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.

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.

Quality of ethnicity data within Scottish health records and implications of misclassification for ethnic inequalities in severe COVID-19: a national linked data study.

BACKGROUND: We compared the quality of ethnicity coding within the Public Health Scotland Ethnicity Look-up (PHS-EL) dataset, and other National Health Service datasets, with the 2011 Scottish Census. METHODS: Measures of quality included the level of missingness and misclassification. We examined the impact of misclassification using Cox proportional hazards to compare the risk of severe coronavirus disease (COVID-19) (hospitalization & death) by ethnic group. RESULTS: Misclassification within PHS-EL was higher for all minority ethnic groups [12.5 to 69.1%] compared with the White Scottish majority [5.1%] and highest in the White Gypsy/Traveller group [69.1%]. Missingness in PHS-EL was highest among the White Other British group [39%] and lowest among the Pakistani group [17%]. PHS-EL data often underestimated severe COVID-19 risk compared with Census data. e.g. in the White Gypsy/Traveller group the Hazard Ratio (HR) was 1.68 [95% Confidence Intervals (CI): 1.03, 2.74] compared with the White Scottish majority using Census ethnicity data and 0.73 [95% CI: 0.10, 5.15] using PHS-EL data; and HR was 2.03 [95% CI: 1.20, 3.44] in the Census for the Bangladeshi group versus 1.45 [95% CI: 0.75, 2.78] in PHS-EL. CONCLUSIONS: Poor quality ethnicity coding in health records can bias estimates, thereby threatening monitoring and understanding ethnic inequalities in health.

Critical success index or F measure to validate the accuracy of administrative healthcare data identifying epilepsy in deceased adults in Scotland.

BACKGROUND: Methods to undertake diagnostic accuracy studies of administrative epilepsy data are challenged by lack of a way to reliably rank case-ascertainment algorithms in order of their accuracy. This is because it is difficult to know how to prioritise positive predictive value (PPV) and sensitivity (Sens). Large numbers of true negative (TN) instances frequently found in epilepsy studies make it difficult to discriminate algorithm accuracy on the basis of negative predictive value (NPV) and specificity (Spec) as these become inflated (usually >90%). This study demonstrates the complementary value of using weather forecasting or machine learning metrics critical success index (CSI) or F measure, respectively, as unitary metrics combining PPV and sensitivity. We reanalyse data published in a diagnostic accuracy study of administrative epilepsy mortality data in Scotland. METHOD: CSI was calculated as 1/[(1/PPV) + (1/Sens) - 1]. F measure was calculated as 2.PPV.Sens/(PPV + Sens). CSI and F values range from 0 to 1, interpreted as 0 = inaccurate prediction and 1 = perfect accuracy. The published algorithms were reanalysed using these and their accuracy re-ranked according to CSI in order to allow comparison to the original rankings. RESULTS: CSI scores were conservative (range 0.02-0.826), always less than or equal to the lower of the corresponding PPV (range 39-100%) and sensitivity (range 2-93%). F values were less conservative (range 0.039-0.905), sometimes higher than either PPV or sensitivity, but were always higher than CSI. Low CSI and F values occurred when there was a large difference between PPV and sensitivity, e.g. CSI was 0.02 and F was 0.039 in an instance when PPV was 100% and sensitivity was 2%. Algorithms with both high PPV and sensitivity performed best in terms of CSI and F measure, e.g. CSI was 0.826 and F was 0.905 in an instance when PPV was 90% and sensitivity was 91%. CONCLUSION: CSI or F measure can combine PPV and sensitivity values into a convenient single metric that is easier to interpret and rank in terms of diagnostic accuracy than trying to rank diagnostic accuracy according to the two measures themselves. CSI or F prioritise instances where both PPV and sensitivity are high over instances where there are large differences between PPV and sensitivity (even if one of these is very high), allowing diagnostic accuracy thresholds based on combined PPV and sensitivity to be determined. Therefore, CSI or F measures may be helpful complementary metrics to report alongside PPV and sensitivity in diagnostic accuracy studies of administrative epilepsy data.

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.

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.

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.

Neonatal and maternal outcomes following SARS-CoV-2 infection and COVID-19 vaccination: a population-based matched cohort study.

Understanding the impact of SARS-CoV-2 infection and COVID-19 vaccination in pregnancy on neonatal and maternal outcomes informs clinical decision-making. Here we report a national, population-based, matched cohort study to investigate associations between SARS-CoV-2 infection and, separately, COVID-19 vaccination just before or during pregnancy and the risk of adverse neonatal and maternal outcomes among women in Scotland with a singleton pregnancy ending at ≥20 weeks gestation. Neonatal outcomes are stillbirth, neonatal death, extended perinatal mortality, preterm birth (overall, spontaneous, and provider-initiated), small-for-gestational age, and low Apgar score. Maternal outcomes are admission to critical care or death, venous thromboembolism, hypertensive disorders of pregnancy, and pregnancy-related bleeding. We use conditional logistic regression to derive odds ratios adjusted for socio-demographic and clinical characteristics (aORs). We find that infection is associated with an increased risk of preterm (aOR=1.36, 95% Confidence Interval [CI] = 1.16-1.59) and very preterm birth (aOR = 1.90, 95% CI 1.20-3.02), maternal admission to critical care or death (aOR=1.72, 95% CI = 1.39-2.12), and venous thromboembolism (aOR = 2.53, 95% CI = 1.47-4.35). We find no evidence of increased risk for any of our outcomes following vaccination. These data suggest SARS-CoV-2 infection during pregnancy is associated with adverse neonatal and maternal outcomes, and COVID-19 vaccination remains a safe way for pregnant women to protect themselves and their babies against infection.

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.

Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.

In Aotearoa New Zealand, zoster vaccine live is used for the prevention of zoster and associated complications in adults. This study assessed the risk of pre-specified serious adverse events following zoster vaccine live immunisation among adults in routine clinical practice. We conducted a self-controlled case series study using routinely collected national data. We compared the incidence of serious adverse events during the at-risk period with the control period. Rate ratios were estimated using Conditional Poisson regression models. Falsification outcomes analyses were used to evaluate biases in our study population. From April 2018 to July 2021, 278,375 received the vaccine. The rate ratio of serious adverse events following immunisation was 0·43 (95% confidence interval [CI]: 0·37-0·50). There was no significant increase in the risk of cerebrovascular accidents, acute myocardial infarction, acute pericarditis, acute myocarditis, and Ramsay-Hunt Syndrome. The herpes zoster vaccine is safe in adults in Aotearoa New Zealand.

Herpes zoster vaccine effectiveness against herpes zoster and postherpetic neuralgia in New Zealand: a retrospective cohort study.

Background: Herpes zoster (HZ) and associated complications cause significant burden to older people. A HZ vaccination programme was introduced in Aotearoa New Zealand in April 2018 with a single dose vaccine for those aged 65 years and a four-year catch up for 66-80 year-olds. This study aimed to assess the 'real-world' effectiveness of the zoster vaccine live (ZVL) against HZ and postherpetic neuralgia (PHN). Methods: We conducted a nationwide retrospective matched cohort study from 1 April 2018 to 1 April 2021 using a linked de-identified patient level Ministry of Health data platform. A Cox proportional hazards model was used to estimate ZVL vaccine effectiveness (VE) against HZ and PHN adjusting for covariates. Multiple outcomes were assessed in the primary (hospitalised HZ and PHN - primary diagnosis) and secondary (hospitalised HZ and PHN: primary and secondary diagnosis, community HZ) analyses. A sub-group analysis was carried out in, adults ≥ 65 years old, immunocompromised adults, Maori, and Pacific populations. Findings: A total of 824,142 (274,272 vaccinated with ZVL matched with 549,870 unvaccinated) New Zealand residents were included in the study. The matched population was 93.4% immunocompetent, 52.2% female, 80.2% European (level 1 ethnic codes), and 64.5% were 65-74 years old (mean age = 71.1±5.0). Vaccinated versus unvaccinated incidence of hospitalised HZ was 0.16 vs. 0.31/1,000 person-years and 0.03 vs. 0.08/1000 person-years for PHN. In the primary analysis, the adjusted overall VE against hospitalised HZ and hospitalised PHN was 57.8% (95% CI: 41.1-69.8) and 73.7% (95% CI:14.0-92.0) respectively. In adults ≥ 65 years old, the VE against hospitalised HZ was 54.4% (95% CI: 36.0-67.5) and VE against hospitalised PHN was 75·5% (95% CI: 19.9-92.5). In the secondary analysis, the VE against community HZ was 30.0% (95% CI: 25.6-34.5). The ZVL VE against hospitalised HZ for immunocompromised adults was 51.1% (95% CI: 23.1-69.5), and PHN hospitalisation was 67.6% (95% CI: 9.3-88.4). The VE against HZ hospitalisation for Maori was 45.2% (95% CI: -23.2-75.6) and for Pacific Peoples was 52.2% (95% CI: -40.6 -83·7). Interpretation: ZVL was associated with a reduction in risk of hospitalisation from HZ and PHN in the New Zealand population. Funding: Wellington Doctoral Scholarship awarded to JFM.

Using Critical Success Index or Gilbert Skill Score as composite measures of positive predictive value and sensitivity in diagnostic accuracy studies: Weather forecasting informing epilepsy research.

The Critical Success Index (CSI) and Gilbert Skill score (GS) are verification measures that are commonly used to check the accuracy of weather forecasting. In this article, we propose that they can also be used to simplify the joint interpretation of positive predictive value (PPV) and sensitivity estimates across diagnostic accuracy studies of epilepsy data. This is because CSI and GS each provide a single measure that takes the weather forecasting equivalent of PPV and sensitivity into account. We have re-analysed data from our recent systematic review of diagnostic accuracy studies of administrative epilepsy data using CSI and GS. We summarise the results and benefits of this approach.

Implications for COVID-19 vaccine uptake: A systematic review.

BACKGROUND: Globally, increasing coronavirus disease (COVID-19) vaccination coverage remains a major public health concern in the face of high rates of COVID-19 hesitancy among the general population. We must understand the impact of the determinants of COVID-19 vaccine uptake when designing national vaccination programmes. We aimed to synthesise nationwide evidence regarding COVID-19 infodemics and the demographic, psychological, and social predictors of COVID-19 vaccination uptake. METHODS: We systematically searched seven databases between July 2021 and March 2022 to retrieve relevant articles published since COVID-19 was first reported on 31 December 2019 in Wuhan, China. Of the 12,502 peer-reviewed articles retrieved from the databases, 57 met the selection criteria and were included in this systematic review. We explored COVID-19 vaccine uptake determinants before and after the first COVID-19 vaccine roll-out by the Food and Drug Authority (FDA). RESULTS: Increased COVID-19 vaccine uptake rates were associated with decreased hesitancy. Concerns about COVID-19 vaccine safety, negative side effects, rapid development of the COVID-19 vaccine, and uncertainty about vaccine effectiveness were associated with reluctance to be vaccinated. After the US FDA approval of COVID-19 vaccines, phobia of medical procedures such as vaccine injection and inadequate information about vaccines were the main determinants of COVID-19 vaccine hesitancy. CONCLUSION: Addressing effectiveness and safety concerns regarding COVID-19 vaccines, as well as providing adequate information about vaccines and the impacts of pandemics, should be considered before implementation of any vaccination programme. Reassuring people about the safety of medical vaccination and using alternative procedures such as needle-free vaccination may help further increase vaccination uptake.

Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study.

OBJECTIVES: To examine neonates in Scotland aged 0-27 days with SARS-CoV-2 infection confirmed by viral testing; the risk of confirmed neonatal infection by maternal and infant characteristics; and hospital admissions associated with confirmed neonatal infections. DESIGN: Population-based cohort study. SETTING AND POPULATION: All live births in Scotland, 1 March 2020-31 January 2022. RESULTS: There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100 000 live births (141/92 009, 0.15%). Among infants born to women with confirmed infection around the time of birth, the confirmed neonatal infection rate was 1812 per 100 000 live births (15/828, 1.8%). Two-thirds (92/141, 65.2%) of neonates with confirmed infection had an associated admission to neonatal or (more commonly) paediatric care. Six of these babies (6/92, 6.5%) were admitted to neonatal and/or paediatric intensive care; however, none of these six had COVID-19 recorded as their main diagnosis. There were no neonatal deaths among babies with confirmed infection. IMPLICATIONS AND RELEVANCE: Confirmed neonatal SARS-CoV-2 infection was uncommon over the first 23 months of the pandemic in Scotland. Secular trends in the neonatal confirmed infection rate broadly followed those seen in the general population, although at a lower level. Maternal confirmed infection at birth was associated with an increased risk of neonatal confirmed infection. Two-thirds of neonates with confirmed infection had an associated admission to hospital, with resulting implications for the baby, family and services, although their outcomes were generally good. Ascertainment of confirmed infection depends on the extent of testing, and this is likely to have varied over time and between groups: the extent of unconfirmed infection is inevitably unknown.

A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection.

Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.

Case-control study developing Scottish Epilepsy Deaths Study Score to predict epilepsy-related death.

This study aimed to develop a risk prediction model for epilepsy-related death in adults. In this age- and sex-matched case-control study, we compared adults (aged ≥16 years) who had epilepsy-related death between 2009 and 2016 to living adults with epilepsy in Scotland. Cases were identified from validated administrative national datasets linked to mortality records. ICD-10 cause-of-death coding was used to define epilepsy-related death. Controls were recruited from a research database and epilepsy clinics. Clinical data from medical records were abstracted and used to undertake univariable and multivariable conditional logistic regression to develop a risk prediction model consisting of four variables chosen a priori. A weighted sum of the factors present was taken to create a risk index-the Scottish Epilepsy Deaths Study Score. Odds ratios were estimated with 95% confidence intervals (CIs). Here, 224 deceased cases (mean age 48 years, 114 male) and 224 matched living controls were compared. In univariable analysis, predictors of epilepsy-related death were recent epilepsy-related accident and emergency attendance (odds ratio 5.1, 95% CI 3.2-8.3), living in deprived areas (odds ratio 2.5, 95% CI 1.6-4.0), developmental epilepsy (odds ratio 3.1, 95% CI 1.7-5.7), raised Charlson Comorbidity Index score (odds ratio 2.5, 95% CI 1.2-5.2), alcohol abuse (odds ratio 4.4, 95% CI 2.2-9.2), absent recent neurology review (odds ratio 3.8, 95% CI 2.4-6.1) and generalized epilepsy (odds ratio 1.9, 95% CI 1.2-3.0). Scottish Epilepsy Deaths Study Score model variables were derived from the first four listed before, with Charlson Comorbidity Index ≥2 given 1 point, living in the two most deprived areas given 2 points, having an inherited or congenital aetiology or risk factor for developing epilepsy given 2 points and recent epilepsy-related accident and emergency attendance given 3 points. Compared to having a Scottish Epilepsy Deaths Study Score of 0, those with a Scottish Epilepsy Deaths Study Score of 1 remained low risk, with odds ratio 1.6 (95% CI 0.5-4.8). Those with a Scottish Epilepsy Deaths Study Score of 2-3 had moderate risk, with odds ratio 2.8 (95% CI 1.3-6.2). Those with a Scottish Epilepsy Deaths Study Score of 4-5 and 6-8 were high risk, with odds ratio 14.4 (95% CI 5.9-35.2) and 24.0 (95% CI 8.1-71.2), respectively. The Scottish Epilepsy Deaths Study Score may be a helpful tool for identifying adults at high risk of epilepsy-related death and requires external validation.

Studying the Long-term Impact of COVID-19 in Kids (SLICK). Healthcare use and costs in children and young people following community-acquired SARS-CoV-2 infection: protocol for an observational study using linked primary and secondary routinely collected healthcare data from England, Scotland and Wales.

INTRODUCTION: SARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been reported in CYP but subsequent healthcare use is unclear. We aim to describe healthcare use in CYP following community-acquired SARS-CoV-2 infection and identify those at risk of ongoing healthcare needs. METHODS AND ANALYSIS: We will use anonymised individual-level, population-scale national data linking demographics, comorbidities, primary and secondary care use and mortality between 1 January 2019 and 1 May 2022. SARS-CoV-2 test data will be linked from 1 January 2020 to 1 May 2022. Analyses will use Trusted Research Environments: OpenSAFELY in England, Secure Anonymised Information Linkage (SAIL) Databank in Wales and Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 in Scotland (EAVE-II). CYP aged ≥4 and <18 years who underwent SARS-CoV-2 reverse transcription PCR (RT-PCR) testing between 1 January 2020 and 1 May 2021 and those untested CYP will be examined.The primary outcome measure is cumulative healthcare cost over 12 months following SARS-CoV-2 testing, stratified into primary or secondary care, and physical or mental healthcare. We will estimate the burden of healthcare use attributable to SARS-CoV-2 infections in the 12 months after testing using a matched cohort study of RT-PCR positive, negative or untested CYP matched on testing date, with adjustment for confounders. We will identify factors associated with higher healthcare needs in the 12 months following SARS-CoV-2 infection using an unmatched cohort of RT-PCR positive CYP. Multivariable logistic regression and machine learning approaches will identify risk factors for high healthcare use and characterise patterns of healthcare use post infection. ETHICS AND DISSEMINATION: This study was approved by the South-Central Oxford C Health Research Authority Ethics Committee (13/SC/0149). Findings will be preprinted and published in peer-reviewed journals. Analysis code and code lists will be available through public GitHub repositories and OpenCodelists with meta-data via HDR-UK Innovation Gateway.