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.

Large variations in all-cause and overdose mortality among >13,000 patients in and out of opioid maintenance treatment in different settings: a comparative registry linkage study.

Background: Opioid maintenance treatment (OMT) has the potential to reduce mortality rates substantially. We aimed to compare all-cause and overdose mortality among OMT patients while in or out of OMT in two different countries with different approaches to OMT. Methods: Two nation-wide, registry-based cohorts were linked by using similar analytical strategies. These included 3,637 male and 1,580 female patients enrolled in OMT in Czechia (years 2000-2019), and 6,387 male and 2,078 female patients enrolled in OMT in Denmark (years 2007-2018). The direct standardization method using the European (EU-27 plus EFTA 2011-2030) Standard was employed to calculate age-standardized rate to weight for age. All-cause and overdose crude mortality rates (CMR) as number of deaths per 1,000 person years (PY) in and out of OMT were calculated for all patients. CMRs were stratified by sex and OMT medication modality (methadone, buprenorphine, and buprenorphine with naloxone). Results: Age-standardized rate for OMT patients in Czechia and Denmark was 9.7/1,000 PY and 29.8/1,000 PY, respectively. In Czechia, the all-cause CMR was 4.3/1,000 PY in treatment and 10.8/1,000 PY out of treatment. The overdose CMR was 0.5/1,000 PY in treatment and 1.2/1,000 PY out of treatment. In Denmark, the all-cause CMR was 26.6/1,000 PY in treatment and 28.2/1,000 PY out of treatment and the overdose CMR was 7.3/1,000 PY in treatment and 7.0/1,000 PY out of treatment. Conclusion: Country-specific differences in mortality while in and out of OMT in Czechia and Denmark may be partly explained by different patient characteristics and treatment systems in the two countries. The findings contribute to the public health debate about OMT management and may be of interest to practitioners, policy and decision makers when balancing the safety and accessibility of OMT.

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.

Can academic detailing reduce opioid prescriptions in chronic non-cancer pain?

BACKGROUND: One measure to support optimal opioid prescription is academic detailing (AD) with one-to-one visits by trained professionals (academic detailers) to general practitioners (GPs). OBJECTIVE: To investigate the usefulness of AD visits on GPs' opioid prescribing patterns in Norway, and academic detailers' experiences with AD visits to GPs on opioid prescription. METHODS: Design: A quantitative registry study on opioid prescriptions and a qualitative focus group interview study with academic detailers. PARTICIPANTS: For the registry study, municipalities where more than 75% of the GPs had received an AD visit were considered intervention municipalities, whereas in the non-intervention municipalities no GPs had received AD-visits. In the focus groups, academic detailers who had conducted three or more AD-visits were invited to participate. INTERVENTION: A campaign on opioid prescription with AD visits using a brochure with key messages based on the national guideline for treatment of chronic non-cancer pain and updated evidence on the potential benefits and risks of prescribing opioids. The AD visits in the campaign were planned for 20-25 min in a one-to-one setting in the GP's office. MAIN MEASURES: The Norwegian Prescription Database (NorPD) was utilized for registry data. Data on amount of drugs dispensed are recoded as Defined Daily Doses (DDDs). RESULTS: Compared to non-intervention, the intervention resulted in a decrease in the number of prevalent and incident users of opioids and incident users of reimbursed opioids for chronic non-cancer pain in municipalities in Central Norway. The results from the focus group interviews were categorized into the themes: "To get in position", "Adjusting messages", "What did the GPs struggle with, in relation to opioid prescription?" and "Did we reach the right recipients with the visits?". CONCLUSIONS: In Central Norway, the intervention resulted in a desired effect on number of opioid users. According to the academic detailers, the GPs' length of working experience and familiarity with the topic gave different presumptions for making use of the information presented in the AD-visits.

Parental drinking, mental health and education, and extent of offspring's healthcare utilisation for anxiety/depression: A HUNT survey and registry study.

AIMS: Certain risk constellations of parental drinking, mental health and years of education are prospectively associated with offspring's risk for a diagnosis of anxiety/depression, but it remains unknown how they may relate to other aspects of offspring's mental health. We examined whether such risk constellations were also prospectively associated with the extent of offspring's utilisation of healthcare services for anxiety/depression. METHODS: The sample included 8773 adolescent offspring of 6696 two-parent families who participated in the Nord-Trøndelag Health Study in Norway. The exposures consisted of five parental risk constellations characterised by drinking frequencies and quantities, years of education and mental health previously derived based on the parental self-reports using latent profile analysis. The outcomes were the number of years in contact, and the total number of consultations/visits, with healthcare services for anxiety/depression in adolescents and young adults as recorded in healthcare registries in the period 2008-2014. Associations were examined using zero-inflated negative binomial regression models, accounting for demographics and offspring's early mental health. RESULTS: Parental risk constellations were not significantly associated with the extent of offspring's healthcare utilisation for anxiety/depression during the seven-year study period, neither in respect of number of years nor in number of contacts. CONCLUSIONS: Offspring of four risky constellations were no more likely to use healthcare services for longer time periods or have more consultations/visits than offspring of the lowest-risk constellation. Parental risk constellations appear more informative for understanding disorder aetiology than for understanding management and treatment of anxiety and depression during adolescence and early adulthood.

Killing pain?: a population-based registry study of the use of prescription analgesics, anxiolytics, and hypnotics among all children, adolescents and young adults in Norway from 2004 to 2019.

The ongoing opioid epidemic has been a global concern for years, increasingly due to its heavy toll on young people's lives and prospects. Few studies have investigated trends in use of the wider range of drugs prescribed to alleviate pain, psychological distress and insomnia in children, adolescents and young adults. Our aim was to study dispensation as a proxy for use of prescription analgesics, anxiolytics and hypnotics across age groups (0-29 years) and sex over the last 15 years in a large, representative general population. The study used data from a nationwide prescription database, which included information on all drugs dispensed from any pharmacy in Norway from 2004 through 2019. Age-specific trends revealed that the prevalence of use among children and adolescents up to age 14 was consistently low, with the exception of a substantial increase in use of melatonin from age 5. From age 15-29, adolescents and young adults used more prescription drugs with increasing age at all time points, especially analgesics and drugs with higher potential for misuse. Time trends also revealed that children from age 5 were increasingly dispensed melatonin over time, while adolescents from age 15 were increasingly dispensed analgesics, including opioids, gabapentinoids and paracetamol. In contrast, use of benzodiazepines and z-hypnotics slightly declined in young adults over time. Although trends were similar for both sexes, females used more prescription drugs than their male peers overall. The upsurge in use of prescription analgesics, anxiolytics and hypnotics among young people is alarming.Trial registration The study is part of the overarching Killing Pain project. The rationale behind the Killing Pain research was pre-registered through ClinicalTrials.gov on April 7, 2020. Registration number NCT04336605; https://clinicaltrials.gov/ct2/show/record/NCT04336605 .

Utilization of antidepressants, anxiolytics, and hypnotics during the COVID-19 pandemic in Scandinavia.

OBJECTIVE: To study patterns of antidepressant, anxiolytic, and hypnotic drug utilization in Denmark, Norway, and Sweden during the first year of the COVID-19 pandemic. METHODS: The monthly observed number of prescription fills of antidepressants, benzodiazepines and benzodiazepine-related hypnotics (BZ), and other anxiolytics and hypnotics (OAH) per population in 2020 were compared with predicted numbers based on analysis of covariance of prescription fills during 2015-2019. RESULTS: In March 2020, there was an increased number of prescription fills for antidepressants, anxiolytics, and hypnotics in youths and adults aged 20-59 years in Denmark, Norway, and Sweden. Antidepressant prescription fills increased between 13.5 % and 31.3 % at the end of 2020 in all age groups in Denmark and 17.4 % in youths in Norway. BZ drug prescription fills increased by 20.8 % at the end of 2020 in the 20-59 year age group in Denmark and decreased by 16.7 % in youths in Sweden. A general increase of prescription fills of OAH at the end of 2020 was observed in all countries (range 24.0-80.0 % in Denmark, 11.5-30.8 % in Norway, and 9.1-12.1 % in Sweden). Increases of prescription fills of OAH occurred earlier in Denmark. LIMITATIONS: Aggregated data with lack of information on indications. CONCLUSIONS: Peaks of utilization of antidepressants, anxiolytics, and hypnotics observed in March 2020 may reflect medication stock piling. Increased antidepressant drug utilization in Denmark and in Norwegian youths together with the general increase in OAH utilization in the Scandinavian countries in late 2020 may indicate an increase of symptoms of depression and anxiety, as well as disturbed sleep.

Morbidity through 3 Years of Age in Children of Women Using Methamphetamine during Pregnancy: A National Registry Study.

BACKGROUND: There is a lack of studies on methamphetamine (MA) exposure and morbidity in children beyond the perinatal period. OBJECTIVES: We compared morbidity in children (0-3 years) with prenatal MA exposure to opioid-exposed and to non-exposed children. METHODS: We used data from a Czech nationwide, registry-based cohort study (2000-2014). Children, who reached 3 years of age, of mothers hospitalized with (i) MA use disorder during pregnancy (MA; n = 194), (ii) opioid use disorder during pregnancy (opioids; n = 166), and (iii) general population (GP; n = 1,294,349) with no recorded history of substance use disorder (SUD). Information on inpatient contacts, length of stay, and diagnoses (International Statistical Classification of Diseases and Related Health Problems 10th Revision [ICD-10]) were assessed. Crude and adjusted odds ratios (aOR), 95% confidence interval (CI) for the risk of hospitalization, and for getting diagnosis from the ICD-10 diagnosis chapters were calculated using binary logistic regression. A stratified analysis on hospitalizations with SUD of mothers was performed. RESULTS: No significant differences were found in the measures of hospitalization between the MA and opioid groups. Children prenatally exposed to MA and opioids had higher numbers of hospitalizations and diagnoses and longer stays in hospital than children in the GP. Increased risks of certain infectious and parasitic diseases were found in both MA (aOR = 1.6; CI: 1.1-2.3) and opioid (aOR = 1.9; 1.3-2.8) groups as compared to the GP group. The most pronounced difference in stratified analysis on maternal hospitalizations related to SUD after birth was observed for injury, poisoning, and certain other consequences of external causes in the strata of the MA group who had hospitalized mothers (aOR 6.3, 1.6-24.6) compared to the strata without maternal hospitalizations (aOR 1.4, 0.9-2.3). CONCLUSION: This study suggests that children born to mothers using MA during pregnancy have similar morbidity during the first 3 years of life but higher than the GP. The excess of risk was primarily due to infections and injuries in the MA group.

Association of Prenatal Exposure to Benzodiazepines and Z-Hypnotics With Risk of Attention-Deficit/Hyperactivity Disorder in Childhood.

Importance: Evidence is limited regarding the safety of prenatal benzodiazepine and z-hypnotic exposure and its association with long-term neurodevelopment in childhood. Objective: To quantify the associations of the timing and number of intervals of prenatal exposure to benzodiazepines and/or z-hypnotics with the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood. Design, Setting, and Participants: This cohort study used data from the 1999 to 2008 population-based Norwegian Mother, Father and Child Cohort Study, which are linked to the Medical Birth Registry of Norway, Norwegian Patient Registry, and Norwegian Prescription Database. Two populations of participants were created: a full sample and a mental health sample. The full sample included mothers and their live-born singletons, whereas the mental health sample was restricted to offspring of mothers who reported anxiety, depression, or sleeping problems during pregnancy or 6 months before pregnancy. Data were analyzed from September 2021 to February 2022. Exposures: Maternal self-report of benzodiazepine and/or z-hypnotic use during pregnancy was grouped into early pregnancy exposure and middle and/or late pregnancy exposure for analysis of the association with timing of exposure, and number of 4-week intervals of exposure was classified (single [1] vs multiple [≥2]) for analysis of the association with number of exposed intervals. Main Outcome and Measures: The outcome was ADHD, defined as time to ADHD diagnosis or filled prescription for ADHD medication. To control for confounding, inverse probability of treatment-weighted Cox proportional hazards regression models were used. Hazard ratios and 95% CIs were estimated. The weights were derived from propensity score modeling of the probability of benzodiazepine and/or z-hypnotic exposure as a function of potential confounders between the exposure and the outcome, including maternal symptoms of depression and anxiety. Results: The full sample comprised 82 201 pregnancies, and the mental health sample included 19 585 pregnancies. In total, 681 offspring (0.8%) in the full sample and 468 offspring (2.4%) in the mental health sample were prenatally exposed to benzodiazepines and/or z-hypnotics. After weighting, exposure in early (hazard ratio, 0.74; 95% CI, 0.39-1.94) and middle and/or late (hazard ratio, 0.76; 95% CI, 0.35-1.61) pregnancy was not associated with increased risk of childhood ADHD. There was no evidence of substantial association between the number of exposed intervals during pregnancy and childhood ADHD. Conclusions and Relevance: Results of this study suggest that there may be no increased risk of childhood ADHD associated with prenatal exposure to benzodiazepines and/or z-hypnotics, regardless of timing of exposure and number of exposed intervals. However, these findings should be interpreted with caution due to low study power.

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.

Individuals Dying of Overdoses Related to Pharmaceutical Opioids Differ from Individuals Dying of Overdoses Related to Other Substances: A Population-Based Register Study.

BACKGROUND: Pharmaceutical opioid (PO) overdose deaths have increased in many Western countries. There are indications that those dying from a PO overdose differ from those dying from other types of overdoses. These differences might pose a challenge as the majority of current preventive measures are tailored toward those with the characteristics of "conventional" overdose deaths. OBJECTIVE: We investigated differences in the characteristics of persons who died from PO overdoses compared to all other overdoses. MATERIAL AND METHODS: Using the Norwegian Cause of Death Registry, we retrieved information on overdoses classified according to ICD-10 and identified PO overdoses (T40.2; T40.4) and all other overdoses (T40.X; T43.6) in 2010-2019. By linking data from nationwide registers, we analyzed data on opioid dispensations and the history of mental and behavioral disorders. 1,224 persons were registered with PO overdoses and 1,432 persons with other overdoses. RESULTS: Persons in the PO overdose group were older and were more frequently women (35.0% vs. 20.5%) than persons with other overdoses. They had a higher prevalence of chronic pain (35.8% vs. 13.2%), history of cancer (8.1% vs. 1.8%), filled prescriptions of analgetic opioids more frequently the month before death (38.8% vs. 12.0%), and used threefold higher doses of prescribed opioids compared to individuals in all other overdose group (66 vs. 26 oral morphine equivalents/day). In the PO overdose group, oxycodone and fentanyl were more frequently dispensed, while codeine was more frequently dispensed in the other overdose groups. A lower proportion of those in the PO overdose group had recorded diagnoses of substance use disorders, schizophrenia, and hyperkinetic disorder compared to the other overdose groups. CONCLUSION: Persons dying from overdoses on POs often differ from the population targeted by existing prevention strategies, as they are more frequently older women with chronic pain and using high doses of prescription opioids.

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.

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.

Parental risk constellations and future alcohol use disorder (AUD) in offspring: A combined HUNT survey and health registries study.

OBJECTIVE: We examined the risk of developing a future alcohol use disorder (AUD) among offspring of families with different constellations of parental risk factors. METHOD: We analyzed a sample of 8,774 offspring (50.2% male) from 6,696 two-parent families who participated in the Nord-Trøndelag Health Study in Norway when offspring were 13-19 years old in 1995-1997 or 2006-2008. Based on population registry information and parental Nord-Trøndelag Health Study self-reports, families were classified via Latent Profile Analysis into fiver risk constellations reflecting parents' education, drinking quantities and frequencies, and mental health. Information about AUD-related diagnoses, treatments, and prescriptions for all offspring in the period between 2008 and 2016 was obtained from 3 national health registries and pooled to reflect any AUD. The likelihood of AUD in offspring was examined with a set of nested logistic regression models. RESULTS: Registry records yielded 186 AUD cases (2.1%). Compared with the lowest-risk constellation, offspring from two constellations were more likely to present with AUD in unadjusted analyses. After adjusting for all covariates, including offspring's alcohol consumption and witnessing parental intoxication during adolescence, AUD risk remained elevated and statistically significant (adjusted odds ratio = 2.34, 95% confidence interval = 1.14, 4.85) for offspring from the constellation characterized by at least weekly binge drinking, low education, and poor mental health in both parents. CONCLUSION: Weekly binge drinking by both parents was associated with future AUD risk among community offspring in Norway when clustered with additional parental risks such as poor mental health and low educational attainment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Association of Timing and Duration of Prenatal Analgesic Opioid Exposure With Attention-Deficit/Hyperactivity Disorder in Children.

Importance: Prior studies have reported that the use of illicit opioids during pregnancy is associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring; however, evidence regarding the association of analgesic opioids is limited. Objective: To examine the association of timing and duration of prenatal analgesic opioid exposure with ADHD in children. Design, Setting, and Participants: This cohort study uses data from the Norwegian Mother, Father and Child Cohort study (1999-2008), a nationwide birth cohort study linked to national health registries, with a mean (SD) follow-up of 10.8 (2.2) years. A total of 73 784 live-born singleton children born to 62 013 mothers who reported a pain-related condition before and/or during pregnancy were included, with 2 comparator groups: (1) mothers who did not use any opioids and (2) mothers who used opioids before pregnancy only. Data were analyzed from June to December 2020. Exposures: Maternal self-report of analgesic opioid use during pregnancy, by timing (early and middle and/or late) and duration (≥5 weeks vs ≤4 weeks). Main Outcomes and Measures: Diagnosis of ADHD or filled prescription for ADHD medication in children and symptoms of ADHD at child age 5 years, measured by Conners' Parent Rating Scale-Revised. Inverse probability of treatment weights were used to control for measured confounding. Cox regression was used to estimate hazard ratios (HRs) and 95% CIs. Results: The analyses of ADHD diagnosis and ADHD symptoms included 73 480 children (35 996 [49.0%] girls; mean [SD] maternal age, 30.0 [4.6] years) and 31 270 children (15 377 [49.2%] girls; mean [SD] maternal age, 30.5 [4.4] years), respectively. Overall, 1726 children in the ADHD diagnosis sample (2.3%) and 667 children in the ADHD symptom sample (2.1%) were exposed to an analgesic opioid at least once during gestation. No associations between timing of prenatal analgesic opioid exposure and ADHD diagnosis or symptoms was found. Exposure for 5 or more weeks was associated with an increased risk of ADHD diagnosis (HR, 1.60, 95% CI, 1.04-2.47) compared with exposure for 4 weeks or less; however, there was no such association for the risk of ADHD symptoms. Conclusions and Relevance: In this cohort study, a slightly elevated risk of ADHD diagnosis after prenatal analgesic opioid exposure for 5 or more weeks was found compared with exposure for 4 weeks or less. This result may be driven by longer duration of use; however, the role of residual or unmeasured confounding cannot be excluded. This finding needs to be replicated in other studies.

Filled prescriptions for opioids among children and adolescents - A nationwide study from 2010 to 2018.

BACKGROUND: Prescribing opioids for children and adolescents should be reserved for advanced life-limiting diseases and moderate-to-severe acute pain. Pediatric codeine use is discouraged by several authorities, but the effects of these recommendations are not fully known. We investigated opioid utilization trends among 0-18-year-olds and characterized those who filled ≥1 opioid prescriptions, with emphasis on those who did so >3 times within a year. METHODS: The prevalence of filled opioid prescriptions among 0-18-year-old Norwegians in 2010-2018 (N = 77,942) was measured from nationwide healthcare registries. Characteristics, healthcare utilization, and other drug use of those who newly filled 1, 2-3, or >3 opioid prescriptions in 2011-2014 were compared to 2015-2018, excluding persons with cancer. RESULTS: From 2010 to 2018, the prevalence of opioid use decreased from 9.0 to 7.0 per 1000 persons. The largest decrease was among children <12 years, from 4.1 to 0.4 per 1000 persons, mainly due to decreasing codeine use. The proportion of those who filled >3 opioid prescriptions was 2.1% in 2011-2014 and 3.1% in 2015-2018. Those with >3 dispensations had a median of 4 contacts/year with secondary healthcare (interquartile range 2-7); the most frequent diagnoses indicated post-surgery follow-up. Most commonly dispensed other drugs were non-steroidal anti-inflammatory drugs. CONCLUSIONS: Opioid dispensations for the young have declined in recent years. Multiple opioid dispensations were rare and associated with frequent healthcare utilization. Reducing codeine is in line with recommendations, but the effects of decreased opioid use on the quality of pain management remain unknown.

Opioid maintenance treatment in the Czech Republic, Norway and Denmark: a study protocol of a comparative registry linkage study.

INTRODUCTION: Opioid maintenance treatment (OMT) varies across settings and between countries. We plan to use data from several nationwide health and population registers to further improve the knowledge base established from earlier studies. Our aim is to study OMT adherence trajectories and to identify factors associated with improved outcomes for OMT patients across the Czech Republic, Norway and Denmark, in order to further improve OMT and our understanding of the key elements of treatment success. METHODS AND ANALYSIS: The registry-based cohort approach across the three countries allows us to link data from a range of registers on the individual level, by using personal identifiers in nationwide cohorts of OMT and non-OMT patients and the general non-using populations. A total of ~21 500 OMT patients over the last two decades in all three countries will be included in the study. The following outcome variables (based on the International Classification of Diseases, 10th Revision codes) will be obtained from relevant registers: treatment adherence to OMT, comorbidity (somatic and mental health), and all-cause and cause-specific mortality. Outcomes of the country-specific analyses will be pooled. ETHICS AND DISSEMINATION: The national OMT cohorts have been approved by the ethics committees in the respective countries. Data will be stored according to national and local guidelines and treated confidentially, and all data will be analysed separately for each country and compared across countries. Findings will be disseminated in peer-reviewed scientific journals, national and international conferences, and in briefings to inform clinical decision-making.

Prenatal exposure to non-steroidal anti-inflammatory drugs and risk of attention-deficit/hyperactivity disorder: A follow-up study in the Norwegian mother, father and child cohort.

PURPOSE: To estimate the association between Attention-Deficit/Hyperactivity Disorder (ADHD) in children in preschool and primary school, and prenatal exposure to non-steroidal anti-inflammatory drugs (NSAIDs) by timing and duration. METHODS: This study was based on the Norwegian Mother, Father and Child Cohort Study linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry (NPR) and the Norwegian Prescription Database (NorPD). NSAID exposure was identified by maternal self-report in pregnancy. Child diagnosis of ADHD was obtained from NPR and NorPD. Symptoms of ADHD at age 5 years were measured using Conners' Parent Rating Scale-Revised, where higher scores correspond to more symptoms. To account for time-varying exposure and confounders, marginal structural models were fitted to estimate hazard ratios and mean difference in z-scores. RESULTS: The analyses on ADHD diagnosis and ADHD symptoms included 56 340 and 34 961 children respectively. Children exposed to NSAIDs prenatally had no increased risk of ADHD diagnosis (first trimester: HR 1.12, 95% CI 0.86;1.45, second trimester: HR 0.98, 95% CI 0.69;1.38, third trimester: HR 0.68, 95% CI 0.31; 1.46) or ADHD symptoms (first trimester: standardized mean difference 0.03, 95% CI -0.03;0.09, second trimester: standardized mean difference 0.03, 95% CI -0.04;0.11, third trimester: standardized mean difference 0.11, 95% CI -0.03; 0.25). There was no duration-response relationship for either outcome. CONCLUSION: Though non-differential misclassification of the exposure may have attenuated results, these findings are reassuring and suggest no substantially increased risk of ADHD diagnosis or symptoms in children prenatally exposed to NSAIDs, regardless of timing or duration.