Helle Kieler

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (100)369.22 Total impact

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    ABSTRACT: Family history of venous thromboembolism (VTE) has been suggested to be more useful in risk assessment than thrombophilia testing. We investigated established genetic susceptibility variants for association with VTE and evaluated a genetic risk score in isolation and combined with known trigger factors, including family history of VTE. A total of 18 single nucleotide polymorphisms (SNPs) selected from the literature were genotyped in 2835 women participating in a Swedish nationwide case-control study (the ThromboEmbolism Hormone Study (TEHS)). Association with VTE was assessed by odds ratios (ORs) with 95% confidence interval (CI) using logistic regression. Clinical and genetic predictors that contributed significantly to the fit of the logistic regression model were included in the prediction models. SNP-SNP interactions were investigated and incorporated into the models if found significant. Risk scores were evaluated by calculating the area under the receiver-operating characteristics curve (AUC). Seven SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446) with 4 SNP-SNP interactions contributed to the genetic risk score for VTE with an AUC of 0.66 (95% CI: 0.64-0.68). After adding clinical risk factors, which included family history of VTE, the AUC attained 0.84 (95% CI: 0.82-0.85). The goodness of fit of the genetic and combined scores improved when significant SNP-SNP interaction terms were included. Prediction of VTE in high-risk individuals was more accurate when a combination of clinical and genetic predictors with SNP-SNP interactions was included in a risk score. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 12/2014; · 6.08 Impact Factor
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    ABSTRACT: Bronchopulmonary dysplasia (BPD) is a frequent chronic lung disease in preterm infants and we aimed to identify factors associated with this condition in infants with respiratory distress syndrome (RDS). This case-control study, using national Swedish data, included 2,255 preterm infants, born before 33 gestational weeks. The 667 BPD cases were oxygen dependent at 36 weeks' post-menstrual age and the 1,558 controls only had RDS. Comparisons included perinatal conditions and pharmacological treatments. Adjusted odds ratios with 95% confidence intervals were calculated in a conditional logistic regression model, with gestational age as the conditioning term. An increased risk of BPD was associated with pre-labour preterm rupture of membranes of more than one week (3.35, 2.16-5.19), small for gestational age (2.73, 2.11-3.55), low Apgar score (1.37, 1.05-1.81), patent ductus arteriosus (1.70, 1.33-2.18), persistent pulmonary hypertension (5.80, 3.21-10.50), pulmonary interstitial emphysema (2.78, 1.37-5.64), pneumothorax (2.95, 1.85-4.72), late onset infections (2.69, 1.82-3.98), intubation (1.56, 1.20-2.03), chest compressions (2.05, 1.15-3.66) and mechanical ventilation (2.16, 1.69-2.77), but not antenatal corticosteroids. Growth restriction and inflammation increased the risk of BPD in preterm infants and pre-labour preterm rupture of membranes, small for gestational age, low Apgar score or need for resuscitation should raise clinical suspicions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Acta paediatrica (Oslo, Norway: 1992). Supplement 12/2014;
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    ABSTRACT: 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.DesignCase–control study using data from national registers.SettingDenmark, Finland, and Norway during the period 1996–2007.PopulationA 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 measuresAssociation 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.ResultsAt 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.Conclusions 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.
    BJOG An International Journal of Obstetrics & Gynaecology 11/2014; · 3.76 Impact Factor
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    ABSTRACT: Objectives The aim of this study was to explore the impact of severe mental illness (SMI) on myocardial infarction survival, and determine the influence of risk factor burden, myocardial infarction severity and different treatments.Design, setting and participantsThis population-based cohort study, conducted in Sweden during the period 1997–2010, included all patients with a first diagnosis of myocardial infarction in the Swedish nationwide myocardial infarction register SWEDEHEART (n = 209 592). Exposure was defined as a diagnosis of SMI (i.e. bipolar disorder or schizophrenia) in the national patient register prior to infarction. Bias-minimized logistic regression models were identified using directed acyclic graphs and included as covariates age, gender, smoking, diabetes, previous cardiovascular disease, myocardial infarction characteristics and treatment.Main outcome measuresThe primary outcomes were 30-day and 1-year mortality, obtained through linkage with national population registers.ResultsPatients with bipolar disorder (n = 442) and schizophrenia (n = 541) were younger (mean age 68 and 63 years, respectively) than those without SMI (n = 208 609; mean age 71 years). The overall 30-day and 1-year mortality rates were 10% and 18%, respectively. Compared with patients without SMI, patients with SMI had higher 30-day [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.55–2.56] and 1-year mortality (OR 2.11, 95% CI 1.74–2.56) in the fully adjusted model. The highest mortality was observed among patients with schizophrenia (30-day mortality: OR 2.58, 95% CI 1.88–3.54; 1-year mortality: OR 2.55, 95% CI 1.98–3.29).ConclusionSMI is associated with a marked higher mortality after myocardial infarction, even after accounting for contributing factors. It is imperative to identify the reasons for this higher mortality.This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 11/2014; · 6.46 Impact Factor
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    ABSTRACT: This work aims to study the effects of hormone therapy (HT) on the risk of cardiovascular outcomes and all-cause mortality in women treated with statins.
    Menopause (New York, N.Y.) 10/2014; · 3.08 Impact Factor
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    ABSTRACT: Treatment guidelines state that all patients with bipolar disorder should use pharmacological prophylaxis; however the actual use of prophylactic drugs after bipolar disorder diagnosis is unknown. Our aim was to assess the use of, and predictors for, pharmacoprophylaxis in newly diagnosed bipolar disorder patients.Methods Data from three Swedish nationwide registers were obtained. We identified patients aged 18–75 with a first time diagnosis of bipolar disorder between 2006 and 2012 (n=31,770) and reviewed subsequent mood-stabilizer and antipsychotic prescription fills. In multivariable Cox regression models, we studied demographic and illness related factors as predictors of prescription fills after diagnosis.ResultsIn total, 72.2% (95% confidence interval [CI] 71.7–72.7%) of the patients filled a prescription of a prophylactic drug within 3 months after diagnosis. Pharmacological prophylaxis was mainly associated with a longer duration of hospitalization at bipolar disorder diagnosis (adjusted hazard ratio [AHR] 2.18; CI 2.02–2.35 for a hospitalization of ≥28 days compared to <7 days) and previous use of any mood-stabilizer or antipsychotic (inpatients: AHR 1.24; CI 1.17–1.31 and outpatients: AHR 1.78; CI 1.73–1.84).LimitationsWe had no information on drug prescriptions that were never filled.Conclusions The proportion of newly diagnosed bipolar disorder patients without pharmacological prophylaxis is substantial. Patients who are naïve to mood-stabilizers and antipsychotics and are hospitalized for a brief period at diagnosis are the ones least likely to initiate pharmacoprophylaxis, suggesting that this group deserves attention in order to improve the long term prognosis.
    Journal of Affective Disorders. 10/2014;
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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: 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 05/2014; · 3.13 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: To investigate the association between exposure to antibiotics in fetal and early life and asthma in childhood, with adjustment for confounding factors. Nationwide prospective population based cohort study, including sibling control design. Swedish population identified from national demographic and health registers. 493 785 children born 2006-10; 180 894 of these were eligible for sibling analyses. Asthma defined as having both an asthma diagnosis and dispensed asthma drugs. The association between antibiotic exposure and asthma was investigated in the whole cohort with Cox proportional hazard regression. A stratified proportional hazards model conditional on sibling group was used to adjust for shared factors within families. Confounding by respiratory infections was assessed by investigating whether specific groups of antibiotics were associated with asthma. Antibiotic exposure in fetal life was associated with an increased risk of asthma in cohort analyses (hazard ratio 1.28, 95% confidence interval 1.25 to 1.32), but not in sibling analyses (0.99, 0.92 to 1.07). In cohort analyses, antibiotics used to treat respiratory infections in childhood were associated with a more pronounced increased risk of asthma (4.12, 3.78 to 4.50) than antibiotics used for urinary tract and skin infections (1.54, 1.24 to 1.92). In sibling analyses, the excess risks after exposure to antibiotics for respiratory infections decreased (2.36, 1.78 to 3.13) and disappeared for antibiotics for urinary tract and skin (0.85, 0.47 to 1.55). Previous positive associations between exposure to antibiotics in fetal and early life and subsequent childhood asthma could have been caused by confounding by shared familial factors, in addition to confounding by respiratory infections. © Örtqvist et al 2014.
    BMJ Clinical Research 01/2014; 349:g6979. · 14.09 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

Publication Stats

742 Citations
369.22 Total Impact Points


  • 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