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Loikas D.,Center for Pharmacoepidemiology | Wettermark B.,Center for Pharmacoepidemiology | Wettermark B.,Karolinska University Hospital | Von Euler M.,Karolinska Institutet | And 3 more authors.
BMJ Open | Year: 2013

Objectives: Ascertain the extent of differences between men and women in dispensed drugs since there is a lack of comprehensive overviews on sex differences in the use of prescription drugs. Design: Cross-sectional population database analysis. Methods: Data on all dispensed drugs in 2010 to the entire Swedish population (9.3 million inhabitants) were obtained from the Swedish Prescribed Drug Register. All pharmacological groups with ambulatory care prescribing accounting for >75% of the total volume in Defined Daily Doses and a prevalence of >1% were included in the analysis. Crude and age-adjusted differences in prevalence and incidence were calculated as risk ratios (RRs) of women/men. Results: In all, 2.8 million men (59%) and 3.6 million women (76%) were dispensed at least one prescribed drug during 2010. Women were dispensed more drugs in all age groups except among children under the age of 10. The largest sex difference in prevalence in absolute numbers was found for antibiotics that were more common in women, 265.5 patients (PAT)/1000 women and 191.3 PAT/1000 men, respectively. This was followed by thyroid therapy (65.7 PAT/1000 women and 13.1 PAT/1000 men) and antidepressants (106.6 PAT/1000 women and 55.4 PAT/1000 men). Age-adjusted relative sex differences in prevalence were found in 48 of the 50 identified pharmacological groups. The pharmacological groups with the largest relative differences of dispensed drugs were systemic antimycotics (RR 6.6 CI 6.4 to 6.7), drugs for osteoporosis (RR 4.9 CI 4.9 to 5.0) and thyroid therapy (RR 4.5 CI 4.4 to 4.5), which were dispensed to women to a higher degree. Antigout agents (RR 0.4 CI 0.4 to 0.4), psychostimulants (RR 0.6 CI 0.6 to 0.6) and ACE inhibitors (RR 0.7 CI 0.7 to 0.7) were dispensed to men to a larger proportion. Conclusions: Substantial differences in the prevalence and incidence of dispensed drugs were found between men and women. Some differences may be rational and desirable and related to differences between the sexes in the incidence or prevalence of disease or by biological differences. Other differences are more difficult to explain on medical grounds and may indicate unequal treatment.


Skoglund C.,Karolinska Institutet | Brandt L.,Center for Pharmacoepidemiology | Almqvist C.,Karolinska University Hospital | D'Onofrio B.M.,Indiana University Bloomington | And 2 more authors.
Journal of Clinical Psychopharmacology | Year: 2016

Adherence to treatment is one of themost consistent factors associated with a favorable addiction treatment outcome. Little is known about factors associatedwith treatment adherence in individuals affected with comorbid attention-deficit/hyperactivity disorder and substance use disorders (SUD). This study aimed to explore whether treatment-associated factors, such as the prescribing physician's (sub)specialty and methylphenidate (MPH) dose, or patient-related factors, such as sex, age, SUD subtype, and psychiatric comorbidity, were associated with adherence to MPH treatment. Swedish national registers were used to identify adult individuals with prescriptions of MPH and medications specifically used in the treatment of SUD or a diagnosis of SUD and/or coexisting psychiatric diagnoses. Primary outcomemeasurewas days in activeMPH treatment in stratified dose groups (≤36 mg, ≥37 mg to ≤54 mg, ≥55 mg to ≤72 mg, ≥73 mg to ≤90 mg, ≥91 mg to ≤108 mg, and ≥109 mg). Lower MPH doses (ie, ≤36 mg day 100) were associated with treatment discontinuation between days 101 and 830 (HR≤36 mg, 1.67; HR37-54mg, 1.37; HR55-72mg, 1.36; HR73-90mg, 1.19; HR≥108mg, 1.09). The results showed a linear trend (P < 0.0001) toward decreased risk of treatment discontinuation along with increase ofMPH doses. In conclusion, this study shows that higherMPH doses were associated with long-term treatment adherence in individuals with attention-deficit/ hyperactivity disorder and SUD.


Bruzelius M.,Karolinska University Hospital | Bruzelius M.,Karolinska Institutet | Ljungqvist M.,KI Sodersjukhuset | Bottai M.,Institute of Environmental Medicine | And 11 more authors.
Thrombosis and Haemostasis | Year: 2016

Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002–2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan- Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between groups. A total of 101 recurrent events occurred during a mean followup time of five years. The overall recurrence rate was 20 per 1,000 person- years (95% CI; 16–24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95% CI; 1.1–2.6)) and F11 rs2289252 (HR=1.8 (95% CI; 1.1–3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction. © Schattauer 2016.


Petridou E.T.,National and Kapodistrian University of Athens | Sergentanis T.N.,National and Kapodistrian University of Athens | Skalkidou A.,Uppsala University | Antonopoulos C.N.,National and Kapodistrian University of Athens | And 5 more authors.
European Journal of Cancer Prevention | Year: 2015

This Swedish nationwide cohort study aims to examine the role of maternal characteristics (maternal age, education, smoking, BMI, diabetes, and preeclampsia) and multiple intrauterine growth measures on the risk of childhood lymphomas. A total of 3 444 136 singleton live births registered in the Swedish Medical Birth Register were analyzed, among whom there were 515 incident non- Hodgkin lymphoma (NHL) cases and 169 Hodgkin lymphoma (HL) cases aged 0-14 years at diagnosis (1973-2007) identified through linkage with the Swedish Cancer Register. Proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) of NHL and HL. Male sex (HR=2.00, 95% CI: 1.66-2.41), older maternal age (HR=1.03, 95% CI: 1.00-1.06, per 1-year increase), and large for gestational age compared with appropriate for gestational age (AGA) birth weight (HR=1.83, 95% CI: 1.20-2.79) were correlated with the risk of NHL; of note, in subanalysis by sex, the latter association was confined to girls (HR=3.37, 95% CI: 1.90-5.97, Pinteraction by sex=0.008). The risk of childhood HL overall was more evident among boys (HR=2.03, 95% CI: 1.46-2.81), whereas indices of accelerated fetal growth were not convincingly associated with the risk of HL. Apart from the established association with sex, the findings point to accelerated intrauterine growth as a risk factor for childhood NHL that may differ by sex. Given the rarity of this condition at birth, however, further studies with more elaborate indices are needed to conclude on its association with rare diseases such as HL. Copyright © 2015 Wolters Kluwer Health, Inc.


Liese J.G.,University of Würzburg | Silfverdal S.A.,Umeå University | Giaquinto C.,University of Padua | Carmona A.,Instituto Hispalense Of Pediatria | And 13 more authors.
Epidemiology and Infection | Year: 2014

We conducted an epidemiological, observational cohort study to determine the incidence and complications of acute otitis media (AOM) in children aged <6 years. Data on physician-diagnosed AOM were collected from retrospective review of medical charts for the year preceding enrolment and then prospectively in the year following enrolment. The study included 5776 children in Germany, Italy, Spain, Sweden, and the UK. AOM incidence was 256/1000 person-years [95% confidence interval (CI) 243-270] in the prospective study period. Incidence was lowest in Italy (195, 95% CI 171-222) and highest in Spain (328, 95% CI 296-363). Complications were documented in <1% of episodes. Spontaneous tympanic membrane perforation was documented in 7% of episodes. Both retrospective and prospective study results were similar and show the high incidence during childhood in these five European countries. Differences by country may reflect true differences and differences in social structure and diagnostic procedures. © 2014 Cambridge University Press.


Benyi E.,Paediatric Endocrinology Unit | Kieler H.,Center for Pharmacoepidemiology | Linder M.,Center for Pharmacoepidemiology | Ritzen M.,Paediatric Endocrinology Unit | And 4 more authors.
Hormone Research in Paediatrics | Year: 2014

Background/Aim: High-dose oestrogen treatment has been used to reduce growth in tall adolescent girls. The long-term safety with regard to cancer has not been clarified. Our aim was to study if this growth reduction therapy affects cancer risk later in life. Methods: A cohort study of 369 (172 treated, 197 untreated) Swedish women who in 1973-1993 were assessed for tall adolescent stature was designed. Data were collected from university hospital records, patient questionnaires, and the Swedish Cancer Register. Results: Risks are presented as odds ratios (ORs) with 95% confidence intervals comparing treated to untreated subjects. In treated subjects, the overall OR for having a tumour (malignant or non-malignant) was 1.7 (0.8-3.8). The ORs were 2.3 (0.4-12.8) for breast tumours, 0.8 (0.2-2.6) for gynaecological tumours, and 6.1 (1.04-∞) for melanoma. When limiting to malignant tumours, the crude ORs were of similar magnitude. Conclusion: The OR for any melanoma was higher in treated than in untreated women, suggesting an increased risk of melanoma associated with high-dose oestrogen treatment during adolescence. Although the risk estimates were increased for overall tumours, breast tumours, malignant gynaecological tumours, and malignant melanoma, these associations were not statistically significant. Our results need to be verified in a larger cohort. © 2014 S. Karger AG, Basel.


Zarrinkoub R.,Karolinska Institutet | Zarrinkoub R.,Public Healthcare Services Committee Administration | Zarrinkoub R.,Storvreten Primary Health Care Center | Wettermark B.,Public Healthcare Services Committee Administration | And 9 more authors.
European Journal of Heart Failure | Year: 2013

AimsThe epidemiology of congestive heart failure (CHF) is likely to have changed due to changes in demography, risk factors, diagnostic procedures, and medical care. Prevailing information is in part old, incomplete, and to some extent contradictory. We determined the current prevalence, incidence, mortality, and 5-year survival rate of CHF, and possible temporal changes in Sweden.Methods and resultsThis was a cross-sectional study on individual patient data from an administrative health data register in the Stockholm region, Sweden, comprising 2.1 million inhabitants. This contained all recorded diagnoses on all consultations in primary and secondary care (defined as specialist outpatient care), and on all hospitalizations. Prevalence, incidence, and mortality were estimated for the entire Swedish population, adjusted for demographic composition in 2010. The study population consisted of 88 038 patients (51% women). The prevalence was 2.2% (both women and men), the incidence was 3.8/1000 person-years (both women and men), and mortality was 3.2/1000 person-years in women and 3.0/1000 person-years in men (P < 0.001); the 5-year survival rate was 48%. Mortality (age adjusted; hazard ratio and 95% confidence intervals) was higher in men, 1.29, 1.24 - 1.34; P < 0.001. Prevalence remained essentially unchanged from 2006 to 2010, while incidence decreased by 24% (P < 0.001) and mortality by 19% (both women and men; P < 0.001).ConclusionsThe estimated prevalence of CHF in Sweden is 2.2%, incidence 3.8/1000 person-years, and mortality 3.1/1000 person-years. There has been a decrease in incidence and mortality from 2006 to 2010 in both women and men, with no major change in prevalence over time. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Cardiology.


Bergendal A.,Center for Pharmacoepidemiology | Kieler H.,Center for Pharmacoepidemiology | Sundstrom A.,Center for Pharmacoepidemiology | Hirschberg A.L.,Karolinska Institutet | Kocoska-Maras L.,Karolinska Institutet
Menopause | Year: 2016

Objective: The aim of the study was to assess the risk of venous thromboembolism (VTE) associated with systemic hormone therapy according to type and to route of administration and the risk of VTE associated with locally administered estrogen. Methods: In this case-control study, conducted in Sweden between 2003 and 2009, we included 838 cases of VTE and 891 controls with a mean age of 55 years. Controls were matched by age to the cases and randomly selected from the population. We used logistic regression to calculate odds ratios (ORs) with 95% CIs and adjusted for smoking, body mass index, and immobilization. Results: Current use of any hormone therapy was associated with an increased risk of VTE (OR 1.72, 95% CI 1.34-2.20). For estrogen in combination with progestogen the OR was 2.85 (95% CI 2.08-3.90), and for estrogen only the OR was 1.31 (95% CI 0.78-2.21). In orally administered estrogen combined with progestogen, the OR was slightly, but not significantly, higher among users of medroxyprogesterone acetate (OR 2.94, 95% CI 1.67-5.36) than among norethisterone acetate users (OR 2.55, 95% CI 1.50-3.40). Transdermal estrogen combined with progestogen was not associated with VTE risk (crude and imprecise ORs ranging from 0.87 to 1.16). For local effect of estrogen, there was no association with VTE risk (OR 0.69, 95% CI 0.43-1.10). Conclusions: The risk of VTE risk is higher in users of systemic combined estrogen-progestogen treatment than in users of estrogen only. Furthermore, the risk of VTE was lower for women who used local estrogen than among those using oral estrogen only. Transdermal estrogen only treatment and estrogen for local effect seem not to be related to an increased risk of VTE. © 2016 by The North American Menopause Society.

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