Background and Objectives: Evidence on postpartum antidepressant effectiveness is limited. We sought to determine the association between different timings of antidepressant initiation within the 0-6 months postpartum and mental outcomes at 6-and 18-months following childbirth. Methods: Using data from the Norwegian Mother, Father and Child Cohort Study (MoBa) linked to a sub-sample of MoBa Genetics, we included 1146 women with psychiatric history before and/or during early pregnancy: 154 (13.4%) antidepressant initiators in the 0-6 months postpartum (37.0% within 0-3, and 63.0% within 4-6 months), and 992 (86.6%) with unmedicated new mental illness episode within same period. Depression/anxiety symptom outcomes at 6 and 18 months postpartum were self-reported. To control for measured confounding, we fit linear and modified Poisson models using overlap weighting, overall and stratified by polygenic score for antidepressant response. Results: Antidepressant initiators within 0-3 months postpartum had reduced severity of depression/anxiety symptoms at 6, but not at 18 months postpartum, compared with unmedicated women (weighted mean difference (MD):-0.23, 95% CI =-0.39,-0.06) and a 44% lower risk of having active, clinically relevant depressive/ anxiety symptoms at 6 months (weighted RR= 0.56, 95% CI = 0.35, 0.91). No association was observed for initiation at 4-6 months postpartum at the 6-month assessment. The associations were evident only among women having high polygenic score for positive antidepressant response (weighted MD:-0.50, 95% CI:-0.84,-0.16), and that persisted at 18 months. Conclusions: Initiation of antidepressant in first 3 months postpartum, but not in months 4-6, is associated with reduced severity of depression/anxiety symptoms at 6 months post-delivery. Effects were most evident among women with higher polygenic scores; however, these findings are exploratory and warrant larger studies.

Objectives We aimed to assess the risk of incident autoimmune and inflammatory conditions during the post-acute period of COVID-19.Design Descriptive network cohort study.Setting Electronic health records from the UK and Dutch primary care, Norwegian linked health registry, hospital records of specialist centres in Spain, France and Korea and healthcare claims from Estonia and the USA.Participants We followed individuals between September 2020 and the latest available data from day 91 after a SARS-CoV-2 negative test (comparator) or a COVID-19 record (exposed patients, ie assessing patients during the post-acute phase). We further established a reinfection cohort (any further COVID-19 record among the exposed patients). We followed patients until an outcome, end of study period, death, day 365 or an infection (comparator only) or reinfection (exposed patients only).Main outcome measures We assessed postural orthostatic tachycardia syndrome (POTS) diagnoses/symptoms, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnoses/symptoms, multi-inflammatory syndrome (MIS) and several autoimmune diseases (rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) and type 1 diabetes mellitus (T1DM)).Meta-analysed crude incidence rate ratios (IRRs) of outcomes after COVID-19 versus negative testing and after reinfection versus a previous COVID-19 record yield the ratios of respective absolute risks of each assessed outcome. We performed subgroup analyses by age, sex and predominant variant periods.Results We included 2 521 812 individuals with a first COVID-19 record, 4 233 145 with a first negative test and 135 551 with a reinfection. Age and sex were largely comparable between exposure groups with a shorter follow-up for the reinfection cohorts. After COVID-19 compared with test-negative patients and equally after reinfection compared with previous COVID-19 patients, we did not observe increased rates for all outcomes and all subgroup analyses. Counts of MIS and JIA were too small for meta-analyses.Conclusions In our descriptive meta-analyses of crude IRRs among databases from various countries and settings, we did not observe increased rates of incident POTS, ME/CFS, RA, IBD, SLE and T1DM in COVID-19 versus test-negative or reinfection versus COVID-19 during the first 9 months of the post-acute phase of COVID-19 or reinfection (>90 days postinfection until month 12). Since causal interpretation cannot be made from this study, further causal research is warranted.

BACKGROUND:Little is known about the association between perinatal antidepressant use and gestational weight gain (GWG) and postpartum weight retention (PPWR). METHODS:We used data from the Norwegian Mother, Father and Child Cohort Study (MoBa), linked to the Medical Birth Registry of Norway (MBRN) and the Norwegian Prescribed Drug Registry (LMR). We included singleton, live birth pregnancies with pre-pregnancy depression/anxiety. Prenatal and perinatal antidepressant use trajectories were constructed using longitudinal k-means clustering. GWG and PPWR at 6/18 months postpartum were calculated using self-reported data. We estimated weighted relative risks (wRR) and 95 % confidence intervals (CI) using modified Poisson regression with robust variance estimators and overlap weights. For a sub-population with available genetics data, we used polygenic risk scores (PRSs) to partially account for confounding by genetic component. RESULTS:Among 3365 pregnancies included, we observed six prenatal and perinatal antidepressant use trajectories: non-users, pre-pregnancy discontinuers, early pregnancy discontinuers, late pregnancy discontinuers, continuers, and post-pregnancy initiators. Pre-pregnancy discontinuers had increased risk of inadequate GWG compared to non-users (wRR 1.34, 95 % CI 1.03-1.73). Early pregnancy discontinuers (wRR 0.89, 95 % CI 0.78-1.02), late pregnancy discontinuers (wRR 0.88, 95 % CI 0.76-1.01), and continuers (wRR 0.86, 95 % CI 0.71-1.05) had a borderline decreased risk of excessive PPWR at 6 months postpartum compared to non-users. We observed no other associations between antidepressant use trajectories and GWG or PPWR. CONCLUSION:These results enhance knowledge on weight-related safety concerns of antidepressant use in the prenatal and perinatal period, specifically regarding GWG and PPWR.

Prior evidence has suggested the multisystem symptomatic manifestations of post-acute COVID-19 condition (PCC). Here we conducted a network cluster analysis of 24 WHO proposed symptoms to identify potential latent subclasses of PCC. Individuals with a positive test of or diagnosed with SARS-CoV-2 after 09/2020 and with at least one symptom within ≥ 90 to 365 days following infection were included. Sub-analyses were conducted among people with ≥ 3 different symptoms. Summary characteristics were provided for each cluster. All analyses were conducted separately in 9 databases from 7 countries, including data from primary care, hospitals, national health claims and national health registries, allowing to validate clusters across the different healthcare settings. 787,078 persons with PCC were included. Single-symptom clusters were common across all databases, particularly for joint pain, anxiety, depression and allergy. Complex clusters included anxiety-depression and abdominal-gastrointestinal symptoms. Substantial heterogeneity within and between PCC clusters was seen across healthcare settings. Current definitions of PCC should be critically reviewed to reflect this variety in clinical presentation.

ABSTRACT Objectives The Observational Medical Outcomes Partnership common data model (OMOP‐CDM) is a useful tool for large‐scale network analysis but currently lacks a structured approach to pregnancy episodes. We aimed to develop and implement a perinatal expansion for the OMOP‐CDM to facilitate perinatal network research. Methods We collaboratively developed a perinatal expansion with input from domain experts and stakeholders to reach consensus. The structure and vocabularies followed the OMOP‐CDM ontological framework principles. We tested the expansion using SIDIAP and Norwegian databases. We developed a diagnostics package for quality control assessment and conducted a descriptive analysis on the captured perinatal data mapped to the OMOP‐CDM. Results The perinatal expansion consists of a pregnancy table and an infant table, each with required and optional variables incorporated into standardized vocabularies. Quality assessment of the perinatal expansion table in SIDIAP and Norwegian databases demonstrated accurate capture of perinatal characteristics. Descriptive analysis measured the number of pregnancies (SIDIAP: 646 530; Norway: 746 671), pregnancy outcomes (e.g., 0.5% stillbirths in SIDIAP and 0.4% in Norway), gestational length (median [IQR] in days, SIDIAP: 273 [56–280]; Norway: 280 [273–286]), number of infants (Norway: 758 806), and birth weight (median [IQR] in grams, Norway: 3520 [3175–3860)], among other relevant variables. Discussion and Conclusion We developed and implemented a perinatal expansion that captures important variables for perinatal research and allows interoperability with existing tables in the OMOP‐CDM, which is expected to facilitate future network studies. The publicly available diagnostics package enables testing the implementation of the extension table and the quality and completeness of available data on pregnancy and pregnancy‐related outcomes in databases mapped to the OMOP CDM.

In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correct context. The REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance (READUS-PV) statement was developed to address this issue by promoting transparent and comprehensive reporting of disproportionality studies. While the statement paper explains in greater detail the procedure followed to develop these guidelines, with this explanation paper we present the 14 items retained for READUS-PV guidelines, together with an in-depth explanation of their rationale and bullet points to illustrate their practical implementation. Our primary objective is to foster the adoption of the READUS-PV guidelines among authors, editors, peer reviewers, and readers of disproportionality analyses. Enhancing transparency, completeness, and accuracy of reporting, as well as proper interpretation of their results, READUS-PV guidelines will ultimately facilitate evidence-based decision making in pharmacovigilance.

The association between maternal COVID-19 vaccination in pregnancy and factors such as high risk for severe COVID-19, pre-existing asthma, prior adverse reproductive history, or paternal COVID-19 vaccination during pregnancy, remains unclear. The aim of this study is two-fold: (i) to describe uptake of COVID-19 vaccine during pregnancy by maternal risk for severe COVID-19 and asthma, and (ii) to comprehensively examine individual and familial factors associated with vaccine uptake during pregnancy in Norway. Based on nation-wide registry-linkage data in Norway, we included 101,659 deliveries with gestational length >= 12 weeks, in 2021-2022. Our outcome measure was uptake of at least one dose of mRNA COVID-19 vaccine during pregnancy, using a narrow (first ever dose) and broad (any dose) definition. We fit univariate and multivariate modified Poisson regression models, clustered by county of residency and adjusted for calendar time, to estimate risk ratios (RR) with 95 % Confidence Intervals (CIs). Gestational uptake of any COVID-19 vaccine dose increased from <1 % before mid Aug-2021, to 38.8 % in the rest of 2021, and 48.9 % in 2022. Only 28.8 % and 33.9 % pregnant individuals with high risk for severe COVID-19 or asthma, respectively, received at least one COVID-19 vaccine dose. Paternal COVID-19 vaccination was strongly associated with greater vaccine uptake by pregnant individuals (adjusted RR: 7.2, 95 % CI: 6.8-7.5). Maternal SARS-CoV-2 infection pre-pregnancy (adjusted RR: 0.31, 95 % CI: 0.26, 0.37), familial and individual migrant status were associated with a considerable decreased likelihood of vaccine uptake in pregnancy. History of miscarriage or pregnancy with congenital anomaly were not associated with vaccine uptake. Despite rising COVID-19 vaccine rates in pregnancy, uptake remained low for high-risk individuals. Paternal vaccination, pre-pregnancy infection, migration status, and maternal citizenship were strongly associated with prenatal vaccine uptake. This knowledge can inform tailoring of future vaccination campaigns.

Factors related with COVID-19 vaccine uptake in children and adolescents in Norway remain unclear, despite this being useful knowledge for future pandemic preparedness. This study aimed to comprehensively examine individual and familial factors associated with vaccine uptake in children and adolescents in Norway. We utilized nationwide registry-data from various health registries and Statistics Norway, encompassing all children and adolescents living in Norway during the pandemic, until 31-Dec-2022. Vaccine uptake is defined as receiving at least one dose of COVID-19 vaccine. We employed a forward stepwise logistic regression model and a random forest machine-learning algorithm to explore the relationship between vaccine uptake and socio-cultural, demographic, and health-related factors. We included 423,548 5-11-year-olds, 269,830 12-15-year-olds, and 120,854 16-17-year-olds. Vaccine uptake in these three groups was respectively 2.6 %, 73.3 %, and 87.3 %. Factors associated with vaccine uptake varied by age group. In youngest children, immigrant background (Odds-ratio (OR) = 1.58, 95 % confidence interval (CI) (1.14-2.19)), born extremely preterm (OR = 2.38, 95 % CI (1.60-3.54)), having risk of severe COVID-19 (OR = 5.40, 95 % CI (4.69-6.23) and maternal COVID-19 vaccination (OR = 6.34, 95 % CI (5.35-7.53)) were positively associated with vaccine uptake. The latter two factors were also strongly, positively associated with vaccine uptake in 12-15-year-olds, while previous SARS-CoV-2 infection was negatively associated (OR = 0.12, 95 % CI (0.11-0.14). Similar findings were observed in 16-17-year-olds. COVID-19 vaccine uptake differed markedly by age group, and major associated factors included socio-demographics and parental COVID-19 vaccination status, prior SARS-CoV-2 infection, but also being born premature and having moderate or high risk of severe COVID-19.

Objective To study the association between COVID-19 vaccination and the risk of post-COVID-19 cardiac and thromboembolic complications. Methods We conducted a staggered cohort study based on national vaccination campaigns using electronic health records from the UK, Spain and Estonia. Vaccine rollout was grouped into four stages with predefined enrolment periods. Each stage included all individuals eligible for vaccination, with no previous SARS-CoV-2 infection or COVID-19 vaccine at the start date. Vaccination status was used as a time-varying exposure. Outcomes included heart failure (HF), venous thromboembolism (VTE) and arterial thrombosis/thromboembolism (ATE) recorded in four time windows after SARS-CoV-2 infection: 0–30, 31–90, 91–180 and 181–365 days. Propensity score overlap weighting and empirical calibration were used to minimise observed and unobserved confounding, respectively. Fine-Gray models estimated subdistribution hazard ratios (sHR). Random effect meta-analyses were conducted across staggered cohorts and databases. Results The study included 10.17 million vaccinated and 10.39 million unvaccinated people. Vaccination was associated with reduced risks of acute (30-day) and post-acute COVID-19 VTE, ATE and HF: for example, meta-analytic sHR of 0.22 (95% CI 0.17 to 0.29), 0.53 (0.44 to 0.63) and 0.45 (0.38 to 0.53), respectively, for 0–30 days after SARS-CoV-2 infection, while in the 91–180 days sHR were 0.53 (0.40 to 0.70), 0.72 (0.58 to 0.88) and 0.61 (0.51 to 0.73), respectively. Conclusions COVID-19 vaccination reduced the risk of post-COVID-19 cardiac and thromboembolic outcomes. These effects were more pronounced for acute COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough versus unvaccinated SARS-CoV-2 infection.

Pregnant women on antidepressants must balance potential fetal harm with the relapse risk. While various clinical and sociodemographic factors are known to influence treatment decisions, the impact of genetic factors remains unexplored. We conducted a cohort study among 2,316 women with diagnosed affective disorders who had redeemed antidepressant prescriptions six months before pregnancy, identified from the Danish Integrated Psychiatric Research study. We calculated polygenic risk scores (PGSs) for major depression (MDD), bipolar disorder (BD), and schizophrenia (SCZ) using individual-level genetic data and summary statistics from genome-wide association studies. We retrieved data on sociodemographic and clinical features from national registers. Applying group-based trajectory modeling, we identified four treatment trajectories across pregnancy and postpartum: Continuers (38.2 %), early discontinuers (22.7 %), late discontinuers (23.8 %), and interrupters (15.3 %). All three PGSs were not associated with treatment trajectories; for instance, the relative risk ratio for continuers versus early discontinuers was 0.93 (95 % CI: 0.81–1.06), 0.98 (0.84–1.13), 1.09 (0.95–1.27) for per 1-SD increase in PGS for MDD, BD, and SCZ, respectively. Sociodemographic factors were generally not associated with treatment trajectories, except for the association between primiparity and continuing antidepressant use. Women who received ≥2 classes or a higher dose of antidepressants had a higher probability of being late discontinuers, interrupters, and continuers. The likelihood of continuing antidepressants or restarting antidepressants postpartum increased with the previous antidepressant treatment duration. Our findings indicate that continued antidepressant use during pregnancy is influenced by the severity of the disease rather than genetic predisposition as measured by PGSs.

BACKGROUND:Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2). METHODS:We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates. FINDINGS:A total of 1 618 395 (CPRD GOLD), 5 729 800 (CPRD AURUM), 2 744 821 (SIDIAP), and 77 603 (CORIVA) vaccinated people and 1 640 371 (CPRD GOLD), 5 860 564 (CPRD AURUM), 2 588 518 (SIDIAP), and 302 267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 (95% CI 0·44-0·67) in CPRD GOLD, 0·48 (0·34-0·68) in CPRD AURUM, 0·71 (0·55-0·91) in SIDIAP, and 0·59 (0·40-0·87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0·85 [0·60-1·20] in CPRD GOLD and 0·84 [0·74-0·94] in CPRD AURUM). INTERPRETATION:Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults. FUNDING:National Institute for Health and Care Research.

ABSTRACTImportanceNo study with available data from birth into late childhood has explored how prenatal antidepressant exposure affects offspring body mass index (BMI) throughout childhood.ObjectiveTo determine the association between prenatal antidepressant exposure and longitudinal differences in child BMI up to age 8 years.Design, Setting, and ParticipantsWe used data from the Norwegian Mother, Father, and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway and the MoBa Genetics. We included 6,084 pregnancy-child dyads (singleton, liveborn) with available parent-reported data on child BMI from birth up to 8 years of age, born to women with depression/anxiety prior to pregnancy. Analysis was performed between January 2023 and April 2024.ExposuresPrenatal antidepressant exposure was categorized as i)continuedantidepressants in pregnancy (n=626); ii)discontinuedantidepressants proximal to pregnancy (n=412); or iii)unexposedto antidepressants both before and during pregnancy (n=5,046).Main outcomes and measuresChild BMI up to 8 years of age. Mean BMI differences over time across antidepressant exposure groups were compared using multilevel mixed-effect linear models.ResultsChildren born to mothers who continued antidepressant into pregnancy had comparable childhood BMIs with those born to unexposed mothers or mothers who discontinued antidepressant proximal to pregnancy. Higher BMI was observed up to 3 years of age among male offspring born to antidepressant continuers compared to discontinuers, especially in those exposed to selective-serotonin-reuptake-inhibitor before pregnancy (mean difference in BMI, β=0.334; 95% CI: 0.081 to 0.588 at baseline). Lower BMI was seen among female offspring born to continued vs. discontinued mothers and the gap became larger over time, especially between low-moderate use of antidepressant vs. discontinuation during pregnancy. Analyses integrating parental genetic liability for depression, BMI, and antidepressant response using polygenic risk scores in a sub-population (n=1,913) suggests potential influence of the genetic component on the differences in BMI across antidepressant trajectory groups in some strata.Conclusion and relevanceThe longitudinal childhood BMI of children born to mothers with pre-pregnancy depression/anxiety did not differ across prenatal antidepressant exposure trajectories. Exploratory analyses revealed differences at specific time frames which might be sex-specific and potentially influenced by genetic liability profiles.KEY POINTSQuestionDoes prenatal antidepressant exposure affect longitudinal childhood BMI?FindingsIn this cohort study of 6084 pregnancy-child dyads in mothers with pre-pregnancy depressive/anxiety disorders, no difference in longitudinal childhood BMI across prenatal antidepressant exposure groups were observed. Exploratory analyses revealed differences at specific time frames which might be sex-specific and potentially influenced by parental genetic liability profiles.MeaningLongitudinal BMI throughout childhood of children born to mothers with pre-pregnancy depression/anxiety did not differ across prenatal antidepressant exposure trajectories. Further research is needed to investigate the time-dependent, sex-specific, and genetic-related aspects of some strata of antidepressant exposure on BMI differences.

Objective: Norwegian health registries covering entire population are used for administration, research, and emergency preparedness. We harmonized these data onto the Observational Medical Outcomes Partnership common data model (OMOP CDM) and enrich real-world data in OMOP format with COVID-19 related data. Methods: Data from six registries (2018-2021) covering birth registrations, selected primary and secondary care events, vaccinations, and communicable disease notifications were mapped onto the OMOP CDM v5.3. An Extract-Transform-Load (ETL) pipeline was developed on simulated data using data characterization documents and scanning tools. We ran dashboard quality checks, cohort generations, investigated differences between source and mapped data, and refined the ETL accordingly. Results: We mapped 1.5 billion rows of data of 5,673,845 individuals. Among these, there were 804,277 pregnancies, 483,585 mothers together with 792,477 children, and 472,948 fathers. We identified 382,516 positive tests for COVID-19 in 380,794 patients. These figures are consistent with results from source data. In addition to 11 million source codes mapped automatically, we mapped 237 non-standard codes to standard concepts and introduced 38 custom concepts to accommodate pregnancy-related terminologies that were not supported by OMOP CDM vocabularies. A total of 3,700/3,705 (99.8%) checks passed. The 5 failed checks could be explained by the nature of the data and only represent a small number of records. Discussion and conclusion: Norwegian registry data were successfully harmonized onto OMOP CDM with high level of concordance and provides valuable source for federated COVID-19 related research. Our mapping experience is highly valuable for data partners with Nordic health registries.

Background:The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations. Methods:A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We defined two cohorts for the main analyses: a SARS-CoV-2 infection cohort [positive polymerase chain reaction (PCR) or rapid lateral flow test (LFT) result or clinical COVID-19 diagnosis] and a general population cohort. Individuals with less than 365 days of prior history or 120 days of follow-up were excluded. We estimated incidence rates (IRs) of the 25 WHO-proposed post-acute COVID-19 symptoms, considering symptoms that occurred ≥90 and ≤365 days after index date, excluding individuals with the respective symptoms 180 days prior to the index event. Stratified analyses were conducted by age and sex. Incidence rate ratios (IRRs) were calculated comparing rates in the infected cohort versus the general population. Results from the different databases were combined using random-effects meta-analyses. Findings:3,019,408 individuals were included in the infection cohort. 1,585,160 of them were female and 1,434,248 of them male. 929,351,505 individuals were included in the general population group. 461,195,036 of them were female and 466,022,004 of them male. The 1-year IR of any post-acute COVID-19 symptom in the COVID-19 infection cohort varied significantly across databases, from 4.4 (95% CI 3.8-5.1) per 100 person-years to 103.9 (95% CI 103.2-104.7). The five most common symptoms were joint pain (from 1.6 (95% CI 1.3-1.9) to 14.3 (95% CI 14.1-14.6)), abdominal pain (from 0.3 (95% CI 0.1-0.5) to 9.9 (95% CI 9.7-10.1)), gastrointestinal issues (from 0.6 (95% CI 0.4-0.9) to 13.3 (95% CI 13.1-13.6)), cough (from 0.3 (95% CI 0.2-0.5) to 9.1 (95% CI 8.9-9.3)), and anxiety (from 0.8 (95% CI 0.6-1.2) to 11.4 (95% CI 11.2-11.6)); whereas muscle spasms (from 0.01 (95% CI 0.008-0.2) to 1.7 (95% CI 1.6-1.8)), pins and needles (from 0.05 (95% CI 0.03-0.0.9) to 1.5 (95% CI 1.4-1.6)), memory issues (from 0.03 (95% CI 0.02-0.06) to 0.8 (95% CI 0.7-0.8)), cognitive dysfunction (from 0.007 (95% CI 0.004-0.01) to 0.6 (95% CI 0.4-0.8)), and altered smell and/or taste (from 0.04 (95% CI 0.03-0.04) to 0.7 (95% CI 0.6-0.8)) were least common. Incidence rates of any post-acute COVID-19 symptoms generally increased with age, with certain symptoms peaking in middle-aged adults (anxiety, depressive disorders, headache, altered smell and taste) and others in pre-school children (gastrointestinal issues and cough). Females had higher incidence rates for most symptoms. Based on the random-effects model, the infected cohort had a higher incidence of any post-acute COVID-19 symptom than the general population, with a meta-analytic incidence rate ratio (meta-IRR) of 1.4 (1-2). A similar pattern was seen for all individual symptoms. The highest meta-IRRs were depressive disorder, 2.6 (1.7-3.9); anxiety, 2.3 (1.4-3.8); allergy, 2.1 (1.7-2.8) and sleep disorders, 2.1 (1.5-2.6). The meta-IRR for altered smell and/or taste was 1.9 (1.3-2.8). Interpretation:Post-acute COVID-19 symptoms, as listed by the WHO, were commonly observed following COVID-19 infection. However, even after standardising research methods, there was significant heterogeneity in the incidence rates from different healthcare settings and geographical locations. This is the first international study of the epidemiology of post-acute COVID-19 symptoms using the WHO-listed symptoms. Its findings contibute to understand the epidemiology of this condition from a multinational approach. Limitations of this study include the lack of consensus of the post-acute COVID-19 definition, as well as the difficulty to capture the impact on daily life of the post-acute COVID-19 symptoms in the available datasets. Funding:This work has been funded by the European Health Data Evidence Network (EHDEN) through an Evidence Generation Fund Grant and by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC).

Our recent study using data from more than 20 million participants has shown that COVID-19 vaccines consistently prevent long COVID symptoms in adults, with meta-analytic calibrated subdistribution hazard ratio (sHRs) of 0·54 (95% CI 0·44–0·67) in CPRD GOLD, 0·48 (0·34–0·68) in CPRD AURUM, 0·71 (0·55–0·91) in SIDIAP, and 0·59 (0·40–0·87) in CORIVA.1Català M Mercadé-Besora N Kolde R et al.The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia.Lancet Respir Med. 2024; 12: 225-236Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar In addition, when considering post-COVID thromboembolic and cardiovascular complications as outcomes of interest, recently published data have shown that vaccination with any COVID-19 first vaccine dose (ChAdOx1, BNT162b2, and mRNA-1273) is associated with reduced risk of post-acute heart failure (0·45 [0·38–0·53] 0–30 days after SARS-CoV-2 infection; 0·61 [0·51–0·73] 91–180 days after SARS-CoV-2 infection), venous thromboembolism (sHR 0·22 [95% CI 0·17–0·29] 0–30 days after SARS-CoV-2 infection; 0·53 [0·40–0·70] 91–180 days after SARS-CoV-2 infection), and arterial thrombosis (0·53 [0·44–0·63] 0–30 days after SARS-CoV-2 infection; 0·72 [0·58–0·88] 91–180 days after SARS-CoV-2 infection).2Mercadé-Besora N Li X Kolde R et al.The role of COVID-19 vaccines in preventing post COVID-19 thromboembolic and cardiovascular complications: a multinational cohort study.Heart. 2024; (published online March 12.)https://doi.org/10.1136/heartjnl-2023-323483Crossref PubMed Scopus (0) Google Scholar With the use of the Observational Medical Outcomes Partnership (OMOP) common data model (CDM), all our analyses were conducted across three European countries (Estonia, Spain, and the UK) without transferring patient data, using federated analyses similar to those used by the European Medicines Agency-funded Data Analysis and Real World Interrogation Network. Here, we show further reproducibility and report results from applying the same analyses to the Norwegian Linked Health Registries at University of Oslo, covering the entire Norwegian population of approximately 5·4 million inhabitants. Data from six registries covering primary and secondary care, hospitalisations, vaccinations, communicable disease notifications, prescriptions, and sociodemographic factors between 2018 and 2021 were mapped to the OMOP CDM. Reproducing previous methods (appendix p 25 and our previous study),1Català M Mercadé-Besora N Kolde R et al.The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia.Lancet Respir Med. 2024; 12: 225-236Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar we generated four study cohorts in line with the Norwegian vaccination campaign rollout between Jan 9, 2021, and Aug 6, 2021: people aged 75 years and older (cohort one); 65 years and older and clinically extremely vulnerable people, and those with underlying health conditions aged 18 years and older (cohort two); 18 years and older with underlying conditions (cohort three); and 18 years and older (cohort four; appendix p 3). We then applied the publicly available scripts to assess the effectiveness of COVID-19 vaccines to prevent long COVID and post-acute complications. A total of 2 364 651 vaccinated and 1 532 935 unvaccinated individuals in Norway were included (appendix p 18). Of the vaccinated individuals, 1576 (0·09%) developed at least one of the 25 WHO-listed symptoms recorded at between 90 and 365 days after the date of a COVID-19 positive test or diagnosis, with no record of that symptom 180 days before SARS-Cov-2 infection, and were therefore identified as long COVID cases, compared with 2922 (0·17%) of the unvaccinated individuals (table). Background characteristics of the study population by cohorts are presented in the appendix (p 4). Adequate covariate balance between the vaccinated and unvaccinated groups was achieved after weighting, as shown in the appendix (p 6). Information regarding follow-up time and censoring information are summarised in the appendix (p 8).TableDiagnostic records from the Norwegian Linked Health Registries at University of Oslo for any long COVID symptoms between 90 and 365 days after SARS-CoV-2 infection, stratified by cohort and exposed statusVaccinatedUnvaccinatedIndividualsCOVID-19Long COVIDIndividualsCOVID-19Long COVIDCohort 1197 174782168 (21·48%)224 2234113751 (18·26%)Cohort 2434 7233266520 (15·92%)321 9777000643 (9·19%)Cohort 3263 0572814370 (13·15%)438 15118 5441267 (6·83%)Cohort 41 469 69739 210518 (1·32%)548 58441 971261 (0·62%)Data shown are n or n (%). Exposure is any COVID-19 vaccine. Outcome is having at least one WHO-listed symptoms 90 days or more following SARS-CoV-2 infection with no history of that symptom in the previous 180 days (long COVID). Cohort 1 includes individuals aged 75 years and older, cohort 2 includes individuals aged 65 years and older and clinically extremely vulnerable people, and those with underlying health conditions aged 18 years and older, cohort 3 includes individuals aged 18 years and older with underlying conditions, and cohort 4 includes individuals aged 18 years and older. Unvaccinated people can be included in different cohorts and contribute to event counts multiple times. Open table in a new tab Data shown are n or n (%). Exposure is any COVID-19 vaccine. Outcome is having at least one WHO-listed symptoms 90 days or more following SARS-CoV-2 infection with no history of that symptom in the previous 180 days (long COVID). Cohort 1 includes individuals aged 75 years and older, cohort 2 includes individuals aged 65 years and older and clinically extremely vulnerable people, and those with underlying health conditions aged 18 years and older, cohort 3 includes individuals aged 18 years and older with underlying conditions, and cohort 4 includes individuals aged 18 years and older. Unvaccinated people can be included in different cohorts and contribute to event counts multiple times. Overall, vaccination with any COVID-19 vaccine (namely BNT162b2, mRNA-1273, and ChAdOx1) reduced the risk of developing long COVID symptoms across all study cohorts: the meta-analytic (sHR) was 0·64 (95% CI 0·55–0·74) if vaccinated people were censored at the second vaccine dose (appendix p 19), in line with our previous study.1Català M Mercadé-Besora N Kolde R et al.The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia.Lancet Respir Med. 2024; 12: 225-236Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Sensitivity analyses without censoring on the second dose for vaccinated groups provided similar results: meta-analytic sHR was 0·55 (0·46–0·66; appendix p 20). Estimates obtained by Fine-Gray method and Cox regression are highly consistent (appendix p 9). As Norway suspended the use of ChAdOx1 vaccine on March 11, 2021, we did not perform comparative effectiveness analyses between BNT162b2 and ChAdOx1, as was done in the main Article. We further analysed the effectiveness of COVID-19 vaccines in preventing post-COVID-19 thromboembolic and cardiovascular complications, replicating a recently published analysis (appendix p 25).2Mercadé-Besora N Li X Kolde R et al.The role of COVID-19 vaccines in preventing post COVID-19 thromboembolic and cardiovascular complications: a multinational cohort study.Heart. 2024; (published online March 12.)https://doi.org/10.1136/heartjnl-2023-323483Crossref PubMed Scopus (0) Google Scholar We studied the same post-acute complications (myocarditis, pericarditis, heart failure, venous thromboembolism, and arterial thrombosis), as seen in four time-windows after SARS-CoV-2 infection: 0–30, 31–90, 91–180, and 181–365 days. These outcomes were rare in our data, and mainly presented in the older populations (cohorts one and two; appendix p 10). In general, vaccination was associated with reduced risk of various post-COVID thromboembolic and cardiovascular complications during acute (0–30 days) and post-acute (31–90 and 91–180 days) phases (appendix pp 21–24). Reduced risk for post-COVID heart failure and venous thromboembolism during the acute phase was observed across four cohorts, except for the older population (age 75 years and older), whose lower risk was found in the post-acute phase. We also found significantly reduced risk for post-COVID arterial thrombosis in the acute phase in all cohorts except for those with underlying conditions. Some limitations regarding the availability of Norwegian data at the time of performing these analyses are worth mentioning. First, our data only cover the period 2018–21, which precluded the follow-up of patients during the omicron predominant time period. Second, diagnostic codes associated with events recorded in secondary care (ie, consultations with specialists and hospitalisations) were only available with three digits (ie, we do not have diagnosis code as I51.4, but as I51) of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems, which hinders the possibility of exploring some conditions in detail. In summary, we show the real-world effectiveness of COVID-19 vaccines to prevent long COVID symptoms and post-COVID thromboembolic and cardiovascular complications among the Norwegian population, consistent with previous findings from other countries (UK, Spain, and Estonia).1Català M Mercadé-Besora N Kolde R et al.The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia.Lancet Respir Med. 2024; 12: 225-236Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 2Mercadé-Besora N Li X Kolde R et al.The role of COVID-19 vaccines in preventing post COVID-19 thromboembolic and cardiovascular complications: a multinational cohort study.Heart. 2024; (published online March 12.)https://doi.org/10.1136/heartjnl-2023-323483Crossref PubMed Scopus (0) Google Scholar Additionally, we show the use of federated analytics applied across national borders to analyse linked real-world data mapped to the OMOP CDM. By applying publicly available scripts, we confirm the generalisability and reproducibility of two recent publications, strengthening their findings. DP-A's department has received grants from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, UCB Biopharma, the European Medicines Agency, and the Innovative Medicines Initiative. DP-A's research group has received consultancy fees from Astra Zeneca and UCB Biopharma. DP-A's department has organised training programmes funded or supported by Amgen, Astellas, Janssen, Synapse Management Partners, and UCB Biopharma. HMEN reports support from the European Health Data and Evidence Network project grant, Innovative Medicines Initiative 2 Joint Undertaking (grant agreement 806968) for harmonisation of the Norwegian registry data into the Observational Medical Outcomes Partnership (OMOP) common data model (CDM). This initiative received support from the EU Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations. All other authors declare no competing interests. Download .pdf (1.32 MB) Help with pdf files Supplementary appendix The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and EstoniaVaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults. Full-Text PDF Open Access

ABSTRACTBackgroundExposure to long‐lasting extreme ambient temperatures in the periconceptional or early pregnancy period might increase the risk of neural tube defects (NTDs). We tested whether prolonged severe heat exposure as experienced during the 2003 extreme heatwave in France, affected the risk of NTDs.MethodsWe retrieved NTD cases spanning from January 1994 to December 2018 from the Paris Registry of Congenital Malformations. The 2003 heatwave was characterized by the long duration and high intensity of nine consecutive days with temperatures ≥35°C. We classified monthly conceptions occurring in August 2003 as “exposed” to prolonged extreme heat around conception (i.e., periconceptional period). We assessed whether the risk of NTDs among cohorts exposed to the prolonged severe heatwave of 2003 in the periconceptional period differed from expected values using Poisson/negative binomial regression.FindingsWe identified 1272 NTD cases from January 1994 to December 2018, yielding a monthly mean count of 4.24. Ten NTD cases occurred among births conceived in August 2003. The risk of NTD was increased in the cohort with periconceptional exposure to the August 2003 heatwave (relative risk = 2.14, 95% confidence interval: 1.46 to 3.13), compared to non‐exposed cohorts. Sensitivity analyses excluding July and September months or restricting to summer months yielded consistent findings.InterpretationEvidence from the “natural experiment” of an extreme climate event suggests an elevated risk of NTDs following exposure to prolonged extreme heat during the periconceptional period.

BACKGROUND:Antibiotics are commonly used in both outpatient and inpatient settings and are responsible for the majority of adverse drug reaction (ADR) reports. We aimed to characterize spontaneously reported ADRs associated with antibiotics and assessing the preventability of these ADRs in a Vietnamese setting.MATERIALS AND METHODS:We conducted a retrospective descriptive study based on ADRs related to antibiotics spontaneously reported by healthcare workers to the National Pharmacovigilance Database of Vietnam (NPDV) between June 2018 and May 2019. The characteristics of included reports were descriptively analyzed. The preventability of reported ADRs was assessed using a standardized preventability scale. We identified the leading causes and described the characteristics associated with preventable ADRs (pADRs).RESULTS:We included 6385 antibiotic-related reports from a total of 12,056 reports submitted to the NPDV during the study period. Beta-lactam antibiotics, mostly broad-spectrum with parenteral route, were suspected in the majority cases. The most commonly reported pADRs were allergic reactions, mostly classified under skin and subcutaneous tissue disorders. Of all included cases, 537 cases (8.4%) were deemed as associated with pADRs. Major causes of pADRs include potentially inappropriate prescribing (352/537, 65.5%) and re-administration of antibiotics causing prior allergy/allergies (99/537, 18.4%). The majority of pADRs involved the use of beta-lactam antibiotics with inappropriate indications.CONCLUSION:ADRs related to antibiotic use represent more than half of ADRs spontaneously reported in Vietnam. Approximately one in every ten reported cases is associated with pADRs. The majority pADRs can be prevented through simple improvement in antibiotic prescribing practices.

The association between antidepressant continuation during pregnancy and postpartum mental health in women with obsessive-compulsive disorder (OCD) is uncertain. We identified 1317 women with live-birth singleton pregnancies and having outpatient/inpatient visits for OCD in the 4 years pre-pregnancy from the Danish registries. We defined three groups based on antidepressant prescriptions filled in the 2 years before pregnancy to delivery: (i) unexposed (n = 449); (ii) discontinuers (n = 346), i.e., with pre-pregnancy antidepressant fills only; (iii) continuers (n = 522), i.e., with antidepressant fills before and during pregnancy. We estimated crude and propensity score weighted hazard ratio (HRs) of postpartum visit for OCD and mood/anxiety disorders using Cox proportional hazard models. In weighted analyses, we found no difference in the probability of a postpartum visit for OCD or MADs with antidepressant continuation compared to unexposed and discontinuers. The likelihood of a postpartum OCD visit was higher in pregnancies having only one prescription fill during pregnancy compared to unexposed (HR = 3.44, 95% CI: 1.24, 9.54) or discontinuers (HR = 2.49, 95% CI: 0.91, 6.83). Continuers in pregnancy without antidepressant fill in the first three months postpartum had higher probability for postpartum visit for mood/anxiety disorders compared to discontinuers (HR = 3.84, 95% CI: 1.49, 9.92). Among pregnant women with pre-existing OCD, we found similar probabilities of a postpartum visit for OCD or mood/anxiety disorders in antidepressant continuers compared to unexposed and discontinuers. Continuers with a single prescription fill during pregnancy or no fill postpartum may have higher risks for these outcomes. Our findings highlight the importance of continuity of treatment throughout the perinatal period.

ImportanceApproximately one-half of women treated for affective disorders discontinue antidepressant use during pregnancy, yet this discontinuation could lead to relapse post partum.ObjectiveTo investigate the associations between longitudinal antidepressant fill trajectories during pregnancy and postpartum psychiatric outcomes.Design, Setting, and ParticipantsThis cohort study used nationwide registers in Denmark and Norway. The sample included 41 475 live-born singleton pregnancies in Denmark (1997-2016) and 16 459 in Norway (2009-2018) for women who filled at least 1 antidepressant prescription within 6 months before pregnancy.ExposuresAntidepressant prescription fills were obtained from the prescription registers. Antidepressant treatment during pregnancy was modeled using the k-means longitudinal method.Main Outcomes and MeasuresInitiation of psycholeptics, psychiatric emergencies, or records of self-harm within 1 year post partum. Between April 1 and October 30, 2022, hazard ratios (HRs) for each psychiatric outcome were estimated using Cox proportional hazards regression models. Inverse probability of treatment weighting was used to control for confounding. Country-specific HRs were pooled using random-effects meta-analytic models.ResultsAmong 57 934 pregnancies (mean [SD] maternal age, 30.7 [5.3] years in Denmark and 29.9 [5.5] years in Norway), 4 antidepressant fill trajectories were identified: early discontinuers (31.3% and 30.4% of the included pregnancies in Denmark and Norway, respectively), late discontinuers (previously stable users) (21.5% and 27.8%), late discontinuers (short-term users) (15.9% and 18.4%), and continuers (31.3% and 23.4%). Early discontinuers and late discontinuers (short-term users) had a lower probability of initiating psycholeptics and having postpartum psychiatric emergencies vs continuers. A moderately increased probability of initiation of psycholeptics was found among late discontinuers (previously stable users) vs continuers (HR, 1.13; 95% CI, 1.03-1.24). This increase in late discontinuers (previously stable users) was more pronounced among women with previous affective disorders (HR, 1.28; 95% CI, 1.12-1.46). No association between antidepressant fill trajectories and postpartum self-harm risk was found.Conclusions and RelevanceBased on pooled data from Denmark and Norway, a moderately elevated probability of initiation of psycholeptics in late discontinuers (previously stable users) vs continuers was found. These findings suggest that women with severe mental illness who are currently on stable treatment may benefit from continuing antidepressant treatment and personalized treatment counseling during pregnancy.