Comparison of sociodemographic factors, healthcare utilisation by general practitioner visits, somatic hospital admissions, and medication use in Norway, Sweden, and Denmark.

PURPOSE: The healthcare systems in Scandinavia inform nationwide registers and the Scandinavian populations are increasingly combined in research. We aimed to compare Norway (NO), Sweden (SE), and Denmark (DK) regarding sociodemographic factors and healthcare. METHODS: In this cross-sectional study, we analyzed aggregated data from the nationwide Scandinavian registers. We calculated country-specific statistics on sociodemographic factors and healthcare use (general practitioner visits, admissions to somatic hospitals, and use of medicines). RESULTS: In 2018, population were 5,295,619 (NO), 10,120,242 (SE), and 5,781,190 (DK). The populations were comparable regarding sex, age, education, and income distribution. Overall, medication use was comparable, while there was more variation in hospital admissions and general practitioner visits. For example, per 1000 inhabitants, 703 (NO), 665 (SE), and 711 (DK) individuals redeemed a prescription, whereas there were 215 (NO), 134 (SE), and 228 (DK) somatic hospital admissions per 1000 inhabitants. General practitioner contacts per 1000 inhabitants were 7082 in DK and 5773 in NO (-data from SE). CONCLUSION: The Scandinavian countries are comparable regarding aggregate-level sociodemographic factors and medication use. Variations are noted in healthcare utilisation as measured by visits to general practitioners and admissions to hospitals. This variation should be considered when comparing data from the Scandinavian countries.

Challenges related to transitioning from hospital to temporary care at a skilled nursing facility: a descriptive study.

PURPOSE: With decreasing number of hospital beds, more citizens are discharged to temporary care at skilled nursing facilities, requiring increasingly complex care in a non-hospital setting. We mapped challenges related to the transition of citizens from hospital to temporary care at a skilled nursing facility in relation to medication management, responsibility of medical treatment, and communication. METHODS: Descriptive study of citizens discharged from Odense University Hospital to temporary care from May 2022 to March 2023. RESULTS: We included 209 citizens (53% women, median age 81 years). Most citizens (97%; n = 109/112) had their medication changed during hospital admission. Citizens used a median of eight medications, including risk medications (96%, n = 108). Medication-related challenges occurred for 37% (n = 77) of citizens and most often concerned missing alignment of medication records. Half of citizens (47%, n = 99) moved into temporary care with all medication needed for further dispensing. Nurses conducted in median three telephone calls (interquartile range [IQR 1-4]) and sent in median two correspondences (IQR 1-3) per citizen within the first 5 days. Nurses most often called the hospital physician (41% of telephone calls, n = 265/643) and sent correspondences to the general practitioner (55% of correspondences, n = 257/469). For 31% (n = 29/95) of citizens requiring action from nursing staff, this could have been avoided if the nurses had had access to the discharge letter. CONCLUSION: We identified several challenges related to the transition of patients from hospital to temporary care, most often related to medication. A third of actions related to medication management were considered avoidable with improved practices around communication.

Mental health and use of psychotropic prescription drugs in adult patients with primary immune thrombocytopenia: a nationwide population-based cohort study.

Patients with primary immune thrombocytopenia (ITP) suffer from reduced survival and quality of life, but the underlying reasons for this are largely undescribed. Mental health and the use of psychotropic drugs in ITP is unknown. We investigated the risk of hospital registered mental health events including fatigue and the use of psychotropic drugs in adult patients with ITP compared with the general population, using nationwide registry-data. We identified 3,749 patients with ITP and 149,849 age-sex matched general population comparators in the Danish Health Registries in the period 1997-2016. The median age was 60 years (IQR 40-73) and 53% were women. We followed the individuals for incident mental health events and estimated the use of psychotropic drugs over calendar-years and in temporal relation to diagnosis of ITP. The first year cumulative incidence of any mental health event was 2.3% (95% confidence interval, 1.9-2.9) in patients and 0.7% (0.6-0.7) in comparators, yielding an adjusted cause-specific hazard ratio (csHR) of 3.57 (2.84-4.50). The corresponding estimates for depression were 1.2% (0.9-1.6) and 0.3% (0.3-0.4) respectively, with an adjusted csHR of 3.53 (2.56-4.85). We found similar findings for anxiety and fatigue, but risks generally diminished after 1-5 years. The use of opioids, antidepressants, and benzodiazepines increased in temporal relation to diagnosis of ITP. The risk of mental health events and the use of psychotropic drugs is higher in adult patients with ITP compared with the general population, and has a temporal relation to diagnosis of ITP emphasizing that mental health in ITP is a concern.

Use of antibiotics for urinary tract infections up to and after care home admission in Denmark: a nationwide study.

PURPOSE: Older people have the highest use of antibiotics for acute and chronic urinary tract infection (UTI), despite diagnostic uncertainty and the growing problem of antibiotic resistance. We aim to describe use-patterns of UTI antibiotics two years prior to and following care home admission in Denmark. METHODS: This was a register-based nationwide drug-utilization study. In a cohort comprising all Danish residents admitted into a care home from 2015 to 2021, we described the use of UTI antibiotics, and examined differences between regions and individual care homes in rates of UTI antibiotic use. Further, we described trends in UTI-related contacts with hospitals in the two years prior to and following care home admission. RESULTS: The cohort comprised 101,297 residents (61% female; median age 84 years). UTI antibiotic use doubled from 7 to 14 treatments/100 residents/month two months prior to care home admission and remained at 10 treatments/100 residents/month the following two years. Prescription of pivmecillinam (55%) was most common. Primary care practitioners prescribed the majority (92%) of UTI antibiotics. UTI-related hospital contacts peaked at two months prior to care home admission, with 6 admissions/100 residents/month, subsequently dropping to 2 admission/100 residents/month. We found considerable variation in UTI antibiotic use, with 10% of care homes responsible for 20% of treatments in 2021. CONCLUSION: Use of UTI antibiotics increased prior to and remained at a stable high level following care home admission in Denmark. Despite variation in use across regions and individual care homes, an overall decrease was seen throughout the years 2016-2021.

Does LDL-C determination method affect statin prescribing for primary prevention? A register-based study in Southern Denmark.

AIMS: Examine whether low-density lipoprotein cholesterol (LDL-C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease. METHODS AND RESULTS: We conducted a register-based retrospective study in the Region of Southern Denmark. Two hospital-based laboratories in the Region directly measure LDL-C whereas four laboratories calculate LDL-C using Friedewald's formula. Physicians do not choose which method is used. We included all statin-naïve patients ≥40 years with no history of cardiovascular disease, diabetes, or chronic kidney disease, who had their LDL-C determined during 2018-2019. There were 202,807 people who had LDL-C determined during the study period (median age 59 years, 44% women) of which 37% had a direct LDL-C measurement. The median reported LDL-C was 3.40 mmol/L (IQR 2.90 to 4.00) for those with a direct measurement versus 3.00 mmol/L (IQR 2.40 to 3.50) for those with calculated LDL-C. For those with direct measurement, re-calculated LDL-C (using Friedewald's formula) was 0.35 mmol/L lower than the reported direct LDL-C measurement. Among those with directly measured LDL-C, 3.6% initiated statins compared with 2.7% of those with a calculated LDL-C. Direct LDL-C measurement led to higher odds of having a statin initiated compared to calculated LDL-C (adjusted odds ratio 1.23, 95% CI 1.17 to 1.30); for those with triglycerides > 1.7 mmol/L the adjusted odds ratio was 1.41 (95% CI 1.30 to 1.52). CONCLUSION: Differences in the reporting of LDL-C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins.

Building transparency and reproducibility into the practice of pharmacoepidemiology and outcomes research.

Real-world evidence (RWE) studies are increasingly used to inform policy and clinical decisions. However, there remain concerns about the credibility and reproducibility of RWE studies. Observational researchers should highlight the level of transparency of their studies by providing a succinct statement addressing study transparency with the publication of every paper, poster, or presentation that reports on a RWE study. In this paper, we propose a framework for an explicit transparency statement that declares the level of transparency a given RWE study has achieved across five key domains: 1) protocol, 2) pre-registration, 3) data, 4) code sharing, and 5) reporting checklists.

Semaglutide (Ozempic®) Use in Denmark 2018 Through 2023 ‒ User Trends and off-Label Prescribing for Weight Loss.

Purpose: A surge in the use of semaglutide injection (Ozempic®) approved to treat type 2 diabetes (T2D) has led to a global supply shortage. We investigated contemporary user rates and clinical characteristics of semaglutide (Ozempic®) users in Denmark, and the extent of "off-label" prescribing for weight loss. Patients and Methods: Nationwide population-based cross-sectional study based on linked health registries January 2018 through December 2023. All adults who received a first prescription of semaglutide once weekly (Ozempic®) were included. We examined quarterly rates of new users and total user prevalences, using other glucagon-like peptide-1 receptor agonists and weight loss medications as comparison. We also investigated user characteristics including T2D, glucose control, comedications, and cardiorenal disease. Results: The new user rate of semaglutide (Ozempic®) remained stable at approximately 4 per 1000 adult person-years between 2019 and 2021 and then accelerated, peaking at 10 per 1000 in the first quarter of 2023 after which it declined sharply. User prevalence increased to 91,626 users in Denmark in 2023. The proportion of semaglutide (Ozempic®) new users who had a record of T2D declined from 99% in 2018 to only 67% in 2022, increasing again to 87% in 2023. Among people with T2D who initiated semaglutide (Ozempic®) in 2023, 52% received antidiabetic polytherapy before initiation, 39% monotherapy, and 8% no antidiabetic therapy. Most T2D initiators had suboptimal glucose control, with 83% having an HbA1c ≥48 mmol/mol and 68% ≥53 mmol/mol despite use of antidiabetic medication, and 29% had established atherosclerotic cardiovascular disease or kidney disease. Conclusion: The use of semaglutide (Ozempic®) in Denmark has increased dramatically. Although not approved for weight loss without T2D, one-third of new users in 2022 did not have T2D. Conversely, most initiators with T2D had a clear medical indication for treatment intensification, and "off-label" use can only explain a minor part of the supply shortage.

Considerations for the use of biochemical laboratory registry data in clinical and public health research.

OBJECTIVES: To inform researchers of central considerations and limitations when applying biochemical laboratory-generated registry data in clinical and public health research. STUDY DESIGN AND SETTING: After review of literature on registry-based studies and the utilization of clinical laboratory registry data, relevant paragraphs and their applicability toward the creation of considerations for the use of biochemical registry data in research were evaluated. This led to the creation of an initial ten considerations. These were elaborated, edited, and merged after several read-throughs by all authors and discussed thoroughly under influence by the authors' personal experiences with laboratory databases and research registries in Denmark, leading to the formulation of five central considerations with corresponding items and illustrative examples. RESULTS: We recommend that the following considerations should be addressed in studies relying on biochemical laboratory-generated registry data: why are biochemical laboratory data relevant to examine the hypothesis, and how were the variable(s) utilized in the study? What were the primary indications for specimen collection in the study population of interest? Were there any pre-analytical circumstances that could influence the test results? Are data comparable between producing laboratories and within the single laboratory over time? Is the database representative in terms of completeness of study populations and key variables? CONCLUSION: It is crucial to address key errors in laboratory registry data and acknowledge potential limitations.

Critical evaluation of cohort study results.

Being able to critically evaluate modern cohort studies is important when being presented with claims based on observational evidence. In this review article, key aspects of the cohort design are presented using an example of a cohort study investigating the association between the use of SGLT2 inhibitors and gout. We describe the active comparator, new user design, modern methods used to address confounding, how to identify the most common sources of bias, and how to interpret study results appropriately.

Critical evaluation of articles on case-control studies.

The case-control design is one of the key designs used in observational research. In this review, we discuss common pitfalls of case-control studies and describe how case-control studies can be critically evaluated. We further assert that a well-conducted case-control study provides the same results, precision, and level of evidence as a corresponding cohort study.

Risk of fractures and use of bisphosphonates in adult patients with immune thrombocytopenia-A nationwide population-based study.

Corticosteroids remain the first-line treatment of immune thrombocytopenia (ITP), but increase the risk of osteoporosis and fractures. Bisphosphonates are used for the treatment of osteoporosis, but their usage among patients with ITP has not been systemically described. We investigated the risk of fractures and the use of bisphosphonates in adult patients with primary (pITP) and secondary ITP (sITP) compared with matched comparators in a nationwide registry-based cohort study. We identified 4030 patients with pITP (median age 60 years [IQR, 40-74]), 550 with sITP (median age 59 years [IQR, 43-74]) and 182 939 age-sex-matched general population comparators. All individuals were followed for incident fractures. Bisphosphonate use was estimated for calendar-years and in temporal relation to the ITP diagnosis. Adjusted cause-specific hazard ratio (csHR) for any fracture was 1.37 (95% confidence interval [CI] 1.23; 1.54) for pITP and 1.54 (1.17; 2.03) for sITP. The first-year csHR was 1.82 (1.39; 2.40) for pITP and 2.78 (1.58; 4.91) for sITP. Bisphosphonate use over calendar-years and in the early years following ITP diagnosis was higher among patients with ITP diagnosis compared with the general population. In conclusion, the risk of fractures and the use of bisphosphonates are higher in patients with ITP compared with the general population.

Validation of Obstetric Diagnosis and Procedure Codes in the Danish National Patient Registry in 2017.

Purpose: This study aimed to systematically evaluate the validity of variables related to pregnancy, delivery, and key characteristics of the infant in the Danish National Patient Register using maternal medical records as the reference standard. Patients and Methods: We reviewed medical records of 1264 women giving birth in the Region of Southern Denmark during 2017. We calculated positive (PPV) and negative (NPV) predictive values, sensitivity, and specificity to estimate the validity of 49 selected variables. Results: The PPV was ≥0.90 on most pregnancy-related variables including parity, pre-gestational BMI, diabetes disorders, and previous cesarean section, while it was lower for hypertensive disorders, especially mild to moderate preeclampsia (0.49, 95% CI 0.32-0.66). Sensitivity ranged from 0.80 to 1.00 on all pregnancy-related variables, except hypertensive disorders (sensitivity 0.38-0.71, lowest for severe preeclampsia). On most delivery-related variables including obstetric surgical procedures (eg cesarean section and induction of labor), pharmacological pain-relief, and gestational age at delivery, PPV's ranged from 0.98 to 1.00 and the corresponding sensitivities from 0.87 to 1.00. Regarding infant-related variables, both the APGAR score registered five minutes after delivery and birthweight yielded a PPV of 1.00. Conclusion: Obstetric coding in the Danish National Patient Register shows very high validity and completeness making it a valuable source for epidemiologic research.

Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study.

OBJECTIVE: Patients receiving immunosuppressives have been excluded from trials for SARS-CoV-2 vaccine efficacy. Investigation of immunosuppressants' impact on effectiveness of vaccines, particularly in patients with immune-mediated inflammatory diseases (IMID), is therefore required. DESIGN: We performed a nationwide cohort study to assess the risk of COVID-19 infection in vaccinated patients with IMID exposed to immunosuppressives compared with IMID unexposed to immunosuppressives. Exposure to immunosuppressives in the 120 days before receiving the second SARS-CoV-2 mRNA vaccination was assessed. Patients were followed from date of second vaccination and weighted Cox models were used to estimate the risk of infection associated with immunosuppressives. Secondary outcomes included hospitalisation and death associated with a positive SARS-CoV-2 test. Risk of infection by immunosuppressant drug class was also analysed. SETTING: This study used population-representative data from Danish national health registries in the period from 1 January to 30 November 2021. RESULTS: Overall, 152 440 patients were followed over 19 341 person years. Immunosuppressants were associated with a significantly increased risk of infection across IMID (HR: 1.4, 95% CI 1.2 to 1.5), in inflammatory bowel disease (IBD) (HR: 1.6, 95% CI 1.4 to 1.9) and arthropathy (HR: 1.3, 95% CI 1.1 to 1.4) but not psoriasis (HR: 1.1, 95% CI 0.9 to 1.4). Immunosuppressants were also associated with an increased risk of hospitalisation across IMID (HR: 1.4, 95% CI 1.1 to 2.0), particularly in IBD (HR: 2.1, 95% CI 1.0 to 4.1). No significantly increased risk of death in immunosuppressant exposed patients was identified. Analyses by immunosuppressant drug class showed increased COVID-19 infection and hospitalisation with anti-tumour necrosis factor (TNF), systemic corticosteroid, and rituximab and other immunosuppressants in vaccinated patients with IMID. CONCLUSION: Immunosuppressive therapies reduced effectiveness of mRNA SARS-CoV-2 vaccination against infection and hospitalisation in patients with IMID. Anti-TNF, systemic corticosteroids, and rituximab and other immunosuppressants were particularly associated with these risks.

Use of prescribed analgesics before and after exercise therapy and patient education in patients with knee or hip osteoarthritis.

The aim of this study was to investigate utilisation patterns of prescribed analgesics before, during, and after an exercise therapy and patient education program among patients with knee or hip osteoarthritis. This cohort study is based on data from the nationwide Good Life with osteoarthritis in Denmark (GLA:D®) patient-register linked with national health registries including data on prescribed analgesics. GLA:D® consists of 8-12 weeks of exercise and patient education. We included 35,549 knee/hip osteoarthritis patients starting the intervention between January 2013 and November 2018. Utilisation patterns the year before, 3 months during, and the year after the intervention were investigated using total dispensed defined daily doses (DDDs) per month per 1000 population as outcome. During the year before the intervention, use of prescribed paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids increased with 85%, 79% and 22%, respectively. During the intervention, use of paracetamol decreased with 16% with a stable use the following year. Use of NSAIDs and opioids decreased with 38% and 8%, respectively, throughout the intervention and the year after. Sensitivity analyses indicated that the prescription of most analgesics changed over time. For paracetamol, NSAIDs, and opioids, 10% of analgesic users accounted for 45%, 50%, and 70%, respectively, of the total DDDs dispensed during the study period. In general, analgesic use increased the year before the intervention followed by a decrease during the intervention and the year after. A small proportion of analgesic users accounted for half or more of all paracetamol, NSAIDs, and opioids dispensed during the study period.

Attitudes towards deprescribing in geriatric psychiatry: A survey among older psychiatric outpatients.

Understanding the patient perspective is a significant part of the deprescribing process. This study aimed to explore the attitudes of older patients with psychiatric disorders towards deprescribing. A total of 72 of psychiatric outpatients (68% women; median age 76 years) completed the validated Danish version of the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. Patients used a median of eight medications (interquartile range 6-12), with 88%, 49% and 24% using antidepressants, antipsychotics and anxiolytics, respectively. Fifty-one percent of patients reported an intrinsic desire to stop one of their medications, while 92% would be willing to stop one on their physician's advice. Seventy-five percent of patients would be worried about missing out on future benefits following deprescribing and 37% had previous bad deprescribing experiences. Use of ≥8 regular medications was associated with more concerns about stopping medication and greater perceived burden of using medication, while use of antipsychotics was not associated with any differences in rPATD factor scores. It is crucial for health care professionals to be aware of patients' specific concerns and past experiences to promote a patient-centred deprescribing approach that takes into account the needs and preferences of older patients with psychiatric disorders.

Effectiveness of the quadrivalent live attenuated influenza vaccine against influenza-related hospitalisations and morbidity among children aged 2 to 6 years in Denmark: a nationwide cohort study emulating a target trial.

BACKGROUND: Scant evidence exists on the real-world effectiveness of quadrivalent live attenuated influenza vaccines (LAIV-4) in younger children. We aimed to assess the real-world effectiveness of LAIV-4 against influenza-related hospital contacts and admission and morbidity. METHODS: Using nationwide Danish health-care registries, we designed a cohort study that emulates a target trial, comparing LAIV-4 to no vaccination in children aged 2-6 years. Eligible children vaccinated from Oct 1, 2021, to Jan 15, 2022, were matched to unvaccinated controls in a 1:1 ratio according to demographic characteristics and risk groups for influenza, and followed-up until May 31, 2022. Primary study outcomes any hospital contact for influenza and influenza-related hospital admissions more than 12 h in duration, while hospital admission for respiratory tract infections, or for wheezing or asthma, and antibiotic prescriptions were evaluated as secondary outcomes. We estimated incidence rate ratios (IRRs) and 95% CIs using Poisson regression for each outcome. Vaccine effectiveness was calculated as 1 - IRR. FINDINGS: Among 308 520 Danish children aged 2-6 years, 95 434 vaccinated children were matched with 95 434 unvaccinated children who acted as controls. Receipt of LAIV-4 compared with no vaccination was associated with a reduced IRR of 0·36 (95% CI 0·27 to 0·46) and estimated vaccine effectiveness of 64·3% (53·6 to 72·6) against influenza-related hospital contacts (76 vs 210 events). The corresponding IRR and vaccine effectiveness against influenza-related hospital admissions were 0·63 (0·38 to 1·05) and 36·9% (-5·2 to 62·1; 24 vs 38 events), respectively. LAIV-4 was not associated with reductions in admission rates for respiratory tract infections (IRR 1·14, 95% CI 0·94 to 1·38), wheezing or asthma (1·04, 0·83 to 1·31), or antibiotic prescriptions for respiratory tract infections (0·97, 0·93 to 1·00). Vaccine effectiveness assessed across risk groups for influenza showed similar effectiveness in children with and without coexisting risk factors for severe influenza. INTERPRETATION: LAIV-4 offered moderate protection in younger children against influenza-related hospital contacts during a season dominated by influenza A(H3N2); however vaccination was not associated with reductions in secondary outcomes. This real-world study thereby supports trial evidence of moderate vaccine effectiveness of LAIV-4 against influenza-related outcomes when implementing broad vaccination schedules in younger children. FUNDING: Beckett-Fonden.

Methodological Considerations for Describing Medication Changes in Relation to Clinical Events and Death: An Applied Example in Patients with Type 2 Diabetes and Cancer.

INTRODUCTION: Certain clinical events reduce life expectancy and necessitate a reassessment of patient treatment. OBJECTIVE: To describe medication changes in relation to a cancer diagnosis and the end of life and to highlight challenges and limitations with such descriptions. METHODS: From a cohort with all Danish patients with type 2 diabetes, we matched patients with incident cancer during 2000-2021 (n = 41,745) with patients without cancer (n = 166,994) using propensity scores. We described their medication usage from cancer diagnosis until death. RESULTS: The 1- and 5-year mortality were 51% and 86%, respectively, in the cancer group, and 13% and 59% in the non-cancer group. In relation to cancer diagnosis and death, the use of symptomatic medications (e.g., opioids, benzodiazepines) increased (10-60 incident medications per 100 patient-months), and the use of preventive medications (e.g., antihypertensives, statins) decreased (5-30% fewer users). The changes in relation to the diagnosis were driven by patients with short observed lengths of survival (< 2 years). In contrast, changes occurring within a year before death were less dependent on survival strata, and > 60% used preventive medications in their last months. CONCLUSIONS: Medication changes in relation to a cancer diagnosis were frequent and correlated to the length of survival. The results showcase the challenges and limited clinical utility of anchoring analyses on events or death. While the former diluted the results by averaging changes across patients with vastly different clinical courses, the latter leveraged information unavailable to the treating clinicians. While medication changes were common near death, preventive medications were often used until death.

Cardiovascular risks of continuing vs. initiating NSAIDs after first-time myocardial infarction or heart failure: a nationwide cohort study.

AIMS: It is unknown whether the cardiovascular risks associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) shortly after first-time myocardial infarction (MI) or heart failure (HF) differ between patients continuing and initiating use. METHODS AND RESULTS: Using nationwide health registries, we conducted a cohort study of all patients with first-time MI or HF during 1996-2018 (n = 273 682). NSAID users (n = 97 966) were categorized as continuing (17%) and initiating (83%) users according to prescription fillings < 60 days before index diagnosis. The primary outcome was a composite of new MI, HF admission, and all-cause death. Follow-up started 30 days after the index discharge date. We used Cox regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs) comparing NSAID users vs. non-users. The most commonly filled NSAIDs were ibuprofen (50%), diclofenac (20%), etodolac (8.5%), and naproxen (4.3%). The composite outcome HR of 1.25 (CI: 1.23-1.27) was driven by initiators (HR = 1.39, 1.36-1.41) and not continuing users (HR = 1.03, 1.00-1.07). The lack of association among continuing users was also observed for individual NSAIDs (ibuprofen and naproxen), except diclofenac (HR = 1.11, 95% CI: 1.05-1.18). Among initiators, the HR was 1.63 (CI: 1.57-1.69) for diclofenac, 1.31 (CI: 1.27-1.35) for ibuprofen, and 1.19 (CI: 1.08-1.31) for naproxen. The results were consistent for both MI and HF patients, the individual components of the composite outcome, and various sensitivity analyses. CONCLUSION: NSAID initiators were more susceptible to adverse cardiovascular outcomes after first-time MI or HF than continuing users.

Prenatal antidepressant exposure and emotional disorders until age 22: a danish register study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants in pregnancy. Animal and some clinical studies have suggested potential increases in depression and anxiety following prenatal SSRI exposure, but the extent to which these are driven by the medication remains unclear. We used Danish population data to test associations between maternal SSRI use during pregnancy and children outcomes up to age 22. METHODS: We prospectively followed 1,094,202 single-birth Danish children born 1997-2015. The primary exposure was ≥ 1 SSRI prescription filled during pregnancy; the primary outcome, first diagnosis of a depressive, anxiety, or adjustment disorder, or redeemed prescription for an antidepressant medication. We used propensity score weights to adjust potential confounders, and incorporated data from the Danish National Birth Cohort (1997-2003) to further quantify potential residual confounding by subclinical factors. RESULTS: The final dataset included 15,651 exposed and 896,818 unexposed, children. After adjustments, SSRI-exposed had higher rates of the primary outcome than those of mothers who either did not use an SSRI (HR = 1.55 [95%CI:1.44,1.67] or discontinued the SSRI use ≥ 3 months prior to conception (HR = 1.23 [1.13,1.34]). Age of onset was earlier among exposed (9 [IQR:7-13] years) versus unexposed (12 [IQR:12-17] years) children (p < 0.01). Paternal SSRI use in the absence of maternal use during the index pregnancy (HR = 1.46 [1.35,1.58]) and maternal SSRI use only after pregnancy (HR = 1.42 [1.35,1.49]) were each also associated with these outcomes. CONCLUSIONS: While SSRI exposure was associated with increased risk in the children, this risk may be driven at least partly by underlying severity of maternal illness or other confounding factors.