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.

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.

Morbidity among Adolescent Hypnotic Drug Users in Norway: An Observational Population-Based Study.

We have previously shown that the use of hypnotic drugs increased among young Scandinavians during 2012-2018. This study aimed to explore psychiatric and somatic morbidity among adolescent hypnotic drug users in a cohort study of 13-17-year-old individuals during 2008-2018 in Norway. Data sources were (i) prescription data from the Norwegian Prescription Database linked to specialist health care diagnoses from the Norwegian Patient Registry and (ii) sleep disorder diagnoses from the Primary Health Care Database. Hypnotic drugs were defined as the sedative antihistamine alimemazine and the ATC group "Hypnotics and Sedatives" (N05C), excluding midazolam. In 2017, 2519 girls (16.5/1000) and 1718 boys (10.7/1000) were incident (new) users of hypnotic drugs. Most of these new users (82% of girls, 77% of boys) were referred to secondary health care, where the most frequent diagnoses were mental and behavioral disorders (51.8% of girls, 46.2% of boys), while only 3.2% received a specific sleep disorder diagnosis. The most common mental and behavioral disorders were "Neurotic stress-related disorders" among girls (27.4%) and "Behavioral and emotional disorders" among boys (23.6%). In conclusion, the trend of increasing hypnotic drug use among adolescents reflects the initiation of hypnotic drugs in a subgroup of the population with a higher disease burden, mainly due to psychiatric disorders, than the general population.

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.

Prevalence and treatment of gestational diabetes in Norway 2010-2020.

AIMS: Estimate prevalence of gestational diabetes mellitus (GDM) and its treatment in Norway 2010-2020 and explore impact of new national GDM guidelines in 2017. METHODS: We identified women giving birth in a nationwide cohort study using registers on births, prescriptions, education, primary and specialist care. For each year, we estimated prevalence of GDM overall, by BMI, age, education, and mother's birthplace; proportions of GDM pregnancies receiving pharmacological treatment; and distribution of the gestational week when GDM was diagnosed. RESULTS: In 633,169 pregnancies, prevalence of GDM increased from 2.6 % in 2010 to 6.0 % in 2016, then stabilized. Similar patterns were seen across strata of BMI, age, education, and maternal birthplace, although prevalence was higher with higher BMI, higher age, lower education, and mothers born in Asia, Africa, or Middle East. The proportion of the GDM population pharmacologically treated increased from 11.6 % in 2010 to 13.6 % in 2016 and 31.6 % in 2020. GDM was diagnosed in recommended gestational week 24-28 in 19 % versus 45 % of GDM pregnancies in 2010 and 2020, respectively. CONCLUSIONS: Both the proportion diagnosed with GDM within recommended time of screening, and who received pharmacological treatment, increased substantially following new guidelines in 2017. Prevalence of GDM increased from 2010 to 2016, then plateaued.

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.

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.

Prenatal opioid exposure and risk of asthma in childhood: a population-based study from Denmark, Norway, and Sweden.

Background: Opioids may modulate the immune function through opioid receptors on immune cells. Long-term consequences of prenatal opioid exposure on the immune system, such as childhood asthma, are unknown. Objectives: To investigate whether prenatal opioid exposure is associated with the risk of childhood asthma. Methods: Cohort study using linked nationwide registers in Denmark (1996-2015), Norway (2005-2015), and Sweden (2006-2013). Children born by mothers who were chronic opioid analgesics users before pregnancy (n = 14,764) or who were receiving opioid maintenance therapy (OMT) before or during pregnancy (n = 1,595) were identified based on information from each of the medical birth registers and prescription registers. Long-term opioid analgesics exposed children were compared to short-term exposed or unexposed, whereas OMT exposed children were compared to OMT unexposed. Asthma among children ≥1 years of age was defined as two or more filled prescriptions of antiasthmatic medication within 365 days, or a diagnosis of asthma. Hazard ratios (HRs) were calculated using Cox proportional hazards regression with attained age as the time scale. Inverse probability of treatment weights based on propensity scores were applied to adjust for measured confounders. Individual level data from Norway and Sweden were pooled, whereas individual level data from Denmark were analyzed separately. For the opioid analgesics comparisons, adjusted HRs (aHR) from the combined Norwegian/Swedish data and the Danish data were pooled in a fixed-effects meta-analysis. Results: For the opioid analgesics cohort, no increased risk of asthma was observed in long-term exposed children neither compared with unexposed [aHR = 0.99 (95% CI 0.87-1.12)], nor compared with short-term exposed [aHR = 0.97 (0.86-1.10)]. No increased risk of asthma was observed in OMT exposed compared with OMT unexposed children [Norway/Sweden: aHR = 1.07 (0.60-1.92), Denmark: aHR = 1.25 (0.87-1.81)]. Results from sensitivity analyses, where potential misclassification of the outcome and misclassification of OMT exposure were assessed, as well as starting follow-up at 6 years of age, showed that the estimates of association were generally robust. Conclusion: We found no association between prenatal exposure to opioids and risk of childhood asthma. Results were consistent across two different opioid exposure groups with different confounder distributions.

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.

Cohort Description: Preventing an Opioid Epidemic in Norway - Focusing on Treatment of Chronic Pain (POINT) - A National Registry-Based Study.

Aim: The POINT project aims to provide evidence to optimise chronic pain management, prevent adverse consequences of opioids, and improve chronic pain patients' pain relief, functional capacity, and quality of life. We describe the outline of the project and its work packages. More specifically, we describe a cohort of persons with chronic pain and a cohort of long-term opioid users identified from a national registry linkage. Data Sources: The project utilises data from nationwide healthcare and population registers in Norway. Using the Norwegian Prescription Database, we identified a cohort of persons who have been dispensed drugs reimbursed for chronic pain and a cohort of persons who used opioids long term from 2010 to 2019. Data from the Norwegian Registry for Primary Health Care and the Norwegian Patient Registry (2008-2019), Cancer Registry (1990-2018) Cause of Death Registry (2010-2019) and demographic and socioeconomic registers from Statistics Norway (2010-2019) were linked to the cohorts. Study Population: There were 568,869 participants with chronic pain. Sixty-three percent of the cohort was women, and the mean age was 57.1 years. There were 336,712 long-term opioid users (58.6% women; 60.9 years). In chronic pain and long-term opioid user cohorts, the most frequent musculoskeletal diagnosis was back pain diagnosed in primary care (27.6% and 30.7%). Psychiatric diagnoses were also common. Main Variables: Upcoming studies will utilise psychiatric and somatic diagnoses from the patient registers, drug use from the prescription register, causes of death, demographics, and socioeconomic status (eg, education, income, workability, immigrant status) as exposures or outcomes. Conclusion and Future Plans: The two cohorts have numerous pain-related diagnoses, especially in the musculoskeletal system, and noticeably frequent somatic and psychiatric morbidity. The POINT project also includes later work packages that explore prescriber and patient perspectives around safe and effective treatment of chronic pain.

Contribution of an extensive medication-based comorbidity index (Rx-Risk) in explaining the excess mortality after hip fracture in older Norwegians: a NOREPOS cohort study.

OBJECTIVES: Patients with hip fracture are typically characterised by extensive comorbidities and excess mortality. Methods that account for a wide range of comorbidities are needed when attempting to identify causal associations in registry-based studies. We aimed to study the association between the prescription-based Rx-Risk Comorbidity Index (abbreviated Rx-Risk) and mortality by history of hip fracture, and to quantify the contribution of Rx-Risk in explaining the excess mortality after hip fracture. SETTING: In this prospective study, we used nationwide registry data from outpatient care. Rx-Risk was based on filled prescriptions recorded in the Norwegian Prescription Database. Medications were mapped to 46 comorbidity categories by Anatomical Therapeutic Chemical code. Information on hip fractures during 1994-2013 was available from the Norwegian Epidemiologic Osteoporosis Studies hip fracture database, and year of death was obtained from Statistics Norway. We estimated 1-year mortality risk (January through December 2014) according to Rx-Risk score based on dispensed prescriptions in 2013, history of hip fracture, age and sex using Poisson regression. PARTICIPANTS: All individuals aged 65 years and older who were alive by the end of 2013 and had filled at least one prescription in an outpatient pharmacy in Norway in 2013 (n=735 968). RESULTS: Mortality increased exponentially with increasing Rx-Risk scores, and it was highest in persons with a history of hip fracture across the major range of Rx-Risk scores. Age- and sex-adjusted mortality risk difference according to history of hip fracture (yes vs no) was 4.4 percentage points (7.8% vs 3.4%). Adjustment for Rx-Risk score further attenuated this risk difference to 3.3 percentage points. CONCLUSIONS: History of hip fracture and comorbidity assessed by Rx-Risk are independent risk factors for mortality in the community-dwelling older population in Norway. Comorbidity explained a quarter of the excess mortality in persons with a history of hip fracture.

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.

Use of Statins in Kidney Transplant Recipients in Norway.

Kidney transplant recipients (KTRs) experience increased risk of cardiovascular disease. Guidelines recommend HMG-CoA reductase inhibitor (statin) therapy when tolerated. We aimed to study changes in the prescription of statins and patients' adherence to treatment over time. A population-based observational study utilizing linked data from the Norwegian Renal Registry (national coverage of 99.9%) and the Norwegian Prescription Database was performed. Data from a total of 2250 first KTRs were included (mean age-54 years, 69% men). Dispensed prescriptions of statins and immunosuppressants for the period 2004-2016 for all first KTRs engrafted in the period 2005-2015 were analyzed. Seventy-two percent received statins the first year after kidney transplantation and the proportion increased with age. The proportion receiving a statin varied according to the time frame of transplantation (77% in 2005-2010 vs. 66% in 2012-2015). Among new users of statins, 82% of the patients were adherent both the second and third year after kidney transplantation, while the corresponding figure for those already receiving statins before transplantation was 97%. Statin continuation rates in KTRs were high. In conclusion, our findings show a slightly lower overall proportion of patients receiving statins after kidney transplants than the national target level of 80%. The proportion of statin users increased with the age of the KTRs but showed a decreasing trend as time progressed.

Describing long-term opioid use utilizing Nordic prescription registers-A Norwegian example.

Previous studies have defined long-term opioid use in varying ways, decreasing comparability, reproducibility and clinical applicability of the research. Based on recommendations from recent systematic reviews, we aimed to develop a methodology to estimate the prevalence of use persisting more than three months utilizing one of the Nordic prescription registers. We used the Norwegian Prescription Register (NorPD) to extract data on all opioid dispensations between 1 January 2004 and 31 October 2019. New users of opioids (washout 365 days) were defined as long-term users if they fulfilled two criteria: (1) they had ≥2 dispensations of opioids, 91-180 days apart; (2) days 0-90 included ≥90 dispensed administration units (e.g., tablets) of opioids. Overall, there were 2,543,224 new users of opioids during the study period. Of these, 354,666 (13.9%) fulfilled the criteria for long-term opioid use at least once. Compared with those who did not fulfil the criteria (short-term users), long-term users were older, more likely women and used tramadol, oxycodone and buprenorphine more frequently as their first opioid. In conclusion, we found that 1/7 of opioid users continued use longer than 3 months. Future outcome research should identify the clinically most important dose requirements for long-term opioid use criteria.

Antipsychotic use in pregnancy and risk of attention/deficit-hyperactivity disorder and autism spectrum disorder: a Nordic cohort study.

BACKGROUND: Antipsychotics are increasingly used among women of childbearing age and during pregnancy. OBJECTIVE: To determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders. Design Population-based cohort study, including a sibling analysis. Setting Nationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016). Participants 4 324 086 children were eligible for inclusion to the study cohort. Intervention Antipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use. Main outcome measures Non-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors. FINDINGS: Among 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD. DISCUSSION: Our findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics. CLINICAL IMPLICATIONS: Results regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.

Possible opioid-saving effect of cannabis-based medicine using individual-based data from the Norwegian Prescription Database.

Some ecological studies have shown that areas with higher use of cannabis may have lower opioid use and fewer opioid-related problems. Newer studies are questioning this finding. Few individually based studies have been performed. Using data from the Norwegian Prescription Database, this study investigated the individual level effect of prescribed cannabis extract (Sativex®) in prescription opioid users on their opioid use in the following year. Looking at all those filling a prescription for Sativex®, opioid use was only marginally lowered in the follow-up period. Some Sativex® users, however, filled more prescriptions for Sativex® and were able to reduce their opioid use substantially. Further studies are needed to elucidate more details on these patients, so as to know who can benefit from such cannabis-based extracts in reducing their opioid use.

Sex differences in psychotropic and analgesic drug use before and after initiating treatment with acetylcholinesterase inhibitors.

BACKGROUND/AIMS: The aim was to explore the impact of sex on prevalence, patterns and trends in the prescription of psychotropics and analgesics in users of acetylcholinesterase inhibitors (AChEIs), before and after AChEI initiation, compared to the general population. METHODS: A prospective study applying data from the Norwegian Prescription Database (NorPD) in the period 2004-2016. Prescription of antidepressants, antipsychotics, analgesics including opioids, benzodiazepines and z-hypnotics in persistent AChEI users was studied in a follow-up period from four years before to two years after AChEI initiation in men and women of four age groups: 37-64, 65-72, 73-80 and 81-88 years. RESULTS: Use of antidepressants, antipsychotics and weaker analgesics increased in both sexes during the follow-up period in 11.764 persistent AChEI users. Women with pre-dementia and dementia stages of AD showed a prescription pattern with more use of psychotropics and opioids than men, except for antipsychotics. CONCLUSION: Female sex showed to have a significant influence on the prescriptions of psychotropics and analgesics in AD patients in a pre-dementia and dementia stage. The exception is for antipsychotics, that men used more than women. The prescription pattern showed a higher extent of polypharmacy of psychotropics and/or opioids in women than in men. The total prescription pattern of analgesics could indicate an undertreatment of pain in pre-dementia and dementia stages, most pronounced in men.

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.