Helle Kieler

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (93)335.75 Total impact

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    ABSTRACT: To investigate associations between combined hormonal contraception and progestogen-only contraception and risks of venous thromboembolism by progestogen and carriership of genetic hemostatic variations.
    Obstetrics and gynecology. 09/2014; 124(3):600-609.
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    ABSTRACT: 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.
    Hormone Research in Paediatrics 06/2014; · 1.55 Impact Factor
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    ABSTRACT: Ulcerative colitis (UC) and Crohn's disease (CD) have been associated with increased risks of adverse birth outcomes. Disease activity and drug exposure may contribute to the association. A cohort from the Swedish health registers including 470,110 singleton births in Sweden from July 2006 to December 2010; 1833 to women with UC and 1220 to women with CD. Birth outcomes for women with UC and CD were compared with outcomes among those without disease. Diseased women were categorized by drug exposure, need of surgery, and hospital admissions as (1) no disease activity and (2) stable or (3) flaring disease. Logistic regression was used to calculate odds ratios with adjustments (aOR) for maternal age, parity, smoking status, body mass index, and comorbidity. There were increased risks of preterm birth for both UC (aOR, 1.78; 95% confidence interval [CI], 1.49-2.13) and CD (aOR, 1.65; 95% CI, 1.33-2.06). Risks were more pronounced in women with flaring disease during pregnancy. Risks of small for gestational age, low Apgar score, and hypoglycemia were also increased. The risk of stillbirth was elevated in women with CD, particularly among those with flaring disease (aOR, 4.48; 95% CI, 1.67-11.90). Thiopurine exposure increased risks for preterm birth, both in women with stable (aOR, 2.41; 95% CI, 1.05-5.51) and with flaring disease (aOR, 4.90; 95% CI, 2.76-8.69). Women with UC and CD are at increased risk of adverse birth outcomes, such as stillbirth, growth restriction, and preterm birth, particularly when they suffer from flares throughout pregnancy. Thiopurine exposure seems to further increase risks, independently of disease activity.
    Inflammatory Bowel Diseases 05/2014; · 5.12 Impact Factor
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    ABSTRACT: Introduction and AimsTo assess opioid-related mortality and correlation with filled prescriptions for buprenorphine and methadone.Design and MethodsA register study, including data from the Swedish Forensic Pathology and Forensic Toxicology databases 2003–2010, the Prescribed Drug Register and the National Patient Register.ResultsA total of 1301 deaths, assessed as related to buprenorphine, methadone or heroin, or a combination of them, were studied. The largest number of fatalities was related to intake of heroin (n = 776), followed by methadone (n = 342) and buprenorphine (n = 168). The total annual number of fatal cases related to the studied drugs more than doubled (116 to 255) during the study period. There were increases in mortality related to both buprenorphine and methadone: from 1 to 49 cases for buprenorphine, and from 19 to 81 cases for methadone. Only one-fifth of the fatal cases had a filled prescription for the maintenance drug assessed as the cause of death.Discussion and Conclusion This study showed that most fatalities were not related to filled prescriptions of maintenance drugs, and a substantial illicit use of buprenorphine and methadone resulting in deaths was revealed. To prevent opioid toxicity deaths it is important to make efforts not only to reduce drug diversion from maintenance programs, but also to improve the control of drug trafficking and other illegal sources. [Wikner BN, Öhman I, Seldén T, Druid H, Brandt L, Kieler H. Opioid-related mortality and filled prescriptions for buprenorphine and methadone. Drug Alcohol Rev 2014]
    Drug and Alcohol Review 05/2014; · 1.55 Impact Factor
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    ABSTRACT: Persistence to statins is low, presumably due to lack of perception of risk. Having a close relative suffering from cardiovascular disease (CVD) might increase persistence to statins. We investigated whether family history of CVD influences the discontinuation of statin treatment. A population-based cohort study was performed. Swedish registers on dispensed drugs, hospitalization and cause of death were linked to the Multi-generation Register. Incident statin users 20-72 years of age were identified between 2006 and 2007 and followed until 30 June 2009. Family history of CVD was defined as the presence of relatives with a previous cardiovascular event. Cox regression was used to study discontinuation and estimate the effect of the family history of CVD, adjusting for gender, age, education, income, healthcare provider, prevention's type, birth's country and residence's county. Stratified analysis by type and severity of cardiovascular event was performed. A total of 86,002 patients were enrolled; 61.5 % had a family history of CVD. Discontinuation of statin therapy was not associated with family history of CVD (HR: 0.98; 95 % CI:0.96-1.01), except for patients with a family history of death from myocardial infarction (MI) (HR: 0.95 95 % CI:0.92-0.98). Young age, foreign background, low income, and statin for primary prevention and for secondary prevention when prescribed by a general practitioner were associated with higher risk of statin discontinuation. Having relatives suffering from CVD did not consistently influence the persistence to statin treatment. A family history of death from MI had a slight significant positive effect on statin persistence, though not clinically relevant.
    European Journal of Clinical Pharmacology 03/2014; · 2.74 Impact Factor
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    ABSTRACT: Introduction We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case–control study (n = 2753) from Sweden. Materials and Methods 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. Results Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181). Conclusions It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.
    Thrombosis Research 01/2014; · 3.13 Impact Factor
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    ABSTRACT: Background It is a matter of debate whether women with an episode of VTE associated with estrogen have a lower risk of recurrence than women with an unprovoked VTE. Objectives To identify risk factors for recurrent VTE in women and to assess the risk of recurrent VTE associated with combined oral contraceptives (CHC) or menopausal hormone treatment (HT), compared to surgery-related and unprovoked VTE. Patients/Methods A cohort of 974 women aged 18–64 years with a first episode of VTE were followed-up for a median time of 5.2 years. All women were previously included as cases in the Swedish nation-wide case–control study “Thrombo Embolism Hormone Study” (TEHS). Hazard ratios for recurrence were calculated using univariable and multivariable Cox proportional hazards model. Results A total of 102 patients (10%) suffered from recurrent VTE. The annual rate of recurrence was 1.0% in patients with surgery/plaster, 2.0% in patients with CHC/HT and 3.2% in patients with unprovoked first VTE. Adjusted hazards ratio (HRa) for recurrence was 0.35 (95% CI 0.20-0.61) in women with VT provoked by surgery/plaster while women with estrogen-associated VTE had a HRa of 0.70 (95% CI 0.43-1.20) compared to women with unprovoked VTE. Conclusion Women 18–64 years are at low risk of recurrent VTE. Women with hormone associated VTE had a lower risk of recurrence than women with unprovoked VTE, but not as low as surgery/cast provoked VTE.
    Thrombosis Research 01/2014; · 3.13 Impact Factor
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    ABSTRACT: Ovarian cancer is a severe disease with a peak incidence in the older age groups where concurrent morbidity is common and could potentially influence mortality rates. Objectives The aim was to study the influence of common comorbidity diagnoses on mortality in ovarian cancer patients. Methods The study population was patients with ovarian cancer in Sweden 1993–2006 (n = 11.139) identified in the national Cancer Register. Comorbidity data was obtained from the Patient Register and mortality from Cause of Death Register. Mortality was analyzed with Cox´ proportional hazards models and subgroup analyses were performed by age and tumour histology. Results Almost all of the assessed comorbidities increased mortality in ovarian cancer patients. Thromboembolism was the most hazardous comorbidity (HR = 1.95, < 1 year after cancer diagnosis and HR = 7.83, 1–5 years after cancer diagnosis) followed by hematologic complications (HR = 1.84 and 7.11 respectively) and infectious disease (HR = 1.48 and 5.28 respectively). The occurrence of diabetes mellitus and hypertension had less impact on mortality. Conclusion Thromboembolism, hemathologic complications and infections had a pronounced effect on mortality rates in women with ovarian cancer. The impact of comorbidity was mainly apparent among those with a more prosperous prognosis, such as longer time since cancer diagnosis, less aggressive tumours and younger age.
    Gynecologic Oncology 01/2014; · 3.93 Impact Factor
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    ABSTRACT: Concerns have been raised about the abuse potential of pregabalin. Therefore, the aim of our study was to characterize patients dispensed pregabalin at higher than the maximum allowed dose in a cohort study based on data extracted from Swedish national registers. All patients dispensed at least three prescriptions of pregabalin between July 2006 and December 2009 were included (n = 48,550). The daily dose was defined as the amount of pregabalin dispensed divided by the number of days between the second and third dispensings. Associations between sociodemographic and clinical variables and dispensing pregabalin at a dose exceeding the maximum daily allowed dose (600 mg) were investigated in multivariate regression models. Of the patients dispensed pregabalin during the study period, 8.5 % were dispensed a dose that exceeded the maximum daily allowed dose. A previous addictive disorder drug treatment or diagnosis was present in 20 and 31 % of patients dispensed pregabalin within and exceeding the recommended dose range, respectively. Our analysis revealed that those patients at increased risk of being dispensed pregabalin at higher than the maximum allowed dose were male [adjusted odds ratio (aOR) 1.40, 95 % confidence interval (CI) 1.31-1.49], were between 18 and 29 years of age compared with those aged ≥65 years (aOR 1.62, 95 % CI 1.45-1.82), had a low income (aOR 1.24, 95 % CI 1.10-1.40), had epilepsy compared with no diagnosis (aOR 1.41, 95 % CI 1.10-1.81), had a previous substance use disorder treatment or diagnosis (aOR 1.41, 95 % CI 1.31-1.52) or had previously been dispensed high doses of drugs with abuse potential (aOR 1.77, 95 % CI 1.62-1.94). Based on our results we conclude that patients at a high risk of addiction and patients with epilepsy are more likely to be dispensed pregabalin at higher than the maximum approved daily dose.
    European Journal of Clinical Pharmacology 10/2013; · 2.74 Impact Factor
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    ABSTRACT: Assessment of factors influencing antipsychotic prescription fills in the early phase of schizophrenia or schizoaffective disorder. We used the Swedish Patient Register to identify patients younger than 45 years with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 (904 patients). Data on medication were obtained from the Prescribed Drug Register. Filling a prescription of an antipsychotic drug after discharge was used to estimate medication adherence. In Cox regression models, we studied sex, country of birth, metropolitan residence, educational level, age, duration of hospitalization, history of substance use disorder, and previous use of antipsychotic drugs as predictors for antipsychotic fills. Among all patients, 53.1% (95% confidence interval [CI] 49.9%-56.4%) had filled an antipsychotic prescription within 1 week from discharge. After 6 months, the proportion had increased to 80.2% (95% CI, 77.4%-82.8%) with no further increase thereafter. Prescription filling of an antipsychotic drug was primarily associated with antipsychotic use before the hospitalization (hazard ratio, 1.64; 95% CI, 1.33-2.03; for patients with access to antipsychotic drugs at admission compared with no previous use) and with longer hospitalization (hazard ratio, 1.60; 95% CI, 1.27-2.02 for 15-28 days compared with shorter hospitalization). Among patients who filled a prescription of an antipsychotic drug after discharge, the majority did so within 1 week. Previous adherent use of antipsychotic drugs and longer hospitalization may be predictors of primary adherence to antipsychotic drug treatment in schizophrenia or schizoaffective disorder.
    Journal of clinical psychopharmacology 10/2013; · 5.09 Impact Factor
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    ABSTRACT: Bronchopulmonary dysplasia (BPD) is a serious, chronic lung disease affecting preterm infants. To identify prenatal risk factors for BPD, focusing on inflammation. Observational cohort study including 106,339 preterm infants, live born before gestational week 37 + 0, from 1988 to 2009 in Sweden. A total of 2,115 infants were diagnosed with BPD, of which 1,393 were born extremely preterm, before gestational week 28 + 0. Information on risk factors was obtained from national health registers and included maternal chronic inflammatory diseases, pregnancy related diseases, and drugs related to treatment of inflammation or infection during pregnancy. Adjusted odds ratios (OR) were calculated in multivariable logistic regression models and are presented with 95% confidence intervals [95% CI]. Preeclampsia was the strongest risk factor for BPD [adjusted OR 2.04, 95% CI 1.83, 2.29]. For extremely preterm infants the adjusted OR was 1.33 [95% CI 1.08, 1.64]. Chorioamnionitis was associated with an increased risk of BPD, but only when including all infants in the analyses [OR 1.33, 95% CI 1.19, 1.48]. No apparent associations were found between maternal chronic inflammatory disease or use of anti-inflammatory drugs and the risk of BPD. Maternal diabetes mellitus, gestational diabetes and maternal use of antibiotics were associated with reduced risks of BPD. Preeclampsia related disorders increased the risk and maternal diabetes mellitus and gestational diabetes reduced the risk for BPD. As angiogenic factors play a role in preeclampsia and diabetes our findings suggest that an impaired angiogenesis may contribute to BPD development. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.
    Pediatric Pulmonology 09/2013; · 2.38 Impact Factor
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    ABSTRACT: The aim of this study was to describe the pediatric population with ADHD and their pharmacological treatment. Using the Swedish National Patient Register and the Prescribed Drug Register we identified individuals below 19 years of age who were diagnosed or medically treated for ADHD for the first time 2006-2007. The unique patient identifiers were used to link information from the two registers to describe demographic characteristics, hospital care and drug treatments. Logistic regression model estimated the association between age, sex, frequency of hospitalization, diagnosis or treatment for other mental disorders and risk of gap in the treatment. Totally the study included 7931 patients of whom 74% were males. The mean age at first diagnosis was 12 years. Some 84% were medically treated for ADHD and approximately 90% received methylphenidate as the first substance. Combination therapy was rare and the most common combination was methylphenidate and atomoxetine. More than 55% of the patients, which could be followed up for two years after start of treatment, had at least one treatment gap of six months. Older age at diagnosis, lower number of hospitalizations and comorbidity with other mental disorders increased risks of gaps in medication. Approximately one fifth of the patients recorded in the National Patient Register as diagnosed with ADHD did not receive pharmacological treatment. Medication adherence seems to be low, when measured as gaps in treatment.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 08/2013; · 3.68 Impact Factor
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    ABSTRACT: To determine factors associated with low persistence in patients initiated on drug treatment for hypertension. Cohort study using medical records for patients with hypertension in 48 Swedish primary healthcare centres. Data were linked to national registers on dispensed drugs, hospitalizations, outpatient hospital consultations, deaths, migration, and socioeconomy. We identified 5225 patients (55 % women, mean age 61 years) initiated on antihypertensive drug treatment during 2006-2007. Persistence was measured for two years by the dispensed drugs. Patients with a gap of >30 days between end of dispensed supply and the next dispensed prescription were classified as non-persistent. This was calculated by Kaplan-Meier analysis. Cox proportional hazard regression was used to estimate hazard ratios for discontinuation. Potential predictors included age, gender, blood pressure before initiation of therapy, cardiovascular comorbidity, educational level, country of birth, and income. Among patients with a dispensed first prescription, 26 % discontinued treatment during the first year, and a further 9 % discontinued during the second year. Discontinuation (all adjusted) was more common in men (P = 0.002) and in younger patients (30-49 years, P < 0.001). Systolic (P < 0.001) but not diastolic blood pressure was positively associated with persistence. Native-born Swedish citizens and patients born in the other Nordic countries had lower discontinuation rates than those born outside the Nordic countries (P < 0.001). Major determinants of discontinuation of antihypertensive drug treatment are male sex, young age, mild-to-moderate systolic blood pressure elevation, and birth outside of Sweden.
    European Journal of Clinical Pharmacology 07/2013; · 2.74 Impact Factor
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    ABSTRACT: To assess prescribing patterns, sociodemographic characteristics and previous disease history in patients receiving pregabalin. An observational study using register data on dispensed drugs and recorded diagnoses for all patients in Stockholm, Sweden, who filled at least one prescription of pregabalin between July 2005 and December 2009. Analyses focused on prevalence, incidence, diagnosis patterns, prior dispensing of other analgesics/psychotropics and persistence to treatment over time. A total of 18,626 patients (mean age 55 years, 63% women) were initiated on treatment between July 2006 and December 2009. Approved indications were recorded in hospital and/or primary care within 1 year prior to the first dispensing for 40% of the patients (epilepsy 1.3%, neuropathic pain 35.5% and generalised anxiety disorder (GAD) 3.6%). Antidepressants were used by 55%, opioids by 49% and sedatives by 48% prior to initiation of pregabalin. One-third (34%) only purchased one prescription and the proportion purchasing pregabalin 1 year after initiation was 42.1% for epilepsy, 36.3% for GAD, 21.5% for neuropathic pain and 25.6% for those without any of the included diagnoses. Pregabalin was mainly used as a second-line drug for the treatment of GAD or neuropathic pain and to a lesser extent as add-on therapy in epilepsy. However, a large proportion of all patients only purchased one prescription and the persistence declined rapidly over time. The issue of potential off-label prescribing or poor registration of diagnoses should also be noted as a high proportion had been prescribed the drug without a record of any of the approved indications.
    International Journal of Clinical Practice 07/2013; · 2.43 Impact Factor
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    ABSTRACT: Combined hormonal contraceptives, menopause hormone treatment and surgery/cast in orthopedic patients are important risk factors for venous thromboembolism (VTE) in women. To evaluate whether self-reported family history can be used for risk assessment concerning hormone and surgery /cast related VTE in women. 1288 women 18-64years with a first event of VTE and 1327 age-matched controls were included in a nation-wide population-based case-control study in Sweden. Odds ratios were calculated by comparing occurrence of VTE in women with and without a positive family history in combination with hormones or surgery/cast. The risk of hormone-associated VTE was doubled in women with a family history of VTE as compared to women with hormones and negative family history. The risk was more than tripled in women with surgery/cast and a positive family history, as compared to surgery/cast patients with negative family history. Women with a positive family history and combined hormonal contraceptive or menopause hormone treatment had an OR of 15.3 (95% CI 6.1-38) and 5.9 (95% CI 3.3-11) respectively compared to women without hormones or family history. The corresponding OR in women with surgery/cast and a positive family history was 67 (95% CI 21-213) compared to women without surgery/cast treatment and a negative family history. Self-reported family history is associated with increased odds of developing VTE on combined hormonal contraceptives, menopause hormone treatment and in connection with surgery or plaster. We believe that assessing family history of VTE can be helpful in identifying high risk patients.
    Thrombosis Research 06/2013; · 3.13 Impact Factor
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    ABSTRACT: PURPOSE: All five Nordic countries have nationwide prescription databases covering all dispensed drugs, with potential for linkage to outcomes. The aim of this review is to present an overview of therapeutic areas studied and methods applied in pharmacoepidemiologic studies using data from these databases. METHODS: The study consists of a Medline-based structured literature review of scientific papers published during 2005-2010 using data from the prescription databases in Denmark, Finland, Iceland, Norway, and Sweden, covering 25 million inhabitants. Relevant studies were analyzed in terms of pharmacological group, study population, outcomes examined, type of study (drug utilization vs. effect of drug therapy), country of origin, and extent of cross-national collaboration. RESULTS: A total of 515 studies were identified. Of these, 262 were conducted in Denmark, 97 in Finland, 4 in Iceland, 87 in Norway, and 61 in Sweden. Four studies used data from more than one Nordic country. The most commonly studied drugs were those acting on the nervous system, followed by cardiovascular drugs and gastrointestinal/endocrine drugs. A total of 228 studies examined drug utilization and 263 focused on the effects and safety of drug therapy. Pregnant women were the most commonly studied population in safety studies, whereas prescribers' adherence to guidelines was the most frequent topic of drug utilization studies. CONCLUSIONS: The Nordic prescription databases, with their possibility of record-linkage, represent an outstanding resource for assessing the beneficial and adverse effects of drug use in large populations, under routine care conditions, and with the potential for long-term follow-up. Copyright © 2013 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 05/2013; · 2.90 Impact Factor
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    ABSTRACT: OBJECTIVE: To explore if antenatal fear of childbirth in men affects their experience of the birth event and if this experience is associated with type of childbirth preparation. DESIGN: Data from a randomized controlled multicentre trial on antenatal education.Setting.15 antenatal clinics in Sweden between January 2006 and May 2007. SAMPLE: 762 men of whom 83 (10.9%) suffered from fear of childbirth. Of these 83 men 39 were randomized to psychoprophylaxis childbirth preparation where men were trained to coach their partners during labor and 44 to Standard care antenatal preparation for childbirth and parenthood without such training. METHODS: Experience of childbirth was compared between men with and without fear of childbirth regardless of randomization, and between fearful men in the randomized groups. Analyses by logistic regression adjusted for socio demographic variables. MAIN OUTCOME MEASURES: Self-reported data on experience of childbirth including an adapted version of the Wijma Delivery Experience Questionnaire (W-DEQ B). RESULTS: Men with antenatal fear of childbirth more often experienced childbirth as frightening than men without fear: adjusted odds ratio 4.68, 95% confidence interval 2.67-8.20. Men with antenatal fear in the Psychoprophylaxis group rated childbirth as frightening less often than those in Standard care: adjusted odds ratio 0.30 95% confidence interval 0.10-0.95. Conclusions Men who suffer from antenatal fear of childbirth are at higher risk of experiencing childbirth as frightening. Childbirth preparation including training as a coach may help fearful men to a more positive childbirth experience. Additional studies are needed to support this conclusion. This article is protected by copyright. All rights reserved.
    Acta Obstetricia Et Gynecologica Scandinavica 04/2013; · 1.85 Impact Factor
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    ABSTRACT: BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) might increase the risk of venous thromboembolism (VTE), and risks might differ by type of NSAID. Compared with men, women have a higher incidence of VTE at younger age, and they more often use NSAIDs. OBJECTIVES: To assess risks of VTE in young and middle-aged women in association with use of NSAIDs. PATIENTS/METHODS: In a nationwide case-control study (Thrombo Embolism Hormone Study) performed in Sweden 2003-2009, we included as cases 1433 women, 18 to 64 years of age with a first time VTE. Controls were 1402 randomly selected women, frequency matched by age. Information was obtained by telephone interviews and DNA analyses of blood samples. We calculated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) adjusting for degree of immobilization, chronic disease, smoking, body mass index, use of hormonal contraception, hormone therapy or other NSAIDs. RESULTS: Use of NSAIDs was not associated with increased risks of VTE (OR = 0.98, 95% CI 0.80-1.19). The OR was 0.88 for propionic acid derivatives (95% CI 0.72-1.10), 1.18 for acetic acid derivatives (95% CI 0.82-1.70) and 1.76 for coxibs (95% CI 0.73-4.27). For users of acetic acid derivatives and coxibs, the ORs increased by cumulative dose. Carriership of the prothrombin gene mutation or factor V Leiden had only minor effects on the results. CONCLUSIONS: We found no increased risks of VTE in association with use of NSAIDs. Users of high cumulative doses of acetic acid derivatives and coxibs had the highest risks, suggesting a relationship with cyclooxygenase selectivity and dose. Copyright © 2013 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 03/2013; · 2.90 Impact Factor
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    ABSTRACT: 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. To study risk of stillbirth and infant mortality associated with use of SSRIs during pregnancy. 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. 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. 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. 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.
    JAMA The Journal of the American Medical Association 01/2013; 309(1):48-54. · 29.98 Impact Factor
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    ABSTRACT: Osteonecrosis of the jaw (ONJ) is an adverse effect of drugs that suppress bone turnover - for example, drugs used for the treatment of postmenopausal osteoporosis. The Danish National Registry of Patients (DNRP) is potentially valuable for monitoring ONJ and its prognosis; however, no specific code for ONJ exists in the International Classification of Diseases 10th revision (ICD-10), which is currently used in Denmark. Our aim was to estimate the positive predictive value (PPV) of an algorithm to capture ONJ cases in the DNRP among women with postmenopausal osteoporosis. We conducted this cross-sectional validation study in the Central and North Denmark Regions, with approximately 1.8 million inhabitants. In total, 54,956 women with postmenopausal osteoporosis were identified from June 1, 2005 through May 31, 2010. To identify women potentially suffering from ONJ, we applied an algorithm based on ICD-10 codes in the DNRP originating from hospital-based departments of oral and maxillofacial surgery (DOMS). ONJ was adjudicated by chart review and defined by the presence of exposed maxillofacial bone for 8 weeks or more, in the absence of recorded history of craniofacial radiation therapy. We estimated the PPV for the overall algorithm and for each separate ICD-10 code used in the algorithm. Charts were obtained and reviewed for all 60 women with an ICD-10 code potentially representing ONJ. Nineteen potential ONJ cases were confirmed, corresponding to an overall PPV of 32% (95% confidence interval: 20%-45%). Among women with postmenopausal osteoporosis, only about one-third of the potential ONJ cases identified by our ICD-10 based algorithm were confirmed by medical chart review, despite the restriction to patients treated at DOMS. To capture true ONJ cases among women with postmenopausal osteoporosis, alternative approaches are needed.
    Clinical Epidemiology 01/2013; 5:263-7.

Publication Stats

720 Citations
335.75 Total Impact Points

Institutions

  • 2002–2014
    • Karolinska Institutet
      • • Center for Pharmacoepidemiology - CPE
      • • Institutionen för medicin, Huddinge
      • • Institutionen för medicinsk epidemiologi och biostatistik
      Solna, Stockholm, Sweden
  • 2013
    • Golestan University of Medical Sciences
      • School of Medicine
      Gorgān, Ostan-e Golestan, Iran
  • 1995–2013
    • Uppsala University
      • Department of Women's and Children's Health
      Uppsala, Uppsala, Sweden
  • 2012
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 2011
    • National and Kapodistrian University of Athens
      • Division of Hygiene - Epidemiology
      Athens, Attiki, Greece
  • 2005
    • University of Gothenburg
      Goeteborg, Västra Götaland, Sweden
  • 2003–2005
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden