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.

Machine learning-driven development of a disease risk score for COVID-19 hospitalization and mortality: a Swedish and Norwegian register-based study.

Aims: To develop a disease risk score for COVID-19-related hospitalization and mortality in Sweden and externally validate it in Norway. Method: We employed linked data from the national health registries of Sweden and Norway to conduct our study. We focused on individuals in Sweden with confirmed SARS-CoV-2 infection through RT-PCR testing up to August 2022 as our study cohort. Within this group, we identified hospitalized cases as those who were admitted to the hospital within 14 days of testing positive for SARS-CoV-2 and matched them with five controls from the same cohort who were not hospitalized due to SARS-CoV-2. Additionally, we identified individuals who died within 30 days after being hospitalized for COVID-19. To develop our disease risk scores, we considered various factors, including demographics, infectious, somatic, and mental health conditions, recorded diagnoses, and pharmacological treatments. We also conducted age-specific analyses and assessed model performance through 5-fold cross-validation. Finally, we performed external validation using data from the Norwegian population with COVID-19 up to December 2021. Results: During the study period, a total of 124,560 individuals in Sweden were hospitalized, and 15,877 individuals died within 30 days following COVID-19 hospitalization. Disease risk scores for both hospitalization and mortality demonstrated predictive capabilities with ROC-AUC values of 0.70 and 0.72, respectively, across the entire study period. Notably, these scores exhibited a positive correlation with the likelihood of hospitalization or death. In the external validation using data from the Norwegian COVID-19 population (consisting of 53,744 individuals), the disease risk score predicted hospitalization with an AUC of 0.47 and death with an AUC of 0.74. Conclusion: The disease risk score showed moderately good performance to predict COVID-19-related mortality but performed poorly in predicting hospitalization when externally validated.

Incidence and treatment outcomes of pulmonary tuberculosis in Islamic Republic of Iran.

Background: Pulmonary tuberculosis is the most common type of tuberculosis and few studies have investigated the incidence and treatment outcome of smear-positive pulmonary tuberculosis in Golestan Province, Islamic Republic of Iran. Aims: To estimate the cumulative incidence and trends in incidence of smear-positive pulmonary tuberculosis in Golestan Province between 2014 and 2019, and to determine the treatment outcomes. Methods: All smear-positive pulmonary tuberculosis cases between 2014 and 2019 recorded in the tuberculosis registry in Golestan Province, Islamic Republic of Iran, were included in this study. The yearly incidence and cumulative incidence were calculated, and differences by sex and residence were examined. Treatment outcomes classified as success and failure were determined. The Mann-Kendall test was used to assess the significance of the trend in incidence. Results: A total of 2047 smear-positive pulmonary tuberculosis cases were evaluated. The cumulative incidence was 18.52 [95% confidence intervals (CI): 17.72-19.33] per 100 000 population during 2014-2019. The incidence of smear-positive pulmonary tuberculosis declined from 23.84 (95% CI: 21.57-26.11) per 100 000 population in 2014 to 15.02 (95% CI: 13.29- 16.75) in 2019. Incidence rate was higher among men and among rural residents. Most patients (85.34%) were cured, 2.05% completed their treatment, 1.17% were lost to follow-up, 4.40% had treatment failure, and 6.45% died. Conclusion: The incidence of pulmonary tuberculosis in Golestan Province, Islamic Republic of Iran, declined during the period of study. However, the proportion of patients who were cured decreased and the proportion who died increased. Interventions are needed to improve the treatment success rate for pulmonary tuberculosis in the province.

Artificial intelligence-driven prediction of COVID-19-related hospitalization and death: a systematic review.

Aim: To perform a systematic review on the use of Artificial Intelligence (AI) techniques for predicting COVID-19 hospitalization and mortality using primary and secondary data sources. Study eligibility criteria: Cohort, clinical trials, meta-analyses, and observational studies investigating COVID-19 hospitalization or mortality using artificial intelligence techniques were eligible. Articles without a full text available in the English language were excluded. Data sources: Articles recorded in Ovid MEDLINE from 01/01/2019 to 22/08/2022 were screened. Data extraction: We extracted information on data sources, AI models, and epidemiological aspects of retrieved studies. Bias assessment: A bias assessment of AI models was done using PROBAST. Participants: Patients tested positive for COVID-19. Results: We included 39 studies related to AI-based prediction of hospitalization and death related to COVID-19. The articles were published in the period 2019-2022, and mostly used Random Forest as the model with the best performance. AI models were trained using cohorts of individuals sampled from populations of European and non-European countries, mostly with cohort sample size <5,000. Data collection generally included information on demographics, clinical records, laboratory results, and pharmacological treatments (i.e., high-dimensional datasets). In most studies, the models were internally validated with cross-validation, but the majority of studies lacked external validation and calibration. Covariates were not prioritized using ensemble approaches in most of the studies, however, models still showed moderately good performances with Area under the Receiver operating characteristic Curve (AUC) values >0.7. According to the assessment with PROBAST, all models had a high risk of bias and/or concern regarding applicability. Conclusions: A broad range of AI techniques have been used to predict COVID-19 hospitalization and mortality. The studies reported good prediction performance of AI models, however, high risk of bias and/or concern regarding applicability were detected.

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.

Initiation of antihypertensive drugs to patients with confirmed COVID-19-A population-based cohort study in Sweden.

PURPOSE: Hypertension is an important risk factor for severe outcomes in patients with COVID-19, and antihypertensive drugs may have a protective effect. However, the pandemic may have negatively impacted health care services for chronic diseases. The aim of this study was to assess initiations of antihypertensive medicines in patients infected by COVID-19. METHODS: A cohort study including all Swedish residents 20-80 years old with a COVID-19 positive test compared with an unexposed group without COVID-19 matched for age, sex, and index date (date of confirmed COVID-19). Data were collected within SCIFI-PEARL, a study including linked data on COVID tests, hospital diagnoses, dispensed prescriptions, and socioeconomic data from Swedish national registers. Initiations of different antihypertensive drugs were studied from March 2020 until October 2020. Associations between COVID-19 and initiation of antihypertensives were assessed by a multivariable Cox proportional hazards model. RESULTS: A total of 224 582 patients (exposed and unexposed) were included. After adjusting for cardiovascular comorbidities and education level, ACEi was the most commonly initiated antihypertensive agent to patients with COVID-19. Hazard ratio and 95% confidence interval for initiation of drug therapy was 1.83 [1.53-2.19] for ACEi, followed by beta-blockers 1.74 [1.55-1.95], calcium channel blockers 1.61 [1.41-1.83], angiotensin receptor blockers 1.61 [1.40-1.86], and diuretics 1.53 [1.32-1.77]. CONCLUSION: All antihypertensive medicines were initiated more frequently in COVID-19 patients. This can either be associated with hypertension caused by the COVID-19 infection, more frequent diagnosis of hypertension among people with COVID-19 since they consult health care, or residual confounding factors not adjusted for in the study.

The Occurrence of Metabolic Risk Factors Stratified by Psoriasis Severity: A Swedish Population-Based Matched Cohort Study.

PURPOSE: To assess the relative risk of metabolic risk factors in patients stratified by psoriasis severity compared with population controls. PATIENTS AND METHODS: A retrospective cohort study was conducted using national Swedish registers. Adult patients with psoriasis were selected if they had a dispensing of anti-psoriasis prescription (2007-2013) and at least one diagnosis within five years before the dispensing date. The patients with psoriasis were matched 1:10 to controls from the general population on birth year, sex, and county. The cohort was further divided into three disease severity groups (mild, moderate, or severe) based on their dispensed anti-psoriasis medication. Subjects were followed from the index date until censoring. We applied flexible parametric modeling to understand the risks of the incident comorbidities hypertension, hypercholesterolemia, and diabetes mellitus among patients with psoriasis from 6 months through 10 years. Hazard ratios and predicted risk (ie, 1 minus the survival probability) of comorbidities were reported. RESULTS: The hazard of hypertension, hypercholesterolemia, and diabetes mellitus is higher among psoriasis patients compared with population controls, and the hazard ratio increases with psoriasis severity. For example, HRs of hypertension for patients with mild, moderate, and severe psoriasis are 1.29 (95% CI: 1.27-1.32), 1.35 (95% CI: 1.32-1.38), and 1.73 (95% CI: 1.64-1.82), respectively. The predicted risk of hypertension, hypercholesterolemia, and diabetes mellitus among patients with severe psoriasis at year ten was 0.58 (95% CI: 0.56, 0.59), 0.33 (95% CI: 0.32, 0.35), and 0.21 (95% CI: 0.20, 0.23), respectively, while it was 0.42 (0.41, 0.43), 0.23 (0.22, 0.23), 0.11 (0.10, 0.11) among controls, respectively. The predicted risk at year ten was similar among patients with mild or moderate psoriasis. CONCLUSION: The HRs and predicted risks of metabolic risk factors are higher among patients with psoriasis compared with matched controls and are more prominent among the severe psoriasis group.

Young patients with risk factors prevalent in the elderly - differences in comorbidity depending on severity of psoriasis: a nationwide cross-sectional study in Swedish health registers.

BACKGROUND: Association between psoriasis severity and cerebro- and cardiovascular comorbidities has rarely been investigated. AIM: We aimed to investigate differences in cerebro- and cardiovascular comorbidities by psoriasis severity. MATERIALS AND METHODS: Using Swedish nationwide health-care registers, new adult users of anti-psoriatic drugs (2007-2013) with a recorded diagnosis of psoriasis/psoriatic arthritis or a filled prescription for calcipotriol were included. Psoriasis severity was based on the type of anti-psoriatic treatment (topical/mild, non-biologic systemic/moderate-to-severe, and biologics/ severe). Age standardized prevalence rates of cerebro- and cardiovascular comorbidities and their risk factors were compared between the groups. RESULTS: We found that severe psoriasis patients (N=2147) were younger than moderate-to-severe (N=11,919) or mild (N=70,796) patients (median 44, 52, and 55 years). Prevalence of hypertension was 29.9%, 32.6%, and 36.5%, myocardial infarction was 2.5%, 2.3%, and 1.8%, and stroke was 2.4%, 2.2%, and 1.1% in mild, moderate-to-severe, and severe psoriasis patients, respectively. Diabetes prevalence was 7.6% in mild, 8.0% in moderate-to-severe, and 10.7% in severe psoriasis. CONCLUSION: Myocardial infarction and stroke were less common in patients with severe psoriasis while, despite being younger, they had a higher prevalence of diabetes and hypertension.

Mortality trends for multiple sclerosis patients in Sweden from 1968 to 2012.

OBJECTIVE: To assess trends in mortality and causes of death for patients with multiple sclerosis (MS) relative to those without MS in Sweden. METHODS: Patients with an MS diagnosis in Sweden between 1964 and 2012 were identified with the Patient Register and the Multiple Sclerosis Register. For this cohort study, each patient with MS (n = 29,617) was matched with 10 individuals without MS (n = 296,164) on sex, year of birth, vital status, and region of residence at the time of MS diagnosis with the Total Population Register. The Causes of Death Register was used to identify causes of death. Cox proportional hazard models were constructed to assess whether risk of mortality was increased for patients with MS. RESULTS: The hazard ratio (HR) for patients with MS was 2.92 (95% confidence interval [CI] 2.86-2.99) for all-cause mortality over the entire study period. The largest differences between the cohorts were death resulting from respiratory (HR 5.07, 95% CI 4.87-5.26) and infectious (HR 4.07, 95% CI 3.70-4.47) diseases. Overall and for each specific cause, there have been improvements for the MS group and a subsequent reduction in the HR. The HR decreased from 6.52 (95% CI 5.79-7.34) for the period of 1968 to 1980 to 2.08 (95% CI 1.95-2.22) for the time period of 2001 to 2012. An interaction between time period and MS exposure showed that the decrease in mortality over time was statistically significant, with a larger decrease for patients with MS than their matched comparators. CONCLUSIONS: There has been a substantial improvement in mortality overall and for each specified cause of death for patients with MS compared with individuals without MS; however, large differences still remain.

Risk of Premenopausal and Postmenopausal Breast Cancer among Multiple Sclerosis Patients.

OBJECTIVE: To investigate risk of premenopausal and postmenopausal breast cancer among Multiple Sclerosis (MS) patients, considering tumor stage. METHODS: The Swedish Patient Register identified 19,330 women with MS between 1968 and 2012, matched individually with a cohort of 193,458 without MS. Matching variables were year of birth, sex, region of residence and vital status at the time of diagnosis. The cancer register identified 471 and 5,753 breast cancer cases among the MS and non-MS cohorts, respectively. Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (CI) for premenopausal and postmenopausal breast cancer. RESULTS: Overall risk of postmenopausal breast cancer was 13% higher among MS patients compared with women without MS (HR = 1.13, 95% CI 1.02-1.26). Stratified analyses showed that the risk was statistically significantly increased in women diagnosed between 1968 and 1980 and those who were diagnosed at age 65 or older age. We observed a non-statistically significant risk only for stage 0-1 postmenopausal breast cancer (HR = 1.17, 95% CI 0.93-1.48). MS was not associated with premenopausal breast cancer. CONCLUSION: The modest increased risk of postmenopausal breast cancer in women with MS may be due to surveillance bias, where contact with health services for one disease increases the risk of a second diagnosis being recorded.

Multiple sclerosis and risk of young-adult-onset Hodgkin lymphoma.

OBJECTIVE: To determine whether there is an association between multiple sclerosis (MS) and young-adult-onset Hodgkin lymphoma (YAHL) as this will signal etiologic similarities relevant both to inherited characteristics and environmental exposures in childhood. METHODS: Swedish general population registers identified a cohort of 29,617 with an MS diagnosis between 1968 and 2012, matched with a cohort of 296,164 without MS. Cox regression was used to assess the association of MS with subsequent YAHL (defined as onset between ages 15 and 39 years; n = 20), with adjustment, for age/period, sex, county of residence, and level of education. RESULTS: The adjusted hazard ratio (and 95% confidence interval) for the association of MS with YAHL is 3.30 (1.01-10.73), resulting from 4 and 16 events in the MS and non-MS cohorts, respectively. All 4 of the YAHL diagnoses in MS occurred in women, and the association of MS with YAHL has a hazard ratio of 4.04 (1.17-13.94) among women. There was no notable association of MS with older-onset Hodgkin lymphoma. CONCLUSION: There may be common risks for YAHL and MS, consistent with an etiologic role in MS for early-life exposures, such as to infectious agents.

Pregnancy history and risk of premenopausal breast cancer-a nested case-control study.

BACKGROUND: Reproductive factors are well-known risk factors for premenopausal breast cancer (PBC). It is unknown whether these associations are modified by familial factors, including genetic and early environment factors. METHODS: Using Swedish health registries, we performed a nested case-control study with two control groups: sister controls and population controls. The study population included women with live singleton births between 1973 and 2010, who also had a full sister who gave birth during this period. All women subsequently diagnosed with PBC were selected as cases (n = 8327). Sisters with the least age difference and without PBC at the time of her sister's diagnosis were selected as sister controls. For each incident case, one population control without previous PBC was selected.The population controls were individually matched with the sister controls on year of birth. Conditional logistic regression was used to estimate associations between reproductive factors and PBC. RESULTS: Increasing parity was inversely associated with PBC using population controls, and multiparity was a risk factor using sister controls. Very preterm delivery (≤ 31 weeks) was associated with a slightly higher PBC risk using sister controls. Preeclampsia was associated with a slightly protective effect using population controls. With respect to other factors, there were no substantial differences in risks of PBC by choice of control group. CONCLUSIONS: The divergent results with regard to parity and PBC risk when using sister and population controls suggest that the influence of childbearing may be modified by genotype. Selection bias when using different control groups must also be considered.

Birth size in the most recent pregnancy and maternal mortality in premenopausal breast cancer by tumor characteristics.

The main aim of this study was to investigate possible associations between measures of offspring size at birth in the most recent pregnancy before premenopausal breast cancer diagnosis and the risks of maternal breast cancer mortality, taking tumor characteristics into account. We also aimed to investigate if these associations are modified by age at childbirth, time since childbirth, parity, and age at diagnosis. We followed 6,019 women from their date of premenopausal breast cancer (diagnosed from 1992 to 2008) until emigration, death or December 31st, 2009, whichever occurred first. We used Cox proportional hazard regression models, adjusted for parity, age at diagnosis, and education level, to estimate associations between women pregnancy, cancer characteristics and offspring birth characteristics, and mothers' mortality risk. In stratified analyses, mortality risks were estimated by tumor stage, ER or PR status. There was no association between offspring birth weight (HR = 1.00, 95 % CI 0.99-1.01, when used as a continuous variable), birth weight for gestational age or ponderal index, and premenopausal breast cancer mortality. Similarly, in analyses stratified by tumor stage, receptor status, and time difference between last pregnancy and date of diagnosis, we found no associations between birth size and breast cancer mortality. Our findings suggest that the hypothesis that "premenopausal breast cancer mortality is associated with offspring birth characteristics in the most recent pregnancy before the diagnosis" may not be valid. In addition, these associations are not modified by tumor characteristics.

Breast cancer risk in opposite-sexed twins: influence of birth weight and co-twin birth weight.

Most, but not all, studies report a positive association between birth weight, as an indirect marker of prenatal hormone exposure, and offspring breast cancer risk, particularly premenopausal breast cancer. Females from opposite-sexed twin pairs may also be prenatally exposed to androgens from their twin brothers. A Swedish study of opposite-sexed twins with a small sample size found a very strong positive association between female birth weight and breast cancer risk. In this case-control study, nested within a cohort of female opposite-sexed twins, we included 543 breast cancer case subjects diagnosed in the period from 1972 to 2008 and 2715 matched control subjects. Conditional logistic regression estimated the breast cancer risk associated with birth weight and other birth characteristics, including gestational age and co-twin birth weight. All statistical tests were two-sided. There was no association between birth weight (odds ratio = 1.01; 95% confidence interval = 0.70 to 1.46) or twin brother's birth weight and risk of breast cancer, which suggests the previously reported strong positive association may have been a chance finding.