Gender differences in psychiatric comorbidity: a population-based study of 40 000 adults with attention deficit hyperactivity disorder.

OBJECTIVE: We aimed at determining whether gender modified associations between ADHD and psychiatric comorbidities in adults. METHOD: We identified adults with ADHD by linking Norwegian national registries and compared them with the remaining adult population (born 1967-1997, ADHD and bipolar during 2004-2015, other psychiatric disorders 2008-2015). Prevalence differences (PDs) and prevalence ratios (PRs) of psychiatric disorders were determined by Poisson regression. Interaction by gender was evaluated on additive (PDs) and multiplicative (PRs) scales. Proportions of psychiatric disorders attributable to ADHD were calculated. RESULTS: We identified 40 103 adults with ADHD (44% women) and 1 661 103 adults (49% women) in the remaining population. PDs associated with ADHD were significantly larger in women than in men for anxiety, depression, bipolar and personality disorders, for example depression in women: 24.4 (95% CI, 23.8-24.9) vs. in men: 13.1 (12.8-13.4). PDs were significantly larger in men for schizophrenia and substance use disorder (SUD), for example SUD in men: 23.0 (22.5-23.5) vs. in women: 13.7 (13.3-14.0). Between 5.6 and 16.5% of psychiatric disorders in the population were attributable to ADHD. CONCLUSION: The association between ADHD and psychiatric comorbidities differed significantly among men and women. Clinicians treating adults with ADHD should be aware of these frequent and gender-specific comorbidities, such that early treatment can be offered.

The limitations of some European healthcare databases for monitoring the effectiveness of pregnancy prevention programmes as risk minimisation measures.

PURPOSE: Pregnancy prevention programmes (PPPs) exist for some medicines known to be highly teratogenic. It is increasingly recognised that the impact of these risk minimisation measures requires periodic evaluation. This study aimed to assess the extent to which some of the data needed to monitor the effectiveness of PPPs may be present in European healthcare databases. METHODS: An inventory was completed for databases contributing to EUROmediCAT capturing pregnancy and prescription data in Denmark, Norway, the Netherlands, Italy (Tuscany/Emilia Romagna), Wales and the rest of the UK, to determine the extent of data collected that could be used to evaluate the impact of PPPs. RESULTS: Data availability varied between databases. All databases could be used to identify the frequency and duration of prescriptions to women of childbearing age from primary care, but there were specific issues with availability of data from secondary care and private care. To estimate the frequency of exposed pregnancies, all databases could be linked to pregnancy data, but the accuracy of timing of the start of pregnancy was variable, and data on pregnancies ending in induced abortions were often not available. Data availability on contraception to estimate compliance with contraception requirements was variable and no data were available on pregnancy tests. CONCLUSION: Current electronic healthcare databases do not contain all the data necessary to fully monitor the effectiveness of PPP implementation, and thus, special data collection measures need to be instituted.

Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study.

OBJECTIVE: To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies. DESIGN: Meta-analysis of aggregated data from three cohort studies. SETTING: Linkage between healthcare databases and EUROCAT congenital anomaly registries. POPULATION: 519 242 pregnancies in Norway (2004-2010), Wales (2000-2010) and Funen, Denmark (2000-2010). METHODS: Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses. MAIN OUTCOME MEASURES: ORs for all congenital anomalies and specific congenital anomalies. RESULTS: Overall exposure prevalence was 3.76%. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99% CI 1.09-1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposed to inhaled corticosteroids (3.40; 99% CI 1.15-10.04). For severe congenital heart defects, an increased OR (1.97; 1.12-3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20-4.67). CONCLUSION: The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations with combination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken. TWEETABLE ABSTRACT: This cohort study found a small increased risk of congenital anomalies for women taking asthma medication.

Use of antidepressants and association with elective termination of pregnancy: population based case-control study.

OBJECTIVE: To assess whether the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, mirtazapine, venlafaxine or other antidepressants is associated with late elective termination of pregnancy. DESIGN: Case-control study using data from national registers. SETTING: Denmark, Finland, and Norway during the period 1996-2007. POPULATION: A total of 14,902 women were included as cases and 148,929 women were included as controls. METHODS: Cases were women with elective termination of pregnancy at 12-23 weeks of gestation. Controls continued their pregnancy and were matched with cases on key factors. MAIN OUTCOME MEASURES: Association between antidepressant use during pregnancy and elective termination of pregnancy at 12-23 weeks of gestation for fetal anomalies, or for maternal ill health or socio-economic disadvantage. RESULTS: At least one prescription of antidepressants was filled by 3.7% of the cases and 2.2% of the controls. Use of any type of antidepressant was associated with elective termination of pregnancy for maternal ill health or socio-economic disadvantage (odds ratio, OR 2.3; 95% confidence interval, 95% CI 2.0-2.5). Elective termination of pregnancy for fetal anomalies was associated with the use of mirtazapine (OR 2.2, 95% CI 1.1-4.5). There was no association between the use of any of the other antidepressants and elective termination of pregnancy for fetal anomalies. CONCLUSION: The use of any type of antidepressants was associated with elective termination of pregnancy at 12-23 weeks for maternal ill health or socio-economic disadvantage, but not with terminations for fetal anomalies. Further studies need to confirm the findings concerning mirtazapine and termination of pregnancy for fetal anomalies.

Total drug treatment and comorbidity in myasthenia gravis: a population-based cohort study.

BACKGROUND AND PURPOSE: Comorbidity in myasthenia gravis (MG) is important for diagnosis, treatment and prognosis. Disease complexity was assessed by examining total drug treatment, immune therapy and comorbidity in a complete national MG cohort. METHODS: All recipients of the MG-specific drug pyridostigmine 2004-2010 registered in the compulsory Norwegian Prescription Database who met the inclusion criteria were included. The pyridostigmine group was compared with the general Norwegian population. RESULTS: Myasthenia gravis patients received co-medication more often than the controls for nearly all groups of medication, including insulins (95% confidence interval 2.0-3.7), thyroid therapy (1.7-2.5), antidepressants (1.3-1.7), anti-infectives (1.2-1.4), lipid-modifying agents (1.1-1.4) and immunomodulating agents (6.8-8.8). CONCLUSIONS: Myasthenia gravis patients are more often treated with non-MG prescription drugs than controls, reflecting frequent co-medication and comorbidity.

Myasthenia gravis epidemiology in a national cohort; combining multiple disease registries.

OBJECTIVES: There is a wide variation in reported prevalence and incidence of myasthenia gravis (MG). In this study, we aimed to evaluate the validity of two nationwide databases by comparing prevalence and incidence rates reported from three recent studies using the two databases as case-finding method. MATERIALS AND METHODS: Two different Norwegian nationwide databases were used: the acetylcholine receptor antibody database (reference cohort) and the Norwegian Prescription Database (NorPD) (study cohort). Presence of acetylcholine receptor antibodies (AChR) is specific for MG. Up to 85% of MG patients are AChR antibody-positive. All samples from the whole country were tested at one laboratory. NorPD contains patient information on all prescriptions of pyridostigmine. RESULTS: Prevalence was 131 per million in the study cohort and 145 per million estimated from the reference cohort (Jan 1, 2008). No significant difference in prevalence between the study cohort and the reference cohort was found (SIR 1.1, 95% CI 1.0-1.2). The annual incidence rate was 16.0 per million in the study cohort and 8.8 per million estimated from the reference cohort, twofold more new MG patients were found in the study cohort compared to estimated figures from the reference cohort (SIR 1.8; 1.4-2.3). CONCLUSIONS: This study confirms an optimal and unbiased case finding in both databases. Our calculated prevalence and incidence rates are in line with previous population-based studies. There was good agreement in prevalence reported from the two databases. The discrepancy in incidence is expected to diminish as years of study are increasing in NorPD.

Increased uptake of social security benefits among long-term survivors of cancer in childhood, adolescence and young adulthood: a Norwegian population-based cohort study.

BACKGROUND: As the number of cancer survivors increases, their health and welfare have come into focus. Thus, long-term medical consequences of cancer at a young age (<25 years), obtained from social security benefit records, were studied. METHODS: Standardised incidence ratios (SIRs) of long-term medical consequences for 5-year cancer survivors, born during 1965-1985, were explored by linking population-based registries in Norway. RESULTS: Among the 5-year cancer survivors (4031 individuals), 29.7% received social security benefits. The survivors had an overall 4.4 times (95% confidence interval (95% CI): 4.1-4.6) higher risk of social security benefit uptake than the cancer-free population. Survivors of malignancies of bone and connective tissues (SIR: 10.8; 95% CI: 9.1-12.9), CNS tumours (SIR: 7.7; 95% CI: 6.9-8.6) and malignancies of the haematopoietic system (SIR: 6.1; 95% CI: 5.3-7.0) had the highest risks of social security benefits uptake. The most notified causes of social security benefit uptake were diseases of the nervous system, and injury and poisoning. CONCLUSION: The uptake of social security benefits among 5-year cancer survivors increased substantially and it may represent a solid outcome measure for the burden of the most severe late effects, especially in countries with comparable social welfare systems.

Metabolic risk factors and skin cancer in the Metabolic Syndrome and Cancer Project (Me-Can).

BACKGROUND: Little is known about the associations of metabolic aberrations with malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). OBJECTIVES: To assess the associations between metabolic factors (both individually and combined) and the risk of skin cancer in the large prospective Metabolic Syndrome and Cancer Project (Me-Can). METHODS: During a mean follow-up of 12 years of the Me-Can cohort, 1728 (41% women) incident MM, 230 (23% women) fatal MM and 1145 (33% women) NMSC were identified. Most NMSC cases (76%) were squamous cell carcinoma (SCC) (873, 33% women). Hazard ratios (HRs) were estimated by Cox proportional hazards regression for quintiles and standardized z-scores (with a mean of 0 and SD of 1) of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and for a combined metabolic syndrome score. Risk estimates were corrected for random error in the measurements. RESULTS: Blood pressure per unit increase of z-score was associated with an increased risk of incident MM cases in men and women [HR 1·17, 95% confidence interval (CI) 1·04-1·31 and HR 1·18, 95% CI 1·03-1·36, respectively] and fatal MM cases among women (HR 2·39, 95% CI 1·58-3·64). In men, all quintiles for BMI above the reference were associated with a higher risk of incident MM. In women, SCC NMSC risk increased across quintiles for glucose levels (P-trend 0·02) and there was a trend with triglyceride concentration (P-trend 0·09). CONCLUSION: These findings suggest that mechanisms linked to blood pressure may be involved in the pathogenesis of MM. SCC NMSC in women could be related to glucose and lipid metabolism.

Outcomes after anti-rheumatic drug use before and during pregnancy: a cohort study among 150,000 pregnant women and expectant fathers.

OBJECTIVES: To study (i) the drug utilization pattern of anti-rheumatic drugs in pregnant women and expectant fathers and (ii) the association between the use of anti-rheumatic drugs during pregnancy and the risk of congenital malformations. METHOD: Pregnancies registered in the Medical Birth Registry of Norway (MBRN) were linked to the Norwegian Prescription Database (NorPD) in the period 2004-2007. Prescriptions for anti-rheumatic drugs issued to women 3 months prior to and during pregnancy and to men 3 months prior to conception were identified. Congenital malformations were recorded according to the European Surveillance of Congenital Anomalies (EUROCAT) guidelines. RESULTS: In 154,976 singleton pregnancies, 1461 of the women (0.9%) and 1198 (0.8%) of the known fathers (150,530) were dispensed anti-rheumatic drugs at least once during the study period: 723 had non-steroidal anti-inflammatory drugs (NSAIDs), 633 prednisolone (CS), 119 sulfasalazine (SASP), 101 azathioprine (AZA), 58 hydroxychloroquine (HQC), 37 etanercept (ETAN), eight methotrexate (MTX), two leflunomide (LEF), and three adalumimab (ADA). Odds ratios (ORs) for malformations in children born of women (w) or men (m) who had received the drugs were OR(w) = 1.06 [95% confidence interval (CI) 0.85-1.32] and OR(m) = 1.19 (95% CI 0.93-1.51), respectively, and for major malformation OR(w) = 1.05 (95% CI 0.79-1.40) and OR(m) = 1.26 (95% CI 0.93-1.71), respectively. None of the children whose mother had received MTX, LEF, ETAN, or ADA were reported to be born with major malformations. CONCLUSIONS: This study revealed no major malformations of the alert drugs MTX, LEF, ETAN, or ADA. Although the numbers are limited, this provides important population-based information to both expectant parents and prescribers.

Effect of the market withdrawal of carisoprodol on use of other prescribed drugs with abuse potential.

Carisoprodol, a centrally acting muscle relaxant indicated for acute lower back pain, has been available in Europe and the United States since 1959. Studies indicating increased risk of abuse or addiction led to withdrawal of the drug from the market in Norway and other EU countries in 2008. In this nationwide longitudinal prescription study of 53,116 individuals in Norway, previous users of carisoprodol switched, to a limited extent, to other prescribed drugs with abuse potential after the withdrawal.

Metabolic syndrome and rare gynecological cancers in the metabolic syndrome and cancer project (Me-Can).

BACKGROUND: Risk factors for rare gynecological cancers are largely unknown. Initial research has indicated that the metabolic syndrome (MetS) or individual components could play a role. MATERIALS AND METHODS: The Metabolic syndrome and Cancer project cohort includes 288,834 women. During an average follow-up of 11 years, 82 vulvar, 26 vaginal and 43 other rare gynecological cancers were identified. Hazard ratios (HRs) were estimated fitting Cox proportional hazards regression models for tertiles and standardized z-scores [with a mean of 0 and a standard deviation (SD) of 1] of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and MetS. Risk estimates were corrected for random error in the measurement of metabolic factors. RESULTS: The MetS was associated with increased risk of vulvar [HR 1.78, 95% confidence interval (CI) 1.30-2.41) and vaginal cancer (HR 1.87, 95% CI 1.07-3.25). Among separate MetS components, 1 SD increase in BMI was associated with overall risk (HR 1.43, 95% CI 1.23-1.66), vulvar (HR 1.36, 95% CI 1.11-1.69) and vaginal cancer (HR 1.79, 95% CI 1.30-2.46). Blood glucose and triglyceride concentrations were associated with increased risk of vulvar cancer (HR 1.98, 95% CI 1.10-3.58 and HR 2.09, 95% CI 1.39-3.15, respectively). CONCLUSION: The results from this first prospective study on rare gynecological cancers suggest that the MetS and its individual components may play a role in the development of these tumors.

Myasthenia gravis requiring pyridostigmine treatment in a national population cohort.

BACKGROUND: Pyridostigmine is the first drug of choice for patients with myasthenia gravis (MG). The drug is not prescribed regularly to any other patient groups. We aimed to determine the prevalence, incidence and gender-specific characteristics of patients with MG needing drug treatment in a well-defined population cohort. METHODS: Data were retrieved from the Norwegian Prescription Database (NorPD) 2004-2007, containing information on all dispensed drugs in Norway. The study population comprised 677 recipients of pyridostigmine who met the following inclusion criteria (one or more): (i) More than one prescription 1 January 2004-31 December 2007, (ii) prescription from a specialist in neurology, (iii) prescription for MG being specified in NorPD. RESULTS: A total of 435 (64%) women and 242 men were included; female:male ratio 1.8:1. Point prevalence (1 January 2008) of symptomatic MG was 131 per million; 92 for men, 170 for women. Seventy-four new users of pyridostigmine were registered in 2007 (42 women, 32 men), i.e. the incidence rate for 2007 being 16 per million; 14 for men, 18 for women. Mean age of incident cases was 59 years; 64 and 55 years, respectively. Prevalence and incidence were significantly higher in the age group ≥ 50 years than < 50 years (P < 0.001), and highest at 70-79 years. Prevalence and incidence did not differ in the five geographical health regions in Norway. CONCLUSIONS: Reported prevalence and incidence are amongst the highest found in similar studies. This may be explained by optimal case identification, higher incidence of drug requiring MG amongst the elderly, and recurrences of previous MG.

The use of free vascularised bone grafts in spinal reconstruction.

The use of free vascularised bone grafts (FVBGs) is an infrequently performed surgical technique for the reconstruction of spinal defects. This field of surgery brings many challenges concerning choice of FVBG, planning of the operative procedure and selection of recipient vessels. This study aims to report our experience with FVBGs, with special emphasis on the planning and surgical technique. Over a period of 10 years (1994-2004), we used FVBG for anterior spinal reconstruction in 23 patients. In 21 patients, a free vascularised fibular graft was used, and in two cases a free vascularised iliac crest graft was used. The spinal segments reconstructed involved the cervical spine (4 cases), the thoracic spine (13 cases) and the thoraco-lumbar and lumbo-sacral spine (6 cases). Re-vascularisation of the FVBG proved to be technically feasible in 22 patients, but failed in one fibular graft due to difficulties with recipient vessels in the lumbar spine. When necessary, the fibula was osteotomized and folded in a double-, triple- or quadruple-barrel construction to increase the strength of the reconstruction. Technical challenges were met with respect to the choice of the recipient vessel at various anatomical sites. The use of FVBG is a valuable technique for the reconstruction of complex spinal disorders. Successful execution requires microvascular expertise with respect to graft harvesting and appropriate choice of recipient vessels. Adequate preoperative planning in a multidisciplinary setting and adherence to the basic principles for spinal reconstruction are required.

Road traffic accident risk in patients with diabetes mellitus receiving blood glucose-lowering drugs. Prospective follow-up study.

AIM: To investigate, at a national level, whether patients using insulin or oral glucose-lowering agents had an increased risk of road traffic accidents compared with non-users. METHODS: All Norwegians aged 18-69 years (3.1 million) were followed from April 2004 until September 2006. Information on drug prescriptions, road traffic accidents and emigration/death was obtained from the following population-based registries: the Prescription Database, the Road Accident Registry and the Central Population Registry. The exposure period was the time from the first prescription of insulin or oral glucose-lowering agent during the study period. The incidence of accidents in the exposed person-time was compared with the incidence of accidents in the unexposed person-time by standardized incidence ratio (SIR). RESULTS: During the study period, 20 494 road traffic accidents with personal injuries were registered in Norway. One hundred and eighty-three accidents were registered for insulin users not taking oral glucose-lowering agents and 219 for users of oral blood glucose-lowering drugs without insulin. The SIR (95% confidence interval) for all ages and both genders combined were: insulin 1.4 (1.2-1.6), oral glucose-lowering agents 1.2 (1.0-1.3) and users of drugs for peptic ulcer and gastro-oesophageal reflux disease (negative comparators) 1.3 (1.2-1.4). The highest SIRs were found among the youngest insulin users (18-34 years old). CONCLUSIONS: A slightly increased risk of being involved in a road traffic accident was observed for drivers prescribed insulin, while no increased risk was observed for drivers prescribed oral glucose-lowering agents. The increased risk observed for insulin users was similar to that observed for users of drugs for peptic ulcer and gastro-oesophageal reflux disease.

Birth and parental characteristics and risk of neuroblastoma in a population-based Norwegian cohort study.

In this population-based Norwegian cohort study (2.1 million children), the impact of birth and parental characteristics on the risk of neuroblastoma (178 cases) was evaluated. In children below the age of 18 months, there was an increased neuroblastoma risk among those with congenital malformations and suggestion of increased risk when the mother had pre-eclampsia.

Changes in physical activity behavior and the development of body mass index during the last 30 years in Norway.

Body mass index (BMI; kg/m(2)) has increased markedly in the last decades. We hypothesized that highly physically active persons both at work and at leisure would be resistant to weight gain. The hypothesis was tested by analyzing Norwegian cross-sectional data collected in the period 1972-2002. Participants were 214,449 men and 206,136 women (aged 20-70 years). During the last 30 years in men and the last 15 years in women, a systematic larger BMI increase per year was observed in the sedentary [regression coefficients (SE) in men 0.060 (0.004) kg/m(2) and women 0.137 (0.012) kg/m(2)] compared with highly physically active groups [regression coefficients (SE) in men 0.036 (0.00 4) kg/m(2), and in women -0.001 (0.039) kg/m(2)]. Analyses were robust to adjustments for age, smoking and education. There was a larger absolute net increase in the prevalence of obesity among the sedentary compared with persons performing light, moderate or heavy physical activity (PA) at leisure. PA level in women both at work and in leisure was not associated with weight gain during the last decades. This association was less evident among men. Men and women who were lightly, moderately or highly active at leisure were less likely to be obese compared with those who were sedentary.

Body size and thyroid cancer in two million Norwegian men and women.

We investigated relations between measured body mass index (BMI) and stature and thyroid cancer (3046 cases) in a large Norwegian cohort of more than two million individuals. The risk of thyroid cancer, especially of the papillary and follicular types, increased moderately with increasing BMI and height in both sexes.

Height and body mass index in relation to cancer of the small intestine in two million Norwegian men and women.

The present study aimed at exploring the relations between body mass index (BMI, (weight in kilograms)/(height in meters)(2)) and stature and cancer of the small intestine (1162 cases) in a large Norwegian cohort (of two million) with measured height and weight. Elevated BMI in males and increasing height in both sexes were associated with a moderately increased risk of cancer of the small intestine.

Combining topical negative pressure and a Bogota bag for managing a difficult laparostomy.

A patient with a severe intra-abdominal infection required a laparostomy. A Bogota bag was combined with topical negative pressure therapy, saving nursing time and enabling successful management of wound fluid.