Statin prescription patterns, adherence, and attainment of cholesterol treatment goals in routine clinical care: a Danish population-based study.

PURPOSE: To examine the annual rate and cumulative prevalence of statin use in Denmark 2004-10, including adherence of use and attainment of cholesterol targets. METHODS: We included all individuals aged 18-86 years with a first statin prescription in Northern Denmark in 2004-10. We calculated the annual rate and cumulative prevalence of statin use. We examined cholesterol values before and after start of statins and the proportion reaching targets according to European guidelines and cardiovascular risk group. RESULTS: The study population consisted of 161,646 new statin users (51% men; median age 62 years). The peak rate of new statin initiators occurred in 2008, and a cumulative prevalence of 94 users per 1,000 population was reached in 2010. In total, 98% of new users started with simvastatin. Eighty-eight percent (142,897) did not switch statin type during follow-up. Overall persistence was 84%. The reduction in median total cholesterol in new statin users was 28% (from 6.3 mmol/L to 4.5 mmol/L), while it was 43% (from 4.0 mmol/L to 2.3 mmol/L) for low-density lipoprotein cholesterol. Among patients with very high cardiovascular risk, 66% attained the recommended total cholesterol target; corresponding figures were 74% among high-risk patients and 80% among low- to moderate-risk patients. Corresponding figures for low-density lipoprotein cholesterol were 54%, 82%, and 88%, respectively. CONCLUSIONS: Statin use has become very prevalent in Danish adults, with high adherence. Cholesterol reduction after statin initiation is similar to that found in clinical trials, yet a substantial proportion of patients does not reach target cholesterol levels.

Use of selective serotonin reuptake inhibitors and lifestyle among women of childbearing age: a Danish cross-sectional survey.

OBJECTIVE: To examine the use of selective serotonin reuptake inhibitors (SSRIs) among Danish women of childbearing age according to lifestyle factors. DESIGN: Cross-sectional survey. SETTING: The Central Denmark Region. PARTICIPANTS: 4234 women (71.5% of the invited women) aged 25-44 years who participated in a public health survey in 2006. OUTCOME MEASURES: Prevalence and prevalence ratios (PRs) of current and former SSRI use among women characterised by selected lifestyle factors. We obtained information on SSRI use through linkage to the Aarhus University Prescription Database covering all pharmacies in the region. RESULTS: Of the 4234 women in the study, 161 (3.8%) were current SSRI users, 60 (1.4%) were recent users, 223 (5.3%) were former users and 3790 (89.5%) were never users. Current use of SSRIs was more prevalent in obese women than in non-obese women (PR 1.5, 95% CI 1.0 to 2.3), in current smokers compared with non-current smokers (PR 1.6, 95% CI 1.1 to 2.2), in women who drank more than seven alcoholic drinks weekly compared with women who drank seven or fewer drinks weekly (PR 1.8, 95% CI 1.2 to 2.8) and in women with an unhealthy diet compared with women with a healthy diet (PR 1.7, 95% CI 1.2 to 2.6). Prevalence of former use of SSRIs was similarly increased except in those with an unhealthy diet (PR 1.1, 95% CI 0.8 to 1.7). SSRI use did not differ according to participation in regular physical activity. CONCLUSIONS: Women with an unhealthy lifestyle were about 1.5-fold more likely to be current or former users of SSRIs than those with a healthy lifestyle. These findings may be useful for quantitative assessment of the contribution of lifestyle factors to uncontrolled confounding in studies of SSRI use in pregnancy.

Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality.

IMPORTANCE: Maternal psychiatric disease is associated with adverse pregnancy outcomes. Use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with congenital anomalies, neonatal withdrawal syndrome, and persistent pulmonary hypertension of the newborn. However, the risk of stillbirth and infant mortality when accounting for previous maternal psychiatric disease remains unknown. OBJECTIVE: To study risk of stillbirth and infant mortality associated with use of SSRIs during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study from all Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at different periods from 1996 through 2007. The study included women with singleton births. We obtained information on maternal use of SSRIs from prescription registries. Maternal characteristics, pregnancy, and neonatal outcomes were obtained from patient and medical birth registries. MAIN OUTCOME MEASURES: We used logistic regression to estimate relative risks of stillbirth, neonatal death, and postneonatal death associated with SSRI use during pregnancy taking into account maternal characteristics and previous psychiatric hospitalization. RESULTS: Among 1,633,877 singleton births in the study, 6054 were stillbirths; 3609, neonatal deaths; and 1578, postneonatal deaths. A total of 29,228 (1.79%) of mothers had filled a prescription for an SSRI during pregnancy. Women exposed to an SSRI presented with higher rates of stillbirth (4.62 vs 3.69 per 1000, P = .01) and postneonatal death (1.38 vs 0.96 per 1000, P = .03) than those who did not. The rate of neonatal death was similar between groups (2.54 vs 2.21 per 1000, P = .24). Yet in multivariable models, SSRI use was not associated with stillbirth (adjusted odds ratio [OR], 1.17; 95% CI, 0.96-1.41; P = .12), neonatal death (adjusted OR, 1.23; 95% CI, 0.96-1.57; P = .11), or postneonatal death (adjusted OR, 1.34; 95% CI, 0.97-1.86; P = .08). Estimates were further attenuated when stratified by previous hospitalization for psychiatric disease. The adjusted OR for stillbirth in women with a previous hospitalization for psychiatric disease was 0.92 (95% CI, 0.66-1.28; P = .62) and was 1.07 (95% CI, 0.84-1.36; P = .59) for those who had not been previously hospitalized. The corresponding ORs for neonatal death were 0.89 (95% CI, 0.58-1.39; P = .62) for women who were hospitalized and 1.14 (95% CI, 0.84-1.56; P = .39) for women who were not. For postneonatal death, the ORs were 1.02 (95% CI, 0.61-1.69; P = .95) for women who were hospitalized and 1.10 (95% CI, 0.71-1.72; P = .66) for women who were not. CONCLUSIONS AND RELEVANCE: Among women with singleton births in Nordic countries, no significant association was found between use of SSRIs during pregnancy and risk of stillbirth, neonatal mortality, or postneonatal mortality. However, decisions about use of SSRIs during pregnancy must take into account other perinatal outcomes and the risks associated with maternal mental illness.

Hospitalisation with otitis media in early childhood and cognitive function in young adult life: a prevalence study among Danish conscripts.

BACKGROUND: Otitis media (OM) is a very common condition in children and occurs during years that are critical to the development of learning, literacy, and math skills. Therefore, among a large cohort of Danish conscripts, we aimed to examine the association between hospitalisation with OM in early childhood and cognitive function and educational level in early adulthood. METHODS: We conducted a population-based prevalence study using linked data from healthcare databases and conscription records of Danish men born between 1977 and 1983. We identified all hospitalisations with OM before 8 years of age. Cognitive function was measured by the Boerge Prien validated group intelligence test (Danish Børge Prien Prøve, BPP). We adjusted for potential confounders with and without stratification by hearing impairment. Furthermore, we examined the association between hospitalisation with OM and the prevalence of having achieved a General Certificate of Secondary Education (GCSE), stratified by quartiles of BPP scores. RESULTS: Of the 18 412 eligible conscripts aged 18-25 years, 1000 (5.5%) had been hospitalised with OM before age 8. Compared with conscripts without such a record, the adjusted prevalence ratio (PR) for a BPP score in the bottom quartile was 1.20 (95% confidence interval [CI]: 1.09-1.33). There was no major difference in the proportion of men with a GCSE and those without among those hospitalised with OM in early childhood. For men in the bottom and upper quartiles of BPP scores, the PRs for early childhood hospitalisation with OM were 0.89 (95% CI: 0.59-1.33) and 0.96 (95% CI, 0.88-1.05), respectively. Among men with severe hearing impairment, the proportion with a BPP score in the bottom quartile did not differ between those with and without an OM hospitalisation [PR = 1.01 (95% CI: 0.78-1.34)]. CONCLUSIONS: Overall, we found that hospitalisation with OM in early childhood was associated with a slightly lower cognitive function in early adulthood. Hospitalisation for OM did not seem to influence the prevalence of GSCE when level of BPP was taken into account.

The impact of statin use on pneumonia risk and outcome: a combined population-based case-control and cohort study.

INTRODUCTION: The impact of statin use on pneumonia risk and outcome remains unclear. We therefore examined this risk in a population-based case-control study and did a 5-year update of our previous 30-day mortality analyses. METHODS: We identified 70,953 adults with a first-time hospitalization for pneumonia between 1997 and 2009 in Northern Denmark. Ten age- and sex-matched population controls were selected for each pneumonia patient. To control for potential confounders, we retrieved individual-level data on other medications, comorbidities, recent surgery, socioeconomic indicators, influenza vaccination, and other markers of frailty or health awareness from medical databases. We followed all pneumonia patients for 30 days after hospital admission. RESULTS: A total of 7,223 pneumonia cases (10.2%) and 64,523 controls (9.1%) were statin users before admission, corresponding to an age- and sex-matched odds ratio (OR) of 1.17 (95% confidence interval [CI]: 1.14-1.21). After controlling for higher comorbidity and a wide range of other potential confounders, the adjusted OR for pneumonia associated with current statin use dropped to 0.80 (95% CI: 0.77-0.83). Previous statin use was not associated with decreased pneumonia risk (adjusted OR = 0.97, 95% CI: 0.91-1.02). Decreased risk remained significant after further adjustment for frailty and health awareness markers. CONCLUSIONS: Current statin use was associated with both a decreased risk of hospitalization for pneumonia and lower 30-day mortality following pneumonia.

Maternal use of antibiotics, hospitalisation for infection during pregnancy, and risk of childhood epilepsy: a population-based cohort study.

BACKGROUND: Maternal infection during pregnancy may be a risk factor for epilepsy in offspring. Use of antibiotics is a valid marker of infection. METHODOLOGY/PRINCIPAL FINDINGS: To examine the relationship between maternal infection during pregnancy and risk of childhood epilepsy we conducted a historical cohort study of singletons born in northern Denmark from 1998 through 2008 who survived ≥29 days. We used population-based medical databases to ascertain maternal use of antibiotics or hospital contacts with infection during pregnancy, as well as first-time hospital contacts with a diagnosis of epilepsy among offspring. We compared incidence rates (IR) of epilepsy among children of mothers with and without infection during pregnancy. We examined the outcome according to trimester of exposure, type of antibiotic, and total number of prescriptions, using Poisson regression to estimate incidence rate ratios (IRRs) while adjusting for covariates. Among 191,383 children in the cohort, 948 (0.5%) were hospitalised or had an outpatient visit for epilepsy during follow-up, yielding an IR of 91 per 100 000 person-years (PY). The five-year cumulative incidence of epilepsy was 4.5 per 1000 children. Among children exposed prenatally to maternal infection, the IR was 117 per 100,000 PY, with an adjusted IRR of 1.40 (95% confidence interval (CI): 1.22-1.61), compared with unexposed children. The association was unaffected by trimester of exposure, antibiotic type, or prescription count. CONCLUSIONS/SIGNIFICANCE: Prenatal exposure to maternal infection is associated with an increased risk of epilepsy in childhood. The similarity of estimates across types of antibiotics suggests that processes common to all infections underlie this outcome, rather than specific pathogens or drugs.

Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries.

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.

Use of penicillin and other antibiotics and risk of multiple sclerosis: a population-based case-control study.

A 2006 study from the United Kingdom found that penicillin use may decrease the risk of multiple sclerosis (MS). To confirm this finding, the authors conducted a nationwide case-control study in Denmark, using the Danish Multiple Sclerosis Registry to identify 3,259 patients with MS onset from 1996 to 2008, and selected 10 population controls per case (n = 32,590), matched on sex and age. Through the National Prescription Database, prescriptions for antibiotics redeemed from 1995 to 2008 and before the date of first MS symptom/index date were identified. Conditional logistic regression analysis was used to compute odds ratios associating antibiotic use with MS occurrence. In total, 1,922 patients (59%) redeemed penicillin prescriptions before the index date and 2,292 (70%) redeemed any type of antibiotic prescription. Penicillin use was associated with an increased risk of MS (odds ratio = 1.21, 95% confidence interval: 1.10, 1.27). Use of any type of antibiotic was similarly associated with an increased risk of MS (odds ratio = 1.41, 95% confidence interval: 1.29, 1.53). The odds ratios for different types of antibiotics ranged between 1.08 and 1.83. Thus, this study found that penicillin use and use of other antibiotics were similarly associated with increased risk of MS, suggesting that the underlying infections may be causally associated with MS.