa Lix, Mariette Chartier, Emily Brownell, Miyosha Tso Deh, Anita Durksen, Razvan Romanescu</p>
Background <p>Differential access to healthcare has contributed to a higher burden of illness and mortality among First Nations compared to other people in Canada. Throughout the Coronavirus Disease 2019 (COVID-19) pandemic, First Nations organizations in Manitoba partnered with public health and Manitoba government officials to ensure First Nations had early, equitable and culturally safe access to COVID-19 diagnostic testing and vaccination. In this study, we examined whether prioritizing First Nations for vaccination was associated with faster uptake of COVID-19 vaccines among First Nations versus All Other Manitobans (AOM).</p> Methods and findings <p>In this retrospective cohort study, we used linked, whole-population administrative data from the Manitoba healthcare system (February 2020 to December 2021) to determine rates of COVID-19 diagnostic testing, infection, and vaccination, and used adjusted restricted mean survival time (RMST) models to test whether First Nations received their first and second vaccine doses more quickly than other Manitobans.The cohort comprised 114,816 First Nations (50.6% female) and 1,262,760 AOM (50.1% female). First Nations were younger (72.3% were age 0 to 39 years) compared to AOM (51% were age 0 to 39 years) and were overrepresented in the lowest 2 income quintiles (81.6% versus 35.6% for AOM). The 2 groups had a similar burden of comorbidities (65.8% of First Nations had none and 6.3% had 3 or more; 65.9% of AOM had none and 6.0% had 3 or more) and existing mental disorders (36.9% of First Nations were diagnosed with a mood/anxiety disorder, psychosis, personality disorder, or substance use disorder versus 35.2% of AOM).First Nations had crude infection rates of up to 17.20 (95% CI 17.15 to 17.24) COVID-19 infections/1,000 person-months compared with up to 6.24 (95% CI 6.16 to 6.32) infections/1,000 person-months among AOM. First Nations had crude diagnostic testing rates of up to 103.19 (95% CI 103.06 to 103.32) diagnostic COVID-19 tests/1,000 person-months compared with up to 61.52 (95% CI 61.47 to 61.57) tests/1,000 person-months among AOM. Prioritizing First Nations to receive vaccines was associated with faster vaccine uptake among First Nations versus other Manitobans. After adjusting for age, sex, income, region of residence, mental health conditions, and comorbidities, we found that First Nations residents received their first vaccine dose an average of 15.5 (95% CI 14.9 to 16.0) days sooner and their second dose 13.9 (95% CI 13.3 to 14.5) days sooner than other Manitobans in the same age group.The study was limited by the discontinuation of population-based COVID-19 testing and data collection in December 2021. As well, it would have been valuable to have contextual data on potential barriers to COVID-19 testing or vaccination, including, for example, information on social and structural barriers faced by Indigenous and other racialized people, or the distrust Indigenous people may have in governments due to historical harms.</p> Conclusion <p>In this study, we observed that the partnered COVID-19 response between First Nations and the Manitoba government, which oversaw creation and enactment of policies prioritizing First Nations for vaccines, was associated with vaccine acceptance and quick uptake among First Nations. This approach may serve as a useful framework for future public health efforts in Manitoba and other jurisdictions across Canada.</p>Health outcomes after myocardial infarction: A population study of 56 million people in EnglandMarlous HallLesley SmithJianhua WuChris HaywardJonathan A. BattyPaul C. LambertHarry HemingwayChris P. Gale10.1371/journal.pmed.10043432024-02-15T14:00:00Z2024-02-15T14:00:00Z<p>by Marlous Hall, Lesley Smith, Jianhua Wu, Chris Hayward, Jonathan A. Batty, Paul C. Lambert, Harry Hemingway, Chris P. Gale</p>
Background <p>The occurrence of a range of health outcomes following myocardial infarction (MI) is unknown. Therefore, this study aimed to determine the long-term risk of major health outcomes following MI and generate sociodemographic stratified risk charts in order to inform care recommendations in the post-MI period and underpin shared decision making.</p> Methods and findings <p>This nationwide cohort study includes all individuals aged ≥18 years admitted to one of 229 National Health Service (NHS) Trusts in England between 1 January 2008 and 31 January 2017 (final follow-up 27 March 2017). We analysed 11 non-fatal health outcomes (subsequent MI and first hospitalisation for heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes mellitus, dementia, depression, and cancer) and all-cause mortality. Of the 55,619,430 population of England, 34,116,257 individuals contributing to 145,912,852 hospitalisations were included (mean age 41.7 years (standard deviation [SD 26.1]); <i>n</i> = 14,747,198 (44.2%) male). There were 433,361 individuals with MI (mean age 67.4 years [SD 14.4)]; <i>n</i> = 283,742 (65.5%) male). Following MI, all-cause mortality was the most frequent event (adjusted cumulative incidence at 9 years 37.8% (95% confidence interval [CI] [37.6,37.9]), followed by heart failure (29.6%; 95% CI [29.4,29.7]), renal failure (27.2%; 95% CI [27.0,27.4]), atrial fibrillation (22.3%; 95% CI [22.2,22.5]), severe bleeding (19.0%; 95% CI [18.8,19.1]), diabetes (17.0%; 95% CI [16.9,17.1]), cancer (13.5%; 95% CI [13.3,13.6]), cerebrovascular disease (12.5%; 95% CI [12.4,12.7]), depression (8.9%; 95% CI [8.7,9.0]), dementia (7.8%; 95% CI [7.7,7.9]), subsequent MI (7.1%; 95% CI [7.0,7.2]), and peripheral arterial disease (6.5%; 95% CI [6.4,6.6]). Compared with a risk-set matched population of 2,001,310 individuals, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (adjusted hazard ratio [aHR] 1.01; 95% CI [0.99,1.02];<i>p</i> = 0.468) and cancer (aHR 0.56; 95% CI [0.56,0.57];<i>p</i> < 0.001).The study includes data from secondary care only—as such diagnoses made outside of secondary care may have been missed leading to the potential underestimation of the total burden of disease following MI.</p> Conclusions <p>In this study, up to a third of patients with MI developed heart failure or renal failure, 7% had another MI, and 38% died within 9 years (compared with 35% deaths among matched individuals). The incidence of all health outcomes, except dementia and cancer, was higher than expected during the normal life course without MI following adjustment for age, sex, year, and socioeconomic deprivation. Efforts targeted to prevent or limit the accrual of chronic, multisystem disease states following MI are needed and should be guided by the demographic-specific risk charts derived in this study.</p>Correction: Migraine and risk of premature myocardial infarction and stroke among men and women: A Danish population-based cohort studyCecilia Hvitfeldt FuglsangLars PedersenMorten SchmidtJan P. VandenbrouckeHans Erik BøtkerHenrik Toft Sørensen10.1371/journal.pmed.10043532024-02-13T14:00:00Z2024-02-13T14:00:00Z<p>by Cecilia Hvitfeldt Fuglsang, Lars Pedersen, Morten Schmidt, Jan P. Vandenbroucke, Hans Erik Bøtker, Henrik Toft Sørensen</p>Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohortLaury SellemBernard SrourGuillaume JavauxEloi ChazelasBenoit ChassaingEmilie ViennoisCharlotte DebrasNathalie Druesne-PecolloYounes EsseddikFabien Szabo de EdelenyiNathalie ArnaultCédric AgaësseAlexandre De SaRebecca LutchiaInge HuybrechtsAugustin ScalbertFabrice PierreXavier CoumoulChantal JuliaEmmanuelle Kesse-GuyotBenjamin AllèsPilar GalanSerge HercbergMélanie Deschasaux-TanguyMathilde Touvier10.1371/journal.pmed.10043382024-02-13T14:00:00Z2024-02-13T14:00:00Z<p>by Laury Sellem, Bernard Srour, Guillaume Javaux, Eloi Chazelas, Benoit Chassaing, Emilie Viennois, Charlotte Debras, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Nathalie Arnault, Cédric Agaësse, Alexandre De Sa, Rebecca Lutchia, Inge Huybrechts, Augustin Scalbert, Fabrice Pierre, Xavier Coumoul, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Pilar Galan, Serge Hercberg, Mélanie Deschasaux-Tanguy, Mathilde Touvier</p>
Background <p>Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort.</p> Methods and findings <p>This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR <sub>high vs. low category</sub> = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design.</p> Conclusions <p>In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk.</p> Trial registration <p>ClinicalTrials.gov NCT03335644.</p>Fetal loss and long-term maternal morbidity and mortality: A systematic review and meta-analysisFlorentia VlachouDespoina IakovouJahnavi DaruRehan KhanLitha PepasSiobhan QuenbyStamatina Iliodromiti10.1371/journal.pmed.10043422024-02-09T14:00:00Z2024-02-09T14:00:00Z<p>by Florentia Vlachou, Despoina Iakovou, Jahnavi Daru, Rehan Khan, Litha Pepas, Siobhan Quenby, Stamatina Iliodromiti</p>
Background <p>Evidence suggests common pathways between pregnancy losses and subsequent long-term maternal morbidity, rendering pregnancy complications an early chronic disease marker. There is a plethora of studies exploring associations between miscarriage and stillbirth with long-term adverse maternal health; however, these data are inconclusive.</p> Methods and findings <p>We systematically searched MEDLINE, EMBASE, AMED, BNI, CINAHL, and the Cochrane Library with relevant keywords and MeSH terms from inception to June 2023 (no language restrictions). We included studies exploring associations between stillbirth or miscarriage and incidence of cardiovascular, malignancy, mental health, other morbidities, and all-cause mortality in women without previous pregnancy loss. Studies reporting short-term morbidity (within a year of loss), case reports, letters, and animal studies were excluded. Study selection and data extraction were performed by 2 independent reviewers. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS) and publication bias with funnel plots. Subgroup analysis explored the effect of recurrent losses on adverse outcomes. Statistical analysis was performed using an inverse variance random effects model and results are reported as risk ratios (RRs) with 95% confidence intervals (CIs) and prediction intervals (PIs) by combining the most adjusted RR, odds ratios (ORs) and hazard ratios (HRs) under the rare outcome assumption. We included 56 observational studies, including 45 in meta-analysis. There were 1,119,815 women who experienced pregnancy loss of whom 951,258 had a miscarriage and 168,557 stillbirth, compared with 11,965,574 women without previous loss. Women with a history of stillbirth had a greater risk of ischaemic heart disease (IHD) RR 1.56, 95% CI [1.30, 1.88]; <i>p</i> < 0.001, 95% PI [0.49 to 5.15]), cerebrovascular (RR 1.71, 95% CI [1.44, 2.03], <i>p</i> < 0.001, 95% PI [1.92, 2.42]), and any circulatory/cardiovascular disease (RR 1.86, 95% CI [1.01, 3.45], <i>p</i> = 0.05, 95% PI [0.74, 4.10]) compared with women without pregnancy loss. There was no evidence of increased risk of cardiovascular disease (IHD: RR 1.11, 95% CI [0.98, 1.27], 95% PI [0.46, 2.76] or cerebrovascular: RR 1.01, 95% CI [0.85, 1.21]) in women experiencing a miscarriage. Only women with a previous stillbirth were more likely to develop type 2 diabetes mellitus (T2DM) (RR: 1.16, 95% CI [1.07 to 2.26]; <i>p</i> < 0.001, 95% PI [1.05, 1.35]). Women with a stillbirth history had an increased risk of developing renal morbidities (RR 1.97, 95% CI [1.51, 2.57], <i>p</i> < 0.001, 95% [1.06, 4.72]) compared with controls. Women with a history of stillbirth had lower risk of breast cancer (RR: 0.80, 95% CI [0.67, 0.96], p-0.02, 95% PI [0.72, 0.93]). There was no evidence of altered risk of other malignancies in women experiencing pregnancy loss compared to controls. There was no evidence of long-term mental illness risk in women with previous pregnancy losses (stillbirth: RR 1.90, 95% CI [0.93, 3.88], 95% PI [0.34, 9.51], miscarriage: RR 1.78, 95% CI [0.88, 3.63], 95% PI [1.13, 4.16]). The main limitations include the potential for confounding due to use of aggregated data with variable degrees of adjustment.</p> Conclusions <p>Our results suggest that women with a history of stillbirth have a greater risk of future cardiovascular disease, T2DM, and renal morbidities. Women experiencing miscarriages, single or multiple, do not seem to have an altered risk.</p>Use of isotretinoin among girls and women of childbearing age and occurrence of isotretinoin-exposed pregnancies in Germany: A population-based studyJonas ReinoldBianca KollhorstNadine WentzellKatharina PlatzbeckerUlrike Haug10.1371/journal.pmed.10043392024-01-25T14:00:00Z2024-01-25T14:00:00Z<p>by Jonas Reinold, Bianca Kollhorst, Nadine Wentzell, Katharina Platzbecker, Ulrike Haug</p>
Background <p>Exposure to isotretinoin during pregnancy must be avoided due to its teratogenicity, but real-world data on its use are scarce. We aimed to describe (i) isotretinoin use in women of childbearing age in Germany; (ii) the occurrence of isotretinoin-exposed pregnancies; and (iii) malformations among children exposed in utero.</p> Methods and findings <p>Using observational data from the German Pharmacoepidemiological Research Database (GePaRD, claims data from approximately 20% of the German population), we conducted annual cross-sectional analyses to determine age-standardized prevalence of isotretinoin use between 2004 and 2019 among girls and women aged 13 to 49 years. In cohort analyses, we estimated the number of exposed pregnancies by assessing whether there was prescription supply overlapping the beginning of pregnancy (estimated supply was varied in sensitivity analyses) or a dispensation within the first 8 weeks of pregnancy. Data of live-born children classified as exposed in a critical period according to these criteria were reviewed to assess the presence of congenital malformations.The age-standardized prevalence of isotretinoin use per 1,000 girls and women increased from 1.20 (95% confidence interval [CI]: 1.16, 1.24) in 2004 to 1.96 (95% CI: 1.92, 2.01) in 2019. In the base case analysis, we identified 178 pregnancies exposed to isotretinoin, with the number per year doubling during the study period, and at least 45% of exposed pregnancies ended in an induced abortion. In sensitivity analyses, the number of exposed pregnancies ranged between 172 and 375. Among live-born children, 6 had major congenital malformations. The main limitation of this study was the lack of information on the prescribed dose, i.e., the supply had to be estimated based on the dispensed amount of isotretinoin.</p> Conclusions <p>Isotretinoin use among girls and women of childbearing age increased in Germany between 2004 and 2019, and there was a considerable number of pregnancies likely exposed to isotretinoin in a critical period. This highlights the importance of monitoring compliance with the existing risk minimization measures for isotretinoin in Germany.</p>Mental health in the COVID-19 pandemic: A longitudinal analysis of the CLoCk cohort studyLaura PanagiSimon R. WhiteSnehal M. Pinto PereiraManjula D. NugawelaIsobel HeymanKishan SharmaTerence StephensonTrudie ChalderNatalia K. RojasEmma DalrympleKelsey McOwatRuth SimmonsOlivia SwannCLoCk ConsortiumTamsin FordRoz Shafran10.1371/journal.pmed.10043152024-01-24T14:00:00Z2024-01-24T14:00:00Z<p>by Laura Panagi, Simon R. White, Snehal M. Pinto Pereira, Manjula D. Nugawela, Isobel Heyman, Kishan Sharma, Terence Stephenson, Trudie Chalder, Natalia K. Rojas, Emma Dalrymple, Kelsey McOwat, Ruth Simmons, Olivia Swann, CLoCk Consortium , Tamsin Ford, Roz Shafran</p>
Background <p>Little is known about the long-term mental health consequences of the pandemic in children and young people (CYP), despite extremely high levels of exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus and the disruption to schooling and leisure activities due to the resultant restrictions. There are mixed findings from systematic reviews of how the pandemic affected CYP’s mental health, which may be due to heterogeneous methods and poor quality studies. Most, but not all, suggest deterioration in mental health but population level studies may obscure the differing experiences of subgroups. The study questions are: (i) are there subgroups of CYP with distinct mental health profiles over the course of the second year of the Coronavirus Disease 2019 (COVID-19) pandemic (between April 2021 and May 2022); and (ii) do vulnerability factors influence CYP’s mental health trajectories.</p> Methods and findings <p>A matched longitudinal cohort study of non-hospitalised test-positive and test-negative 11- to 17-year-old CYP in England were recruited from the UK Health Security Agency having undergone PCR testing for COVID-19. They completed the Strengths and Difficulties Questionnaire (SDQ) at least twice over a 12-month follow-up period. Overall, 8,518 of 17,918 (47.5%) CYP who returned their first SDQ at 3 or 6 months post-testing were included in the analytical sample. Associations between age, sex, ethnicity, socioeconomic status (SES), and an educational health and care plan (EHCP, indicating special educational needs) on SDQ score trajectories were examined separately, after adjusting for PCR test result. Findings from multilevel mixed-effects linear regression model showed that on average mental health symptoms as measured by the total SDQ score increased over time (<i>B</i> = 0.11 (per month), 95% CI = 0.09 to 0.12, <i>p</i> < 0.001) although this increase was small and not clinically significant. However, associations with time varied by age, such that older participants reported greater deterioration in mental health over time (<i>B</i> = 0.12 (per month), 95% CI = 0.10 to 0.14 for 15 to 17y; 0.08 (95% CI = 0.06 to 0.10) for 11 to 14y; p<sub>interaction</sub> = 0.002) and by sex, with greater deterioration in girls. Children with an EHCP experienced less deterioration in their mental health compared to those without an EHCP. There was no evidence of differences in rate of change in total SDQ by ethnicity, SES, or physical health. Those with worse prior mental health did not appear to be disproportionately negatively affected over time. There are several limitations of the methodology including relatively low response rates in CLoCk and potential for recall bias.</p> Conclusions <p>Overall, there was a statistically but not clinically significant decline in mental health during the pandemic. Sex, age, and EHCP status were important vulnerability factors that were associated with the rate of mental health decline, whereas ethnicity, SES, and prior poor physical health were not. The research highlights individual factors that could identify groups of CYP vulnerable to worsening mental health.</p>Single-dose azithromycin for infant growth in Burkina Faso: Prespecified secondary anthropometric outcomes from a randomized controlled trialAli SiéMamadou OuattaraMamadou BountogoClarisse DahThierry OuedraogoValentin BoudoElodie LebasHuiyu HuBenjamin F. ArnoldKieran S. O’BrienThomas M. LietmanCatherine E. Oldenburg10.1371/journal.pmed.10043452024-01-23T14:00:00Z2024-01-23T14:00:00Z<p>by Ali Sié, Mamadou Ouattara, Mamadou Bountogo, Clarisse Dah, Thierry Ouedraogo, Valentin Boudo, Elodie Lebas, Huiyu Hu, Benjamin F. Arnold, Kieran S. O’Brien, Thomas M. Lietman, Catherine E. Oldenburg</p>
Background <p>Antibiotic use during early infancy has been linked to childhood obesity in high-income countries. We evaluated whether a single oral dose of azithromycin administered during infant-well visits led to changes in infant growth outcomes at 6 months of age in a setting with a high prevalence of undernutrition in rural Burkina Faso.</p> Methods and findings <p>Infants were enrolled from September 25, 2019, until October 22, 2022, in a randomized controlled trial designed to evaluate the efficacy of a single oral dose of azithromycin (20 mg/kg) compared to placebo when administered during well-child visits for prevention of infant mortality. The trial found no evidence of a difference in the primary endpoint. This paper presents prespecified secondary anthropometric endpoints including weight gain (g/day), height change (mm/day), weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and mid-upper arm circumference (MUAC). Infants were eligible for the trial if they were between 5 and 12 weeks of age, able to orally feed, and their families were planning to remain in the study area for the duration of the study. Anthropometric measurements were collected at enrollment (5 to 12 weeks of age) and 6 months of age. Among 32,877 infants enrolled in the trial, 27,298 (83%) were followed and had valid anthropometric measurements at 6 months of age. We found no evidence of a difference in weight gain (mean difference 0.03 g/day, 95% confidence interval (CI) −0.12 to 0.18), height change (mean difference 0.004 mm/day, 95% CI −0.05 to 0.06), WAZ (mean difference −0.004 SD, 95% CI −0.03 to 0.02), WLZ (mean difference 0.001 SD, 95% CI −0.03 to 0.03), LAZ (mean difference −0.005 SD, 95% CI −0.03 to 0.02), or MUAC (mean difference 0.01 cm, 95% CI −0.01 to 0.04). The primary limitation of the trial was that measurements were only collected at enrollment and 6 months of age, precluding assessment of shorter-term or long-term changes in growth.</p> Conclusions <p>Single-dose azithromycin does not appear to affect weight and height outcomes when administered during early infancy.</p> Trial registration <p>ClinicalTrials.gov NCT03676764</p>Association of a healthy beverage score with total mortality in the adult population of Spain: A nationwide cohort studyMontserrat Rodríguez-AyalaCarolina Donat-VargasBelén Moreno-FrancoDiana María MéridaJosé Ramón BanegasFernando Rodríguez-ArtalejoPilar Guallar-Castillón10.1371/journal.pmed.10043372024-01-23T14:00:00Z2024-01-23T14:00:00Z<p>by Montserrat Rodríguez-Ayala, Carolina Donat-Vargas, Belén Moreno-Franco, Diana María Mérida, José Ramón Banegas, Fernando Rodríguez-Artalejo, Pilar Guallar-Castillón</p>
Background <p>Despite the substantial evidence of the relationship between diet and mortality, the role of beverage consumption patterns is not well known. The aim of this study was to assess the association of the adherence to a Healthy Beverage Score (HBS) and all-cause mortality in a representative sample of the Spanish adult population.</p> Methods and findings <p>We conducted an observational cohort study using data from the Study on Nutrition and Cardiovascular Risk in Spain (ENRICA), which included 12,161 community-dwelling individuals aged ≥18 years recruited in 2008 to 2010 and followed until January 2022. At baseline, food consumption was collected using a validated diet history. The HBS consists of 7 items, each of which is scored from 1 to 4 (highest adherence). The HBS ranges from 7 to 28 points with a higher score representing a healthier pattern. Adherence was assigned as a higher consumption of low-fat milk, and coffee and tea, a lower consumption of whole-fat milk, no consumption of fruit juice, artificially sweetened beverages, or sugar-sweetened beverages, and no or moderate consumption of alcohol. Total mortality was ascertained by linkage to the Spanish National Death Index. Statistical analyses were performed with Cox models and adjusted for the main confounders, including sociodemographic, lifestyle, dietary variables, and morbidity.After a mean follow-up of 12.5 years (SD: 1.7; range: 0.5 to 12.9), a total of 967 deaths occurred. For all-cause mortality, the fully adjusted hazard ratio (HR) for the highest versus lowest sex-specific quartiles of HBS was 0.72 (95% confidence interval [0.57, 0.91], p linear-trend = 0.015), corresponding to an 8.3% reduction in the absolute risk of death. A linear relationship between the risk of death and the adherence to the HBS was observed using restricted cubic splines. The results were robust to sensitivity analyses. The main limitation was that repeated measurements on beverage consumption were not available and beverage consumption could have changed during follow-up.</p> Conclusions <p>In this study, we observed that higher adherence to the HBS was associated with lower total mortality. Adherence to a healthy beverage pattern could play a role in the prevention of premature mortality.</p>1-year weight change after diabetes diagnosis and long-term incidence and sustainability of remission of type 2 diabetes in real-world settings in Hong Kong: An observational cohort studyHongjiang WuAimin YangEric S. H. LauXinge ZhangBaoqi FanRonald C. W. MaAlice P. S. KongElaine ChowWing-Yee SoJuliana C. N. ChanAndrea O. Y. Luk10.1371/journal.pmed.10043272024-01-23T14:00:00Z2024-01-23T14:00:00Z<p>by Hongjiang Wu, Aimin Yang, Eric S. H. Lau, Xinge Zhang, Baoqi Fan, Ronald C. W. Ma, Alice P. S. Kong, Elaine Chow, Wing-Yee So, Juliana C. N. Chan, Andrea O. Y. Luk</p>
Background <p>Clinical trials have demonstrated that remission of type 2 diabetes can be achieved following sustained weight loss. However, the feasibility of achieving diabetes remission through weight management in real-world settings remains unclear. In this study, we aimed to examine the association of weight change at 1 year after diabetes diagnosis with long-term incidence and sustainability of type 2 diabetes remission in real-world settings in Hong Kong.</p> Methods and findings <p>This was a population-based observational cohort study. The territory-wide Risk Assessment and Management Programme for Diabetes Mellitus (RAMP-DM) provides regular comprehensive assessments of metabolic control and complication screening for people with diabetes in Hong Kong. We included 37,326 people with newly diagnosed type 2 diabetes who were enrolled in the RAMP-DM between 2000 and 2017, followed until 2019. Diabetes remission was defined as 2 consecutive HbA1c <6.5% measurements at least 6 months apart in the absence of glucose-lowering drugs (GLDs) and with no record of GLDs at least 3 months before these measurements. During a median follow-up of 7.9 years, 6.1% (2,279) of people achieved diabetes remission, with an incidence rate of 7.8 (95% CI: 7.5, 8.1) per 1,000 person-years. After adjusting for age at diabetes diagnosis, sex, assessment year, body mass index, other metabolic indices, smoking, alcohol drinking, and medication use, the hazard ratio (HR) for diabetes remission was 3.28 (95% CI: 2.75, 3.92; <i>p</i> < 0.001) for people with ≥10% weight loss within 1 year of diagnosis, 2.29 (95% CI: 2.03, 2.59; <i>p</i> < 0.001) for those with 5% to 9.9% weight loss, and 1.34 (95% CI: 1.22, 1.47; <i>p</i> < 0.001) for those with 0% to 4.9% weight loss compared to people with weight gain. During a median follow-up of 3.1 years, 67.2% (1,531) of people who had achieved diabetes remission returned to hyperglycaemia, with an incidence rate of 184.8 (95% CI: 175.5, 194.0) per 1,000 person-years. The adjusted HR for returning to hyperglycaemia was 0.52 (95% CI: 0.41, 0.65; <i>p</i> < 0.001) for people with ≥10% weight loss, 0.78 (95% CI: 0.68, 0.92; <i>p</i> = 0.002) for those with 5% to 9.9% weight loss, and 0.90 (95% CI: 0.80, 1.01; <i>p</i> = 0.073) for those with 0% to 4.9% weight loss compared to people with weight gain. Diabetes remission was associated with a 31% (HR: 0.69, 95% CI: 0.52, 0.93; <i>p</i> = 0.014) decreased risk of all-cause mortality. The main limitation of the study is that the reliability of HbA1c used to define diabetes remission can be affected by other medical conditions. Furthermore, we did not have data on bariatric surgery.</p> Conclusions <p>In this study, greater weight loss within the first year of diabetes diagnosis was associated with an increased likelihood of achieving diabetes remission and a decreased risk of returning to hyperglycaemia among those who had achieved diabetes remission. However, both the incidence of diabetes remission and the probability of its long-term sustainability were low with conventional management in real-world settings, in an era when the importance of weight loss was not fully appreciated. Our study provides evidence for policymakers to design and implement early weight management interventions and diabetes remission initiatives.</p>ACCORD (ACcurate COnsensus Reporting Document): A reporting guideline for consensus methods in biomedicine developed via a modified DelphiWilliam T. GattrellPatricia LogulloEsther J. van ZuurenAmy PriceEllen L. HughesPaul BlazeyChristopher C. WinchesterDavid ToveyKeith GoldmanAmrit Pali HunginNiall Harrison10.1371/journal.pmed.10043262024-01-23T14:00:00Z2024-01-23T14:00:00Z<p>by William T. Gattrell, Patricia Logullo, Esther J. van Zuuren, Amy Price, Ellen L. Hughes, Paul Blazey, Christopher C. Winchester, David Tovey, Keith Goldman, Amrit Pali Hungin, Niall Harrison</p>
Background <p>In biomedical research, it is often desirable to seek consensus among individuals who have differing perspectives and experience. This is important when evidence is emerging, inconsistent, limited, or absent. Even when research evidence is abundant, clinical recommendations, policy decisions, and priority-setting may still require agreement from multiple, sometimes ideologically opposed parties. Despite their prominence and influence on key decisions, consensus methods are often poorly reported. Our aim was to develop the first reporting guideline dedicated to and applicable to all consensus methods used in biomedical research regardless of the objective of the consensus process, called ACCORD (ACcurate COnsensus Reporting Document).</p> Methods and findings <p>We followed methodology recommended by the EQUATOR Network for the development of reporting guidelines: a systematic review was followed by a Delphi process and meetings to finalize the ACCORD checklist. The preliminary checklist was drawn from the systematic review of existing literature on the quality of reporting of consensus methods and suggestions from the Steering Committee. A Delphi panel (<i>n</i> = 72) was recruited with representation from 6 continents and a broad range of experience, including clinical, research, policy, and patient perspectives. The 3 rounds of the Delphi process were completed by 58, 54, and 51 panelists. The preliminary checklist of 56 items was refined to a final checklist of 35 items relating to the article title (<i>n</i> = 1), introduction (<i>n</i> = 3), methods (<i>n</i> = 21), results (<i>n</i> = 5), discussion (<i>n</i> = 2), and other information (<i>n</i> = 3).</p> Conclusions <p>The ACCORD checklist is the first reporting guideline applicable to all consensus-based studies. It will support authors in writing accurate, detailed manuscripts, thereby improving the completeness and transparency of reporting and providing readers with clarity regarding the methods used to reach agreement. Furthermore, the checklist will make the rigor of the consensus methods used to guide the recommendations clear for readers. Reporting consensus studies with greater clarity and transparency may enhance trust in the recommendations made by consensus panels.</p>Health system assessment for access to care after injury in low- or middle-income countries: A mixed methods study from Northern MalawiJohn WhitakerIdara EdemElla TogunAbena S. AmoahAlbert DubeLindani ChirwaBoston MunthaliGiulia BrunelliThomas Van BoeckelRory RickardAndrew JM LeatherJustine Davies10.1371/journal.pmed.10043442024-01-22T14:00:00Z2024-01-22T14:00:00Z<p>by John Whitaker, Idara Edem, Ella Togun, Abena S. Amoah, Albert Dube, Lindani Chirwa, Boston Munthali, Giulia Brunelli, Thomas Van Boeckel, Rory Rickard, Andrew JM Leather, Justine Davies</p>
Background <p>Injuries represent a vast and relatively neglected burden of disease affecting low- and middle-income countries (LMICs). While many health systems underperform in treating injured patients, most assessments have not considered the whole system. We integrated findings from 9 methods using a 3 delays approach (delays in seeking, reaching, or receiving care) to prioritise important trauma care health system barriers in Karonga, Northern Malawi, and exemplify a holistic health system assessment approach applicable in comparable settings.</p> Methods and findings <p>To provide multiple perspectives on each conceptual delay and include data from community-based and facility-based sources, we used 9 methods to examine the injury care health system. The methods were (1) household survey; (2) verbal autopsy analysis; (3) community focus group discussions (FGDs); (4) community photovoice; (5) facility care-pathway process mapping and elucidation of barriers following injury; (6) facility healthcare worker survey; (7) facility assessment survey; (8) clinical vignettes for care process quality assessment of facility-based healthcare workers; and (9) geographic information system (GIS) analysis. Empirical data collection took place in Karonga, Northern Malawi, between July 2019 and February 2020. We used a convergent parallel study design concurrently conducting all data collection before subsequently integrating results for interpretation. For each delay, a matrix was created to juxtapose method-specific data relevant to each barrier identified as driving delays to injury care. Using a consensus approach, we graded the evidence from each method as to whether an identified barrier was important within the health system.We identified 26 barriers to access timely quality injury care evidenced by at least 3 of the 9 study methods. There were 10 barriers at delay 1, 6 at delay 2, and 10 at delay 3. We found that the barriers “cost,” “transport,” and “physical resources” had the most methods providing strong evidence they were important health system barriers within delays 1 (seeking care), 2 (reaching care), and 3 (receiving care), respectively. Facility process mapping provided evidence for the greatest number of barriers—25 of 26 within the integrated analysis. There were some barriers with notable divergent findings between the community- and facility-based methods, as well as among different community- and facility-based methods, which are discussed. The main limitation of our study is that the framework for grading evidence strength for important health system barriers across the 9 studies was done by author-derived consensus; other researchers might have created a different framework.</p> Conclusions <p>By integrating 9 different methods, including qualitative, quantitative, community-, patient-, and healthcare worker-derived data sources, we gained a rich insight into the functioning of this health system’s ability to provide injury care. This approach allowed more holistic appraisal of this health system’s issues by establishing convergence of evidence across the diverse methods used that the barriers of cost, transport, and physical resources were the most important health system barriers driving delays to seeking, reaching, and receiving injury care, respectively. This offers direction and confidence, over and above that derived from single methodology studies, for prioritising barriers to address through health service development and policy.</p>Tropical cyclone-specific mortality risks and the periods of concern: A multicountry time-series studyWenzhong HuangZhengyu YangYiwen ZhangThomas VogtBen ArmstrongWenhua YuRongbin XuPei YuYanming LiuAntonio GasparriniSamuel HundessaEric LavigneTomas MolinaTobias GeigerYue Leon GuoChristian OttoSimon HalesFarnaz PourzandShih-Chun PanKe JuElizabeth A. RitchieShanshan LiYuming GuoMCC Collaborators10.1371/journal.pmed.10043412024-01-22T14:00:00Z2024-01-22T14:00:00Z<p>by Wenzhong Huang, Zhengyu Yang, Yiwen Zhang, Thomas Vogt, Ben Armstrong, Wenhua Yu, Rongbin Xu, Pei Yu, Yanming Liu, Antonio Gasparrini, Samuel Hundessa, Eric Lavigne, Tomas Molina, Tobias Geiger, Yue Leon Guo, Christian Otto, Simon Hales, Farnaz Pourzand, Shih-Chun Pan, Ke Ju, Elizabeth A. Ritchie, Shanshan Li, Yuming Guo, MCC Collaborators </p>
Background <p>More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale.</p> Methods and findings <p>Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan.</p> Conclusions <p>The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability.</p>Understudied and underaddressed: Femicide, an extreme form of violence against women and girlsChen ReisSarah R. Meyer10.1371/journal.pmed.10043362024-01-18T14:00:00Z2024-01-18T14:00:00Z<p>by Chen Reis, Sarah R. Meyer</p>
Little is known about the prevalence and dynamics of femicide, a persistent form of violence against women and girls, due to challenges associated with its documentation. Research by Abrahams and colleagues comparing rates of femicide in South Africa over 18 years, however, suggests that femicide is preventable.
In this Perspective, Chen Reis and Sarah Meyer discuss the incidence and dynamics of femicide globally and highlight the urgent need for better data and documentation to enact policies aimed at prevention, early detection, and timely intervention in cases of femicide.Femicide, intimate partner femicide, and non-intimate partner femicide in South Africa: An analysis of 3 national surveys, 1999–2017Naeemah AbrahamsShibe MhlongoEsnat ChirwaBianca DekelAsiphe KeteloCarl LombardNwabisa ShaiLeane RamsoomarShanaaz MathewsGérard LabuschagneRichard MatzopoulosMegan PrinslooLorna J. MartinRachel Jewkes10.1371/journal.pmed.10043302024-01-18T14:00:00Z2024-01-18T14:00:00Z<p>by Naeemah Abrahams, Shibe Mhlongo, Esnat Chirwa, Bianca Dekel, Asiphe Ketelo, Carl Lombard, Nwabisa Shai, Leane Ramsoomar, Shanaaz Mathews, Gérard Labuschagne, Richard Matzopoulos, Megan Prinsloo, Lorna J. Martin, Rachel Jewkes</p>
Background <p>In most countries, reliable national statistics on femicide, intimate partner femicide (IPF), and non-intimate partner femicide (NIPF) are not available. Surveys are required to collect robust data on this most extreme consequence of intimate partner violence (IPV). We analysed 3 national surveys to compare femicide, IPF, and NIPF from 1999 to 2017 using age-standardised rates (ASRs) and incidence rate ratios (IRRs).</p> Methods and findings <p>We conducted 3 national mortuary-based retrospective surveys using weighted cluster designs from proportionate random samples of medicolegal laboratories. We included females 14 years and older who were identified as having been murdered in South Africa in 1999 (<i>n</i> = 3,793), 2009 (<i>n</i> = 2,363), and 2017 (<i>n</i> = 2,407). Further information on the murdered cases were collected from crime dockets during interviews with police investigating officers. Our findings show that South Africa had an IPF rate of 4.9/100,000 female population in 2017. All forms of femicide among women 14 years and older declined from 1999 to 2017. For IPF, the ASR was 9.5/100,000 in 1999. Between 1999 and 2009, the decline for NIPF was greater than for IPF (IRR for NIPF 0.47 (95% confidence interval (CI) 0.42 to 0.53) compared to IRR for IPF 0.69 (95% CI 0.63 to 0.77). Rates declined from 2009 to 2017 and did not differ by femicide type. The decline in IPF was initially larger for women aged 14 to 29, and after 2009, it was more pronounced for those aged 30 to 44 years. Study limitations include missing data from the police and having to use imputation to account for missing perpetrator data.</p> Conclusions <p>In this study, we observed a reduction in femicide overall and different patterns of change in IPF compared to NIPF. The explanation for the reductions may be due to social and policy interventions aimed at reducing IPV overall, coupled with increased social and economic stability. Our study shows that gender-based violence is preventable even in high-prevalence settings, and evidence-based prevention efforts must be intensified globally. We also show the value of dedicated surveys in the absence of functional information systems.</p>Impact on wine sales of removing the largest serving size by the glass: An A-B-A reversal trial in 21 pubs, bars, and restaurants in EnglandEleni MantzariMinna VentselEmily PecheyIlse LeeMark A. PillingGareth J. HollandsTheresa M. Marteau10.1371/journal.pmed.10043132024-01-18T14:00:00Z2024-01-18T14:00:00Z<p>by Eleni Mantzari, Minna Ventsel, Emily Pechey, Ilse Lee, Mark A. Pilling, Gareth J. Hollands, Theresa M. Marteau</p>
Background <p>Interventions that alter aspects of the physical environments in which unhealthy behaviours occur have the potential to change behaviour at scale, i.e., across populations, and thereby decrease the risk of several diseases. One set of such interventions involves reducing serving sizes, which could reduce alcohol consumption. The effect of modifying the available range of serving sizes of wine in a real-world setting is unknown. We aimed to assess the impact on the volume of wine sold of removing the largest serving size by the glass from the options available in licensed premises.</p> Methods and findings <p>The study was conducted between September 2021 and May 2022 in 21 licensed premises in England that sold wine by the glass in serving sizes greater than 125 ml (i.e., 175 ml or 250 ml) and used an electronic point of sale till system. It used an A-B-A reversal design, set over 3 four-weekly periods. “A” represented the nonintervention periods during which standard serving sizes were served and “B” the intervention period when the largest serving size for a glass of wine was removed from the existing range in each establishment: 250 ml (18 premises) or 175 ml (3 premises). The primary outcome was the daily volume of wine sold, extracted from sales data. Twenty-one premises completed the study, 20 of which did so per protocol and were included in the primary analysis. After adjusting for prespecified covariates, the intervention resulted in −420·8 millilitres (ml) (95% confidence intervals (CIs) −681·4 to −160·2 <i>p</i> = 0·002) or −7·6% (95% CI −12·3%, −2·9%) less wine being sold per day. There was no evidence that sales of beer and cider or total daily revenues changed but the study was not powered to detect differences in these outcomes. The main study limitation is that we were unable to assess the sales of other alcoholic drinks apart from wine, beer, and cider, estimated to comprise approximately 30% of alcoholic drinks sold in participating premises.</p> Conclusions <p>Removing the largest serving size of wine by the glass from those available reduced the volume of wine sold. This promising intervention for decreasing alcohol consumption across populations merits consideration as part of alcohol licensing regulations.</p> Trial registration <p>ISRCTN https://doi.org/10.1186/ISRCTN33169631; OSF https://osf.io/xkgdb.</p>Maternal intrahepatic cholestasis of pregnancy and neurodevelopmental conditions in offspring: A population-based cohort study of 2 million Swedish childrenShuyun ChenViktor H. AhlqvistHugo SjöqvistOlof StephanssonCecilia MagnussonChristina DalmanHåkan KarlssonBrian K. LeeRenee M. Gardner10.1371/journal.pmed.10043312024-01-16T14:00:00Z2024-01-16T14:00:00Z<p>by Shuyun Chen, Viktor H. Ahlqvist, Hugo Sjöqvist, Olof Stephansson, Cecilia Magnusson, Christina Dalman, Håkan Karlsson, Brian K. Lee, Renee M. Gardner</p>
Background <p>Intrahepatic cholestasis of pregnancy (ICP) is the most common obstetric liver disorder and is associated with an increased risk of iatrogenic preterm birth and adverse infant outcomes. Hence, there are several plausible pathways through which ICP could affect offspring neurodevelopment. However, to the best of our knowledge, no studies have investigated these associations. Thus, we aimed to determine whether ICP is associated with offspring neurodevelopmental conditions.</p> Methods and findings <p>In this Swedish register-based cohort study, we included singleton non-adopted children born in Sweden between the 1st of January 1987 and the 31st of December 2010, who were resident in Sweden >5 years, with no missing covariate information, which we followed until the 31st of December 2016. Maternal ICP diagnosis and the date of the initial diagnosis during pregnancy were obtained from the National Patient Register. Offspring diagnoses of attention deficit/hyperactivity disorder (ADHD), autism, or intellectual disability were obtained from the National Patient Register, and the dispensation of ADHD medications were obtained from the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression while controlling for observed confounders and unobserved confounders shared among full siblings and maternal full cousins.A total of 2,375,856 children were included in the study; 81.6% of them were of Nordic origin, and 51.4% were male. Of these, 10,378 (0.44%) were exposed to ICP. During a median of 18 years follow-up (interquartile range 11 to 24), 143,746 (6.05%) of children were diagnosed with a neurodevelopmental condition. After adjusting for child’s sex, birth year, birth month, maternal age, highest parental education level, maternal birth country, birth order, maternal psychiatric history, ICP was associated with increased odds of offspring neurodevelopmental conditions (OR 1.22, 95% CI 1.13 to 1.31), particularly among those exposed to early-onset ICP (OR 2.38, 95% CI 1.71 to 3.30) as compared to ICP diagnosed after reaching term (≥37 weeks of gestation) (OR 1.08, 95% CI 0.97 to 1.20). The findings of early-onset ICP were consistent in family-based analyses. Within-family comparisons of full maternal cousins yielded an OR of 2.99 (95% CI 1.48 to 6.04), and comparisons of full siblings showed an OR of 1.92 (95% CI 0.92 to 4.02), though the latter was less precise. The findings were consistent across specific neurodevelopmental conditions and different analytical approaches. The primary limitations of this study included its observational design, the absence of data on ICP therapeutics, and the lack of bile acid measures.</p> Conclusions <p>In this study, we observed that exposure to ICP during gestation is associated with an increased likelihood of neurodevelopmental conditions in offspring, particularly in cases of early-onset ICP. Further studies are warranted to better understand the role of early-ICP in offspring neurodevelopment.</p>Suicide attempt and death by suicide among parents of young individuals with cancer: A population-based study in Denmark and SwedenQianwei LiuKrisztina D. LászlóDang WeiFen YangKatja FallUnnur ValdimarsdóttirMaria FeychtingJiong LiFang Fang10.1371/journal.pmed.10043222024-01-16T14:00:00Z2024-01-16T14:00:00Z<p>by Qianwei Liu, Krisztina D. László, Dang Wei, Fen Yang, Katja Fall, Unnur Valdimarsdóttir, Maria Feychting, Jiong Li, Fang Fang</p>
Background <p>The psychological toll on parents of a child receiving a cancer diagnosis is known to be high, but there is a knowledge gap regarding suicidal behavior among these parents. The aim of this study was to investigate the risk of suicide attempt and death by suicide in relation to having a child with cancer.</p> Methods and findings <p>We performed a binational population-based and sibling-controlled cohort study, including all parents with a child diagnosed with cancer in Denmark (1978 to 2016) or Sweden (1973 to 2014), 10 matched unexposed parents per exposed parent (population comparison), and unaffected full siblings of the exposed parents (sibling comparison). Suicide attempt was identified through the Patient Register and the Psychiatric Central Register in Denmark and the Patient Register in Sweden, whereas death by suicide was identified through the Danish Causes of Death Register and the Swedish Causes of Death Register. In population comparison, we used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of suicide attempt and death by suicide associated with cancer diagnosis of a child, adjusting for sex, age, country of residence, calendar year, marital status, highest attained educational level, household income, history of cancer, history of psychiatric disorder, and family history of psychiatric disorder. The sibling comparison was performed to assess the role of familial confounding in the studied associations.The population comparison consisted of 106,005 exposed parents and 1,060,050 matched unexposed parents, with a median age of 56 at cohort entry and 46.9% male. During the median follow-up of 7.3 and 7.2 years, we observed 613 (incidence rate [IR], 58.8 per 100,000 person-years) and 5,888 (IR, 57.1 per 100,000 person-years) cases of first-onset suicide attempt among the exposed and unexposed parents, respectively. There was an increased risk of parental suicide attempt during the first years after a child’s cancer diagnosis (HR, 1.15; 95% CI, [1.03, 1.28]; <i>p</i> = 0.01), particularly when the child was 18 or younger at diagnosis (HR, 1.25; 95% CI, [1.08, 1.46]; <i>p</i> = 0.004), when the child was diagnosed with a highly aggressive cancer (HR, 1.60; 95% CI, [1.05, 2.43]; <i>p</i> = 0.03), or when the child died due to cancer (HR, 1.63; 95% CI, [1.29, 2.06]; <i>p</i> < 0.001). The increased risk did not, however, maintain thereafter (HR, 0.86; 95% CI: [0.75, 0.98]; <i>p</i> = 0.03), and there was no altered risk of parental death by suicide any time after the child’s cancer diagnosis. Sibling comparison corroborated these findings. The main limitation of the study is the potential residual confounding by factors not shared between full siblings.</p> Conclusions <p>In this study, we observed an increased risk of parental suicide attempt during the first years after a child’s cancer diagnosis, especially when the child was diagnosed during childhood, or with an aggressive or fatal form of cancer. There was, however, no altered risk of parental death by suicide at any time after a child’s cancer diagnosis. Our findings suggest extended clinical awareness of suicide attempt among parents of children with cancer, especially during the first few years after cancer diagnosis.</p>The forecasted prevalence of comorbidities and multimorbidity in people with HIV in the United States through the year 2030: A modeling studyKeri N. AlthoffCameron StewartElizabeth HumesLucas GeraceCynthia BoydKelly GeboAmy C. JusticeEmily P. HyleSally B. CoburnRaynell LangMichael J. SilverbergMichael A. HorbergViviane D. LimaM. John GillMaile KarrisPeter F. RebeiroJennifer ThorneAshleigh J. RichHeidi CraneMari KitahataAnna RubtsovaCherise WongSean LengVincent C. MarconiGypsyamber D’SouzaHyang Nina KimSonia NapravnikKathleen McGinnisGregory D. KirkTimothy R. SterlingRichard D. MooreParastu Kasaie10.1371/journal.pmed.10043252024-01-12T14:00:00Z2024-01-12T14:00:00Z<p>by Keri N. Althoff, Cameron Stewart, Elizabeth Humes, Lucas Gerace, Cynthia Boyd, Kelly Gebo, Amy C. Justice, Emily P. Hyle, Sally B. Coburn, Raynell Lang, Michael J. Silverberg, Michael A. Horberg, Viviane D. Lima, M. John Gill, Maile Karris, Peter F. Rebeiro, Jennifer Thorne, Ashleigh J. Rich, Heidi Crane, Mari Kitahata, Anna Rubtsova, Cherise Wong, Sean Leng, Vincent C. Marconi, Gypsyamber D’Souza, Hyang Nina Kim, Sonia Napravnik, Kathleen McGinnis, Gregory D. Kirk, Timothy R. Sterling, Richard D. Moore, Parastu Kasaie</p>
Background <p>Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030.</p> Methods and findings <p>Using the PEARL model—an agent-based simulation of PWH who have initiated ART in the US—the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information).In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART—reaching 908,000 individuals by 2030—PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts.</p> Conclusions <p>The PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.</p>Mapping clinical interactions in an Australian tertiary hospital emergency department for patients presenting with risk of suicide or self-harm: Network modeling from observational dataMichael H. McCulloughMichael SmallBinu JayawardenaSean Hood10.1371/journal.pmed.10042412024-01-12T14:00:00Z2024-01-12T14:00:00Z<p>by Michael H. McCullough, Michael Small, Binu Jayawardena, Sean Hood</p>
Background <p>Reliable assessment of suicide and self-harm risk in emergency medicine is critical for effective intervention and treatment of patients affected by mental health disorders. Teams of clinicians face the challenge of rapidly integrating medical history, wide-ranging psychosocial factors, and real-time patient observations to inform diagnosis, treatment, and referral decisions. Patient outcomes therefore depend on the reliable flow of information through networks of clinical staff and information systems. This study aimed to develop a quantitative data-driven research framework for the analysis of information flow in emergency healthcare settings to evaluate clinical practice and operational models for emergency psychiatric care.</p> Methods and findings <p>We deployed 2 observers in a tertiary hospital emergency department during 2018 for a total of 118.5 h to record clinical interactions along patient trajectories for presentations with risk of self-harm or suicide (<i>n</i> = 272 interactions for <i>n</i> = 43 patient trajectories). The study population was reflective of a naturalistic sample of patients presenting to a tertiary emergency department in a metropolitan Australian city. Using the observational data, we constructed a clinical interaction network to model the flow of clinical information at a systems level. Community detection via modularity maximization revealed communities in the network closely aligned with the underlying clinical team structure. The Psychiatric Liaison Nurse (PLN) was identified as the most important agent in the network as quantified by node degree, closeness centrality, and betweenness centrality. Betweenness centrality of the PLN was significantly higher than expected by chance (>95th percentile compared with randomly shuffled networks) and removing the PLN from the network reduced both the global efficiency of the model and the closeness centrality of all doctors. This indicated a potential vulnerability in the system that could negatively impact patient care if the function of the PLN was compromised. We developed an algorithmic strategy to mitigate this risk by targeted strengthening of links between clinical teams using greedy cumulative addition of network edges in the model. Finally, we identified specific interactions along patient trajectories which were most likely to precipitate a psychiatric referral using a machine learning model trained on features from dynamically constructed clinical interaction networks. The main limitation of this study is the use of nonclinical information only (i.e., modeling is based on timing of interactions and agents involved, but not the content or quantity of information transferred during interactions).</p> Conclusions <p>This study demonstrates a data-driven research framework, new to the best of our knowledge, to assess and reinforce important information pathways that guide clinical decision processes and provide complementary insights for improving clinical practice and operational models in emergency medicine for patients at risk of suicide or self-harm. Our findings suggest that PLNs can play a crucial role in clinical communication, but overreliance on PLNs may pose risks to reliable information flow. Operational models that utilize PLNs may be made more robust to these risks by improving interdisciplinary communication between doctors. Our research framework could also be applied more broadly to investigate service delivery in different healthcare settings or for other medical specialties, patient groups, or demographics.</p>