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Aleksi Hamina,1,* Ingvild Odsbu,2,* Petter Christian Borchgrevink,3,4 Li-Chia Chen,5 Thomas Clausen,1 Ketil Arne Espnes,6,7 Kine Gjesdal,8,9 Marte Handal,1,10 Sirpa Hartikainen,11 Vidar Hjellvik,10 Marianne Therese Smogeli Holter,12 Trond Høibø,13 Geana Paula Kurita,14– 16 Harald Christian Langaas,7 Torgeir Gilje Lid,8,9 Torunn Hatlen Nøst,3,17 Per Sjøgren,15 Svetlana Skurtveit1,2 On behalf of the POINT study group1Norwegian Centre for Addiction Research (SERAF), Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 2Department of Mental Disorders, Division of Mental and Physical Health, the Norwegian Institute of Public Health, Oslo, Norway; 3Department of Pain and Complex Disorders, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; 4Institute of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; 5Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK; 6Department of Clinical Pharmacology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; 7Regional Medicines Information and Pharmacovigilance Centre (RELIS), Department of Clinical Pharmacology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; 8Faculty of Health Sciences, University of Stavanger, Stavanger, Norway; 9Center for Alcohol and Drug Research (KORFOR), Stavanger University Hospital, Stavanger, Norway; 10Department of Chronic Diseases, Division of Mental and Physical Health, the Norwegian Institute of Public Health, Oslo, Norway; 11School of Pharmacy, University of Eastern Finland, Kuopio, Finland; 12Department of Psychology, Faculty of Social Sciences, University of Oslo, Oslo, Norway; 13Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway; 14Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 15Department of Oncology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark; 16Department of Anaesthesiology, Pain and Respiratory Support, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark; 17Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway*These authors contributed equally to this workCorrespondence: Ingvild Odsbu, Department of Mental Disorders, Division of Mental and Physical Health, Norwegian Institute of Public Health, PO Box 222 Skøyen, Oslo, 0213, Norway, Tel +47 41454379, Email ingvild.odsbu@fhi.noAim: 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.Keywords: opioids, chronic pain, healthcare registers

Background: The use of medication for Attention-Deficit/Hyperactivity Disorder (ADHD) increased globally throughout the early 2000s. This study examine trends in prevalences and incidences of medication use in Norway from 2006 to 2022., Methods: Data from the Norwegian Prescription Database were used to present one-year-prevalence and incidence rates of ADHD medication (ATC-group N06BA and C02AC02) for the overall population (ages 6-64) and within sex and age subgroups of children (ages 6-17) and adults (ages 18-64). Incident use was defined as the dispensing of medication, with no recorded use in the previous two calendar years., Results: The overall prevalence of ADHD medication use in 6- to 64-year-olds increased from 5.2 to 19.4 per 1000 in the period, most pronounced from 2020 and onwards. While males experienced a nearly threefold increase in use (from 7.3 to 20.6 per 1000), the use among females increased almost sixfold during the study period (from 3.0 to 18.1 per 1000). Consequently, the male-to-female prevalence-ratio decreased from 2.4 to 1. Children exhibited a higher prevalence of use compared to adults throughout the period, although the largest relative increase was observed in adults, particularly in female adults. In children the male-to-female ratio decreased from 3.2 to 2.0, primarily due to an increasing use in 13-17-year-old females. Among adults, prevalences were similar across most age groups, with the highest rates observed among those aged 18-24, where female use exceeded male use by the end of the period. The male-to-female prevalence-ratio in adults decreased from 1.6 to 0.9 during the period. Parallel to prevalent use, overall incident use increased from 1.4 to 5.0 per 1000 during the period, with the most pronounced increase occurring from 2020 and onwards. From this point, incident use among females aged 13-17, 18-24, and 25-34, exceeded that of males. The male-to-female incidence-ratio decreased from 1.8 to 0.9. The overall incidence to prevalence ratio remained similar throughout the period, being 0.27 in 2006 and 0.25 in 2022., Conclusion: A sustained increase in the prevalence of ADHD medication use was observed, with the most pronounced rise occurring among females and adults from 2020 and onwards. By 2022, the overall gender disparity in ADHD medication use had diminished, which should be considered in the context of a steep increase in incident use among adolescent and young adult females starting from 2020., (© 2024. The Author(s).)

Cutaneous adverse reactions to mRNA COVID-19 vaccines in patients with preexisting dermatologic disease include bullous eruptions, pityriasis rubra pilaris, dermatomyositis, and granuloma annulare. Erythroderma is a rare but severe adverse reaction not previously seen. This case report describes the development of erythroderma in a 73-year-old male with a history of atopic dermatitis, with widespread erythema and scaling covering 95% of his body surface area, which developed sequentially after receiving each dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccination. The patient's condition improved significantly with appropriate dermatologic treatment, including systemic and topical corticosteroids and dupilumab. Thus, it is imperative to recognize erythroderma as a potential side effect of the Pfizer-BioNTech COVID-19 vaccine, particularly in patients with preexisting dermatologic conditions. Early diagnosis and treatment are vital for managing this potentially life-threatening reaction and preventing severe complications., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Handal et al.)

Transverse sinus stenosis (TSS) is an abnormality in the cerebral venous system in which the narrowing of the transverse sinus of the brain leads to obstructed cerebral venous outflow. It is an infrequent, incidental radiological finding. However, it is not uncommon among patients with chronic headaches of unclear cause, particularly those that remain unexplained after initial evaluation or those that are refractory to medical treatment. Its diagnosis frequently eludes the initial workup, and a high degree of suspicion should be maintained since its identification can lead to potentially curative treatment. This report describes the case of a 36-year-old female with a history of chronic headache who was found to have TSS. This paper discusses its etiology, pathophysiology, clinical presentation, radiological findings, and management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Handal et al.)

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.

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.

Standard pulse oximeters estimate arterial blood saturation (SaO 2 ) non-invasively by emitting and detecting light of a specific wavelength through a cutaneous vascular bed, such as a digit or the ear lobe. The quantity measured at these peripheral sites is designated as oxygen saturation (SpO 2 ). Most reliable pulse oximeters are calibrated from measurements of healthy volunteers using some form of oxygen desaturation method. As the degree of inducible hypoxemia is limited, the calibration below achievable desaturation levels is usually extrapolated, leading to potential measurement error at low SaO 2 values, especially in highly pigmented skin. Such skin color-related errors (SCRE) are the topic of this scoping review. Specifically, this study aimed to identify the combined impact of skin color and reduced SaO 2 on the non-invasive assessment of SpO 2 and report the consequences of potential inaccuracies. Three databases were searched (Cumulated Index to Nursing and Allied Health Literature (CINAHL), PubMed, and Web of Science) for peer-reviewed prospective and retrospective studies published in English between 2000 and 2022 involving human patients with hypoxemia that included a measure of skin color (Fitzpatrick scale or race/ethnicity). Ten studies met the criteria and were included in the final review. Eight of these studies reported statistically significant higher pulse oximeter readings in darker-skinned patients with hypoxia compared to their arterial blood gas measurements. Occult hypoxia was more prevalent in Black and Hispanic patients than in White patients. Minority patients overall (Black, Asian, and American Indian) were more likely to have a SaO 2 < 88% that was not detected by pulse oximetry (occult hypoxemia) during hospitalization. With greater levels of hypoxemia, the differences between SpO 2 and SaO 2 were greater. If SaO 2 was < 90%, then SpO 2 was overestimated in all ethnicities but worse in minorities. In conclusion, the bias found in pulse oximeter readings in the skin of color broadly impacts patients with hypoxemia. The failure of SpO 2 measuring devices to detect occult hypoxemia can delay the delivery of life-saving treatment to critically ill patients requiring respiratory rehabilitation and supplemental oxygen therapy. This may lead to adverse health outcomes, increased in-hospital mortality, and complications such as organ dysfunction. An improvement in pulse oximeter detection mechanisms that would include all skin pigmentations is therefore much desired to optimize individual healthcare status and minimize disparities in treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Aoki et al.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gabrhelík, Hesse, Nechanská, Handal, Mravčík, Tjagvad, Thylstrup, Seid, Bukten, Clausen and Skurtveit.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer NT declared a shared affiliation with the author(s) MH and SS to the handling editor at the time of review., (Copyright © 2023 Odsbu, Handal, Hjellvik, Hernandez-Diaz, Kieler, Nørgaard, Skurtveit, Esen and Mahic.)

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., (© 2023. The Author(s).)

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.

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.

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Autism spectrum disorder (ASD) has a high rate of comorbidity. While many children with ASD are exposed to psychotropic medicines, their efficacy and safety in these patients are unclear. There is a need for more detailed knowledge on which medicines are most commonly used and for which disorders. We aimed to investigate (a) prevalence and incidence rate of ASD among Norwegian children, and further, among newly diagnosed ASD children in 2014, study the (b) co-occurrence of neuropsychiatric disorders, (c) use of psychotropic drugs, and (d) the relationship between co-occurring diagnoses and use of psychotropic drugs. Method: Nationwide registry-based study of children 2-17 years old in Norway. Results: The ASD prevalence was 0.76% and the incidence rate was 0.12% in 2014. Of the children who received an initial ASD diagnosis in 2014 ( n = 1,234), 64.8% had one or more co-occurring neuropsychiatric diagnosis. Psychotropic medication use was moderate (~20% used stimulants or hypnotics) in general, and low in children without comorbidity (nearly only hypnotics). There was a good accordance between co-occurring diagnoses and indication for the prescribed medications. Conclusions: Children with newly diagnosed ASD mainly received psychotropic drugs to treat co-occurring neuropsychiatric conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Kiselev, Handal, Hjellvik, Reichborn-Kjennerud, Stoltenberg, Suren, Havdahl and Skurtveit.)

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.

Background: WHO guidelines emphasise the need for descriptions of clinical practice and observational studies on risk and benefits of pharmacotherapies in pregnancy. The aims of the present study were to: (1) Describe opioid maintenance treatment (OMT) in the Scandinavian countries in general, and specifically for pregnant women, (2) Describe a project which utilises a new approach using registry-linkage data to examine associations between prenatal exposure to OMT and child outcomes: a Scandinavian cohort study of pregnant women in OMT during pregnancy (ScopeOMT)., Data: Guidelines describing the treatment of persons with opioid use disorders in general, and specifically for pregnant women. Scandinavian registry-linkage data from ScopeOMT., Results: Registry data show that approximately 800 pregnant women received OMT during pregnancy in the period of the ScopeOMT study. Similarities across the Scandinavian countries include access to free healthcare and treatment; multidisciplinary teams trained to support pregnant women in OMT; buprenorphine as the recommended drug when initiating therapy; and a holistic focus on the patients' lives. An important difference is that Norwegian women who use illegal substances that may harm the foetus may be admitted - voluntarily, or against their will - for parts of, or the remainder of the pregnancy to inpatient treatment at specialised clinics., Conclusion: Many similarities in the treatment provided to opioid-dependent persons in the Scandinavian countries place this area in an excellent position to combine the efforts and carry out observational studies concerning the safety of OMT during pregnancy., Competing Interests: Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Importance: Understanding the safety profile of medications used in pregnancy is crucial for clinical decision-making. Few studies exist on the associations of exposure to benzodiazepines and benzodiazepine-like hypnotic drugs (z-hypnotics) in pregnancy with pregnancy outcomes., Objective: To determine whether exposure to benzodiazepines or z-hypnotics in pregnancy is associated with greater risk of negative immediate pregnancy outcomes compared with nonexposure., Design, Setting, and Participants: This questionnaire-based cohort study used data from the Norwegian Mother, Father and Child cohort study (MoBa), which also includes data from the Medical Birth Registry of Norway. Pregnant women were recruited from all over Norway from 1999 and 2008. The first child was born in October 1999 and the last in July 2009. This analysis included women who completed 3 questionnaires, twice during pregnancy and once 6 months after delivery. Data analyses were conducted from September to November 2019., Exposures: Self-reported exposure to benzodiazepines or z-hypnotics during pregnancy, characterized in terms of any exposure, timing (ie, early, middle, or late), and duration of exposure., Main Outcomes and Measures: The main outcomes were gestational age at delivery, risk of preterm delivery, birth weight, birth weight relative to gestational age and sex, risk of being small for gestational age, head circumference, Apgar score less than 7 at 5 minutes, and risk of neonatal respiratory distress. Continuous outcomes are reported using effect estimates as mean differences, and binary outcomes are reported using risk ratios., Results: The MoBa study included 114 234 mother-child dyads. This analysis of MoBa data includes 82 038 singleton pregnancies among 69 434 unique women. Mean (SD) maternal age was 30.2 (4.5) years, and 37 641 pregnancies (45.9%) were in primiparous women. Exposure to benzodiazepines or z-hypnotics was reported in 679 pregnancies (0.8%). After adjusting for all measured baseline and postbaseline confounders, benzodiazepine or z-hypnotic use during pregnancy was associated with lower birth weight (mean difference, -79.3 [95% CI, -126.7 to -31.9] g), lower gestational age at birth (mean difference, -2.1 [95% CI, -3.3 to -0.9] days), and higher risk of preterm birth (risk ratio, 1.41 [95% CI, 1.03 to 1.94]). We found no significant association of exposure to benzodiazepines or z-hypnotics with the child's birth weight relative to gestational age and sex (z score), or any of the other immediate birth outcomes., Conclusions and Relevance: These findings suggest that the magnitude of the association of exposure to benzodiazepines or z-hypnotics with gestational age is not necessarily clinically significant. The absence of an association of exposure to benzodiazepines or z-hypnotics with z score for birth weight relative to gestational age and sex suggests that association of exposure to benzodiazepines or z-hypnotics with birth weight could be explained by earlier delivery rather than impaired intrauterine growth.

Background: Paternal lifestyle during sperm development can have an impact on foetal development. This study surveys demographic characteristics and lifestyle factors among expectant fathers who reported use of cannabis and cocaine in the six-month period before conception. We also study the associations between mothers' and fathers' use of cannabis and cocaine., Methods: This is a cross-sectional study from the Norwegian Mother and Child Cohort Study (MoBa) using self-reported data on demographic variables and cannabis and cocaine use six months before conception. Associations were assessed using logistic regression and chi-square tests., Results: A strong association was found between use of cannabis and cocaine and lifestyle habits such as alcohol and cigarette use. Alcohol consumption four or more times a week gave an adjusted odds ratio (a OR ) of 9.7 (95% CI 7.2-13.0) for cannabis and an a OR 21.6 (95% CI 11.5-40.3) for cocaine. There was also a strong association between maternal and paternal use of cannabis and cocaine., Conclusion: Use of cannabis and cocaine close to pregnancy seems to be closely linked to other risk factors, and further studies on how paternal drug use affects the foetus are warranted. The strong association between maternal and paternal use of cannabis and cocaine may be used to inform healthcare workers to make good risk assessments., Competing Interests: Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Background: It is generally agreed that prescribing of antipsychotic drugs to older patients should be reduced, but figures for the prescribing of these drugs to older patients living at home in Norway are not available. The study aimed to investigate developments in prescribing of antipsychotic drugs among older patients living at home from 2006 to 2018, and whether there were differences in prescribing rates between the age groups 65-74 years, 75-84 years and 85 years or older., Material and Method: Data were retrieved from the Norwegian Prescription Database. All persons aged 65 years or older who were dispensed at least one antipsychotic drug in 2006, 2010, 2014 and 2018 were included, and gender-specific prevalence for the ten most widely used antipsychotic drugs was calculated., Results: The proportion of patients aged 65 or older who were prescribed antipsychotic drugs in the period decreased for both sexes. For the age group 65-74 years, an increase was found from 2014 to 2018. There was a clear decrease in the prescribing rate for prochlorperazine and levomepromazine, whereas prescriptions for quetiapine increased., Interpretation: Attention should be paid to the increase in prescribing of antipsychotic drugs for the youngest age group of older patients (65-74 years) in the last four years, along with the increase in prescribing of quetiapine for older patients.

There is lack of knowledge about the safety of treatment with methadone and buprenorphine as part of opioid maintenance treatment (OMT) during pregnancy. The purpose of this study was to examine neonatal outcomes concerning the use of OMT during pregnancy. We used nationwide registry linkages from the Czech Republic (2000-2014) and Norway (2004-2013). We compared prenatally OMT-exposed newborns with (a) newborns of women hospitalized with opioid use disorder during pregnancy in the Czech sample and (b) newborns with neonatal abstinence syndrome (NAS) in Norway. We performed multivariate linear and binary logistic regression exploring the associations between OMT and neonatal outcomes (growth parameters, gestational age, fetal death, small for gestational age, Apgar score, and NAS). Regression coefficients ( b ) and odds ratios (ORs) were estimated. The cohorts consisted of 333 Czech, and 235 Norwegian OMT-exposed newborns, and 106 and 294 newborns in the comparison groups, respectively. In both countries, the neonatal growth parameters were similar in the OMT and the comparison groups. In Norway, OMT exposure prolonged gestational age (adjusted b  = 0.96 weeks, 95% confidence interval [CI] =0.39-1.53) while the odds of preterm birth and Apgar score at 5 minutes were lower than in the comparison group (adjusted OR = 0.35, 0.16-0.75 and aOR = 0.21, 0.06-0.78, respectively). Newborns of women in OMT had similar growth parameters as newborns of women with opioid use disorders who were not in OMT during pregnancy. Overall, our findings do not suggest that OMT results in worse neonatal outcomes., Competing Interests: None of the authors has anything to disclose.

Importance: The reproductive safety of benzodiazepine/z-hypnotic exposure on child longer-term developmental risks remains unresolved., Objective: To quantify the association of motor, communication, and attention-deficit/hyperactivity disorder (ADHD) symptoms in preschoolers with gestational benzodiazepine/z-hypnotic exposure by timing and duration and coexposure to opioids or antidepressants., Design, Setting, and Participants: Nationwide, population-based Norwegian Mother and Child Cohort Study, recruiting pregnant women from 1999 to 2008, with child follow-up from ages 6, 18, and 36 months to ages 5, 7, and 8 years. Follow-up of teenagers is ongoing. The study included women with depressive/anxiety (n = 4195), sleeping (n = 5260), or pain-related (n = 26 631) disorders before and/or during pregnancy., Exposures: For the timing analyses, children exposed to benzodiazepines/z-hypnotics in midpregnancy (weeks 17-28) or late pregnancy (week 29 or later) vs those born to nonmedicated women. For the duration and coexposure analyses, benzodiazepine/z-hypnotic treatment for multiple 4-week intervals vs 1 and co-use of benzodiazepine/z-hypnotic with opioids or antidepressants vs sole benzodiazepine/z-hypnotic use., Main Outcomes and Measures: Parent-reported motor and communication skills (Ages and Stages Questionnaires) and ADHD symptoms (Conners' Parent Rating Scale-Revised) at child median age of 5.1 years (interquartile range, 5.0-5.3 years) as standardized mean scores. General linear propensity score-adjusted and marginal structural models were fitted. Analyses were stratified by maternal disorder., Results: Of 41 146 eligible pregnancy-child dyads, 36 086 children (18 330 boys and 17 756 girls) were included, of whom 283 (0.8%) were prenatally exposed to benzodiazepines/z-hypnotics (134 in the depressive/anxiety, 60 in the sleeping, and 89 in the pain-related disorders). There was no increased risk for greater ADHD symptoms or fine motor deficits after intrauterine benzodiazepine/z-hypnotic exposure at different time points. Children born to women with depressive/anxiety disorders who took benzodiazepines/z-hypnotics in late pregnancy had greater gross motor (weighted β, 0.67; 95% CI, 0.21-1.13) and communication (weighted β, 0.35; 95% CI, 0.04-0.65) deficits than unexposed children. There was no evidence for substantial duration or coexposure associations., Conclusions and Relevance: These findings suggest no substantial detrimental risk on child fine motor and ADHD symptoms after prenatal benzodiazepine/z-hypnotic exposure alone or in combination with opioids or antidepressants. Residual confounding by indication and/or a higher drug dose regimen among women with anxiety/depression may explain the moderate association of gross motor and communication deficits with late-pregnancy benzodiazepine/z-hypnotic use.

Background: In heroin-related deaths, it is often of interest to determine the approximate time span between intake of heroin and death, and to decide whether heroin or other opioids have been administered. In some autopsy cases, peripheral blood cannot be sampled due to decomposition, injuries or burns. The aim of the present study was to investigate whether measurements of heroin metabolites in matrices other than peripheral blood can be used to differentiate between rapid and delayed heroin deaths, and if morphine/codeine ratios measured in other matrices can separate heroin from codeine intakes., Methods: In this study, we included 51 forensic autopsy cases where morphine was detected in peripheral blood. Samples were collected from peripheral and cardiac blood, pericardial fluid, psoas and lateral vastus muscles, vitreous humor and urine. The opioid analysis included 6-acetylmorphine (6-AM), morphine, morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G) and codeine. Urine was only used for qualitative detection of 6-AM. 45 heroin-intake cases were divided into rapid deaths (n=24), based on the detection of 6-AM in blood, or delayed deaths (n=21), where 6-AM was detected in at least one other matrix but not in blood. An additional 6 cases were classified as codeine-intake cases, based on a morphine/codeine ratio below unity (<1) in peripheral blood, without detecting 6-AM in any matrix., Results: The median morphine concentrations were significantly higher in the rapid compared with the delayed heroin deaths in all matrices (p=0.004 for vitreous humor and p<0.001 for the other matrices). In the rapid heroin deaths, the M3G/morphine concentration ratios were significantly lower than in the delayed deaths both in peripheral and cardiac blood (p<0.001), as well as in pericardial fluid (p<0.001) and vitreous humor (p=0.006), but not in muscle. The morphine/codeine ratios measured in cardiac blood, pericardial fluid and the two muscle samples resembled the ratios in peripheral blood, although codeine was less often detected in other matrices than peripheral blood., Conclusions: Measurements of heroin-metabolites in cardiac blood, pericardial fluid and vitreous humor provide information comparable to that of peripheral blood regarding rapid and delayed heroin deaths, e.g. M3G/morphine ratios <2 indicate a rapid death while ratios >3 indicate a delayed death. However, considerable overlap in results from rapid and delayed deaths was observed, and measurements in muscle appeared less useful. Furthermore, matrices other than peripheral blood can be used to investigate morphine/codeine ratios, but vitreous humor seems less suited., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In some forensic autopsies blood is not available, and other matrices are sampled for toxicological analysis. The aims of the present study were to examine whether heroin metabolites can be detected in different post-mortem matrices, and investigate whether analyses in other matrices can give useful information about concentrations in peripheral blood. Effects of ethanol on the metabolism and distribution of heroin metabolites were also investigated. We included 45 forensic autopsies where morphine was detected in peripheral blood, concomitantly with 6-acetylmorphine (6-AM) detected in any matrix. Samples were collected from peripheral blood, cardiac blood, pericardial fluid, psoas muscle, lateral vastus muscle, vitreous humor and urine. Opioid analysis included 6-AM, morphine, codeine, and morphine glucuronides. The 6-AM was most often detected in urine (n = 39) and vitreous humor (n = 38). The median morphine concentration ratio relative to peripheral blood was 1.3 (range 0-3.6) for cardiac blood, 1.4 (range 0.07-5.3) for pericardial fluid, 1.2 (range 0-19.2) for psoas muscle, 1.1 (range 0-1.7) for lateral vastus muscle and 0.4 (range 0.2-3.2) for vitreous humor. The number of 6-AM positive cases was significantly higher (P = 0.03) in the ethanol positive group (n = 6; 86%) compared to the ethanol negative group (n = 14; 37%) in peripheral blood. The distribution of heroin metabolites to the different matrices was not significantly different between the ethanol positive and the ethanol negative group. This study shows that toxicological analyses of several matrices could be useful in heroin-related deaths. Urine and vitreous humor are superior for detection of 6-AM, while concentrations of morphine could be assessed from peripheral or cardiac blood, pericardial fluid, psoas muscle and lateral vastus muscle.

Background: Different methods in pharmacoepidemiology can be used to study hypnotic use in children. But neither questionnaire-based data nor prescription records can be considered a "gold standard". This study aimed to investigate the agreement between mother-reported questionnaire-based data and prescription record data for hypnotic drugs in children aged 0-18 months. The agreement was compared to the agreement for a group of antiepileptic drugs., Methods: Prescription record data were collected from the Norwegian prescription database for 47,413 children also surveyed in the Norwegian mother and child cohort between 2005 and 2009. Agreement between in the two data sources was calculated using Cohens Kappa. Multinomial logistic regression was used to calculate the effect of sociodemographic variables on discrepancies in data sources., Results: The agreement between mother-reported and dispensed hypnotics was less than 50% for all hypnotics. Sensitivity of reporting increased with number of filled prescriptions. The agreement of antiepileptic drugs was 92.9% in the same population. Of several sociodemographic factors only paternal educational level and maternal work situation was significantly related to agreement between prescription record and survey data., Conclusion: There was a moderate agreement between reported use and dispensed hypnotic drugs for infants and toddlers. Results indicate that sociodemographic factors play only a minor role in explaining discrepancy.

Background: During pregnancy, many women experience sleep problems and anxiety that require treatment. The long-term safety for the child of maternal benzodiazepine (BZD) and z-hypnotic use during pregnancy remains controversial., Method: We conducted a cohort and a sibling control study using data from the Norwegian Mother and Child Cohort Study. Data on use of BZD and z-hypnotics, internalizing and externalizing outcomes, and covariates were collected from mothers at gestational weeks 17 and 30 and when children were 0.5, 1.5, and 3 years of age. The total sample consisted of 71,996 children (19,297 siblings) at 1.5 years and 55,081 children (13,779 siblings) at 3 years. Short-term use was defined as use in one pregnancy period only. Long-term use was defined as use in two or more pregnancy periods. Linear full cohort random-effect and sibling-matched fixed-effect regression models were used to compare internalizing and externalizing behavior in children prenatally exposed compared to those unexposed in the full cohort of pregnancies accounting for family clusters, as well as within sibling clusters comparing pregnancies with discordant exposures. Propensity score (PS) adjustment included variables on indication for use (sleep problems, symptoms of anxiety and depression) and other potential confounding factors., Results: Long-term prenatal exposure to BZD or z-hypnotics was associated with increased internalizing behavior in crude cohort analyses and at age 1.5 years after PS adjustment in sibling-matched fixed-effect models [β 0.60, 95% confidence interval 0.17-0.95]. Analyses on specific drug groups showed that prenatal exposure to BZD-anxiolytics was associated with increased internalizing problems at both 1.5 years [β 0.25, 0.01-0.49] and 3 years [β 0.26, 0.002-0.52] while exposure to z-hypnotics was not associated with any adverse outcomes after adjustment., Conclusion: The findings suggest a moderate association between BZD-anxiolytic exposure and child internalizing problems that is not likely due to stable familial confounding factors.

Licit and illicit drug use in pregnant women constitutes a long lasting and serious problem worldwide. Information on long-term effects of maternal drug use on the child is limited. Nationwide registers provide a great potential to study short and long-term consequences for children exposed to licit and illicit drugs during pregnancy. We discuss this potential, with a special emphasis on exposure to methamphetamine, heroin and prescription drugs used for opioid maintenance treatment (OMT). We also discuss the advantages of register data and of merging such data from different regions. The Czech and Scandinavian registers are largely comparable and provide great opportunities to conduct innovative research. For instance, using Czech and Scandinavian cohorts we can compare groups with similar characteristics, such as mothers in OMT and mothers addicted to other drugs while also controlling for important confounding factors such as health and socio-economic status., (Copyright© by the National Institute of Public Health, Prague 2016.)

Background: Benzodiazepines are frequently prescribed to patients with drug use disorders. However, it has previously been difficult to distinguish whether this frequent prescribing was due to underlying psychiatric disorders or inappropriate prescribing. In a nationwide cohort study, we investigated the prescribing of benzodiazepines to patients with drug use disorders in connection with treatment admission., Methods: Benzodiazepine prescriptions to patients (N = 33203) aged 18 to 67 years admitting for outpatient treatment for drug use disorders in Denmark, 2000 to 2010, were studied by using linked data from nationwide health registries. Factors associated with increasing amounts of benzodiazepine use within the first year after admission were assessed by multinomial logistic regression. Proportions of very long-term benzodiazepine prescription were calculated., Results: During the first year after admission to treatment, 26.2 % of patients were prescribed benzodiazepines. Of these, 35.5 % were prescribed benzodiazepines at dose levels that might indicate inappropriate use (>365 Defined Daily Dose per year), and 34.6 % were prescribed more than one type of benzodiazepines. Diazepam was the most commonly prescribed type. Among patients with opioid use, 43.2 % were prescribed benzodiazepines which were three times higher than for patients with cannabis (12.2 %) or central stimulating drugs (13.8 %) as their primary drug use. Admitting to treatment for a drug use disorder did not increase the specialized psychiatric treatment coverage of this patient group, disregarding use of prescribed benzodiazepines. 29.5 % were new users of prescribed benzodiazepines, and of these, 27.5 % continued into very long-term use (≥4 years after admission) during the study period., Conclusions: Benzodiazepines were commonly prescribed to patients admitting to treatment for drug use disorders, and included prescription of multiple and non-optimal types, high doses, and very long-term prescriptions. These findings point towards inappropriate prescribing of benzodiazepines in many cases more than treatment for psychiatric disorders.

This is an update of the Norwegian Mother and Child Cohort Study (MoBa) cohort profile which was published in 2006. Pregnant women attending a routine ultrasound examination were initially invited. The first child was born in October 1999 and the last in July 2009. The participation rate was 41%. The cohort includes more than 114 000 children, 95 000 mothers and 75 000 fathers. About 1900 pairs of twins have been born. There are approximately 16 400 women who participate with more than one pregnancy. Blood samples were obtained from both parents during pregnancy and from mothers and children (umbilical cord) after birth. Samples of DNA, RNA, whole blood, plasma and urine are stored in a biobank. During pregnancy, the mother responded to three questionnaires and the father to one. After birth, questionnaires were sent out when the child was 6 months, 18 months and 3 years old. Several sub-projects have selected participants for in-depth clinical assessment and exposure measures. The purpose of this update is to explain and describe new additions to the data collection, including questionnaires at 5, 7, 8 and 13 years as well as linkages to health registries, and to point to some findings and new areas of research. Further information can be found at [www.fhi.no/moba-en]. Researchers interested in collaboration and access to the data can complete an electronic application available on the MoBa website above., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Time-trend studies on psychotropic drugs among children and adolescents are scarce, and most of them are outdated. The purpose of this study was to study prevalences of psychotropic drug use during 2004-2014 among Norwegians aged <18 years, overall and in psychotropic sub-groups., Methods: Data were obtained from the Norwegian Prescription Database, which covers all dispensed prescription drugs in Norway from 2004 and onwards. Psychotropic drugs included: antipsychotics (ATC-group N05A), anxiolytics (N05B), hypnotic/sedatives (N05C), antidepressants (N06A), stimulants (N06BA), and alimemazine (R06AD01). Period (1-year) prevalence of use, overall and in subgroups of psychotropic drugs, was estimated by identifying individuals <18 years who had at least one psychotropic drug dispensed during each year., Results: Psychotropic drug use increased in 0-17 year olds over an 11-year period, in which the main contributing drugs were stimulants (boys overall; 15.0 to 20.8/1000, girls overall; 3.8 to 8.5/1000), hypnotic/sedative drugs in adolescents (boys overall; 4.2 to 10.8/1000, girls overall; 2.6 to 8.8/1000) and to some extent antidepressants among adolescent girls (girls overall from 3.1 to 4.0/1000). Psychotropic drug use was, however, reduced by half in the youngest children, attributed to reduction of alimemazine only (1-year olds: boys; from 36.6 to 10.2/1000, girls; 26.9 to 7.2/1000). A higher level of psychotropic drug use was observed among younger boys, but there is a shift towards girls using more psychotropic drugs than boys during adolescence for all psychotropic drugs except for stimulants., Conclusion: Different trends in psychotropic drug use exist in age and gender subgroups. Psychotropic drug use has decreased among the youngest children, attributed to alimemazine, and increased in older children and adolescents, attributed mainly to stimulants and hypnotics/sedatives.

Although many studies have addressed adverse outcomes in children of parents with alcohol abuse/dependence, less is known about the possible long-term effects of more normative patterns of parental alcohol consumption, including drinking at lower risk levels and heavy episodic or binge drinking. The extent of harm from parental drinking may therefore be underestimated. With this research proposal, we describe a project that aims to assess possible long-term adverse effects of parental drinking by combining survey and nationwide registry data. Advantages of a longitudinal general population cohort design include that it allows for detailed information on parental drinking through survey data and identification of possible negative long-term health and social outcomes from exposure to parental drinking 1-19 years after exposure through continuously updated nationwide registers. The rich information available from combining survey and registry data allows us to take into account important confounders, mediators, and moderators.

Background: The various benzodiazepines have essentially the same mechanism of action and differ from one another primarily through differences in pharmacokinetics. There is no pharmacological basis for using more than one benzodiazepine for the same patient. The purpose of the study was to examine the occurence of co-medication with different types of benzodiazepines in Norway., Material and Method: Data were obtained from the Norwegian Prescription Database. Patients who received at least one benzodiazepine in 2008 were included (n = 299,185). The percentage of users who were co-medicated with at least two different benzodiazepines and the amounts prescribed were calculated and stratified by gender and age., Results: It is highly probably that 27,861 (14,6%) of patients who received at least two benzodiazepines in the course of 2008 used two different benzodiazepines simultaneously. 13,267 (6.9%) of the patients were prescribed at least two different benzodiazepines on the same prescription. A larger number of women were co-medicated with different benzodiazepines, but the proportion of comedication was higher in men than in women, and most frequent in the age group 18-49 years., Interpretation: There is an extensive and unfortunate prescription practice whereby the same patient is prescribed different benzodiazepines that are used concurrently. Patients who use different benzodiazepines concurrently are mainly prescribed these by one and the same doctor.

Objective: To assess the medical care costs of hypertension and their impact on the health care expenditures and on Mexico's Gross National Product (GNP)., Material and Methods: An ecological study was conducted from June to November 1999, at Instituto Mexicano del Seguro Social (Mexican Institute of Social Security, IMSS), in Monterrey, Nuevo Leon, Mexico. A random sample of medical charts of patients with hypertension was selected, to extract data on utilization of health services and unitary costs per care episode. The cost per care episode and per hypertensive patient was calculated by adjusting the unitary cost as a function of standard and extreme utilization of IMSS health services. The resulting figure was then projected to the total population of hypertensive patients and compared to the annual health care expenditures of Mexico., Results: The annual cost per patient with hypertension was $1,067 in the standard scenario and $3,913 in the extreme scenario. The annual expenditures from hypertension corresponded to 13.95% of the budget allocated to health care and to 0.71%, of Mexico's GNP. These figures changed to 51.17% and 2.61% in the extreme scenario, respectively., Conclusions: The costs of hypertension medical care account for a good portion of healthcare resources. This problem should be analyzed by multidisciplinary health teams in search of more efficient medical care alternatives.