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BACKGROUND: We investigated perinatal outcomes among live births from international migrant and local-born mothers in a cohort of low-income individuals in Brazil. METHODS: We linked nationwide birth registries to mortality records and socioeconomic data from the CIDACS Birth Cohort and studied singleton live births of women aged 10-49 years from 1st January 2011 to 31st December 2018. We used logistic regressions to investigate differences in antenatal care, adverse pregnancy outcomes, and neonatal (i.e., ≤28 days) mortality among international migrants compared to non-migrants in Brazil; and explored the interaction between migration, race/ethnicity and living in international border municipalities. RESULTS: We studied 10,279,011 live births, of which 9469 (0.1 %) were born to international migrants. Migrant women were more likely than their Brazilian-born counterparts to have a previous foetal loss (ORadj: 1.16, 1.11-1.22), a delayed start of antenatal care (i.e., beyond 1st trimester) (1.22, 95%CI:1.16-1.28), a newborn who is large for gestational age (1.29, 1.22-1.36), or a newborn with congenital anomalies (1.37, 1.14-1.65). Conversely, migrant women were less likely to deliver prematurely (0.89, 0.82-0.95) or have a low birth weight infant (0.74, 0.68-0.81). There were no differences in neonatal mortality rates between migrants and non-migrants. Our analyses also showed that, when disparities in perinatal outcomes were present, disparities were mostly concentrated among indigenous mothers in international borders and among live births of Black mothers in non-borders. CONCLUSION: Although live births of international migrants generally have lower rates of adverse birth outcomes, our results suggest that indigenous and Black migrant mothers may face disproportionate barriers to accessing antenatal care.

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The COVID-19 pandemic has brought about valuable insights regarding models, data, and experiments. In this narrative review, we summarised the existing literature on these three themes, exploring the challenges of providing forecasts, the requirement for real-time linkage of health-related datasets, and the role of 'experimentation' in evaluating interventions. This literature review encourages us to broaden our perspective for the future, acknowledging the significance of investing in models, data, and experimentation, but also to invest in areas that are conceptually more abstract: the value of 'team science', the need for public trust in science, and in establishing processes for using science in policy. Policy-makers rely on model forecasts early in a pandemic when there is little data, and it is vital to communicate the assumptions, limitations, and uncertainties (theme 1). Linked routine data can provide critical information, for example, in establishing risk factors for adverse outcomes but are often not available quickly enough to make a real-time impact. The interoperability of data resources internationally is required to facilitate sharing across jurisdictions (theme 2). Randomised controlled trials (RCTs) provided timely evidence on the efficacy and safety of vaccinations and pharmaceuticals but were largely conducted in higher income countries, restricting generalisability to low- and middle-income countries (LMIC). Trials for non-pharmaceutical interventions (NPIs) were almost non-existent which was a missed opportunity (theme 3). Building on these themes from the narrative review, we underscore the importance of three other areas that need investment for effective evidence-driven policy-making. The COVID-19 response relied on strong multidisciplinary research infrastructures, but funders and academic institutions need to do more to incentivise team science (4). To enhance public trust in the use of scientific evidence for policy, researchers and policy-makers must work together to clearly communicate uncertainties in current evidence and any need to change policy as evidence evolves (5). Timely policy decisions require an established two-way process between scientists and policy makers to make the best use of evidence (6). For effective preparedness against future pandemics, it is essential to establish models, data, and experiments as fundamental pillars, complemented by efforts in planning and investment towards team science, public trust, and evidence-based policy-making across international communities. The paper concludes with a 'call to actions' for both policy-makers and researchers.

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Background: Non-invasive diabetes risk models are a cost-effective tool in large-scale population screening to identify those who need confirmation tests, especially in resource-limited settings. Aims: This study aimed to evaluate the ability of six non-invasive risk models (Cambridge, FINDRISC, Kuwaiti, Omani, Rotterdam, and SUNSET model) to identify screen-detected diabetes (defined by HbA1c) among Ghanaian migrants and non-migrants. Study design: A multicentered cross-sectional study. Methods: This analysis included 4843 Ghanaian migrants and non-migrants from the Research on Obesity and Diabetes among African Migrants (RODAM) Study. Model performance was assessed using the area under the receiver operating characteristic curves (AUC), Hosmer-Lemeshow statistics, and calibration plots. Results: All six models had acceptable discrimination (0.70 ≤ AUC <0.80) for screen-detected diabetes in the overall/combined population. Model performance did not significantly differ except for the Cambridge model, which outperformed Rotterdam and Omani models. Calibration was poor, with a consistent trend toward risk overestimation for screen-detected diabetes, but this was substantially attenuated by recalibration through adjustment of the original model intercept. Conclusion: Though acceptable discrimination was observed, the original models were poorly calibrated among populations of African ancestry. Recalibration of these models among populations of African ancestry is needed before use.

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BACKGROUND: This study estimated ethnoracial inequalities in maternal and congenital syphilis in Brazil, understanding race as a relational category product of a sociopolitical construct that functions as an essential tool of racism and its manifestations. METHODS: We linked routinely collected data from Jan 1, 2012 to Dec 31, 2017 to conduct a population-based study in Brazil. We estimated the attributable fraction of race (skin colour) for the entire population and specific subgroups compared with White women using adjusted logistic regression. We also obtained the attributable fraction of the intersection between two social markers (race and education) and compared it with White women with more than 12 years of education as the baseline. FINDINGS: Of 15 810 488 birth records, 144 564 women had maternal syphilis and 79 580 had congenital syphilis. If all women had the same baseline risk as White women, 35% (95% CI 34·89-36·10) of all maternal syphilis and 41% (40·49-42·09) of all congenital syphilis would have been prevented. Compared with other ethnoracial categories, these percentages were higher among Parda/Brown women (46% [45·74-47·20] of maternal syphilis and 52% [51·09-52·93] of congenital syphilis would have been prevented) and Black women (61% [60·25-61·75] of maternal syphilis and 67% [65·87-67·60] of congenital syphilis would have been prevented). If all ethnoracial groups had the same risk as White women with more than 12 years of education, 87% of all maternal syphilis and 89% of all congenital syphilis would have been prevented. INTERPRETATION: Only through effective control of maternal syphilis among populations at higher risk (eg, Black and Parda/Brown women with lower educational levels) can WHO's global health initiative to eliminate mother-to-child transmission of syphilis be made feasible. Recognising that racism and other intersecting forms of oppression affect the lives of minoritised groups and advocating for actions through the lens of intersectionality is imperative for attaining and guaranteeing health equity. Achieving health equality needs to be addressed to achieve syphilis control. Given the scale and complexity of the problem (which is unlikely to be unique to Brazil), structural issues and social markers of oppression, such as race and education, must be considered to prevent maternal and congenital syphilis and improve maternal and child outcomes globally. FUNDING: Wellcome Trust, CNPq-Brazil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

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Purpose: To assess the risk of incident cardiovascular outcomes after COVID-19 by level of cardiovascular risk in waves one and two of the pandemic in England in 2020. Patients and methods: We conducted a self-controlled case-series study among adults aged 40-84 years with no pre-existing cardiovascular disease using linked data from the Clinical Practice Research Datalink. We generated season-adjusted incidence ratios (IRs) for first acute cardiovascular event after SARS-CoV-2 infection compared with baseline time before and >91 days after infection. We used composite and individual acute cardiovascular event outcomes including myocardial infarction, major ventricular arrhythmia, left ventricular heart failure, and ischemic stroke. We stratified by cardiovascular risk, using diagnosed hypertension and QRISK3 predicted risk, and by wave one and two of the pandemic. Results: We included 1762 individuals, 76.6% had a QRISK3 score ≥10% and 59.4% had hypertension. The risk of any cardiovascular event was elevated in the 1-7 days after infection (IR 7.14 [95% CI 6.06-8.41]) and, while the effect size tapered, the risk remained for 15-28 days after infection (1.74 [1.33-2.26]). Risks were similar for individual event type, differing by level of cardiovascular risk, and in wave one and two of the pandemic. . Conclusion: SARS-CoV-2 infection is associated with early elevations in the risk of first acute cardiovascular event, across cardiovascular risk levels and in both wave one and two of the pandemic. Prevention of COVID-19 is important to avert cardiovascular complications.

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Background: We sought to examine sex-specific risks for incident cardiovascular disease (CVD) across the full glycaemic spectrum. Methods: Using data from UK Biobank, we categorised participants' glycated haemoglobin (HbA1c) at baseline as low-normal (<35 mmol/mol), normal (35-41 mmol/mol), pre-diabetes (42-47 mmol/mol), undiagnosed diabetes (≥48 mmol/mol), or diagnosed diabetes. Our outcomes were coronary artery disease (CAD), atrial fibrillation, deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, heart failure, and a composite outcome of any CVD. Cox regression estimated sex-specific associations between HbA1c and each outcome, sequentially adjusting for socio-demographic, lifestyle, and clinical characteristics. Findings: Among 427,435 people, CVD rates were 16.9 and 9.1 events/1000 person-years for men and women, respectively. Both men and women with pre-diabetes, undiagnosed diabetes, and, more markedly, diagnosed diabetes were at higher risks of CVD than those with normal HbA1c, with relative increases more pronounced in women than men. Age-adjusted HRs for pre-diabetes and undiagnosed diabetes ranged from 1.30 to 1.47; HRs for diagnosed diabetes were 1.55 (1.49-1.61) in men and 2.00 (1.89-2.12) in women (p-interaction <0.0001). Excess risks attenuated and were more similar between men and women after adjusting for clinical and lifestyle factors particularly obesity and antihypertensive or statin use (fully adjusted HRs for diagnosed diabetes: 1.06 [1.02-1.11] and 1.17 [1.10-1.24], respectively). Interpretation: Excess risks in men and women were largely explained by modifiable factors, and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications. Addressing these risk factors could reduce sex disparities in risk of CVD among people with and without diabetes. Funding: Diabetes UK (#15/0005250) and British Heart Foundation (SP/16/6/32726).

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To better understand the declining rates of routine childhood vaccination in Brazil, we investigated the association between measles, mumps, and rubella (MMR) first dose vaccine coverage and deprivation at the municipality level. Using routinely collected data from 5565 Brazilian municipalities from 2006 to 2020, we investigated the association between municipality-level MMR vaccine first dose coverage (i.e., as a continuous variable and as a percentage of municipalities attaining the 95% target coverage) in relation to quintiles of municipality-level deprivation, measured by the Brazilian Deprivation Index (Índice Brasileiro de Privação, IBP), and geographic regions. From 2006 to 2020, the mean municipality-level MMR vaccine coverage declined across all deprivation quintiles and regions of Brazil, by an average of 1.2% per year. The most deprived quintile of municipalities had higher coverage on average, but also the steepest declines in coverage (i.e., an annual decline of 1.64% versus 0.61% in the least deprived quintile) in the period of 2006-2020, and the largest drop in coverage at the beginning of the COVID-19 pandemic (2019-2020). Across all deprivation quintiles and regions (except for the Southeast region), less than 50% of municipalities in Brazil met the 95% MMR coverage target in 2020.The decrease in MMR first dose vaccine coverage in Brazil is widespread, but steeper declines have been observed in the most deprived municipalities. To promote vaccine equity and prevent future outbreaks, further research is urgently needed to understand the causal mechanisms underlying the observed associations between municipality-level MMR vaccine coverage and deprivation.

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Importance: Fluoroquinolone use has been associated with increased hospitalization with aortic aneurysm or dissection in noninterventional studies, but the reason for this observed association is unclear. Objective: To determine the association between fluoroquinolone use and aortic aneurysm or dissection using multiple study designs and multiple databases to increase the robustness of findings. Design, Setting, and Participants: Cohort and case-crossover studies were conducted separately in 2 databases of UK primary care records. Clinical Practice Research Datalink Aurum and GOLD primary care records were linked to hospital admissions data. Adults with a systemic fluoroquinolone or cephalosporin prescription between April 1997 and December 2019 were included in the cohort study. Adults hospitalized with aortic aneurysm or dissection within the eligibility period were included in the case-crossover study. Individuals meeting inclusion criteria in the case-crossover study were matched 1:3 to control individuals on age, sex, index date, and clinical practice to adjust for calendar trends in prescribing. Data were analyzed from January to July 2022. Exposures: Systemic fluoroquinolone or comparator antibiotic. Main Outcomes and Measures: Hazard ratios (HRs) were estimated in the cohort study for the association between prescription of fluoroquinolones and hospitalization with aortic aneurysm or dissection using stabilized inverse probability of treatment-weighted Cox regression. Odds ratios (OR) were estimated in the case-crossover study for the association between systemic fluoroquinolone use and hospitalization with aortic aneurysm or dissection using a conditional logistic regression model. Estimates were pooled across databases using fixed-effects meta-analysis. Results: In the cohort study, we identified 3 134 121 adults in Aurum (mean [SD] age, 52.5 [20.3] years; 1 969 257 [62.8%] female) and 452 086 in GOLD (mean [SD] age, 53.9 [20.2] years; 286 502 [63.4%] female) who were prescribed fluoroquinolones or cephalosporins. In crude analyses, fluoroquinolone relative to cephalosporin use was associated with increased hospitalization with aortic aneurysm or dissection (pooled HR, 1.28; 95% CI, 1.13-1.44; P < .001) but after adjustment for potential confounders, this association disappeared (pooled adjusted HR, 1.03; 95% CI, 0.91-1.17; P = .65). In the case-crossover study, we identified 84 841 individuals hospitalized with aortic aneurysm or dissection in Aurum (mean [SD] age, 75.5 [10.9]; 23 551 [27.8%] female) and 10 357 in GOLD (mean [SD] age, 75.6 [10.5]; 2809 [27.1%] female). Relative to nonuse, fluoroquinolone use was associated with an increase in hospitalization with aortic aneurysm or dissection, but no association was found relative to other antibiotics (vs cephalosporin pooled OR, 1.05; 95% CI, 0.87-1.27; vs trimethoprim, 0.89; 95% CI, 0.75-1.06; vs co-amoxiclav, 0.98; 95% CI, 0.82-1.18). Conclusions and Relevance: The results in this study suggest that estimates of association of fluoroquinolones with aortic aneurysm or dissection may be affected by confounding. When such confounding is accounted for, no association was evident, providing reassurance on the safety of fluoroquinolones with respect to aortic aneurysm or dissection.

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Adult-onset diabetes mellitus (here: aDM) is not a uniform disease entity. In European populations, five diabetes subgroups have been identified by cluster analysis using simple clinical variables; these may elucidate diabetes aetiology and disease prognosis. We aimed at reproducing these subgroups among Ghanaians with aDM, and establishing their importance for diabetic complications in different health system contexts. We used data of 541 Ghanaians with aDM (age: 25-70 years; male sex: 44%) from the multi-center, cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) Study. Adult-onset DM was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L, documented use of glucose-lowering medication or self-reported diabetes, and age of onset ≥ 18 years. We derived subgroups by cluster analysis using (i) a previously published set of variables: age at diabetes onset, HbA1c, body mass index, HOMA-beta, HOMA-IR, positivity of glutamic acid decarboxylase autoantibodies (GAD65Ab), and (ii) Ghana-specific variables: age at onset, waist circumference, FPG, and fasting insulin. For each subgroup, we calculated the clinical, treatment-related and morphometric characteristics, and the proportions of objectively measured and self-reported diabetic complications. We reproduced the five subgroups: cluster 1 (obesity-related, 73%) and cluster 5 (insulin-resistant, 5%) with no dominant diabetic complication patterns; cluster 2 (age-related, 10%) characterized by the highest proportions of coronary artery disease (CAD, 18%) and stroke (13%); cluster 3 (autoimmune-related, 5%) showing the highest proportions of kidney dysfunction (40%) and peripheral artery disease (PAD, 14%); and cluster 4 (insulin-deficient, 7%) characterized by the highest proportion of retinopathy (14%). The second approach yielded four subgroups: obesity- and age-related (68%) characterized by the highest proportion of CAD (9%); body fat-related and insulin-resistant (18%) showing the highest proportions of PAD (6%) and stroke (5%); malnutrition-related (8%) exhibiting the lowest mean waist circumference and the highest proportion of retinopathy (20%); and ketosis-prone (6%) with the highest proportion of kidney dysfunction (30%) and urinary ketones (6%). With the same set of clinical variables, the previously published aDM subgroups can largely be reproduced by cluster analysis in this Ghanaian population. This method may generate in-depth understanding of the aetiology and prognosis of aDM, particularly when choosing variables that are clinically relevant for the target population.

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The COVID-19 vaccines were developed and rigorously evaluated in randomized trials during 2020. However, important questions, such as the magnitude and duration of protection, their effectiveness against new virus variants, and the effectiveness of booster vaccination, could not be answered by randomized trials and have therefore been addressed in observational studies. Analyses of observational data can be biased because of confounding and because of inadequate design that does not consider the evolution of the pandemic over time and the rapid uptake of vaccination. Emulating a hypothetical "target trial" using observational data assembled during vaccine rollouts can help manage such potential sources of bias. This article describes 2 approaches to target trial emulation. In the sequential approach, on each day, eligible persons who have not yet been vaccinated are matched to a vaccinated person. The single-trial approach sets a single baseline at the start of the rollout and considers vaccination as a time-varying variable. The nature of the confounding depends on the analysis strategy: Estimating "per-protocol" effects (accounting for vaccination of initially unvaccinated persons after baseline) may require adjustment for both baseline and "time-varying" confounders. These issues are illustrated by using observational data from 2 780 931 persons in the United Kingdom aged 70 years or older to estimate the effect of a first dose of a COVID-19 vaccine. Addressing the issues discussed in this article should help authors of observational studies provide robust evidence to guide clinical and policy decisions.

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BACKGROUND: Congenital syphilis (CS) is a major and avoidable cause of neonatal death worldwide. In this study, we aimed to estimate excess all-cause mortality in children under 5 years with CS compared to those without CS. METHODS AND FINDINGS: In this population-based cohort study, we used linked, routinely collected data from Brazil from January 2011 to December 2017. Cox survival models were adjusted for maternal region of residence, maternal age, education, material status, self-declared race and newborn sex, and year of birth and stratified according to maternal treatment status, non-treponemal titers and presence of signs and symptoms at birth. Over 7 years, a total of 20 057 013 live-born children followed up (through linkage) to 5 years of age, 93 525 were registered with CS, and 2 476 died. The all-cause mortality rate in the CS group was 7·84/1 000 person-years compared with 2·92/1 000 person-years in children without CS, crude hazard ratio (HR) = 2·41 (95% CI 2·31 to 2·50). In the fully adjusted model, the highest under-five mortality risk was observed among children with CS from untreated mothers HR = 2·82 (95% CI 2·63 to 3·02), infants with non-treponemal titer higher than 1:64 HR = 8·87 (95% CI 7·70 to 10·22), and children with signs and symptoms at birth HR = 7·10 (95% CI 6·60 to 7·63). Among children registered with CS, CS was recorded as the underlying cause of death in 33% (495/1 496) of neonatal, 11% (85/770) of postneonatal, and 2·9% (6/210) of children 1 year of age. The main limitations of this study were the use of a secondary database without additional clinical information and the potential misclassification of exposure status. CONCLUSIONS: This study showed an increased mortality risk among children with CS that goes beyond the first year of life. It also reinforces the importance of maternal treatment that infant non-treponemal titers and the presence of signs and symptoms of CS at birth are strongly associated with subsequent mortality. TRIAL REGISTRATION: Observational study.

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Background: To understand if migrants living in poverty in low and middle-income countries (LMICs) have mortality advantages over the non-migrant population, we investigated mortality risk patterns among internal and international migrants in Brazil over their life course. Methods: We linked socio-economic and mortality data from 1st January 2011 to 31st December 2018 in the 100 Million Brazilian Cohort and calculated all-cause and cause-specific age-standardised mortality rates according to individuals' migration status for men and women. Using Cox regression models, we estimated the age- and sex-adjusted mortality hazard ratios (HR) for internal migrants (i.e., Brazilian-born individuals living in a different Brazilian state than their birth) compared to Brazilian-born non-migrants; and for international migrants (i.e., people born in another country) compared to Brazilian-born individuals. Findings: The study followed up 45,051,476 individuals, of whom 6,057,814 were internal migrants, and 277,230 were international migrants. Internal migrants had similar all-cause mortality compared to Brazilian non-migrants (aHR = 0.99, 95% CI = 0.98-0.99), marginally higher mortality for ischaemic heart diseases (aHR = 1.04, 95% CI = 1.03-1.05) and higher for stroke (aHR = 1.11, 95% CI = 1.09-1.13). Compared to Brazilian-born individuals, international migrants had 18% lower all-cause mortality (aHR = 0.82, 95% CI = 0.80-0.84), with up to 50% lower mortality from interpersonal violence among men (aHR = 0.50, 95% CI = 0.40-0.64), but higher mortality from avoidable causes related to maternal health (aHR = 2.17, 95% CI = 1.17-4.05). Interpretation: Although internal migrants had similar all-cause mortality, international migrants had lower all-cause mortality compared to non-migrants. Further investigations using intersectional approaches are warranted to understand the marked variations by migration status, age, and sex for specific causes of death, such as elevated maternal mortality and male lower interpersonal violence-related mortality among international migrants. Funding: The Wellcome Trust.

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Background: While cardiovascular disease (CVD) is a risk factor for severe COVID-19, the association between predicted cardiovascular risk and severe COVID-19 among people without diagnosed CVD is unclear. Methods: We carried out historical, population-based cohort studies among adults aged 40-84 years in England using linked data from the Clinical Practice Research Datalink. Individuals were categorized into: existing CVD, raised cardiovascular risk (defined using QRISK3 score ≥10%) and low risk (QRISK3 score <10%) at 12/03/2020. We described incidence and severe outcomes of COVID-19 (deaths, intensive care unit [ICU] admissions, hospitalisations, major adverse cardiovascular events [MACE]) for each group. Among those with a COVID-19 record to 31/12/2020, we re-classified cardiovascular risk at infection and assessed the risk of severe outcomes using multivariable Cox regression with complete case analysis. We repeated analyses using hypertension to define raised cardiovascular risk. Findings: Among 6,059,055 individuals, 741,913 (12.2%) had established CVD, 1,929,627 (31.8%) had a QRISK3 score ≥10% and 3,387,515 (55.9%) had a QRISK3 score <10%. Marked gradients were seen in the incidence of all severe COVID-19 outcomes by cardiovascular risk profile. Among those with COVID-19 (N = 146,760), there was a strong association between raised QRISK3 score and death: adjusted hazard ratio [aHR] 8.77 (7.62-10.10), N = 97,725, which remained present, though attenuated in age-stratified results. Risks of other outcomes were also higher among those with raised QRISK3 score: aHR 3.66 (3.18-4.21) for ICU admissions, 3.38 (3.22-3.56) for hospitalisations, 5.43 (4.44-6.64) for MACE. When raised cardiovascular risk was redefined by hypertension status, only the association with MACE remained: aHR 1.49 (1.20-1.85), N = 57,264. Interpretation: Individuals without pre-existing CVD but with raised cardiovascular risk (by QRISK3 score) were more likely to experience severe COVID-19 outcomes and should be prioritised for prevention and treatment. Addressing cardiovascular risk factors could improve COVID-19 outcomes. Funding: BMA Foundation for Medical Research/Rosetrees Trust, Wellcome, BHF.

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Background: In the UK, previous work suggests ethnic inequalities in hypertension management. We studied ethnic differences in hypertension management and their contribution to blood pressure (BP) control. Methods: We conducted a cohort study of antihypertensive-naïve individuals of European, South Asian and African/African Caribbean ethnicity with a new raised BP reading in UK primary care from 2006 to 2019, using the Clinical Practice Research Datalink (CPRD). We studied differences in: BP re-measurement after an initial hypertensive BP, antihypertensive initiation, BP monitoring, antihypertensive intensification, antihypertensive persistence/adherence and BP control one year after antihypertensive initiation. Models adjusted for socio-demographics, BP, comorbidity, healthcare usage and polypharmacy (plus antihypertensive class, BP monitoring, intensification, persistence and adherence for BP control models). Findings: A total of 731,506 (93.5%), 30,379 (3.9%) and 20,256 (2.6%) people of European, South Asian and African/African Caribbean ethnicity were studied. Hypertension management indicators were similar or more favourable for South Asian than European groups (OR/HR [95% CI] in fully-adjusted models of BP re-measurement: 1.16 [1.09, 1.24]), antihypertensive initiation: 1.49 [1.37, 1.62], BP monitoring: 0.97 [0.94, 1.00] and antihypertensive intensification: 1.10 [1.04, 1.16]). For people of African/African Caribbean ethnicity, BP re-measurement rates were similar to those of European ethnicity (0.98 [0.91, 1.05]), and antihypertensive initiation rates greater (1.48 [1.32, 1.66]), but BP monitoring (0.91 [0.87, 0.95]) and intensification rates lower (0.93 [0.87, 1.00]). Persistence and adherence were lower in South Asian (0.48 [0.45, 0.51] and 0.51 [0.47, 0.56]) and African/African Caribbean (0.38 [0.35, 0.42] and 0.39 [0.36, 0.43]) than European groups. BP control was similar in South Asian and less likely in African/African Caribbean than European groups (0.98 [0.90, 1.06] and 0.81 [0.74, 0.89] in age, gender and BP adjusted models). The latter difference attenuated after adjustment for persistence (0.91 [0.82, 0.99]) or adherence (0.92 [0.83, 1.01]), and was absent for antihypertensive-adherent people (0.99 [0.88, 1.10]). Interpretation: We demonstrate that antihypertensive initiation does not vary by ethnicity, but subsequent BP control was notably lower among people of African/African Caribbean ethnicity, potentially associated with being less likely to remain on regular treatment. A nationwide strategy to understand and address differences in ongoing management of people on antihypertensives is imperative. Funding: Diabetes UK.

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BACKGROUND: Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018. METHODS AND FINDINGS: In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls. CONCLUSION: The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.

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INTRODUCTION: The impact of long COVID on health-related quality of-life (HRQoL) and productivity is not currently known. It is important to understand who is worst affected by long COVID and the cost to the National Health Service (NHS) and society, so that strategies like booster vaccines can be prioritised to the right people. OpenPROMPT aims to understand the impact of long COVID on HRQoL in adults attending English primary care. METHODS AND ANALYSIS: We will ask people to participate in this cohort study through a smartphone app (Airmid), and completing a series of questionnaires held within the app. Questionnaires will ask about HRQoL, productivity and symptoms of long COVID. Participants will be asked to fill in the questionnaires once a month, for 90 days. Questionnaire responses will be linked, where possible, to participants' existing health records from primary care, secondary care, and COVID testing and vaccination data. Analysis will take place using the OpenSAFELY data platform and will estimate the impact of long COVID on HRQoL, productivity and cost to the NHS. ETHICS AND DISSEMINATION: The Proportionate Review Sub-Committee of the South Central-Berkshire B Research Ethics Committee has reviewed and approved the study and have agreed that we can ask people to take part (22/SC/0198). Our results will provide information to support long-term care, and make recommendations for prevention of long COVID in the future. TRIAL REGISTRATION NUMBER: NCT05552612.

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BACKGROUND: Lymphocyte skin homing in atopic eczema (AE) may induce lymphopenia. OBJECTIVE: To determine if AE is associated with lymphopenia. METHODS: We used UK primary care electronic health records (Clinical Practice Research Datalink GOLD) for a matched cohort study in adults (18 years+) (1997-2015) with at least one recorded lymphocyte count. We matched people with AE to up to five people without. We used multivariable logistic regression to estimate the association between AE and lymphopenia (two low lymphocyte counts within 3 months) and linear mixed effects regression to estimate the association with absolute lymphocyte counts using all available counts. Cox proportional hazard models were used to investigate the effect of lymphopenia on common infections. We replicated the study using US survey data (National Health and Nutrition Examination Survey [NHANES]). RESULTS: Among 71,731 adults with AE and 126,349 adults without AE, we found an adjusted odds ratio (OR) for lymphopenia of 1.16 (95% CI: 1.09-1.23); the strength of association increased with increasing eczema severity. When comparing all recorded lymphocyte counts from adults with AE (n = 1,497,306) to those of people without AE (n = 4,035,870) we saw a lower mean lymphocyte (adjusted mean difference -0.047 × 109 /L [95% CI: -0.051 to -0.043]) in those with AE. The difference was larger for men, with increasing age, and with increasing AE severity and was present among people with AE not treated with immunosuppressive drugs. In NHANES (n = 22,624), the adjusted OR for lymphopenia in adults with AE was 1.30 (95% CI: 0.80-2.11), and the adjusted mean lymphocyte count difference was -0.03 × 109 /L (95% CI: -0.07 to 0.02). Despite having a lower lymphocyte count, adjusting for time with lymphopenia, did not alter risk estimates of infections. CONCLUSION: Atopic eczema, including increasing AE severity, is associated with a decreased lymphocyte count, regardless of immunosuppressive drug use. Whether the lower lymphocyte count has wider health implications for people with severe eczema warrants further investigation.

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BACKGROUND: Cardiovascular risks are raised in cancer survivors but cancer history is not included in cardiovascular risk scores that inform preventive decisions. AIM: To assess whether cancer diagnosis should be included in cardiovascular risk scores. DESIGN AND SETTING: Cohort study using data from English general practices linked to hospital, cancer registration, and death registration data from 1990 to 2015. METHOD: Adults alive 1 year after a first cancer diagnosis and age, sex, general practice, and calendar- time matched cancer-free individuals were included. Individuals with <2 years of follow-up before index, recent statin prescriptions, or pre-existing coronary heart or cerebrovascular disease were excluded. Cox proportional hazard models used to develop QRISK3 scores were replicated with added cancer history variables. Whether independent hazard ratios for these variables met thresholds for inclusion in QRISK3 (>10% relative difference with P<0.01) was assessed. RESULTS: In total, 81 420 cancer survivors and 413 547 cancer-free individuals were followed for a median 5.2 years (interquartile range [IQR] 2.8- 9.1) and 6.3 years (IQR 3.5-10.2), respectively. Including a 1-year cancer survivorship variable in a QRISK3-based model met the threshold for inclusion for males (independent hazard ratio [iHR] 1.16, 95% confidence interval [CI] = 1.11 to 1.20, P<0.001) but not females (iHR 1.07, 95% CI = 1.01 to 1.14, P = 0.02). When including cancer type, the threshold was met for both sexes with history of haematological cancer (males: iHR 1.27, 95% CI = 1.16 to 1.40, P <0.001; females: iHR 1.59, 95% CI = 1.32 to 1.91, P<0.001) and for males but not females with history of solid cancers (males: iHR 1.13, 95% CI = 1.08 to 1.18, P <0.001; females: iHR 1.04, 95% CI = 0.98 to 1.10, P = 0.19). CONCLUSION: Developers should consider including cancer history variables in future cardiovascular risk models.

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OBJECTIVE: We aimed (1) to evaluate the agreement between two methods (equation and bio-impedance analysis [BIA]) to estimate skeletal muscle mass (SMM), and (2) to assess if SMM was associated with all-cause mortality risk in individuals across different geographical sites in Peru. METHODS: We used data from the CRONICAS Cohort Study (2010-2018), a population-based longitudinal study in Peru to assess cardiopulmonary risk factors from different geographical settings. SMM was computed as a function of weight, height, sex and age (Lee equation) and by BIA. All-cause mortality was retrieved from national vital records. Cox proportional-hazard models were developed and results presented as hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: At baseline, 3216 subjects, 51.5% women, mean age 55.7 years, were analysed. The mean SMM was 23.1 kg (standard deviation [SD]: 6.0) by Lee equation, and 22.7 (SD: 5.6) by BIA. Correlation between SMM estimations was strong (Pearson's ρ coefficient = 0.89, p < 0.001); whereas Bland-Altman analysis showed a small mean difference. Mean follow-up was 7.0 (SD: 1.0) years, and there were 172 deaths. In the multivariable model, each additional kg in SMM was associated with a 19% reduction in mortality risk (HR = 0.81; 95% CI: 0.75-0.88) using the Lee equation, but such estimate was not significant when using BIA (HR = 0.98; 95% CI: 0.94-1.03). Compared to the lowest tertile, subjects at the highest SMM tertile had a 56% reduction in risk of mortality using the Lee equation, but there was no such association when using BIA estimations. CONCLUSION: There is a strong correlation and agreement between SMM estimates obtained by the Lee equation and BIA. However, an association between SMM and all-cause mortality exists only when the Lee equation is used. Our findings call for appropriate use of approaches to estimate SMM, and there should be a focus on muscle mass in promoting healthier ageing.

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