Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study.

BACKGROUND AND AIMS: The benefit of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) and intermediate stroke risk is debated. In a nationwide Norwegian cohort with a non-sex CHA2DS2-VASc risk score of one, this study aimed to investigate (i) stroke and bleeding risk in AF patients with and without OAC treatment, and (ii) the risk of stroke in non-anticoagulated individuals with and without AF. METHODS: A total of 1 118 762 individuals including 34 460 AF patients were followed during 2011-18 until ischaemic stroke, intracranial haemorrhage, increased CHA2DS2-VASc score, or study end. One-year incidence rates (IRs) were calculated as events per 100 person-years (%/py). Cox regression models provided adjusted hazard ratios (aHRs [95% confidence intervals]). RESULTS: Among AF patients, the ischaemic stroke IR was 0.51%/py in OAC users and 1.05%/py in non-users (aHR 0.47 [0.37-0.59]). Intracranial haemorrhage IR was 0.28%/py in OAC users and 0.19%/py in non-users (aHR 1.23 [0.88-1.72]). Oral anticoagulant use was associated with an increased risk of major bleeding (aHR 1.37 [1.16-1.63]) but lower risk of the combined outcome of ischaemic stroke, major bleeding, and mortality (aHR 0.57 [0.51-0.63]). Non-anticoagulated individuals with AF had higher risk of ischaemic stroke compared to non-AF individuals with the same risk profile (aHR 2.47 [2.17-2.81]). CONCLUSIONS: In AF patients at intermediate risk of stroke, OAC use was associated with overall favourable clinical outcomes. Non-anticoagulated AF patients had higher risk of ischaemic stroke compared to the general population without AF with the same risk profile.

The medication-based Rx-Risk Comorbidity Index and risk of hip fracture - a nationwide NOREPOS cohort study.

BACKGROUND: Few previous studies have assessed overall morbidity at the individual level with respect to future risk of hip fracture. The aim of this register-based cohort study was to examine the association between morbidity measured by the medication-based Rx-Risk Comorbidity Index (Rx-Risk) and the risk of first hip fracture. METHODS: Individual-level data on medications dispensed from pharmacies (2005-2016) was retrieved from the Norwegian Prescription Database and used to calculate Rx-Risk for each calendar year. Information on first hip fractures (2006-2017) was obtained from a nationwide hip fracture database. Individuals ≥ 51 years who filled at least one prescription during the study period comprised the population at risk. Using Rx-Risk as a time-varying exposure variable, relative risk estimates were obtained by a negative binomial model. RESULTS: During 2006-2017, 94,104 individuals sustained a first hip fracture. A higher Rx-Risk was associated with increased risk of hip fracture within all categories of age and sex. Women with the highest Rx-Risk (> 25) had a relative risk of 6.1 (95% confidence interval (CI): 5.4, 6.8) compared to women with Rx-Risk ≤ 0, whereas the corresponding relative risk in women with Rx-Risk 1-5 was 1.4 (95% CI: 1.3, 1.4). Similar results were found in men. Women > 80 years with Rx-Risk 21-25 had the highest incidence rate (514 (95% CI: 462, 566) per 10, 000 person years). The relative increase in hip fracture risk with higher Rx-Risk was most pronounced in the youngest patients aged 51-65 years. CONCLUSIONS: Rx-Risk is a strong predictor of hip fracture in the general outpatient population and may be useful to identify individuals at risk in a clinical setting and in future studies.

Fatal drug overdoses in individuals treated pharmacologically for chronic pain: a nationwide register-based study.

INTRODUCTION: Chronic pain patients may be at an increased risk for drug overdoses as a result of comorbid psychiatric disorders and treatment with risk-increasing prescription medications, such as opioids. We aimed to characterise fatal drug overdoses and investigate factors associated with the deaths among individuals who had been treated pharmacologically for chronic pain. METHODS: We included all individuals who received analgesics reimbursed for chronic pain in Norway during 2010-9 (n=569 047). Among this population, we identified all individuals with drug overdoses as cause of death (cases). Extracting data from national registries on diagnoses, filled prescriptions, and socioeconomic variables, we used a nested case-control design to compare the cases with age- and sex-matched controls from the study population. RESULTS: Overall, 623 (0.11%) individuals in the study population died of an overdose. Most, 66.8%, had overdosed accidentally, and 61.9% as a result of pharmaceutically available opioids. Compared with the controls (n=62 245), overdoses overall were associated strongly with substance use disorders (adjusted odds ratio 7.78 [95% confidence interval 6.20-9.77]), use of combinations of opioids, benzodiazepines and related drugs and gabapentinoids (4.60 [3.62-5.85]), previous poisoning with pharmaceuticals (2.78 [2.20-3.51]), and with living alone the last year of life (2.11 [1.75-2.54]). Intentional overdoses had a stronger association with previous poisonings with pharmaceuticals whereas accidental overdoses were strongly associated with substance use disorders. CONCLUSIONS: This study shows the need for better identification of overdose and suicide risk in individuals treated for chronic pain. Extra caution is needed when treating complex comorbid disorders, especially with overdose risk-increasing medications.

The epidemiology of major depression among adults in Norway: an observational study on the concurrence between population surveys and registry data - a NCDNOR project.

BACKGROUND: Mental health problems, and major depression in particular, are important public health issues. Following trends in the prevalence of major depression is difficult because of the costs and complications of diagnostic interviews and general population self-report health surveys. Scandinavian countries, however, have several central, population-based health registries. We aimed to investigate how well these registries capture the epidemiology of major depression in the population. METHODS: In two Norwegian regional surveys of general population health, each repeated after 10 years, responders were asked to report depressive symptoms using the Hopkins Symptom Checklist (HSCL) or the Hospital Anxiety and Depression Scale (HADS). Data were linked to three central health registries capturing contact with primary care, specialist care and prescriptions for antidepressants, to investigate how well these registries reflected self-reported depressive symptoms. RESULTS: Most responders scored low on Hopkins Symptom Checklist (HSCL) and the Hospital Anxiety and Depression Scale (HADS), but 10% and 13%, respectively, scored above cut-off, with only minor changes between the two survey times. Females scored higher than males. Older people scored lower than younger, and a social gradient was visible. Around 12% of those who scored above the cut-off on either scale were recorded in the central health registries during the following year. This correlation was highest in primary care data, followed by prescription data and lowest in specialist care. Females were more often recorded in registries (p < 0.001), as were younger people (p < 0.001). CONCLUSIONS: There was a strong association between scores on screening for major depression in the general population surveys and being recorded in central health registries. There was a low sensitivity of these registries. and there was some variation in how sensitive the central health registries were in picking up depression, especially for males and older people. However, the stability of the measures over time suggests we may get an impression of the prevalence of major depression in the general population by using data from the central health registries. A combination of primary care data, prescription data and specialist care data have a higher sensitivity.

[Mental disorders and symptoms with persistent opioid use for chronic non-cancer pain ­ a registry study]. / Psykiske lidelser og plager ved vedvarende opioidbruk for langvarige ikke-kreftrelaterte smerter ­ en registerstudie.

Background: Knowledge of mental disorders among patients with persistent opioid use for the treatment of chronic non-cancer pain is essential, as mental disorders and symptoms can exacerbate or perpetuate pain and impact on the ability of patients to manage their illness. We have studied the prevalence of mental disorders and symptoms, including substance use disorders, in patients with persistent opioid use in 2019. Material and method: Persons ≥ 18 years with persistent opioid use and persons ≥ 18 years with at least one registered mental disorder in the specialist healthcare service in 2019 were included. Data were retrieved from national health registries in Norway. Patients who received opioids reimbursed for the treatment of chronic pain were compared with those who received opioids without reimbursement. Results: The prevalence of mental disorders and symptoms was 34 % among 14 403 persons who received reimbursed opioids, and 42 % among 38 001 persons who received opioids without reimbursement. This is equivalent to a two to threefold increase in prevalence compared to the general population. There was a particularly higher prevalence of anxiety disorders and substance use disorders. The prevalence of mental disorders and symptoms was highest in the age group 18-44 years (49-55 %). Interpretation: Among patients with persistent opioid use, a large proportion had mental disorders and symptoms, which are known risk factors for developing problematic opioid use and opioid use disorder.

Incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer - A nationwide cohort study.

OBJECTIVES: To evaluate both incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer. DESIGN: A prospective study. SETTING: Population-based registries. POPULATION: 1.76 million women, including 17 500 women with gynaecological cancers. METHODS: Data from the Cancer Registry of Norway was linked to the Norwegian Prescription Database and other national databases. MAIN OUTCOME MEASURES: Prevalence ratios (PRs) and hazard ratios (HRs), with 95% confidence intervals (CIs), of dispensed drugs in gynaecological cancer patients (up to 15 years after diagnosis) were estimated by log-binomial and Cox regression, respectively, with cancer-free women as reference. RESULTS: For gynaecological cancer patients, the incidence of drugs used for pain control was higher than in cancer-free women, especially the first 5 years after diagnosis, and the prevalence was high at least 10 years after. The prevalence of sex hormones was high in women with gynaecological cancer at least 10 years after diagnosis (cervical and ovarian cancer PR = 23, 95% CI 18-30 and PR = 29, 95% CI 15-38, respectively), but low in cancer-free women (0.3%). Patients with uterine corpus cancer had a higher prevalence of antidiabetics before and at least 10 years after diagnosis, most pronounced in women diagnosed before age 50 (PR = 10, 95% CI 5.0-21). The prevalence of antidepressants was moderately elevated in women with gynaecological cancers. CONCLUSIONS: Gynaecological cancer survivors, particularly cervical and ovarian cancer survivors, had an increased long-term use of drugs for pain control and sex hormones. Survivors of uterine corpus cancer used antidiabetics more often, both before and after diagnosis.

National health registries - a 'goldmine' for studying non-communicable disease occurrence in Norway - the NCDNOR project.

To estimate occurrence of non-communicable diseases (NCDs) over the life-course in the Norwegian population, national health registries are a vital source of information since they fully represent the entire non-institutionalised population. However, as they are mainly established for administrative purposes, more knowledge about how NCDs are recorded in the registries is needed. To establish this, we begin by counting the number of individuals registered annually with one or more NCDs in any of the registries. The study population includes all inhabitants who lived in Norway from 2004 to 2020 (N~6.4m). The NCD outcomes are diabetes, cardiovascular diseases, chronic obstructive lung diseases, cancer and mental disorders/substance use disorders. Further, we included hip fractures in our NCD concept. The data sources used to identify individuals with NCDs, including detailed information on diagnoses in primary and secondary health care and dispensings of prescription drugs, are the Cancer Registry of Norway, The Norwegian Patient Registry, The Norwegian Control and Payment of Health Reimbursement database, and The Norwegian Prescription Database. The number of individuals registered annually with an NCD diagnosis and/or a dispensed NCD drug increased over the study period. Changes over time may reflect changes in disease incidence and prevalence, but also changes in disease-specific guidelines, reimbursement schemes and access to and use of health services. Data from more than one health registry to identify individuals with NCDs are needed since the registries reflect different levels of health care services and therefore may reflect disease severity.

Association between medical androgen deprivation therapy and long-term cardiovascular disease and all-cause mortality in nonmetastatic prostate cancer.

Studies have suggested that prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are at increased risk of developing or exacerbating cardiovascular disease (CVD). We aimed to explore the association between ADT for PCa and subsequent CVD and all-cause mortality in this nationwide, longitudinal study. We also evaluated the role of cardiovascular risk and ADT duration to determine effect modification. Norwegian registry data were used to identify patients with PCa from 2008-18 and who received primary ADT in the first year after diagnosis. The associations between ADT and composite cardiovascular events, and the individual components of myocardial infarction, stroke and heart failure, in addition to atrial fibrillation and all-cause mortality, were explored using time-varying Cox regression models. We included 30 923 PCa patients, of whom 8449 (27%) received primary ADT. Mean follow-up was 2.9 and 3.8 years for CVD events and mortality, respectively. We found an association between ADT and composite CVD (adjusted HR 1.13: 95% CI 1.05-1.21), myocardial infarction (1.18: 1.05-1.32), stroke (1.21: 1.06-1.38), heart failure (1.23: 1.13-1.35) and all-cause mortality (1.49: 1.39-1.61). These associations persisted in those with low and moderate CVD risk and ADT longer than 7 months. A relationship between ADT and composite CVD and all-cause mortality was observed, especially in those with moderate CVD risk and longer treatment duration. Future studies with more detailed cancer data are needed to verify the clinical relevance of these results, especially when considering all-cause mortality within the context of treatment guidelines and benefits of ADT.

Long-term use of opioids and concomitant use of other habit-forming drugs. / Vedvarende bruk av opioider og samtidig bruk av andre vanedannende legemidler.

BACKGROUND: Long-term use of opioids may have undesirable consequences. We have investigated long-term opioid use in patient groups that were prescribed opioids for various indications (chronic pain, palliative care, other (white prescriptions, not generally covered by the Norwegian National Insurance Scheme)) as well as the groups' concomitant use of some other addictive medications. MATERIAL AND METHOD: Persons registered in the Norwegian Prescription Database with at least one filled prescription of an opioid in the period 2011-19 were included. Long-term use in a calendar year was defined as the dispensing of > 180 defined daily doses or > 4 500 mg oral morphine equivalents distributed over at least 3 periods of 3 months. RESULTS: The number of long-term opioid users was 50 422 in 2011 and 59 996 in 2019 (10.1 and 10.7 % of all opioid users). The number who received opioids on blue prescription (partly covered by the Norwegian National Insurance Scheme) for chronic pain increased in the period by 9 952 persons, but the majority (n=38 006, 63.3 %) continued to receive opioids exclusively on white prescription in 2019. A total of 15 623 (41.1 %) and 14 881 (39.2 %), respectively, of the long-term opioid users who received opioids solely on white prescription in 2019 also received benzodiazepines and Z-hypnotics in the same year. Of the 23 967 long-term users who also received benzodiazepines, 88 % were dispensed opioids and benzodiazepines on the same day at least once in 2019. INTERPRETATION: Prolonged prescribing of opioids on white prescription and concurrent prescribing of other addictive drugs may indicate undesirable use with no clear indication.

Prescriptions of analgesics during chronic cancer disease trajectories: A complete national cohort study.

PURPOSE: Pain management principles vary considerably between chronic noncancer, acute and cancer pain. Cancer patients responding to oncological treatment may live with low tumor burden for years. Opioid treatment should reflect that the ratio between benefits and risks in these patients is different from patients with a rapidly progressive disease. Our study investigated the prescription patterns of analgesics in patients who died 6 to 9 years after cancer diagnosis. PATIENTS AND METHODS: A pharmaco-epidemiological study based on the Norwegian Prescription Database and Cancer Registry of Norway. The 1-year periodic prevalence of receiving different analgesics and of persistent opioid use were analyzed. Persistent opioid use was defined as >365 Defined Daily Doses or >9000 mg Oral Morphine Equivalents during 365 days with prescriptions in all quarters of the 365 days period. Data were reported for the first 7 years for patients who lived 8-9 years after cancer diagnosis (N = 1502), while for patients who lived 6-7 years (N = 3817) data was reported for the first 5 years after diagnosis. RESULTS: Compared to age- and gender adjusted general population, the 1-year periodic prevalence of opioid prescription was doubled the first year after diagnosis and remained raised with approximately 50%. The prevalence of persistent opioid use was threefold of the general population. Approximately 55% of patients with persistent opioid use 4 years after a cancer diagnosis were co-medicated with high doses of benzodiazepines and/or benzodiazepine-related hypnotics. CONCLUSION: The findings of increased opioid use raise concerns regarding whether the benefits outweigh risks and side effects in this population.

Prescribed drugs in 27 000 individuals after diagnosis of colorectal cancer: A population-based cohort study.

BACKGROUND: The prevalence of prescribed drugs in survivors of colorectal cancer (CRC) was evaluated. METHODS: Data from the Cancer Registry of Norway were linked to the Norwegian Prescription Database for a study population of 3.52 million individuals. Prevalence ratios (PRs) with 95% confidence intervals (CIs) of prescribed drugs in CRC-survivors compared to the cancer-free population, were estimated by log-binomial regression, adjusting for age and education. RESULTS: Almost 27 000 individuals, aged 20 to 84, were diagnosed with CRC during 2005 to 2014. The first year after diagnosis, the prevalence of prescribed drugs was higher in CRC-survivors compared with the cancer-free population, especially drugs for anxiety and tension, and steroid-responsive conditions. PRs for several drugs, especially drugs used for mental and behavioural disorders, decreased with time since diagnosis. The prevalence of drugs used for anxiety and tension was elevated 10 years after diagnosis; PRs the first year after diagnosis were 20 (95% CI: 18-22) in males and 17 (16-18) in females. Ten years after diagnosis PRs were 5.0 (3.1-7.9) and 2.0 (1.0-3.8), respectively. In absolute numbers, the largest increase, compared to the cancer-free population, was in drugs used for gastric acid disorders and pain. The prevalence of neuromodulatory drugs was higher in CRC-survivors. CONCLUSIONS: The prevalence of several drugs was higher in CRC-survivors than in the cancer-free population 10 years after diagnosis. The largest absolute excess in prevalence was for gastric acid disorder and pain medications, while the relative prevalence of drugs used for anxiety and tension was high in CRC-survivors. Long persisting neuropathia was indicated.

Association Between Prescribed Hypnotics in Infants and Toddlers and Later ADHD: A Large Cohort Study from Norway.

As previously indicated an association may exist between early sleep problems in infants and toddlers, and a diagnosis of attention deficit hyperactivity disorder (ADHD). The aim of this study was to study if this association could be replicated in a complete nationwide cohort of children. Prospective cohort study using national registries. All children born in Norway from January 2004 to December 2010 were included (N = 410,555). Information on hypnotic drugs dispensed to children 0-3 years of age outside of institutions was collected from the Norwegian Prescription Database and used as a proxy for sleep problems. The outcome ADHD (ICD-10), as diagnosed by specialists in the Child Mental Health Service, was obtained from the Norwegian Patient Registry. Data were analysed using weighted estimation in Cox regression. The unadjusted weighted hazard ratio (wHR) for a later diagnosis of ADHD in children dispensed two or more prescriptions for any hypnotic drug, compared to zero prescriptions, was 2.30 [95% confidence interval (CI) 1.63-3.23] for girls and 1.75 (95% CI 1.48-2.07) for boys. For the sedative antihistamine trimeprazine the corresponding wHR was 3.71 (95% CI 1.83-7.52) for girls and 2.78 (95% CI 2.04-3.80) for boys. After adjusting for parental ADHD and parental education the wHR for trimeprazine users was 2.81 (95% CI 1.34-5.88) for girls and 2.33 (95% CI 1.70-3.20) for boys. Infants and toddlers who were dispensed hypnotics had an increased risk of ADHD at school age. This association was most pronounced with the use of trimeprazine, a drug traditionally prescribed to toddlers for sleep problems in Norway. After adjusting for parental ADHD and educational level the risk for ADHD among the trimeprazine users was still more than twice the risk among controls.

In utero opioid exposure and risk of infections in childhood: A multinational Nordic cohort study.

PURPOSE: There is an increasing number of children with in utero exposure to opioids. Knowledge about opioid safety in pregnancy, particularly for outcomes later in childhood is scarce. It has been suggested that opioids can modulate immune system and increase the risk of infections. Our goal was to study the impact of in utero opioid exposure on the immune system and the risk of infections in childhood. METHODS: This population-based cohort study used nationwide registers from Denmark, Norway, and Sweden. Among pregnant women we identified users of opioids for two different indications, opioids used in opioid maintenance therapy (OMT) and opioids used for treatment of pain. We followed the exposed children and studied susceptibility for infections measured as number of antibiotic prescriptions expressed as Incidence rate ratios (IRRs) and diagnoses in specialist health care expressed as hazard ratios (HRs). RESULTS: After adjustment we did not observe increased risk for filling antibiotic prescriptions in children exposed to OMT opioids compared with OMT discontinuers (IRR, 1.08; 95% CI 0.81-1.44 in Norway and Sweden, and IRR, 0.74; 95% CI 0.63-0.88 in Denmark), or for diagnosis of infection in specialist health care (HR 0.83; 95% CI 0.55-1.26 in Norway and Sweden, and 0.82; 95% CI 0.62-1.10 in Denmark). CONCLUSIONS: In this population-based cohort study, we did not observe increased risk of infections among children prenatally exposed to OMT opioids when compared to OMT discontinuers, nor long-term analgesic opioids exposed when compared to short-term analgesic opioids exposed.

SARS-CoV-2 in children and adolescents in Norway: confirmed infection, hospitalisations and underlying conditions. / Sars-CoV-2 hos barn og ungdom i Norge: påvist smitte, sykehusinnleggelser og underliggende tilstander.

BACKGROUND: Children and adolescents are at lower risk of disease caused by SARS-CoV-2. We describe the incidence of confirmed infection and hospitalisation of children and adolescents under the age of 20 in Norway, and specifically among those with underlying conditions. MATERIAL AND METHOD: The Norwegian Directorate of Health has collaborated with the Norwegian Institute of Public Health on the establishment of a data extraction system to monitor the coronavirus outbreak. Data from the specialist health service (Norwegian Patient Registry, NPR), and the primary health service (Norwegian Registry for Primary Health Care, NRPHC) are linked to data on positive SARS-CoV-2 tests from the Surveillance System for Communicable Diseases (MSIS). This covers all persons living in Norway as of 1 March 2020, with data on confirmed infection up to and including 13 May 2020 and on hospitalisations up to and including 30 April 2020. RESULTS: Of 8 125 persons with confirmed SARS-CoV-2 in the whole population, 493 (6.1 %) were under 20 years old. The median age of the under-20s was 15 years, and 252 (51 %) were girls. 3 % were hospitalised. No deaths were registered among patients aged under 20 in Norway. We found a somewhat larger share with confirmed SARS-CoV-2 in the group with diseases of the neuromuscular system. INTERPRETATION: Few children and adolescents have had SARS-CoV-2 confirmed, and only a very few have been hospitalised. Underlying conditions may result in a lower threshold for testing, and hence a higher incidence of confirmed infection in this group, although higher risk cannot be excluded.

Prescribing of opioids for chronic pain on reimbursable prescription. / Forskrivning av opioider på blå resept mot langvarige smerter.

BACKGROUND: In 2008 the reimbursable prescription scheme was amended so that patients with severe, chronic pain could be prescribed opioids on reimbursable prescription. The purpose of this study was to investigate the prescribing of opioids on reimbursable prescription, the proportion of patients who started opioid treatment on reimbursable prescription who became long-term users, and the number of patients in 2018 who received higher dosages than the reimbursable prescription scheme permits. MATERIAL AND METHOD: Data were retrieved from the Norwegian Prescription Registry. Persons aged 18 or over who were dispensed at least one opioid on reimbursable prescription for severe, chronic pain in the period 2008-2018, were included. RESULTS: The number of patients who were prescribed opioids on reimbursable prescription increased during the study period, and in 2018 the number was 17 383. Of these, 331 (1.9 %) were prescribed more than 300 mg oral morphine equivalents per day. After nine years, 48 % of the patients who started with opioids in 2009 were still being prescribed opioids on reimbursable prescription. INTERPRETATION: A high proportion of patients with severe, chronic pain who started with opioids on reimbursable prescription became long-term users. A number of patients received higher dosages than are recommended.

Underlying conditions in adults with COVID-19. / Underliggende tilstander hos voksne med covid-19.

BACKGROUND: Cardiovascular diseases, cancer, type-2 diabetes and chronic obstructive pulmonary disease (COPD) were initially noted as the most common diseases among individuals who were hospitalised for COVID-19. However, the evidence base is weak. The objective of this study is to describe how selected diseases were distributed among adults with confirmed COVID-19 (COVID-19 positive tests) and among those hospitalised for COVID-19 compared to the general population. MATERIAL AND METHOD: We used data from the Norwegian Patient Registry, the Norwegian Registry for Primary Health Care and the Norwegian Surveillance System for Communicable Diseases for adults from the age of 20 and older for the period 1 March 2020-13 May 2020. RESULTS: Of all those who tested positive for COVID-19, 7 632 (94 %) were aged 20 years or older, and 1 025 (13.4 %) of these had been hospitalised. Among those hospitalised with COVID-19, there was a higher proportion of individuals with cardiovascular diseases (18.3 % versus 15.6 %), cancer (6.9 % versus 5.4 %), type-2 diabetes (8.6 % versus 5.2 %) and COPD (3.8 % versus 2.7 %) than in the general population as a whole after adjusting for age. The proportion of hospitalised patients with asthma, other chronic respiratory disease, cardiovascular disease, ongoing cancer treatment, complications related to hypertension, obesity and overweight, neurological disorders and cardiac and renal failure was also higher than in the general population. There were few differences between persons who had tested positive for COVID-19 and the general population in terms of underlying conditions. INTERPRETATION: Among those hospitalised for COVID-19, there was a higher proportion of patients with underlying illnesses than in the general population. This may indicate that these patients tend to have a more severe course of disease or that they are more likely to be hospitalised compared to healthy individuals. The results must be interpreted with caution, since the sample of COVID-19 individuals is non-random.

Adjusting for unmeasured confounding using validation data: Simplified two-stage calibration for survival and dichotomous outcomes.

In epidemiology, one typically wants to estimate the risk of an outcome associated with an exposure after adjusting for confounders. Sometimes, outcome and exposure and maybe some confounders are available in a large data set, whereas some important confounders are only available in a validation data set that is typically a subset of the main data set. A generally applicable method in this situation is the two-stage calibration (TSC) method. We present a simplified easy-to-implement version of the TSC for the case where the validation data are a subset of the main data. We compared the simplified version to the standard TSC version for incidence rate ratios, odds ratios, relative risks, and hazard ratios using simulated data, and the simplified version performed better than our implementation of the standard version. The simplified version was also tested on real data and performed well.

Trends in prescription drug use during pregnancy and postpartum in Norway, 2005 to 2015.

PURPOSE: To explore trends in use of maternal medication 3 months prior to, during and 3 months after pregnancy. METHODS: Data on births from the Medical Birth Registry of Norway were linked to the Norwegian Prescription Database, identifying women's use of medications around pregnancy. All women giving birth in Norway during 2005 to 2015 (638 532 singleton births to 414 567 women) were included. Proportions of pregnant women using different medications in association with pregnancy, and annual relative change in medication use during 2005 to 2015, were calculated. RESULTS: In Norway, 60% of pregnant women used prescription medications during pregnancy (2005-15), increasing from 57% in 2005 to 62% in 2015. The annual relative increase was 0.9% (95% CI: 0.8-1.0). In the first trimester, approximately 17% of the women used medications regarded as potentially teratogenic during 2005 to 2015, increasing from 15% to 19%. Overall, this proportion was higher in the first than in the second (8.9%) and third (8.0%) trimesters, and higher than in the 3 months after pregnancy (14%). The annual relative increase of medications regarded as potentially teratogenic in the first trimester was 2.5% (95% CI: 2.3-2.7). CONCLUSIONS: The proportion of women using potentially teratogenic medications in the first trimester of pregnancy have increased during the last decade. Clinicians need to be aware of the possibility of pregnancy when prescribing potentially teratogenic medication to women of fertile age and focus this in the consultations. The increasing trends call for the need of routine surveillance of adverse birth outcomes linked to medication use in pregnancy.

Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study.

AIMS/HYPOTHESIS: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. METHODS: National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. RESULTS: A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences. CONCLUSIONS/INTERPRETATION: The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.

Increased cancer incidence and mortality among people with opioid use-related disorders: A nation-wide cohort study.

BACKGROUND AND AIMS: Studies on cancer incidence and mortality among people with opioid use-related disorders are lacking. We aimed to measure cancer-specific incidence, mortality and survival among people diagnosed with opioid use-related disorders in Norway during 2010-18. DESIGN AND SETTING: This was a cohort study conducted in Norway during 2010-18. PARTICIPANTS: Individuals (n = 20 710) diagnosed with opioid use-related disorders. MEASUREMENTS: We conducted a cohort study utilizing a data-linkage of national health and population registers. Information on opioid use-related disorders was extracted from specialized healthcare, malignancies from the Cancer Registry of Norway and deaths from Cause of Death Registry. Cancer incidence and mortality were compared with the general population by calculating sex-specific age-standardized incidence (SIR) and mortality (SMR) ratios. One-year survival rates were computed. FINDINGS: Compared with the general population, people with opioid use-related disorders were at an increased risk of developing cancer overall [SIR = 1.2, 95% confidence interval (CI) = 1.1-1.3] with a higher than twofold cancer mortality rate (SMR = 2.3, 95% CI = 2.0-2.7). Excess risk was observed for liver (12.6, 95% CI = 9.1-17.0), larynx (4.7, 95% CI = 1.7-10.2), lung (3.5, 95% CI = 2.8-4.3) and pancreas cancer (2.6, 95% CI = 1.6-4.0), whereas reduced risk was found for melanoma (0.5, 95% CI = 0.3-0.9), breast (0.6, 95% CI = 0.4-0.9) and prostate cancers (0.3, 95% CI = 0.1-0.4). Site-specific SMRs were significantly elevated for liver (12.3, 95% CI = 8.5-17.2), lung (3.9, 95% CI = 3.0-5.0), pancreas (3.0, 95% CI = 1.7-4.8) and colon cancers (1.9, 95% CI = 1.1-3.1). The average 1-year survival rate after a cancer diagnosis was low in liver, pancreas and colon cancer, ranging from 10 to 15% less than that of the general population. CONCLUSIONS: In Norway, cancer incidence and cancer-related mortality appear to be elevated among individuals with opioid use-related disorders.