Helle Kieler

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (129)542.49 Total impact

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    ABSTRACT: Background: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. Methods: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed.
    Full-text · Article · Jun 2016
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    ABSTRACT: Background: Infections after diagnosis of primary chronic immune thrombocytopenia (cITP) have mostly been connected to the immunomodulation treatment. Infections may trigger autoimmune diseases and may be a complication of an already impaired immune system. Objectives: to investigate the association of cITP with infection before diagnosis. We also estimated incidence of cITP based on the new definition by the International ITP Working Group. Methods: We identified 1,087 adults with primary cITP between 2006 and 2012 using the Swedish Patient Register. Data on infections not already associated to secondary ITP were also retrieved from the register. The Standardized Incidence Ratios (SIR), using the rates from the general population, and 95% confidence intervals (CI), were estimated as a measure of relative risk. We used data from the Prescribed Drug Register to estimate SIR for anti-infective treatment. Results: Incidence of cITP was 2.30 per 100,000 person-year (95% CI 2.15-2.45). cITP was associated with an increased risk of serious infections requiring inpatient or outpatient care within five years before cITP diagnosis (SIR=8.74 95% CI 7.47-10.18). Higher magnitude SIRs were observed for candidiasis, viral infection of unspecified site and acute upper respiratory infections. For anti-infective drugs SIR was 1.37 (1.25-1.50) and the highest SIRs were observed for amoxicillin, macrolides, nitrofurantoin and antivirals. Conclusion: Patients with cITP have increased risks of infection and anti-infective treatments before their cITP diagnosis, with more marked risk for candidiasis and viral infections. The findings indicate that infection is not only related to the immunomodulation treatment but also to the disease itself. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: Purpose: Persistence to statins is low, in part due to lack of perception of cardiovascular (CV) risk. High values of low-density lipoprotein cholesterol (LDL-C) might increase the motivation for patients to be persistent. We investigated whether the baseline LDL-C value influences the discontinuation of statin treatment in patients with and without previous CV events. Methods: A cohort study was performed using information from the Swedish national registers concerning dispensed drugs, hospital contacts, cause of death, and socioeconomic status, and linked with data from clinical laboratories. Incident statin users 20 years of age or older and starting treatment between 2006 and 2007 were identified and followed for 1 year. Baseline LDL-C level was defined as the last available laboratory test result during 6 months before the index statin dispensing. Cox regression was used to study discontinuation and estimate the effect on persistence of the baseline LDL-C value adjusting for sex, age, income, comorbidity, previous CV events, type of prescriber, and country of birth. Subgroup analyses stratifying by previous CV events and by diagnosis of diabetes among subjects without previous CV events were performed. Results: A total of 29,389 patients were identified; 35.4 % had a previous CV event. A high baseline LDL-C value was associated with a lower discontinuation rate (hazard ratio (HR) 0.81, 95 % confidence interval (CI) 0.72-0.91) in patients without previous CV events. When stratifying further by diabetes diagnosis, the association was confirmed only in patients without diabetes. No association between LDL-C and persistence was found in patients with previous CV events. Conclusions: High levels of LDL-C were positively associated with statin persistence in newly treated diabetes patients without previous CV events.
    Full-text · Article · Dec 2015 · European Journal of Clinical Pharmacology
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    ABSTRACT: Background: The purpose was to describe utilization of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), including trends in prevalence, characteristics of users, drug switching and changes in prescribed doses in a large group of pregnant women across four Nordic countries. Methods: A drug utilization study based on linked individual-level data from the nationwide prescription- and medical birth registers in Denmark, Iceland, Norway and Sweden. The study population comprised all pregnancies in these countries, resulting in a live birth or stillbirth after gestational week 22 from January 1st 2008 to December 31st 2012 (N = 1 162 470). In addition to the main study drugs SSRIs and SNRIs, we included (concurrent) use of other antidepressants, antipsychotics, anxiolytics and hypnotics. Results: A total of 38 219 (3.3%) pregnancies were exposed to SSRIs and 5 634 (0.5%) to SNRIs. Prevalence of SSRI and SNRI use varied by country (1.8% in Norway to 7.0% in Iceland). Use and prescribed dosages decreased with each passing trimester of pregnancy; prevalence was 2.7% at conception, and 2.1%, 1.7% and 1.3% respectively in 1st, 2nd and 3rd trimester. In 0.6% of pregnancies women filled a prescription before pregnancy and in every trimester. In one third of exposed pregnancies, women were also dispensed anxiolytics, hypnotics or sedatives. Conclusion: Use of SSRI and SNRI use during pregnancy varied between the Nordic countries, but the overall prevalence remained low and relatively stable from 2008 to 2012. The low prevalence of use and high proportion of women who discontinue treatment in pregnancy raise questions about adequate treatment of depression in pregnant women.
    Full-text · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: Background: Patients with a history of venous thromboembolism (VTE) seem to have an increased risk of arterial cardiovascular disease (CVD). Objectives: To evaluate the risk of CVD and overall mortality after a first episode of VTE in women and to assess common risk factors for VTE and CVD. Patients/methods: We performed a cohort study inviting 1433 women with a previous VTE (exposed) and 1402 women without VTE (unexposed). The cohort was derived from TEHS, a Swedish population-based case-control study on risk factors for VTE in women age 18-64years. The women were recruited in 2002-2009. During 2011 information on CVD and mortality was obtained from a questionnaire and from the Swedish Patient Register and the Cause of Death Register. Hazard ratios (HR) for CVD and their 95% confidence intervals (CI) were calculated using Cox regression. In multivariate analyses we adjusted for age, smoking, diabetes mellitus, hypertension and body mass index. Results: 2108 (75%) women (mean age 47±13years) accepted participation. During the total follow up of 11,920 person years 35 (3.2%, 95% CI 0.7-2.1) among the exposed and 14 (1.4%, 95% CI 0.2-4.3) among the unexposed had any CVD event. The adjusted HR for CVD was 2.0 (95% CI 1.1-3.9) the adjusted HR for mortality was 2.3 (95% CI 1.2-4.6) CONCLUSION: Women with a previous VTE had a two-fold increased risk of CVD and overall mortality. Adjusting for cardiovascular risk factors only modestly changed the estimates.
    No preview · Article · Dec 2015 · Thrombosis Research
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    Full-text · Conference Paper · Nov 2015
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    ABSTRACT: 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 follow-up 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 cumulativerecurrence 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.
    No preview · Article · Oct 2015 · Thrombosis and Haemostasis
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    ABSTRACT: Disclosures: All authors have completed the ICMJE Form for Disclosure of Potential Conflicts of Interest. None of the authors have any personal conflict of interest of relevance to the manuscript. Centre for Pharmacoepidemiology at Karolinska institutet and the Department of Clinical Epidemiology at Aarhus University Hospital receive financial support from several pharmaceutical companies. The study was independently developed from a post-authorization safety study commissioned by the European Medicines Agency through Janssen Biotech. The company did not participate in study design, interpretation of the data or the decision to submit the manuscript.
    No preview · Article · Sep 2015
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    ABSTRACT: In North America, 4% to 10% of pregnant women take selective serotonin reuptake inhibitors (SSRIs) for depression. Some studies have reported an increased risk of congenital cardiovascular defects in the infants delivered to women who used SSRIs during pregnancy, although studies on these and other risks have yielded conflicting results. A previous study also reported that venlafaxine, a serotonin-norepinephrine reuptake inhibitor used as an alternative to SSRIs, was associated with some birth defects, but there are limitations in previous study on both SSRIs and venlafaxine, and further study is needed. The current study aimed to evaluate the association between the use of these drugs and risk of specific birth defects. The study population included women who gave birth to a live singleton in Denmark, Finland, Norway, Iceland, and Sweden between 1996 and 2010. Data came from national registries. Exposure in utero was defined as instances when a woman filed a prescription for SSRI from 30 days before the first day of her last period to 97 days after the last period. Birth defects assessed included a range of cardiovascular defects as well as anal atresia, hypospadias, clubfoot, limb reduction defects, craniosynostosis, omphalocele, gastroschisis, and cystic kidneys. Statistical analyses estimated odds ratios (ORs) for these types of birth defects and were adjusted for confounding factors including maternal age at delivery, maternal smoking during pregnancy, concurrent drug use, maternal diabetes, birth order, and country and year of delivery. A sibling-controlled analysis included 2288 singleton live births. Of a full study cohort of 2,303,647 women, 1.6% (36,772) were exposed to SSRIs or venlafaxine during the first trimester. During the study period, the rate of infants exposed to these drugs increased from 0.6% in 1996-2000 to 1.5% in 2001-2005 and then to 2.2% in 2006-2010. Of the 36,772 exposed, 1357 infants (3.7%) had a diagnosis of a major birth defect as compared with 3.2% (71,374 of 2,226,875) of unexposed infants (adjusted OR, 1.13; 95% confidence interval [CI], 1.06-1.20). In exposed infants, 1.5% had overall cardiac birth defects, whereas 1.2% of unexposed infants had diagnoses of cardiac birth defects (OR, 1.15; 95% CI, 1.05-1.26). The prevalence of birth defects was associated with in utero exposure to each specific SSRI, as well as venlafaxine, but not including escitalopram (adjusted ORs between 1.13 and 1.34). However, in the sibling cohort analysis, adjusted OR was 1.06 (95% CI, 0.91-1.24). The study did not find a substantial teratogenic effect of SSRIs or venlafaxine. Although the prevalence of some defects were higher in the group of exposed infants, the lack of association in the sibling control group suggest no substantial increase in the prevalence of birth defects among infants exposed to SSRIs or venlafaxine.
    Full-text · Article · Sep 2015 · Obstetrical and Gynecological Survey

  • No preview · Article · May 2015 · Maturitas
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    ABSTRACT: Background Up to one-third of women receive prescriptions for systemic antibacterial medications during pregnancy. This paper looks at the association between maternal use of systemic antibacterial medications during pregnancy and childhood cancer risk in the offspring using the prospective data on medication.MethodsA population-based follow-up study was carried out using Danish and Swedish register data. Exposure was maternal redemption of a prescription for a systemic antibacterial in the 3 months prior to pregnancy and during pregnancy (exposure window) documented in the national prescription registers, and offspring were followed up from birth to a cancer diagnosis, death, emigration, day before 15th birthday or end of follow-up, whichever came first. Timing, dosage, specific medication types and types of childhood cancer were also considered.ResultsMothers of 35.1% (n = 506 194) of the children filled at least one prescription for systemic antibacterials during the exposure window. Exposed children had a hazard ratio of 1.08 (95% confidence interval: 0.97, 1.20) compared with unexposed children. Statistically significant results were found for some specific medications (for example, ‘other antibacterials’/Anatomical Therapeutic Chemical code J01X) and combinations of cancer types and specific medications (leukaemia and other antibacterials, and hepatic cancers and tetracyclines).Conclusions The results of this study indicate that most antibacterial drugs used during pregnancy were not related to childhood cancer risk in the offspring. However, some may be associated with the development of some specific types of childhood cancers. Our findings need to be replicated in an independent data source. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · May 2015 · Pharmacoepidemiology and Drug Safety
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    ABSTRACT: Objective To assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular birth defects even when accounting for lifestyle or other familial confounding. Design Multicountry population based cohort study, including sibling controlled design. Setting Nordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers at different periods in 1996-2010. Population The full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects. Main outcome measure Prevalence of birth defects, including subtypes of cardiac defects. Odds ratio of birth defects from logistic and conditional logistic regression. Results Among 36 772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2 266 875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% confidence interval 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% confidence interval 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects. Conclusions In this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.
    Full-text · Article · Apr 2015 · BMJ (online)
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    ABSTRACT: The increased use of antibiotics has occurred while there is also a rising incidence of childhood asthma. One concern is that the rise in asthma is due to either mothers receiving antibiotics during pregnancy or increased antibiotic use in infants and young children. No study to date has investigated the association between exposure to antibiotics from the start of pregnancy and childhood asthma while also accounting for the influence of familial confounders. This study was performed to examine the association between exposure to antibiotics in fetal life or childhood and development of asthma in children followed from start of their mother’s pregnancy to school age. Data on parents and siblings, information on exposure, and outcomes were obtained from nationwide population-based registers. Antibiotics were categorized as “any antibiotics,” “airway antibiotics,” and “urinary tract or skin and soft tissue antibiotics” based on usual prescriptive use. Children were considered to have asthma if the diagnosis was made and they received 2 or more dispensed prescriptions for common asthma medications. Maternal asthma was defined as the mother having fulfilled the criteria of dispensed asthma drugs or a diagnosis of asthma made during the study period. The association between antibiotic exposure and asthma was analyzed in the entire cohort of children, with a sibling control design then used to adjust for familial factors and reported as hazard ratios (HRs). The controls were all full siblings who did not have asthma but were in the study when the index child developed asthma. Of 493,785 children in the cohort analyses, 180,894 were eligible for the sibling control analyses. Overall, 6% of the children in the cohorts had asthma, with 20% and 16% of those in the full and sibling cohorts, respectively, exposed to antibiotics in fetal life. At least 1 prescription of any antibiotic was filled for 62% of children in both cohorts; 4% of children in both cohorts were exposed to antibiotics in the hospital. Any antibiotic in fetal life was significantly associated with a 36% increased risk of asthma in childhood with a comparable increased risk for airway antibiotics (HR, 1.41; 95% confidence interval [CI], 1.37–1.46). The excess risk associated with urinary tract/skin antibiotics, although lower, was still associated with asthma (HR, 1.25; 95% CI, 1.20–1.30). After adjustment for confounding variables, antibiotic exposure in fetal life remained significantly associated with asthma but was reduced for any and airway antibiotics. In the sibling controls, the association disappeared; the adjusted HRs (aHRs) were 0.98 (95% CI, 0.90–1.07) for airway antibiotics and 0.98 (95% CI, 0.88–1.10) for urinary tract/skin antibiotics. In the overall cohort, the highest risk for asthma was among those children treated with antibiotics during childhood (aHR, 3.71; 95% CI, 3.41–4.03). When compared with sibling controls, all estimates were lower than in the overall cohort analyses (aHR, 2.11; 95% CI, 1.61–2.76). For both airway and urinary tract/skin antibiotics, cohort analyses showed a decreased HR with increasing age, but the difference in risk was more pronounced after exposure to airway antibiotics (aHR, 4.12, 95% CI 3.78–4.50) compared with urinary tract/skin antibiotics (aHR1.54; 95% CI, 1.24–1.92) in the youngest children. In analyses with sibling controls, estimates were decreased compared with the cohort analyses, where the association with airway antibiotics remained significant (aHR, 2.36; 95% CI, 1.78–3.13), and the association between urinary tract/skin antibiotics and asthma disappeared (aHR, 0.85; 95% CI, 0.47–1.55). Significant associations were found for all groups of antibiotics for exposure in first year of life and incidence of asthma from the age of 2 years in the cohort analyses, but in this subgroup, no associations remained statistically significant in the sibling control analyses. In the full cohort, a dose-response relationship was noted for an increasing number of prescriptions for all groups of antibiotics and asthma (P < 0.001, all age groups). In sibling analyses, the dose-response relationship remained for any and airway antibiotics (P < 0.001, all age groups), but not for urinary tract/skin antibiotics (P = 0.22–0.97 for different age groups). A positive association exists between exposure to antibiotics in fetal life/childhood and subsequent asthma. In siblings, these associations disappeared or decreased, suggesting that the association might be confounded by factors (eg, environment, inheritable) shared in families.
    No preview · Article · Apr 2015 · Obstetrical and Gynecological Survey
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    ABSTRACT: Several studies have shown that the prevalence of the frequent chronic conditions of atopic dermatitis, asthma, and allergy has increased substantially for reasons not fully understood. Atopic diseases affect quality of life in both children and their family members. Using national registers, we sought to establish up-to-date incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in the Danish and Swedish child populations. Children born in Denmark from 1997 to 2011 or born in Sweden from 2006 to 2010 participated in this cross-national, population-based cohort study. Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in the Danish and Swedish child cohorts were ascertained through disease-specific dispensed prescribed medication, specific hospital contacts, or both. In both countries the incidence rate of atopic dermatitis was stable during the study periods. The incidence rate of asthma increased until 2006 and stabilized for the rest of the study period in Denmark and increased in Sweden. The incidence rate of allergic rhinoconjunctivitis decreased in both countries. The study revealed similar trends, with stable incidence rates of atopic dermatitis in both Danish and Swedish children, an increase and then stabilization in asthma incidence rates in Denmark and an increase in Sweden, and a decrease in allergic rhinoconjunctivitis incidence rates. At age 5 years, one third of all children were affected with at least one of the conditions of atopic dermatitis, asthma, or allergic rhinoconjunctivitis. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · The Journal of allergy and clinical immunology
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    ABSTRACT: Aim: The aim of the study reported here was to develop and validate an algorithm to identify children with hemodynamically significant CHD according to recommendations for palivizumab prophylaxis in register-based research. Methods: By using a strategy of combining criteria for age at diagnosis, diagnostic codes, surgical procedure codes, and dispensing records, we created an algorithm to define the spe-cific cases with hemodynamically significant CHD in which palivizumab could be advocated according to recommendations.
    Full-text · Article · Jan 2015 · Clinical Epidemiology
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    ABSTRACT: Register studies are a valuable tool, when monitoring the safety of drugs. The Swedish Prescribed Drug Register (PDR) was established in 2005 and keeps records of all prescribed drugs dispensed in community pharmacies. Drugs prescribed in-hospital are not registered on an individual level, which may hamper the validity of register-based studies on drugs potentially administered in-hospital. The objective was to assess the ability of the PDR to identify children treated with the monoclonal antibody palivizumab, which is used for prophylaxis against respiratory syncytial virus (RSV) infection in children. Palivizumab exposure as filled prescriptions recorded in the PDR was assessed by indication of treatment (preterm-born children, bronchopulmonary dysplasia, or hemodynamically significant heart disease) and presented as numbers and proportions. For a random sample of children with an indication for treatment and without record of palivizumab exposure in the drug register, numbers and proportions by indication of treatment as noted in medical records were presented. The extent of underreporting in the drug register was estimated by indication for treatment. Through the national health registers, 2,317 children were identified as being at risk for severe infection with RSV infection and 75% had no records indicating palivizumab exposure in the PDR. In a random sample of 176 children at high risk for RSV infection and with no records of palivizumab prescription fills in the PDR, 47% had been treated with palivizumab according to medical records. The PDR underestimated palivizumab treatment with 49% in children born preterm, 42% in children with bronchopulmonary dysplasia, and 23% in those with a hemodynamically significant heart disease. Our findings underline the need of improving the information in the Swedish national registers concerning drugs administered in-hospital.
    Full-text · Article · Jan 2015 · Clinical Epidemiology
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    ABSTRACT: 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.
    No preview · Article · Jan 2015 · European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP)
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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.
    Full-text · Article · Dec 2014 · Journal of Thrombosis and Haemostasis
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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.
    Full-text · Article · Dec 2014 · Acta paediatrica (Oslo, Norway: 1992). Supplement

  • No preview · Article · Dec 2014 · Pediatric Blood & Cancer

Publication Stats

1k Citations
542.49 Total Impact Points

Institutions

  • 2002-2015
    • Karolinska Institutet
      • • Center for Pharmacoepidemiology - CPE
      • • Department of Medicine, Solna
      • • Clinical Epidemiology Unit
      • • Department of Medical Epidemiology and Biostatistics
      Solna, Stockholm, Sweden
  • 2014
    • Lund University
      Lund, Skåne, Sweden
  • 2009-2014
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 1995-2011
    • Uppsala University
      • Department of Women's and Children's Health
      Uppsala, Uppsala, Sweden
  • 2003-2005
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden