[Show abstract][Hide abstract] 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.
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.
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.
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.
[Show abstract][Hide abstract] 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.
Thrombosis and Haemostasis 10/2015; 115(2). DOI:10.1160/TH15-06-0459 · 4.98 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 01/2015; Publish Ahead of Print(6). DOI:10.1097/CEJ.0000000000000122 · 3.03 Impact Factor
[Show abstract][Hide abstract] 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; 13(2). DOI:10.1111/jth.12808 · 5.72 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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; DOI:10.1111/1471-0528.13164 · 3.45 Impact Factor
[Show abstract][Hide abstract] 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; 277(6). DOI:10.1111/joim.12329 · 6.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
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.
We included women aged 40 to 74 years and living in Sweden who filled a first statin prescription between 2006 and 2007. Women were categorized as HT users or as nonusers. Information on dispensed drugs, comorbidity, cardiovascular outcomes, and all-cause mortality was obtained from national health registers.
A total of 40,958 statin users--2,862 (7%) HT users and 38,096 nonusers--were followed for a mean of 4.0 years. In total, 70% of the women used statins as primary prevention. Among HT users, there were five cardiovascular deaths per 10,000 person-years. The corresponding rate among nonusers was 18, which yielded a hazard ratio of 0.38 (95% CI, 0.12-1.19). The all-cause mortality rates were 33 and 87, respectively, and the hazard ratio was 0.53 (95% CI, 0.34-0.81). There were no associations with cardiovascular events. A similar pattern was found for both primary and secondary prevention.
HT is associated with a reduced risk of all-cause mortality in women treated with statins. Although confounding factors, such as lifestyle and disease severity, might have influenced the results, HT does not seem to be detrimental to statin-treated women.
Menopause (New York, N.Y.) 10/2014; 22(4). DOI:10.1097/GME.0000000000000345 · 3.36 Impact Factor
[Show abstract][Hide abstract] 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.