Increased risk of hospitalization, intensive care and death due to COVID-19 in patients with adrenal insufficiency: A Swedish nationwide study.

BACKGROUND: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown. METHODS: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. RESULTS: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59-2.43), intensive care admission (2.76, 1.49-5.09) and death (2.29, 1.60-3.28). CONCLUSION: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

Survival of Critically Ill COVID-19 Patients in Sweden During the First Two and a Half Years of the Pandemic.

OBJECTIVES: Some studies have examined survival trends among critically ill COVID-19 patients, but most were case reports, small cohorts, and had relatively short follow-up periods. We aimed to examine the survival trend among critically ill COVID-19 patients during the first two and a half years of the pandemic and investigate potential predictors across different variants of concern periods. DESIGN: Prospective cohort study. SETTING: Swedish ICUs, between March 6, 2020, and December 31, 2022. PATIENTS: Adult COVID-19 ICU patients of 18 years old or older from the Swedish Intensive Care Register (SIR) that were linked to multiple other national registers. MEASUREMENT AND MAIN RESULTS: Survival probability and predictors of COVID-19 death were estimated using Kaplan-Meier and Cox regression analysis. Of 8975 patients, 2927 (32.6%) died. The survival rate among COVID-19 critically ill patients appears to have changed over time, with a worse survival in the Omicron period overall. The adjusted hazard ratios (aHRs) comparing older and younger ages were consistently strong but slightly attenuated in the Omicron period. After adjustment, the aHR of death was significantly higher for men, older age (40+ yr), low income, and with comorbid chronic heart disease, chronic lung disease, impaired immune disease, chronic renal disease, stroke, and cancer, and for those requiring invasive or noninvasive respiratory supports, who developed septic shock or had organ failures (p < 0.05). In contrast, foreign-born patients, those with booster vaccine, and those who had taken steroids had better survival (aHR = 0.87; 95% CI, 0.80-0.95; 0.74, 0.65-0.84, and 0.91, 0.84-0.98, respectively). Observed associations were similar across different variant periods. CONCLUSIONS: In this nationwide Swedish cohort covering over two and a half years of the pandemic, ICU survival rates changed over time. Older age was a strong predictor across all periods. Furthermore, most other mortality predictors remained consistent across different variant periods.

A Capture-Recapture-based Ascertainment Probability Weighting Method for Effect Estimation With Under-ascertained Outcomes.

Outcome under-ascertainment, characterized by the incomplete identification or reporting of cases, poses a substantial challenge in epidemiologic research. While capture-recapture methods can estimate unknown case numbers, their role in estimating exposure effects in observational studies is not well established. This paper presents an ascertainment probability weighting framework that integrates capture-recapture and propensity score weighting. We propose a nonparametric estimator of effects on binary outcomes that combines exposure propensity scores with data from two conditionally independent outcome measurements to simultaneously adjust for confounding and under-ascertainment. Demonstrating its practical application, we apply the method to estimate the relationship between health care work and coronavirus disease 2019 testing in a Swedish region. We find that ascertainment probability weighting greatly influences the estimated association compared to conventional inverse probability weighting, underscoring the importance of accounting for under-ascertainment in studies with limited outcome data coverage. We conclude with practical guidelines for the method's implementation, discussing its strengths, limitations, and suitable scenarios for application.

Impact of the early COVID-19 pandemic on adult mental health-related dispensed medications, hospitalizations and specialist outpatient visits in Norway and Sweden: Interrupted time series analysis.

AIMS: Norway and Sweden had different early pandemic responses that may have impacted mental health management. The aim was to assess the impact of the early COVID-19 pandemic on mental health-related care. METHODS: We used national registries in Norway and Sweden (1 January 2018-31 December 2020) to define 2 cohorts: (i) general adult population; and (ii) mental health adult population. Interrupted times series regression analyses evaluated step and slope changes compared to prepandemic levels for monthly rates of medications (antidepressants, antipsychotics, anxiolytics, hypnotics/sedatives, lithium, opioid analgesics, psychostimulants), hospitalizations (for anxiety, bipolar, depressive/mood, eating and schizophrenia/delusional disorders) and specialist outpatient visits. RESULTS: In Norway, immediate reductions occurred in the general population for medications (-12% antidepressants to -7% hypnotics/sedatives) except for antipsychotics; and hospitalizations (-33% anxiety disorders to -17% bipolar disorders). Increasing slope change occurred for all medications except psychostimulants (+1.1%/month hypnotics/sedatives to +1.7%/month antidepressants); and hospitalization for anxiety disorders (+5.5%/month), depressive/mood disorders (+1.7%/month) and schizophrenia/delusional disorders (+2%/month). In Sweden, immediate reductions occurred for antidepressants (-7%) and opioids (-10%) and depressive/mood disorder hospitalizations (-11%) only with increasing slope change in psychostimulant prescribing of (0.9%/month). In contrast to Norway, increasing slope changes occurred in specialist outpatient visits for depressive/mood disorders, eating disorders and schizophrenia/delusional disorders (+1.5, +1.9 and +2.3%/month, respectively). Similar changes occurred in the pre-existing mental health cohorts. CONCLUSION: Differences in early COVID-19 policy response may have contributed to differences in adult mental healthcare provision in Norway and Sweden.

Drug utilisation in children and adolescents before and after the start of the COVID-19 pandemic: Interrupted time-series analyses in three European countries.

BACKGROUND: The COVID-19 pandemic has affected children and adolescents in several ways, including worsened mental health, improvement of asthma, and increases in diabetes ketoacidosis. Less is known about how medication use in children and adolescents has been affected by the pandemic. OBJECTIVES: To explore how the COVID-19 pandemic affected drug utilisation in children and adolescents in Norway, Sweden, and Italy, by child age. METHODS: We conducted a longitudinal drug utilisation study among all children and adolescents (<18 years old) in Norway and Sweden and a nationwide paediatric database covering 3% of the paediatric population in Italy. We conducted an interrupted time-series analysis from January 2018 to December 2021, with March 2020 as the interruption point. Dispensing or prescription rates of antidepressants, anxiolytics, sleep medications, attention-deficit/hyperactivity disorder (ADHD) medications, insulin, and asthma medications were examined. RESULTS: The study population in January 2018 consisted of 3,455,521 children and adolescents (136,188 from Italy, 1,160,431 from Norway, and 2,158,902 from Sweden). For sleep medications and insulin, there were only minor changes in level or trend in some age groups after March 2020. For asthma medications, the pandemic was associated with an immediate decrease in dispensing in Norway and Sweden (range of change in level: -19.2 to -3.7 dispensings per 1000 person-months), and an increasing trend in all countries afterward (range of change in trend: 0.3-6.4 dispensings per 1000 person-months), especially for the youngest age groups. Among adolescents, the pandemic was associated with an increased trend for ADHD medications, antidepressants, and anxiolytics in Norway and Sweden, but not in Italy. CONCLUSIONS: The increasing trend of psychotropic medication dispensing, especially among adolescents after the start of the pandemic, is concerning and should be investigated further. Aside from a temporary effect on asthma medication dispensing, the pandemic did not greatly affect the dispensing of the medications investigated.

Exacerbation Risk and Mortality in Global Initiative for Chronic Obstructive Lung Disease Group A and B Patients with and without Exacerbation History.

Rationale: Risk stratification of patients according to chronic obstructive pulmonary disease severity is clinically important and forms the basis of therapeutic recommendations. No studies have examined the association for Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and group B patients with (A1 and B1, respectively) and without (A0 and B0, respectively) an exacerbation in the past year with future exacerbations, hospitalizations, and mortality in perspective with the new GOLD ABE classification. Objectives: The aim was to examine the association between GOLD A0, A1, B0, B1, and E patients and future exacerbations, respiratory and cardiovascular hospitalizations, and mortality. Methods: In this nationwide cohort study, we identified patients with a diagnosis of chronic obstructive pulmonary disease, aged ⩾30 years, and registered in the Swedish National Airway Register between January 2017 and August 2020. Patients were stratified in GOLD groups A0, A1, B0, B1, and E and were followed until January 2021 for exacerbations, hospitalizations, and mortality in national registries. Measurements and Main Results: The 45,350 eligible patients included 25% A0, 4% A1, 44% B0, 10% B1, and 17% E. Moderate exacerbations, all-cause and respiratory hospitalizations, and all-cause and respiratory mortality increased by GOLD group A0-A1-B0-B1-E, except for moderate exacerbations, which were higher in A1 than in B0. Group B1 had a substantially higher hazard ratio for future exacerbation (2.56; 95% confidence interval [95% CI] 2.40-2.74), all-cause hospitalization (1.28; 1.21-1.35), and respiratory hospitalization (1.44; 1.27-1.62), but not all-cause (1.04; 0.91-1.18) or respiratory (1.13; 0.79-1.64) mortality than group B0. The exacerbation rate for group B1 was 0.6 events per patient-year versus 0.2 for group B0 (rate ratio, 2.55; 95% CI, 2.36-2.76). Results were similar for group A1 versus group A0. Conclusions: Stratification of GOLD A and B patients with one or no exacerbation in the past year provides valuable information on future risk, which should influence treatment recommendations for preventive strategies.

The sociodemographic patterning of sick leave and determinants of longer sick leave after mild and severe COVID-19: a nationwide register-based study in Sweden.

BACKGROUND: Studies on sociodemographic differences in sick leave after coronavirus disease 2019 (COVID-19) are limited and research on COVID-19 long-term health consequences has mainly addressed hospitalized individuals. The aim of this study was to investigate the social patterning of sick leave and determinants of longer sick leave after COVID-19 among mild and severe cases. METHODS: The study population, from the Swedish multi-register observational study SCIFI-PEARL, included individuals aged 18-64 years in the Swedish population, gainfully employed, with a first positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 1 January 2020 until 31 August 2021 (n = 661 780). Using logistic regression models, analyses were adjusted for sociodemographic factors, vaccination, prior sick leave, comorbidities and stratified by hospitalization. RESULTS: In total, 37 420 (5.7%) individuals were on sick leave due to COVID-19 in connection with their first positive COVID-19 test. Individuals on sick leave were more often women, older, had lower income and/or were born outside Sweden. These differences were similar across COVID-19 pandemic phases. The highest proportion of sick leave was seen in the oldest age group (10.3%) with an odds ratio of 4.32 (95% confidence interval 4.18-4.47) compared with the youngest individuals. Among individuals hospitalized due to COVID-19, the sociodemographic pattern was less pronounced, and in some models, even reversed. The intersectional analysis revealed considerable variability in sick leave between sociodemographic groups (range: 1.5-17.0%). CONCLUSION: In the entire Swedish population of gainfully employed individuals, our findings demonstrated evident sociodemographic differences in sick leave due to COVID-19. In the hospitalized group, the social patterning was different and less pronounced.

Assessing Heterogeneity of Treatment Effect in Real-World Data.

Increasing availability of real-world data (RWD) generated from patient care enables the generation of evidence to inform clinical decisions for subpopulations of patients and perhaps even individuals. There is growing opportunity to identify important heterogeneity of treatment effects (HTE) in these subgroups. Thus, HTE is relevant to all with interest in patients' responses to interventions, including regulators who must make decisions about products when signals of harms arise postapproval and payers who make coverage decisions based on expected net benefit to their beneficiaries. Prior work discussed HTE in randomized studies. Here, we address methodological considerations when investigating HTE in observational studies. We propose 4 primary goals of HTE analyses and the corresponding approaches in the context of RWD: to confirm subgroup effects, to describe the magnitude of HTE, to discover clinically important subgroups, and to predict individual effects. We discuss other possible goals including exploring prognostic score- and propensity score-based treatment effects, and testing the transportability of trial results to populations different from trial participants. Finally, we outline methodological needs for enhancing real-world HTE analysis.

A population-based, retrospective cohort study of the association between ABO blood group and risk of COVID-19.

BACKGROUND: Several studies have investigated associations between ABO blood group and risk of COVID-19, with inconsistent results. OBJECTIVE: To study associations between ABO blood group and risk of different stages of COVID-19. METHODS: The study was based on nationwide registers encompassing all blood-grouped persons in Sweden, and all of their COVID-19-related outcomes. Associations between ABO blood group and COVID-19 outcomes were estimated using Poisson regression models. Analyses were conducted overall and stratified by vaccination status. RESULTS: A total of 4,986,878 individuals were included. The incidence rate ratios of testing positive for COVID-19 were 1.08 (95% confidence interval [CI], 1.07-1.08), 1.06 (95% CI, 1.05-1.07), and 1.01 (95% CI, 1.00-1.01) for blood groups A, AB, and B, respectively, as compared to O. Similar associations were seen for risk of hospital admissions, intensive care unit admissions, and risk of death. For most outcomes, associations with ABO blood group were much attenuated or even reversed in vaccinated individuals. CONCLUSIONS: Individuals with blood groups A, AB, and B are at increased risk of contracting COVID-19 as well as developing more severe forms of the disease.

Comparison of clinician diagnosis of COVID-19 with real time polymerase chain reaction in an adult-representative population in Sweden.

BACKGROUND: Due to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population. METHODS: COVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19. RESULTS: Of 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77-80%) and 93% (95%CI 93-93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53-55%), while negative predictive value (NPV) was 98% (95%CI 98-98%) and Youden's index 71% (95%CI 70-72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden's index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74-90%]) than those without (78% [95%CI 77-79%]) COPD. CONCLUSIONS: The accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR.

Characteristics and outcomes of COVID-19 patients with and without asthma from the United States, South Korea, and Europe.

Objective: Large international comparisons describing the clinical characteristics of patients with COVID-19 are limited. The aim of the study was to perform a large-scale descriptive characterization of COVID-19 patients with asthma.Methods: We included nine databases contributing data from January to June 2020 from the US, South Korea (KR), Spain, UK and the Netherlands. We defined two cohorts of COVID-19 patients ('diagnosed' and 'hospitalized') based on COVID-19 disease codes. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes in people with asthma defined by codes and prescriptions.Results: The diagnosed and hospitalized cohorts contained 666,933 and 159,552 COVID-19 patients respectively. Exacerbation in people with asthma was recorded in 1.6-8.6% of patients at presentation. Asthma prevalence ranged from 6.2% (95% CI 5.7-6.8) to 18.5% (95% CI 18.2-18.8) in the diagnosed cohort and 5.2% (95% CI 4.0-6.8) to 20.5% (95% CI 18.6-22.6) in the hospitalized cohort. Asthma patients with COVID-19 had high prevalence of comorbidity including hypertension, heart disease, diabetes and obesity. Mortality ranged from 2.1% (95% CI 1.8-2.4) to 16.9% (95% CI 13.8-20.5) and similar or lower compared to COVID-19 patients without asthma. Acute respiratory distress syndrome occurred in 15-30% of hospitalized COVID-19 asthma patients.Conclusion: The prevalence of asthma among COVID-19 patients varies internationally. Asthma patients with COVID-19 have high comorbidity. The prevalence of asthma exacerbation at presentation was low. Whilst mortality was similar among COVID-19 patients with and without asthma, this could be confounded by differences in clinical characteristics. Further research could help identify high-risk asthma patients.[Box: see text]Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2025392 .

Genetic susceptibility to airway inflammation and exposure to short-term outdoor air pollution.

BACKGROUND: Air pollution is a large environmental health hazard whose exposure and health effects are unequally distributed among individuals. This is, at least in part, due to gene-environment interactions, but few studies exist. Thus, the current study aimed to explore genetic susceptibility to airway inflammation from short-term air pollution exposure through mechanisms of gene-environment interaction involving the SFTPA, GST and NOS genes. METHODS: Five thousand seven hundred two adults were included. The outcome measure was fraction of exhaled nitric oxide (FeNO), at 50 and 270 ml/s. Exposures were ozone (O3), particulate matter < 10 µm (PM10), and nitrogen dioxide (NO2) 3, 24, or 120-h prior to FeNO measurement. In the SFTPA, GST and NOS genes, 24 single nucleotide polymorphisms (SNPs) were analyzed for interaction effects. The data were analyzed using quantile regression in both single-and multipollutant models. RESULTS: Significant interactions between SNPs and air pollution were found for six SNPs (p < 0.05): rs4253527 (SFTPA1) with O3 and NOx, rs2266637 (GSTT1) with NO2, rs4795051 (NOS2) with PM10, NO2 and NOx, rs4796017 (NOS2) with PM10, rs2248814 (NOS2) with PM10 and rs7830 (NOS3) with NO2. The marginal effects on FeNO for three of these SNPs were significant (per increase of 10 µg/m3):rs4253527 (SFTPA1) with O3 (ß: 0.155, 95%CI: 0.013-0.297), rs4795051 (NOS2) with PM10 (ß: 0.073, 95%CI: 0.00-0.147 (single pollutant), ß: 0.081, 95%CI: 0.004-0.159 (multipollutant)) and NO2 (ß: -0.084, 95%CI: -0.147; -0.020 (3 h), ß: -0.188, 95%CI: -0.359; -0.018 (120 h)) and rs4796017 (NOS2) with PM10 (ß: 0.396, 95%CI: 0.003-0.790). CONCLUSIONS: Increased inflammatory response from air pollution exposure was observed among subjects with polymorphisms in SFTPA1, GSTT1, and NOS genes, where O3 interacted with SFTPA1 and PM10 and NO2/NOx with the GSTT1 and NOS genes. This provides a basis for the further exploration of biological mechanisms as well as the identification of individuals susceptible to the effects of outdoor air pollution.

The burden of disease due to COVID-19 in Sweden 2020-2021: A disability-adjusted life years (DALYs) study.

BACKGROUND: The burden of COVID-19 disease can be measured in terms of disability-adjusted life years (DALYs), which is composed of two components: the years of life lost through premature death (YLL) and the number of years lived with disability (YLD), adjusted for level of disability. This study measured DALYs due to COVID-19 in Sweden and compared it to the burden of other diseases. METHODS: The methodology used in the calculation of DALYs was based on the Global Burden of Disease guidelines. The number of patients diagnosed with mild/moderate, severe or critical COVID-19 and/or post-COVID-19 condition between March 2020 and October 2021 was extracted from national registries and used for YLD calculations. In addition, the numbers of death due to COVID-19 in different age groups were used for the YLL calculation. RESULTS: During the study period, 152,877 DALYs were lost to COVID-19 in Sweden, 99.3% of which was attributed to YLL. Loss of DALYs occurred mainly among the elderly, with 66.8% of DALYs attributed to individuals >70 years old. Compared to other diseases, the burden of COVID-19 in 2020 ranked as the eighth leading cause of DALY lost. CONCLUSIONS: Similar to other countries, the burden of COVID-19 in Sweden was concentrated mainly among the elderly, who contributed most of the DALY lost due to premature mortality. Yet, DALY loss remained lower for COVID-19 than for several other diseases. The contribution of YLD to DALYs lost was minimal. However empirical data on the occurrence and disability of post-COVID-19 condition are scarce, and YLD may therefore be underestimated.

Occupational role and COVID-19 among foreign-born healthcare workers in Sweden: a registry-based study.

BACKGROUND: Many studies report that foreign-born healthcare workers (HCWs) in high-income countries have an elevated risk of COVID-19. However, research has not yet specifically evaluated the distribution of COVID-19 among foreign-born workers in different healthcare work groups. We examined the risk of COVID-19 infection and hospitalization among foreign-born HCWs in different occupational roles in Sweden. METHODS: We linked occupational data (2019) of 783 950 employed foreign-born workers (20-65 years) to COVID-19 data registered between 1 January 2020 and 30 September 2021. We used Cox proportional hazards regression to estimate the hazard ratio (HR) with 95% confidence intervals (95% CIs) of COVID-19 infection and hospitalization in eight healthcare occupational groups vs. non-HCWs and assessed whether region of birth modified the association between healthcare occupations and COVID-19. RESULTS: All HCWs had a higher risk of COVID-19 outcomes than non-HCWs, but the risk differed by occupational role. Hospital-based assistant nurses had the highest risk (infection: HR 1.78; 95% CI 1.72-1.85; hospitalization: HR 1.79; 95% CI 1.52-2.11); allied HCWs had the lowest risk (infection: HR 1.22; 95% CI 1.10-1.35; hospitalization: HR 0.98; 95% CI 0.59-1.63). The relative hazard of the outcomes varied across foreign-born workers from different regions. For example, the relative risk of COVID-19 infection associated with being a physician compared to a non-HCW was 31% higher for African-born than European-born workers. CONCLUSIONS: The risk of COVID-19 among foreign-born HCWs differed by occupational role and immigrant background. Public health efforts that target occupational exposures as well as incorporate culturally responsive measures may help reduce COVID-19 risk among foreign-born HCWs.

Seek COVER: using a disease proxy to rapidly develop and validate a personalized risk calculator for COVID-19 outcomes in an international network.

BACKGROUND: We investigated whether we could use influenza data to develop prediction models for COVID-19 to increase the speed at which prediction models can reliably be developed and validated early in a pandemic. We developed COVID-19 Estimated Risk (COVER) scores that quantify a patient's risk of hospital admission with pneumonia (COVER-H), hospitalization with pneumonia requiring intensive services or death (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis using historical data from patients with influenza or flu-like symptoms and tested this in COVID-19 patients. METHODS: We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries containing data collected on or before 4/27/2020. We used a 2-step process to develop 3 scores using historical data from patients with influenza or flu-like symptoms any time prior to 2020. The first step was to create a data-driven model using LASSO regularized logistic regression, the covariates of which were used to develop aggregate covariates for the second step where the COVER scores were developed using a smaller set of features. These 3 COVER scores were then externally validated on patients with 1) influenza or flu-like symptoms and 2) confirmed or suspected COVID-19 diagnosis across 5 databases from South Korea, Spain, and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. RESULTS: Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved good performance in influenza and COVID-19 cohorts. For COVID-19 the AUC ranges were, COVER-H: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration varied across the validations with some of the COVID-19 validations being less well calibrated than the influenza validations. CONCLUSIONS: This research demonstrated the utility of using a proxy disease to develop a prediction model. The 3 COVER models with 9-predictors that were developed using influenza data perform well for COVID-19 patients for predicting hospitalization, intensive services, and fatality. The scores showed good discriminatory performance which transferred well to the COVID-19 population. There was some miscalibration in the COVID-19 validations, which is potentially due to the difference in symptom severity between the two diseases. A possible solution for this is to recalibrate the models in each location before use.

Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study.

PURPOSE: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. METHODS: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. RESULTS: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from -39.4% in Romagna to -14.2% in Scotland) and nasal preparations (from -34.4% in Lithuania to -5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. CONCLUSIONS: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas.

Worse patient-reported outcomes and higher risk of reoperation and adverse events after total hip replacement in patients with opioid use in the year before surgery: a Swedish register-based study on 80,483 patients.

Background and purpose - Recent studies indicate that preoperative use of opioids could be associated with higher rates of complications and worse patient-reported outcomes (PROs) after orthopedic surgery. We investigated the prevalence of preoperative opioid use and analyzed its influence on risk of revision, adverse events (AE), and PROs in patients with total hip replacement (THR). Patients and methods - This observational study included 80,483 patients operated on in 2008-2016 with THRs due to osteoarthritis. Data was obtained from the Swedish Hip Arthroplasty Register, Statistics Sweden's sociodemographic registers, the Swedish National Patient Register, and the Prescribed Drug Register. We focused on patients with ≥ 4 opioid prescriptions filled 1 year prior to THR. To control for confounding, we used propensity scores to weight subjects in our analyses. Logistic and linear regression was used for outcome variables with adjustments for sociodemographic variables and comorbidities. Results - Patients with ≥ 4 opioid prescriptions in the year before THR (n = 14,720 [18%]) had a higher risk of revision within 2 years (1.8% vs. 1.1% OR 1.4, 95% CI 1.3-1.6) and AE within 90 days (9.4% vs. 6.4% OR 1.2, 95% CI 1.2-1.3) compared with patients without opioid treatment in the preoperative period. Patients with ≥ 4 opioid prescriptions rated 5 points worse on a 0-100 scale of Pain Visual Analogue Scale (VAS) and 9 points worse on a general health (EQ) VAS 1 year postoperatively. Interpretation - Having ≥ 4 opioid prescriptions filled in the year before surgery is associated with a higher risk of revision, adverse events, and worse PROs after THR. Consequently, preoperative opioid treatment should be addressed in the clinical assessment of patients eligible for THR.

Characteristics and outcomes of 627 044 COVID-19 patients living with and without obesity in the United States, Spain, and the United Kingdom.

BACKGROUND: A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity. METHODS: We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status. RESULTS: We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8-40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0-33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity. CONCLUSION: We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies.

Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study.

OBJECTIVES: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA. METHODS: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%. RESULTS: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis. CONCLUSION: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation. TRIAL REGISTRATION: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.

COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.

OBJECTIVE: Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. METHODS: A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization. RESULTS: We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%). CONCLUSION: Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.