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Competing Interests: PH and KF were employed by company Genetic Analysis AS. The remaining 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.

Background: The prevalence of prescribed drugs in survivors of colorectal cancer (CRC) was evaluated., Methods: Data from the Cancer Registry of Norway were linked to the Norwegian Prescription Database for a study population of 3.52 million individuals. Prevalence ratios (PRs) with 95% confidence intervals (CIs) of prescribed drugs in CRC-survivors compared to the cancer-free population, were estimated by log-binomial regression, adjusting for age and education., Results: Almost 27 000 individuals, aged 20 to 84, were diagnosed with CRC during 2005 to 2014. The first year after diagnosis, the prevalence of prescribed drugs was higher in CRC-survivors compared with the cancer-free population, especially drugs for anxiety and tension, and steroid-responsive conditions. PRs for several drugs, especially drugs used for mental and behavioural disorders, decreased with time since diagnosis. The prevalence of drugs used for anxiety and tension was elevated 10 years after diagnosis; PRs the first year after diagnosis were 20 (95% CI: 18-22) in males and 17 (16-18) in females. Ten years after diagnosis PRs were 5.0 (3.1-7.9) and 2.0 (1.0-3.8), respectively. In absolute numbers, the largest increase, compared to the cancer-free population, was in drugs used for gastric acid disorders and pain. The prevalence of neuromodulatory drugs was higher in CRC-survivors., Conclusions: The prevalence of several drugs was higher in CRC-survivors than in the cancer-free population 10 years after diagnosis. The largest absolute excess in prevalence was for gastric acid disorder and pain medications, while the relative prevalence of drugs used for anxiety and tension was high in CRC-survivors. Long persisting neuropathia was indicated., (© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objectives: To investigate child and parental characteristics of medication use for attention-deficit/hyperactivity disorder (ADHD). Methods: Participants were part of the prospective population-based Norwegian Mother, Father and Child Cohort study (MoBa) ( n  = 114,500 children, 95,000 mothers, and 75,000 fathers). This cohort was linked to the Norwegian Prescription Database (NorPD) and the Norwegian Patient Registry (NPR) to compare child and parental characteristics in children medicated and not medicated for ADHD during years 2008-2013. Results: One thousand seven hundred and sixty-four children (74% boys) with ADHD (International Classification of Diseases [ICD-10]: F90 and F98.8) were identified. One thousand three hundred and sixty-two (77%) used medication. Boys and girls did not differ in the use of ADHD medication (both 77%). Mean age at first prescription was 9 years in both boys and girls, and age at ADHD diagnosis was 8 years in medicated and unmedicated children. Significantly more hyperkinetic conduct disorders (F90.1), and significantly fewer with attention-deficit disorder (F98.8) were found among the medicated children compared to the unmedicated children. The medicated children also had a significantly lower global functioning (Child Global Assessment Scale). Child disruptive symptoms reported in the MoBa child age 3 year questionnaire were significantly higher in children who used medication compared to the nonusers ( t  = 2.2, p  = 0.03), and group differences in ADHD symptoms at age 3 years were close to significant ( t  = 1.8, p  = 0.07). Other preschool child and parental characteristics were not significantly different in the two groups. Conclusion: In this large birth cohort study, where a great majority of children with ADHD used medication, only child characteristics were significantly associated with the use of medication. We could not replicate previous findings suggesting that "environmental factors," such as parental education and psychopathology, drive medication use. The small differences between medicated and unmedicated children in this cohort study, where a majority used medication, might be due to strong established clinical practices where medication is offered as a treatment option, particularly for hyperkinetic conduct disorder in an egalitarian high-income society.

Background: Increasing attention has been given to the long-term effects of assisted reproductive technology (ART). This study assessed the validity and completeness of ART as registered in the Medical Birth Registry of Norway (MBRN) using drug prescription data from the Norwegian Prescription Database (NorPD) as reference., Methods: In this nationwide registry validation study, we included all pregnancies recorded in the MBRN between 2005 and 2017. We estimated sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the MBRN, using data from the NorPD as reference. We obtained the total percentage of ART pregnancies that could be identified (completeness) from both registries using the capture-recapture method. We analyzed subgroups by maternal age, gestational length, mode of ART treatment, health region, and mode of registration of ART (ART institution or birth notification form)., Results: Twenty-three thousand seven hundred eighteen of a total 765,789 pregnancies were registered as ART pregnancies through the MBRN and 20,807 as ART pregnancies through the NorPD. The sensitivity of the MBRN was 85.1% (95% confidence interval [CI] = 84.7, 85.6) and the PPV was 74.7% (74.1-75.2). Sensitivity declined with increasing maternal age: 71.5% (69.4-73.7) in the age group 40-44 years, and 40.7% (22.2-59.3) in the ages above 45 years. Completeness when combining data was 96.2% (96.0-96.5)., Conclusions: Our analysis shows that, when identifying women pregnant through ART, NorPD data complemented MBRN data to obtain a more complete count of all women giving birth after ART in Norway.

Purpose: To describe recent international trends in antiepileptic drug (AED) use during pregnancy and individual patterns of use including discontinuation and switching., Methods: We studied pregnancies from 2006 to 2016 within linked population-based registers for births and dispensed prescription drugs from Denmark, Finland, Iceland, Norway, Sweden, and New South Wales, Australia and claims data for public and private insurance enrollees in the United States. We examined the prevalence of AED use: the proportion of pregnancies with ≥1 prescription filled from 3 months before pregnancy until birth, and individual patterns of use by trimester., Results: Prevalence of AED use in almost five million pregnancies was 15.3 per 1000 (n = 75 249) and varied from 6.4 in Sweden to 34.5 per 1000 in the publicly-insured US population. AED use increased in all countries in 2006-2012 ranging from an increase of 22% in Australia to 104% in Sweden, and continued to rise or stabilized in the countries in which more recent data were available. Lamotrigine, clonazepam, and valproate were the most commonly used AEDs in the Nordic countries, United States, and Australia, respectively. Among AED users, 31% only filled a prescription in the 3 months before pregnancy. Most filled a prescription in the first trimester (59%) but few filled prescriptions in every trimester (22%)., Conclusions: Use of AEDs in pregnancy rose from 2006 to 2016. Trends and patterns of use of valproate and lamotrigine reflected the safety data available during this period. Many women discontinued AEDs during pregnancy while some switched to another AED., (© 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: Medication exposures in pregnancy are often defined by one or more prescription fills. Harmful effects could be underestimated if rapid discontinuation of use after pregnancy recognition is common. We used conception, a critical biological period, as an intervention in a novel application of interrupted time series analysis (ITSA)., Methods: Among 645 049 pregnancies from the Medical Birth Registry (2005-2015) linked to the Norwegian Prescription Database, we modeled the total number of prescription fills in the 12 weeks before and after estimated conception date with ITSA. We examined psychostimulants, antidepressants, antipsychotics, and antiepileptics (AEDs; separated by use for epilepsy or other indications). We used relative measures (%) to compare model coefficients. We also compared number of pregnancies defined as exposed when the earliest fill considered was 30 days before the last menstrual period (LMP -30 days), LMP, or estimated conception date (LMP +14 days)., Results: We observed a sudden decline in prescription fills from 2 weeks after conception and decreasing fills thereafter for psychostimulants, antidepressants, AEDs for other indications, and antipsychotics excluding incident users. Fills for AEDs for epilepsy did not fall after conception. Only 77% of pregnancies with fills for psychostimulants from LMP and 58% with fills from LMP -30 days had fills from conception. Similar figures for AEDs for epilepsy were 99% and 96%., Conclusions: This application shows that ITSA can help researchers understand rapid changes in patient behavior around conception that have consequences for exposure misclassification in pregnancy drug safety studies. ITSA results can help pharmacoepidemiologists guide study exposure definitions., (© 2020 John Wiley & Sons Ltd.)

Purpose: Melanoma is the cancer with the most rapidly rising incidence rate in Norway. Although exposure to ultraviolet radiation (UVR) is the major environmental risk factor, other factors may also contribute. Antidepressants have cancer inhibiting and promoting side effects, and their prescription rates have increased in parallel with melanoma incidence. Thus, we aimed to prospectively examine the association between use of antidepressants and melanoma by using nation-wide data from the Cancer Registry of Norway, the National Registry, the Norwegian Prescription Database and the Medical Birth Registry of Norway., Patient and Methods: All cases aged 18-85 with a primary cutaneous invasive melanoma diagnosed during 2007-2015 (n=12,099) were matched to population controls 1:10 (n=118,467) by sex and year of birth using risk-set sampling. We obtained information on prescribed antidepressants and other potentially confounding drug use (2004-2015). Conditional logistic regression was used to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs) for the association between overall and class-specific use of antidepressants and incident melanoma., Results: Compared with ≤1 prescription, ≥8 prescriptions of antidepressants overall were negatively associated with melanoma (RR 0.81 CI 0.75-0.87). Class-specific analyses showed decreased RRs for selective serotonin reuptake inhibitors (RR 0.82 CI 0.73-0.93) and mixed antidepressants (RR 0.77 CI 0.69-0.86). The negative association was found for both sexes, age ≥50 years, residential regions with medium and highest ambient UVR exposure, all histological subtypes, trunk, upper and lower limb sites and local disease., Conclusion: Use of antidepressants was associated with decreased risk of melanoma. There are at least two possible explanations for our results; cancer-inhibiting actions induced by the drug and less UVR exposure among the most frequent users of antidepressants., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Berge et al.)

Background: Hyperkinetic disorder is one of the most frequently used psychiatric diagnoses among children and adolescents in Norway. It has previously been shown that use of the diagnosis varies widely by county., Material and Method: We estimated the proportion of children with hyperkinetic disorder using patient data from the Norwegian Patient Registry and population data from the Norwegian Population Registry. The estimations were made for both Norway as a whole and by county. Assessment and documentation of the diagnosis were surveyed by linking the Norwegian Patient Registry and the Norwegian Mother and Child Cohort Study. We reviewed medical records from specialist mental health services for children and adolescents and assessed whether the diagnoses met the research criteria for hyperkinetic disorder., Results: At 12 years of age, 5.4 % of Norwegian boys and 2.1 % of Norwegian girls had been diagnosed with hyperkinetic disorder by specialist health services. The proportion of children varied between 1.4 % and 5.5 % among the counties. A review of medical records for 549 children showed that 49 % of the diagnoses were reliably documented in the records. The main reasons that the diagnosis was not documented were a discrepancy between the information in the medical record and diagnostic criteria (38 %) and inadequate differential diagnostic assessment (46 %)., Interpretation: There was considerable geographic variation in the proportions of children and adolescents with hyperkinetic disorder. A large percentage of the diagnoses were not reliably documented in medical records. The guideline for evaluation, diagnostics and medical recordkeeping should be reviewed.

Background: The use of medications to treat attention deficit hyperactivity disorder (ADHD) has increased, but the prevalence of ADHD medication use across different world regions is not known. Our objective was to determine regional and national prevalences of ADHD medication use in children and adults, with a specific focus on time trends in ADHD medication prevalence., Methods: We did a retrospective, observational study using population-based databases from 13 countries and one Special Administrative Region (SAR): four in Asia and Australia, two in North America, five in northern Europe, and three in western Europe. We used a common protocol approach to define study populations and parameters similarly across countries and the SAR. Study populations consisted of all individuals aged 3 years or older between Jan 1, 2001, and Dec 31, 2015 (dependent on data availability). We estimated annual prevalence of ADHD medication use with 95% CI during the study period, by country and region and stratified by age and sex. We reported annual absolute and relative percentage changes to describe time trends., Findings: 154·5 million individuals were included in the study. ADHD medication use prevalence in 2010 (in children aged 3-18 years) varied between 0·27% and 6·69% in the countries and SAR assessed (0·95% in Asia and Australia, 4·48% in North America, 1·95% in northern Europe, and 0·70% in western Europe). The prevalence of ADHD medication use among children increased over time in all countries and regions, and the absolute increase per year ranged from 0·02% to 0·26%. Among adults aged 19 years or older, the prevalence of any ADHD medication use in 2010 varied between 0·003% and 1·48% (0·05% in Asia and Australia, 1·42% in North America, 0·47% in northern Europe, and 0·03% in western Europe). The absolute increase in ADHD medication use prevalence per year ranged from 0·0006% to 0·12%. Methylphenidate was the most commonly used ADHD medication in most countries., Interpretation: Using a common protocol and data from 13 countries and one SAR, these results show increases over time but large variations in ADHD medication use in multiple regions. The recommendations of evidence-based guidelines need to be followed consistently in clinical practice. Further research is warranted to describe the safety and effectiveness of ADHD medication in the short and long term, and to inform evidence-based guidelines, particularly in adults., Funding: None., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Importance: Given the rapidly increasing use of stimulant medications during pregnancy and among women of reproductive age who may become pregnant inadvertently, there is a need to better understand their safety., Objective: To examine the risk of congenital malformations associated with intrauterine exposure to stimulants., Design, Setting, and Participants: Cohort study of the Medicaid-insured population in the United States nested in the 2000-2013 US Medicaid Analytic eXtract, with follow-up of safety signals detected in the Medicaid Analytic eXtract data using the Nordic Health registries (2003-2013) (Denmark, Finland, Iceland, Norway, and Sweden). A total of 1 813 894 publicly insured pregnancies in the United States and 2 560 069 singleton pregnancies in the 5 Nordic countries ending in live births were included. Relative risks were estimated accounting for underlying psychiatric disorders and other potential confounders. Relative risk estimates for the US and Nordic data were pooled using a fixed-effects meta-analytic approach. The study was conducted from July 1, 2015, to March 31, 2017., Exposures: Methylphenidate and amphetamines dispensed during the first trimester., Main Outcomes and Measures: Major congenital malformations and subgroup of cardiac malformations., Results: In the US data, of the 1 813 894 pregnancies evaluated, 35.0 per 1000 infants not exposed to stimulants were diagnosed as having congenital malformations, compared with 45.9 per 1000 infants for methylphenidate and 45.4 for amphetamines. For cardiac malformations, the risks were 12.7 (95% CI, 12.6-12.9), 18.8 (95% CI, 13.8-25.6), and 15.4 (95% CI, 12.5-19.0) per 1000 infants, respectively. The adjusted relative risks for methylphenidate were 1.11 (95% CI, 0.91-1.35) for any malformation and 1.28 (95% CI, 0.94-1.74) for cardiac malformations. No increased risks were observed for amphetamines: 1.05 (95% CI, 0.93-1.19) for any malformations and 0.96 (95% CI, 0.78-1.19) for cardiac malformations. Findings were confirmed in sensitivity analyses accounting for proxies of unmeasured confounders and increasing the specificity of the exposure and outcome definitions. Replication of the analyses for methylphenidate using the Nordic data including 2 560 069 pregnancies yielded a relative risk of 1.28 (95% CI, 0.83-1.97) for cardiac malformations, resulting in a pooled estimate of 1.28 (95% CI, 1.00-1.64)., Conclusions and Relevance: These findings suggest a small increase in the risk of cardiac malformations associated with intrauterine exposure to methylphenidate but not to amphetamines. This information is important when weighing the risks and benefits of alternative treatment strategies for attention-deficit/hyperactivity disorder in women of reproductive age and during early pregnancy.

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

Background: New rules for absence with stricter requirements for documentation were introduced in upper secondary schools in the autumn of 2016. We investigated the use of general practice services and dispensing of prescription drugs among 16 – 18-year-olds in the autumn of 2016 and compared this with equivalent figures for the period 2013 – 15., Material and Method: We retrieved information on consultations in general practice (GP) and dispensing of prescription drugs to 15 – 18-year-olds in the period 2013 – 16 from the Directorate of Health’s system for control and payment of health reimbursements (KUHR) and the Norwegian Prescription Database respectively. The number of consultations and dispensing of drugs were compared to previous years using Poisson regression (reference year 2015). The incidence rate ratio (IRR) was used as an outcome measure., Results: The number of GP consultations for 16 – 18-year-olds was 30 % higher in the autumn of 2016 than in the autumn of 2015 (IRR 1.30, 95 % confidence interval (CI) 1.29 – 1.31). In the same period, the dispensing of drugs to this age group increased by 8 % (IRR 1.08, 95 % CI 1.08 – 1.09). Among the diagnosis groups, respiratory tract infections had the largest increase (IRR 2.21, 95 % CI 2.17 – 2.25). The largest increase in drug dispensing was found for remedies for coughs and colds (IRR 1.73, 95 % CI 1.65 – 1.80)., Interpretation: The increase in consultations in general practice and dispensing of drugs to 16 – 18-year-olds coincided in time with the introduction of new rules for absence from school. We hold it to be highly likely that the changes were caused by the stricter rules for documentation of absence from school.

Background: Studies from several countries have reported that children youngest in grade are at higher risk of attention-deficit/hyperactivity disorder (ADHD) diagnosis and treatment. Norwegian children start school the year they turn six, making children born in December youngest in their grade. We used data on medication, specialist healthcare diagnoses, and primary healthcare diagnoses from national registers to investigate associations between birth month and ADHD., Methods: All children born in Norway between 1998 and 2006 ( N=509,827) were followed from age six until 31 December 2014. We estimated hazard ratios for ADHD medication and diagnoses by birth month in Cox proportional-hazards models. We compared risk among siblings to control for potentially confounding socioeconomic factors, and assessed risk of receiving ADHD medication by birth month while attending different grades in cross-sectional time-series analyses., Results: At end of follow-up, 5.3% of boys born in October-December had received ADHD medication, compared with 3.7% of boys born in January-March. Corresponding numbers for girls were 2.2% and 1.3%, respectively. The adjusted hazard ratio for ADHD medication for children born in October-December (reference: January-March) was 1.4 (95% confidence interval: 1.4-1.5) for boys and 1.8 (1.7-2.0) for girls. Analyses with diagnoses as outcome showed consistent results, and analyses restricted to siblings within the study population also supported the findings. Analysis by grade revealed an increased risk for children born late in the year from grade 3 onwards, with most marked differences in higher grades., Conclusions: Children youngest in grade had the highest risk of receiving ADHD treatment. Differences were most marked among older children.

Background: miRNAs play important roles in multiple biological processes, and deregulation has been linked to several human diseases, including cancer. Studying changes in miRNA expression in cancer development is commonly performed in vitro in human cancer cell lines using quantitative polymerase chain reaction (qPCR), a method requiring the use of a robust reference gene that displays stable expression across all samples., Materials and Methods: Using the NormFinder software, a selection of commonly used endogeneous controls and miRNAs were tested in six human cancer cell lines to identify for the most suitable gene for use as a reference., Results: The frequently used endogenous control U6B small nuclear RNA (RNU6B) was found to be an unsuitable reference for normalization. The most suitable single endogeneous control identified was miR-25-3p, whereas the best combination of two endogeneous controls was miR-25-3p and miR-93-5p., Conclusion: We identified a single and a pair of miRNAs suitable for use as endogenous controls when performing qPCR-based miRNA expression analyses in human cancer cell lines., (Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.)

Background: During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination., Methods: We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables., Results: There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17)., Conclusions: Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.).

Purpose: To investigate the association between mental distress, other factors, and subsequent use of psychotropic drugs in adolescents aged 15-16 years., Methods: This study is based on information retrieved from the Norwegian Youth Health Surveys (2000-2003) and linked to prescription data from the Norwegian Prescription Database (2004-2009). The study population included 11,620 adolescents aged 15-16 (87% response rate) years. Self-reported mental distress (Hopkins Symptom Checklist-10 score 1.85) was recorded along with health and lifestyle habits, education plans, and family economics. Incident psychotropic drug use (outcome measure) was defined ≥1 prescriptions of one of the following psychotropic drugs: anxiolytics, hypnotics, antidepressants, or phenothiazines registered in the Norwegian Prescription Database., Results: Overall, 15.5% of the adolescents reported mental distress, 75% of them were girls. For both genders, incident psychotropic use was significantly higher among those reporting mental distresses at baseline, compared with the rest of the participants. The highest psychotropic drug use was observed among mentally distressed girls (27.7%). Mental distress was significantly associated with incident use of psychotropic drugs (odds ratio: 2.25, 95% confidence interval: 1.97-2.55). After adjustment for confounding factors and inclusion of potential mediating factors, the odds ratio attenuated to 1.59 (95% confidence interval: 1.35-1.86)., Conclusions: The prevalence of mental distress among adolescents may have consequences for health promotion. Public health nurses in Norway, working in health centers and schools, have a responsibility to promote health and prevent health problems. They have the opportunity and a responsibility to identify vulnerable young people., (Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs., Design: Population based cohort study using data from the national health registers., Setting: Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007., Participants: More than 1.6 million infants born after gestational week 33., Main Outcome Measures: Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs., Results: Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0)., Conclusions: The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.

Lower respiratory tract infections are common in small children, and are often associated with obstruction of the respiratory tract and coughing. In Norway, symptomatic treatment with ephedrine is common in children. The clinical effect of such treatment is not sufficiently documented and serious adverse drug reactions have been reported in small children administered sympathomimetic medication. This article presents current knowledge of clinical effects and adverse drug reactions of ephedrine in infants and children, and discusses the practical implications of these findings.

Background: Since 2004, glucosamine has been available as a prescription drug for symptomatic treatment of mild to moderate osteoarthritis. The aim of this study was to characterize glucosamine utilization patterns, and patients' concomitant use of other analgesics, as well as the prescribers' medical specialty., Material and Methods: We searched the Norwegian Prescription Database for all glucosamine prescriptions dispensed during the years 2004, 2005 and 2006, and prescriptions for analgesics with codeine, and non-steroidal anti-inflammatory drugs (NSAIDs) reimbursed for arthrosis for the same patients., Results: In the three-year period, 91,107 patients received 297,558 prescriptions for glucosamine-corresponding to a total cost for patients of 70 mill. NOK. 86 % of patients were more than 50 years old, 69 % were women. Among physicians with a known specialty, 84 % of prescribers were specialists in general practice. 33.3 % of patients used glucosamine all three years. Among the patients who used glucosamine regularly 19 % were prescribed NSAIDs, while 22 % of them used analgesics containing codeine. Patients who started taking glucosamine did not reduce their use of analgetics containing codeine. A positive correlation was seen between use of glucosamine and use of NSAIDs., Interpretation: Glucosamine use is not associated with use of less other pain-relieving drugs. This may reflect insufficient clinical effect of glucosamine.

Purpose: To evaluate the effect of the consumption of benzodiazepines at age 40-42 years on prescription of opioids later in life., Methods: A cohort of 6707 men and 6683 women aged 40-42 years reported no use of analgesics in health surveys in 1985-1989. This cohort was linked to the Norwegian prescription database (NorPD) and their prescriptions of opioids during 2004-2006 were analysed. Low-high, moderate-high and high prescription frequency of opioids were defined as at least 6, 12 or 16 prescriptions during January 2004-December 2006. Non-steroid anti-inflammatory drugs (NSAIDs) were used as comparators., Results: The unadjusted odds ratios (ORs) for low-high prescription frequency of opioids for men and women using benzodiazepines were 3.8 (95%CI 2.5-5.7) and 3.4 (2.6-4.4), respectively, as compared with non-users. After adjustment for alcohol, smoking habits and socio-economic variables, the ORs were lowered for both sexes: 2.6 (1.7-4.0) in men and 2.5 (1.9-3.3) in women. The adjusted OR for those with high prescription of opioids was higher for both sexes: 4.5 (2.4-8.5) in men and 3.7 (2.4-5.7) in women. A stratified analysis revealed no relationship between benzodiazepine use and later low and moderate prescription frequency of opioids among teetotallers. The adjusted ORs for low-high prescription frequency NSAID use for men and women using benzodiazepines were 1.6 (1.1-2.4) and 1.6 (1.3-2.0), respectively., Conclusion: In this study population, a history of benzodiazepine use raised the chance of being prescribed opioids later in life among those who also used alcohol.

What Is Already Known About This Subject: Mothers are using medicines during pregnancies; the extent varies across the world and is generally difficult to compare. In this registry-based study, we examined more than 100,000 Norwegian pregnancies and described the drug prescription pattern of both fathers and mothers around conception and during pregnancy (mothers)., What This Study Adds: In every trimester of pregnancy, about 30% of the mothers was dispensed a drug. The total drug exposure did not seem to diminish throughout pregnancy. One-quarter of the fathers was dispensed drugs during the last 3 months prior to conception., Aims: The primary aim of this study was to describe the use of prescribed drugs in both mothers and fathers before and during pregnancy in Norway., Methods: This population-based cohort study was based on data retrieved from the Medical Birth Registry of Norway and the Norwegian Prescription Database. These registries cover the entire population of Norway. Information on >100,000 births during 2004-2006 in the birth registry was linked to prescription data. Prescriptions issued to mothers just prior to, during and after the pregnancies as well as prescriptions to fathers just prior to conception were identified., Results: Among mothers, 83% were prescribed drugs during the period 3 months prior to estimated conception until 3 months after giving birth. The mothers who received drugs were prescribed on average 3.3 different Anatomical Therapeutic Chemical (ATC) codes (range 1-38). During pregnancy, 57% were prescribed drugs. In the first trimester, 33% of mothers were dispensed drugs, while the figure was 29% for mothers in the last trimester. Among fathers, 25% used prescribed drugs during the 3 months prior to conception, with on average 1.9 different ATC codes (range 1-22)., Conclusion: Large proportions of both fathers and mothers were dispensed drugs prior to conception or during pregnancy. While there is a high awareness of the issues involved in maternal drug use in pregnancy, possible teratogenic effects of drug use in fathers shortly before conception should be further explored.

Background: Use of antidepressants (especially selective serotonin reuptake inhibitors (SSRIs) and venlafaxine) for treatment of children and adolescents with major depression, anxiety disorders or obsessive-compulsive disorders (OCD) has been discussed, because of marginal effects and an increased risk for suicidal thoughts and actions. The European and Norwegian health authorities issued a series of warnings and recommendations from the summer 2003 till the summer of 2005. The newly established Norwegian Prescription Database was used to investigate whether these warnings have had an effect., Material and Methods: The number of SSRI users was compared monthly to the number of venlafaxine users in the period 2004 to 2006. Users below 18 of age were compared to those aged 18 or above. New users of SSRIs and venlafaxine in 2005 and 2006 were characterized according to age, gender and the medical specialty of the doctor giving the first prescription for the drugs., Results: The SSRIs/venlafaxine user proportion for those below 18 years of age was 17% lower in 2005 than in 2004. Among older users the number rose by 2%. Fluoxetin was the most frequently prescribed drug among young first time users. Non-specialist MDs prescribed most of the drugs., Interpretation: Antidepressants are used less by children and adolescents in Norway than in many other countries, but the warnings against SSRIs and venlafaxine seem to have had an effect anyway. Also the official recommendation to use fluoxetine seems to have been followed.

Background: Stimulants are an important part of the treatment of ADHD. The present study examines the prescribing of stimulants for ADHD in Nordland County in 2004 compared to data from 1999., Material and Methods: Individual prescription data were retrieved from the Norwegian Prescription Database (NorPD) for 1.1.2004-30.06.2004. Sales figures for stimulants in Nordland and Norway as a whole were retrieved from the Norwegian Institute of Public Health for the period 1999-2004., Results: In 2004, 487 children aged 4-17 years (1.1% of the age-group) and 68 adults received at least one prescription of stimulants. The prevalence was highest among 10-13 year-olds; 0.8% in girls and 2.4% in boys. Boys represented 78% of the users <18 years. Child psychiatrists prescribed to half of the children, and adult psychiatrists prescribed to 74% of the adults. Sale of stimulants in defined daily doses has increased 5-fold from 1999 to 2004., Interpretation: This increase in stimulant prescribing must be viewed in the light of the increasing number of physicians working in child psychiatry coupled with the development of better neuropsychological services. These changes may have contributed to an increase in the number of children diagnosed with ADHD and consequently an increase in children treated with stimulants.

Background and Objective: The validity of using self-reported or parental reported asthma symptoms and/or doctor-diagnosed asthma in the estimation of asthma prevalence among children has been questioned. The aim of this study was to assess the prevalence of dispensed anti-asthmatic medications as a proxy of asthma among children and adolescents aged 0-19 years in Norway., Methods: Prescription data on subjects aged 0-19 years receiving at least one prescription for an anti-asthmatic during 2004 were retrieved from the nationwide Norwegian Prescription Database., Results: Overall, 108,719 (9.1% of the Norwegian population aged 0-19 years) individuals received at least one prescription for medication(s) for obstructive airway diseases. The application of criteria that restricted the study population to those receiving inhaled anti-asthmatic medications and those receiving medications reimbursed by the Norwegian health care system for asthma resulted in the identification of 64,458 (5.4%) individuals (4.6% of girls and 6.2% of boys). The prevalence varied by age, with a maximum in both genders at about 2 years of age (7.0% of girls and 10.1% of boys) and a minimum in girls at about 10 years of age (3.3%) and in boys at about 19 years of age (3.5%). Anti-asthmatic inhalants were more frequently prescribed among boys than among girls during the first 15 years of life. Of the children treated, 75% received inhaled glucocorticoids (ICS) in combination with beta2-agonists, of whom 38% received a fixed combination in one inhaler., Conclusions: In 2004, about 1 in 20 Norwegians aged 0-19 years were in need of medical treatment for asthma for at least 3 months, reflecting ongoing and clinically important asthma. A rather high proportion of children received fixed combinations of ICS and long-acting beta2-agonists, which may indicate moderate to severe asthma.

Background: In Norway there has in later years been much discussion of misuse of flunitrazepam. From 1 January 2003 the drug was moved up one level in the schedule of controlled substances. On 1 August 2004 the manufacturer of the Rohypnol brand withdrew it from the Norwegian market. How did these two events influence the sales and use of drugs containing flunitrazepam?, Materials and Methods: Sales figures for drugs containing flunitrazepam from the statistics database at the Norwegian Institute of Public Health were studied. The Norwegian prescription database was used to describe new (incident) users of flunitrazepam and the two brands of this drug sold in Norway in 2004., Results and Discussion: Restrictions on the prescription status of flunitrazepam lead to a decrease in sales from 7.2 defined daily doses (DDD) per 1000 inhabitants per day in 2002 to 3.0 DDD per 1000 inhabitants per day in 2003. This decrease was only partly compensated for by an increase in the sales of nitrazepam (from 5.0 to 6.0 DDD per 1000 inhabitants per day). During the years 1999 to 2004 there was a steady increase in the sales of benzodiazepine-related hypnotics (zopiclone and zolpidem). This shift could mean a change from flunitrazepam to zopiclone. The withdrawal of Rohypnol in August 2004 had only minor effects on the total sales of flunitrazepam. The decline in sales of Rohypnol was almost compensated for by the increase in the overall sales of Flunipam. This was reflected in the fact that in the later months of 2004 there were many new (incident) users of Flunipam, but few new users of flunitrazepam-containing drugs in total. It could be concluded that the restrictions on prescription status of flunitrazepam had a much higher impact than the withdrawal of the Rohypnol brand.

Background: Little information is available about Norwegian adolescents' use of medical drugs., Material and Methods: Self-reported drug use was recorded by means of a self-administered questionnaire handed out in classrooms to all 10th grade students in four counties. In all, 5846 boys and 5862 girls participated during the years 2000-2002., Results: Forty-one percent of boys and 64% of girls had used drugs during the last four weeks. Non-prescription analgesics had been used by 25% of the boys and by more than half of the girls. Daily use of prescription analgesics was reported by approximately 1% in both sexes, while more girls than boys had used these drugs during the last four weeks. In all, 15% of the boys and 16% of the girls reported use of allergy medicines during the last four weeks and 6% of the boys and 7% of the girls had used asthma medicines. During the same period, 1.4% of the boys and 1.8% of the girls had used hypnotics. Anxiolytics had been used by 1.9%, while 0.8% reported use of antidepressants., Interpretation: Drug use is common among adolescents in Norway. Except for analgesics, there were only minor sex differences in drug use. The proportion of drug users did not vary significantly between counties.