Impact of the COVID-19 Pandemic on Influenza Hospital Admissions and Deaths in Wales: Descriptive National Time Series Analysis.

Background: The COVID-19 pandemic and the ensuing implementation of control measures caused widespread societal disruption. These disruptions may also have affected community transmission and seasonal circulation patterns of endemic respiratory viruses. Objective: We aimed to investigate the impact of COVID-19-related disruption on influenza-related emergency hospital admissions and deaths in Wales in the first 2 years of the pandemic. Methods: A descriptive analysis of influenza activity was conducted using anonymized pathology, hospitalization, and mortality data from the Secure Anonymised Information Linkage Databank in Wales. The annual incidence of emergency hospitalizations and deaths with influenza-specific diagnosis codes between January 1, 2015, and December 31, 2021, was estimated. Case definitions of emergency hospitalization and death required laboratory confirmation with a polymerase chain reaction test. Trends of admissions and deaths were analyzed monthly and yearly. We conducted 2 sensitivity analyses by extending case definitions to include acute respiratory illnesses with a positive influenza test and by limiting admissions to those with influenza as the primary diagnosis. We also examined yearly influenza testing trends to understand changes in testing behavior during the pandemic. Results: We studied a population of 3,235,883 Welsh residents in 2020 with a median age of 42.5 (IQR 22.9-61.0) years. Influenza testing in Wales increased notably in the last 2 months of 2020, and particularly in 2021 to 39,720 per 100,000 people, compared to the prepandemic levels (1343 in 2019). The percentage of influenza admissions matched to an influenza polymerase chain reaction test increased from 74.8% (1890/2526) in 2019 to 85.2% (98/115) in 2021. However, admissions with a positive test per 100,000 population decreased from 17.0 in 2019 to 2.7 and 0.6 in 2020 and 2021, respectively. Similarly, deaths due to influenza with a positive influenza test per 100,000 population decreased from 0.4 in 2019 to 0.0 in 2020 and 2021. Sensitivity analyses showed similar patterns of decreasing influenza admissions and deaths in the first 2 years of the COVID-19 pandemic. Conclusions: Nonpharmaceutical interventions to control COVID-19 were associated with a substantial reduction in the transmission of the influenza virus, with associated substantial reductions in hospital cases and deaths observed. Beyond the pandemic context, consideration should be given to the role of nonpharmaceutical community-driven interventions to reduce the burden of influenza.

Estimating the Global and Regional Burden of Streptococcus pneumoniae Meningitis in Children: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Streptococcus pneumoniae (Spn) has been a leading cause of bacterial meningitis in children. The most recent estimation of the global burden of Spn meningitis indicates a positive trajectory in eliminating Spn through the implementation of pneumococcal conjugate vaccines. However, continuous monitoring and assessment of the disease burden are necessary due to the evidence of serotype replacement, antibiotic resistance, and the impact of the recent COVID-19 pandemic. OBJECTIVE: The aim of this systematic review is to provide an updated and focused assessment of the global and regional burden of Spn meningitis in children, which can guide policies and strategies to reduce the disease burden. METHODS: Population-based studies published from January 1, 2000, to January 1, 2022, were preliminarily searched from the electronic databases PubMed, Embase, Global Health (CABI), and CINAHL Plus without any language restrictions. Studies were included if they reported the incidence, prevalence, mortality, or case-fatality ratio (CFR) for Spn meningitis in children aged 0-4 years; meningitis was confirmed by cerebrospinal fluid culture; the study period was a minimum of 1 year; the number of reported cases was at least 10; and the study had no methodological ambiguities. The article screening process follows the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Characteristics including study period, setting, World Health Organization region, income level, vaccination information, and participant data (age, number of cases, deaths, sequelae, and risk factors) will be extracted from the included studies. Search results will be updated and incorporated into our review prior to finalizing the extraction of data. Generalized linear mixed models meta-analysis will be performed to estimate the pooled incidence and CFR. We will further assess the risk of bias and heterogeneity, and will perform subgroup and sensitivity analyses to provide a meaningful interpretation of the current burden and literature for pneumococcal meningitis. RESULTS: Our preliminary search in December 2021 yielded 9295 articles. Out of 275 studies that were assessed with our eligibility criteria, 117 articles were included. Data extraction and analysis are expected to be complete by January 2025. We plan to publish the results from the full study, including an updated search in 2024, by March 2025. CONCLUSIONS: Given that the major burden of Spn meningitis affects children under the age of 5 years, this systematic review will provide a thorough understanding of the global burden of Spn meningitis in this vulnerable population over a span of 2 decades. Insights into incidence trends, geospatial distribution, risk factors, and sequelae will be valuable for stakeholders, policy makers, and the academic community. This information will aid in the ongoing monitoring of the disease and in enhancing targeted vaccine programs to further mitigate the impact of the disease on children worldwide. TRIAL REGISTRATION: PROSPERO CRD42021293110; https://tinyurl.com/kc3j5k4m. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50678.

The global and regional prevalence of restless legs syndrome among adults: A systematic review and modelling analysis.

Background: Restless legs syndrome (RLS) is a prevalent neuro-sensory disorder that impairs quality of life. In this systematic review and modelling study, we estimated the global and regional prevalence of RLS and its associated factors. Methods: We searched PubMed, Embase, and Medline for population-based studies on RLS prevalence published up to 12 November 2023. The included studies reported prevalence using the International Restless Leg Syndrome Study Group's (IRLSSG) minimal diagnostic criteria without limitations on frequency, duration, or severity. We applied a multilevel multivariable mixed-effects meta-regression to generate the age-specific and sex-specific prevalence of RLS for high socio-demographic index (H-SDI) and low and middle socio-demographic index (LM-SDI) regions. We pooled odds ratios (ORs) for RLS associated factors using random-effects models. Finally, we derived the regional prevalence and cases of RLS based on an associated factor-based model. Results: From 52 articles across 23 countries, the global RLS prevalence in 2019 was estimated to be 7.12% (95% confidence interval (CI) = 5.15-9.76) among adults 20-79 years of age, equating to 356.07 million (95% CI = 257.61-488.09) affected individuals. Prevalence was similar in H-SDI (7.29%; 95% CI = 5.04-10.41) and LM-SDI (7.10%; 95% CI = 5.16-9.70) regions, with the majority of cases in LM-SDI countries (323.06 million; 90.73%). Europe had the highest (7.60%; 95% CI = 5.44-10.52) and Africa the lowest regional prevalence (6.48%; 95% CI = 4.70-8.87). The Western Pacific Region, meanwhile, had the most cases (111.91 million; 95% CI = 80.93-153.42). Factors positively associated with RLS included advanced age (OR = 1.13; 95% CI = 1.04-1.24), smoking (OR = 1.46; 95% CI = 1.29-1.64), depression (OR = 1.71; 95% CI = 1.26-2.32), and diabetes (OR = 1.54; 95% CI = 1.19-1.97). Conclusions: A considerable global burden of RLS exists. Effective strategies are needed to increase awareness and optimise resource allocation to address this often-overlooked condition. High-quality epidemiological investigations employing standardised and rigorous criteria for RLS are essential for addressing RLS burden more effectively. Registration: PROSPERO: CRD42020161860.

Association between antibody responses post-vaccination and severe COVID-19 outcomes in Scotland.

Several population-level studies have described individual clinical risk factors associated with suboptimal antibody responses following COVID-19 vaccination, but none have examined multimorbidity. Others have shown that suboptimal post-vaccination responses offer reduced protection to subsequent SARS-CoV-2 infection; however, the level of protection from COVID-19 hospitalisation/death remains unconfirmed. We use national Scottish datasets to investigate the association between multimorbidity and testing antibody-negative, examining the correlation between antibody levels and subsequent COVID-19 hospitalisation/death among double-vaccinated individuals. We found that individuals with multimorbidity ( ≥ five conditions) were more likely to test antibody-negative post-vaccination and 13.37 [6.05-29.53] times more likely to be hospitalised/die from COVID-19 than individuals without conditions. We also show a dose-dependent association between post-vaccination antibody levels and COVID-19 hospitalisation or death, with those with undetectable antibody levels at a significantly higher risk (HR 9.21 [95% CI 4.63-18.29]) of these serious outcomes compared to those with high antibody levels.

Prevalence and risk factors for long COVID among adults in Scotland using electronic health records: a national, retrospective, observational cohort study.

Background: Long COVID is a debilitating multisystem condition. The objective of this study was to estimate the prevalence of long COVID in the adult population of Scotland, and to identify risk factors associated with its development. Methods: In this national, retrospective, observational cohort study, we analysed electronic health records (EHRs) for all adults (≥18 years) registered with a general medical practice and resident in Scotland between March 1, 2020, and October 26, 2022 (98-99% of the population). We linked data from primary care, secondary care, laboratory testing and prescribing. Four outcome measures were used to identify long COVID: clinical codes, free text in primary care records, free text on sick notes, and a novel operational definition. The operational definition was developed using Poisson regression to identify clinical encounters indicative of long COVID from a sample of negative and positive COVID-19 cases matched on time-varying propensity to test positive for SARS-CoV-2. Possible risk factors for long COVID were identified by stratifying descriptive statistics by long COVID status. Findings: Of 4,676,390 participants, 81,219 (1.7%) were identified as having long COVID. Clinical codes identified the fewest cases (n = 1,092, 0.02%), followed by free text (n = 8,368, 0.2%), sick notes (n = 14,469, 0.3%), and the operational definition (n = 64,193, 1.4%). There was limited overlap in cases identified by the measures; however, temporal trends and patient characteristics were consistent across measures. Compared with the general population, a higher proportion of people with long COVID were female (65.1% versus 50.4%), aged 38-67 (63.7% versus 48.9%), overweight or obese (45.7% versus 29.4%), had one or more comorbidities (52.7% versus 36.0%), were immunosuppressed (6.9% versus 3.2%), shielding (7.9% versus 3.4%), or hospitalised within 28 days of testing positive (8.8% versus 3.3%%), and had tested positive before Omicron became the dominant variant (44.9% versus 35.9%). The operational definition identified long COVID cases with combinations of clinical encounters (from four symptoms, six investigation types, and seven management strategies) recorded in EHRs within 4-26 weeks of a positive SARS-CoV-2 test. These combinations were significantly (p < 0.0001) more prevalent in positive COVID-19 patients than in matched negative controls. In a case-crossover analysis, 16.4% of those identified by the operational definition had similar healthcare patterns recorded before testing positive. Interpretation: The prevalence of long COVID presenting in general practice was estimated to be 0.02-1.7%, depending on the measure used. Due to challenges in diagnosing long COVID and inconsistent recording of information in EHRs, the true prevalence of long COVID is likely to be higher. The operational definition provided a novel approach but relied on a restricted set of symptoms and may misclassify individuals with pre-existing health conditions. Further research is needed to refine and validate this approach. Funding: Chief Scientist Office (Scotland), Medical Research Council, and BREATHE.

Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts.

SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5-17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5-11 year-olds were less likely to receive their first vaccine compared to 16-17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06-0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13-0.29).

Global, regional, and national burden and quality of care of multiple myeloma, 1990-2019.

Background: Multiple myeloma (MM) is the second most common haematologic malignancy, presenting a great disease burden on the general population; however, the quality of care of MM is overlooked. We therefore assessed gains and disparity in quality of care worldwide from 1990 to 2019 based on a novel summary indicator - the quality of care index (QCI) - and examined its potential for improvement. Methods: Using the Global Burden of Disease 2019 data set, we calculated the QCI of MM for 195 countries and territories. We used the principal component analysis to extract the first principal component of ratios with the combinations of mortality to incidence, prevalence to incidence, disability-adjusted life years to prevalence, and years of life lost to years lived with disability as QCI. We also conducted a series of descriptive and comparative analyses of QCI disparities with age, gender, period, geographies, and sociodemographic development, and compared the QCI among countries with similar socio-demographic index (SDI) through frontier analysis. Results: The age-standardised rates of MM were 1.92 (95% uncertainty interval (UI) = 1.68, 2.12) in incidence and 1.42 (95% UI = 1.24, 1.52) in deaths per 100 000 population in 2019, and were predicted to increase in the future. The global age-standardised QCI increased from 51.31 in 1990 to 64.28 in 2019. In 2019, New Zealand had the highest QCI at 99.29 and the Central African Republic had the lowest QCI at 10.74. The gender disparity of QCI was reduced over the years, with the largest being observed in the sub-Saharan region. Regarding age, QCI maintained a decreasing trend in patients aged >60 in SDI quintiles. Generally, QCI improved with the SDI increase. Results of frontier analysis suggested that there is a potential to improve the quality of care across all levels of development spectrum. Conclusions: Quality of care of MM improved during the past three decades, yet disparities in MM care remain across different countries, age groups, and genders. It is crucial to establish local objectives aimed at enhancing MM care and closing the gap in health care inequality.

A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.

ABSTRACT: Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.

Risk of winter hospitalisation and death from acute respiratory infections in Scotland: national retrospective cohort study.

OBJECTIVES: We undertook a national analysis to characterise and identify risk factors for acute respiratory infections (ARIs) resulting in hospitalisation during the winter period in Scotland. DESIGN: A population-based retrospective cohort analysis. SETTING: Scotland. PARTICIPANTS: The study involved 5.4 million residents in Scotland. MAIN OUTCOME MEASURES: Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association between risk factors and ARI hospitalisation. RESULTS: Between 1 September 2022 and 31 January 2023, there were 22,284 (10.9% of 203,549 with any emergency hospitalisation) ARI hospitalisations (1759 in children and 20,525 in adults) in Scotland. Compared with the reference group of children aged 6-17 years, the risk of ARI hospitalisation was higher in children aged 3-5 years (aHR = 4.55; 95% CI: 4.11-5.04). Compared with those aged 25-29 years, the risk of ARI hospitalisation was highest among the oldest adults aged ≥80 years (aHR = 7.86; 95% CI: 7.06-8.76). Adults from more deprived areas (most deprived vs. least deprived, aHR = 1.64; 95% CI: 1.57-1.72), with existing health conditions (≥5 vs. 0 health conditions, aHR = 4.84; 95% CI: 4.53-5.18) or with history of all-cause emergency admissions (≥6 vs. 0 previous emergency admissions, aHR = 7.53; 95% CI: 5.48-10.35) were at a higher risk of ARI hospitalisations. The risk increased by the number of existing health conditions and previous emergency admission. Similar associations were seen in children. CONCLUSIONS: Younger children, older adults, those from more deprived backgrounds and individuals with greater numbers of pre-existing conditions and previous emergency admission were at increased risk for winter hospitalisations for ARI.

Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.

BACKGROUND: Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. METHODS: We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. RESULTS: The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. CONCLUSIONS: VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.

Global health economics: The Equitable Impact Sensitive Tool (EQUIST) - development, validation, implementation and evaluation of impact (2011 to 2022).

Background: The Equitable Impact Sensitive Tool (EQUIST) was developed to address the limitations of the traditional cost-effectiveness analysis (CEA) in global health, which often overlooked equity considerations. Its primary aim was to create more effective and efficient health systems by explicitly incorporating equity as a key driver in health policy decisions. This was done in response to the recognition that, while CEA helped reduce mortality rates through interventions like childhood vaccinations, it was insufficient in addressing growing inequalities in health, especially in low-and-middle-income countries (LMICs). Methods: The development of EQUIST involved a multi-stage process which began in 2011 with the recognition of the need for a more nuanced approach than CEA alone. This led to a proposal for creating a tool that balanced cost-effectiveness with equity. The conceptual framework, developed between March and May 2012, included assessments of intervention efficiency by equity strata, effectiveness, impact, and cost-effectiveness. Key to EQUIST's development was its integration with other data science platforms, notably the Lives Saved Tool and the Marginal Budgeting for Bottlenecks tool, allowing EQUIST to draw on comprehensive data sets and thus enabling a more detailed analysis of health interventions' impacts across different socio-economic strata. Results: EQUIST was validated in 2012 through applications in five representative countries, demonstrating its ability to identify more equitable and cost-effective health interventions which targeted vulnerable populations, leading to more lives saved compared to traditional methods. It was then used to develop investment cases for the Global Financing Facility, resulting in significant funding being made available for maternal and child health programmes. Consequently, EQUIST directly influenced the development of national health policies and resource allocations in over 26 African countries. Conclusions: EQUIST has proven to be a valuable tool in developing health policies that are both cost-effective and equitable. In the future, it will be further integrated with other tools and expanded in scope to address broader health issues, including adolescent health and human immunodeficiency virus/acquired immunodeficiency syndrome programme planning. Overall, EQUIST represents a paradigm shift in global health economics, emphasising the importance of equity alongside cost-effectiveness in health policy decisions. Its development and implementation have had a tangible impact on health outcomes, particularly in LMICs, where it has been instrumental in reducing maternal and child mortality while addressing health inequities.

External validation of the QCovid 2 and 3 risk prediction algorithms for risk of COVID-19 hospitalisation and mortality in adults: a national cohort study in Scotland.

OBJECTIVE: The QCovid 2 and 3 algorithms are risk prediction tools developed during the second wave of the COVID-19 pandemic that can be used to predict the risk of COVID-19 hospitalisation and mortality, taking vaccination status into account. In this study, we assess their performance in Scotland. METHODS: We used the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 national data platform consisting of individual-level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR virology testing, hospitalisation and mortality data. We assessed the discrimination and calibration of the QCovid 2 and 3 algorithms in predicting COVID-19 hospitalisations and deaths between 8 December 2020 and 15 June 2021. RESULTS: Our validation dataset comprised 465 058 individuals, aged 19-100. We found the following performance metrics (95% CIs) for QCovid 2 and 3: Harrell's C 0.84 (0.82 to 0.86) for hospitalisation, and 0.92 (0.90 to 0.94) for death, observed-expected ratio of 0.24 for hospitalisation and 0.26 for death (ie, both the number of hospitalisations and the number of deaths were overestimated), and a Brier score of 0.0009 (0.00084 to 0.00096) for hospitalisation and 0.00036 (0.00032 to 0.0004) for death. CONCLUSIONS: We found good discrimination of the QCovid 2 and 3 algorithms in Scotland, although performance was worse in higher age groups. Both the number of hospitalisations and the number of deaths were overestimated.

National and subnational incidence, mortality and associated factors of colorectal cancer in China: A systematic analysis and modelling study.

Background: Due to their known variation by geography and economic development, we aimed to evaluate the incidence and mortality of colorectal cancer (CRC) in China over the past decades and identify factors associated with CRC among the Chinese population to provide targeted information on disease prevention. Methods: We conducted a systemic review and meta-analysis of epidemiolocal studies on the incidence, mortality, and associated factors of CRC among the Chinese population, extracting and synthesising data from eligible studies retrieved from seven global and Chinese databases. We pooled age-standardised incidence rates (ASIRs) and mortality rates (ASMRs) for each province, subregion, and the whole of China, and applied a joinpoint regression model and annual per cent changes (APCs) to estimate the trends of CRC incidence and mortality. We conducted random-effects meta-analyses to assess the effect estimates of identified associated risk factors. Results: We included 493 articles; 271 provided data on CRC incidence or mortality, and 222 on associated risk factors. Overall, the ASIR of CRC in China increased from 2.75 to 19.39 (per 100 000 person-years) between 1972 and 2019 with a slowed-down growth rate (APC1 = 5.75, APC2 = 0.42), while the ASMR of CRC decreased from 12.00 to 7.95 (per 100 000 person-years) between 1974 and 2020 with a slight downward trend (APC = -0.89). We analysed 62 risk factors with synthesized data; 16 belonging to the categories of anthropometrics factors, lifestyle factors, dietary factors, personal histories and mental health conditions were graded to be associated with CRC risk among the Chinese population in the meta-analysis limited to the high-quality studies. Conclusions: We found substantial variation of CRC burden across regions and provinces of China and identified several associated risk factors for CRC, which could help to guide the formulation of targeted disease prevention and control strategies. Registration: PROSPERO: CRD42022346558.

Understanding and reporting odds ratios as rate-ratio estimates in case-control studies.

Background: We noted that there remains some confusion in the health-science literature on reporting sample odds ratios as estimated rate ratios in case-control studies. Methods: We recap historical literature that definitively answered the question of when sample odds ratios (ORs) from a case-control study are consistent estimators for population rate ratios. We use numerical examples to illustrate the magnitude of the disparity between sample ORs in a case-control study and population rate ratios when sufficient conditions for them to be equal are not satisfied. Results: We stress that in a case-control study, sampling controls from those still at risk at the time of outcome event of the index case is not sufficient for a sample OR to be a consistent estimator for an intelligible rate ratio. In such studies, constancy of the exposure prevalence together with constancy of the hazard ratio (HR) (i.e., the instantaneous rate ratio) over time is sufficient for this result if sampling time is not controlled; if time is controlled, constancy of the HR will suffice. We present numerical examples to illustrate how failure to satisfy these conditions adds a small systematic error to sample ORs as estimates of population rate ratios. Conclusions: We recommend that researchers understand and critically evaluate all conditions used to interpret their estimates as consistent for a population parameter in case-control studies.

The prevalence of vitamin A deficiency and its public health significance in children in low- and middle-income countries: A systematic review and modelling analysis.

Background: Vitamin A deficiency (VAD) is widely recognised as a major public health concern in low- and middle-income countries (LMICs). Despite various interventions implemented in many countries, a lack of reliable data is hindering progress. We aimed to consolidate available data and quantify estimates of the prevalence of VAD among children ≤18 years in LMICs. Methods: We searched PubMed, Medline and Embase for studies reported the prevalence of VAD or marginal (m)VAD among children. A multilevel mixed-effects meta-regression approach was applied to establish the regression models for VAD and mVAD prevalence. The total numbers of children affected by VAD and mVAD in LMICs in 2019 were separately calculated from the estimated age- and socio-demographic index (SDI)-specific prevalence with their corresponding United Nations Population Division populations projections. We estimated areas of significant public health concern in 165 LMICs using the lower confidence interval (CI) of VAD prevalence. Results: A total of 116 articles from 40 LMICs were retained. In 2019, VAD and mVAD affected 333.95 million (95% CI = 253.00-433.74) and 556.13 million (95% CI = 388.83-767.94) children and adolescents in 165 LMICs, respectively, corresponding to a prevalence of 14.73% (95% CI = 11.16-19.14) and 24.54% (95% CI = 17.15-33.88). The prevalence of both VAD and mVAD was the highest in children aged 0-5 years at 19.53% (95% CI = 15.03-24.91) and 28.22% (95% CI = 20.00-38.24), respectively, with both steadily decreasing to 10.09% (95% CI = 7.44-13.50) and 20.76% (95% CI = 14.16-29.50) in adolescents aged 13-18 years. The prevalence of VAD was significantly higher in the low SDI region at 29.67% (95% CI = 22.67-37.53) compared to 5.17% (95% CI = 3.14-8.43) estimated in the high-middle SDI region. 68 of the 165 LMICs (41.21%) were classified as areas of moderate to severe VAD public health significance. Conclusions: VAD continues to pose a significant public health concern in many low-income settings. Development in LMICs is a crucial factor for VAD, with a disproportionately higher burden in low SDI regions. Registration: This study protocol was registered with PROSPERO, CRD42020220654.

Predictors of incomplete COVID-19 vaccine schedule among adults in Scotland: Two retrospective cohort analyses of the primary schedule and third dose.

BACKGROUND: Vaccination continues to be the key public health measure for preventing severe COVID-19 outcomes. Certain groups may be at higher risk of incomplete vaccine schedule, which may leave them vulnerable to COVID-19 hospitalisation and death. AIM: To identify the sociodemographic and clinical predictors for not receiving a scheduled COVID-19 vaccine after previously receiving one. METHODS: We conducted two retrospective cohort studies with ≥3.7 million adults aged ≥18 years in Scotland. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) of not receiving a second, and separately a third dose between December 2020 and May 2022. Independent variables included sociodemographic and clinical factors. RESULTS: Of 3,826,797 people in the study population who received one dose, 3,732,596 (97.5%) received two doses, and 3,263,153 (86.5%) received all doses available during the study period. The most strongly associated predictors for not receiving the second dose were: being aged 18-29 (reference: 50-59 years; aOR:4.26; 95% confidence interval (CI):4.14-4.37); hospitalisation due to a potential vaccine related adverse event of special interest (AESI) (reference: not having a potential AESI, aOR:3.78; 95%CI: 3.29-4.35); and living in the most deprived quintile (reference: least deprived quintile, aOR:3.24; 95%CI: 3.16-3.32). The most strongly associated predictors for not receiving the third dose were: being 18-29 (reference: 50-59 years aOR:4.44; 95%CI: 4.38-4.49), living in the most deprived quintile (reference: least deprived quintile aOR:2.56; 95%CI: 2.53-2.59), and Black, Caribbean, or African ethnicity (reference: White ethnicity aOR:2.38; 95%CI: 2.30-2.46). Pregnancy, previous vaccination with mRNA-1273, smoking history, individual and household severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, and having an unvaccinated adult in the household were also associated with incomplete vaccine schedule. CONCLUSION: We observed several risk factors that predict incomplete COVID-19 vaccination schedule. Vaccination programmes must take immediate action to ensure maximum uptake, particularly for populations vulnerable to severe COVID-19 outcomes.

Ethnic inequalities in positive SARS-CoV-2 tests, infection prognosis, COVID-19 hospitalisations and deaths: analysis of 2 years of a record linked national cohort study in Scotland.

BACKGROUND: This study aims to estimate ethnic inequalities in risk for positive SARS-CoV-2 tests, COVID-19 hospitalisations and deaths over time in Scotland. METHODS: We conducted a population-based cohort study where the 2011 Scottish Census was linked to health records. We included all individuals ≥ 16 years living in Scotland on 1 March 2020. The study period was from 1 March 2020 to 17 April 2022. Self-reported ethnic group was taken from the census and Cox proportional hazard models estimated HRs for positive SARS-CoV-2 tests, hospitalisations and deaths, adjusted for age, sex and health board. We also conducted separate analyses for each of the four waves of COVID-19 to assess changes in risk over time. FINDINGS: Of the 4 358 339 individuals analysed, 1 093 234 positive SARS-CoV-2 tests, 37 437 hospitalisations and 14 158 deaths occurred. The risk of COVID-19 hospitalisation or death among ethnic minority groups was often higher for White Gypsy/Traveller (HR 2.21, 95% CI (1.61 to 3.06)) and Pakistani 2.09 (1.90 to 2.29) groups compared with the white Scottish group. The risk of COVID-19 hospitalisation or death following confirmed positive SARS-CoV-2 test was particularly higher for White Gypsy/Traveller 2.55 (1.81-3.58), Pakistani 1.75 (1.59-1.73) and African 1.61 (1.28-2.03) individuals relative to white Scottish individuals. However, the risk of COVID-19-related death following hospitalisation did not differ. The risk of COVID-19 outcomes for ethnic minority groups was higher in the first three waves compared with the fourth wave. INTERPRETATION: Most ethnic minority groups were at increased risk of adverse COVID-19 outcomes in Scotland, especially White Gypsy/Traveller and Pakistani groups. Ethnic inequalities persisted following community infection but not following hospitalisation, suggesting differences in hospital treatment did not substantially contribute to ethnic inequalities.