Swedish National Health Registers Research Articles

Using fathers as a negative control exposure to test the Developmental Origins of Health and Disease Hypothesis: A case study on maternal distress and offspring asthma using Swedish register data.

Developmental Origins of Health and Disease Hypothesis (DOHaD) studies are often observational in nature and are therefore prone to biases from loss to follow-up and unmeasured confounding. Register-based studies can reduce these issues since they allow almost complete follow-up and provide information on fathers that can be used in a negative control analysis to assess the impact of unmeasured confounding. The aim of this study was to propose a causal model for testing DOHaD using paternal exposure as a negative control, and its application to maternal distress in pregnancy and offspring asthma. A causal diagram including shared and parent-specific measured and unmeasured confounders for maternal (fetal) and paternal exposures is proposed. The case study consisted of all children born in Sweden from July 2006 to December 2008 ( n=254,150). Information about childhood asthma, parental distress and covariates was obtained from the Swedish national health registers. Associations between maternal and paternal distress during pregnancy and offspring asthma at age five years were assessed separately and with mutual adjustment for the other parent's distress measure, as well as for shared confounders. Maternal distress during pregnancy was associated with offspring asthma risk; mutually adjusted odds ratio (OR) (OR 1.32, 95% CI 1.23, 1.43). The mutually adjusted paternal distress-offspring asthma analysis (OR 1.05, 95% CI 0.97, 1.13) indicated no evidence for unmeasured confounding shared by the mother and father. Using paternal exposure in a negative control model to test the robustness of fetal programming hypotheses can be a relatively simple extension of conventional observational studies but limitations need to be considered.

Abdominal adhesions in gynaecologic surgery after caesarean section: a longitudinal population-based register study.

The aim of the study was to evaluate the association between abdominal adhesions at the time of gynaecologic surgery and a history of caesarean delivery, and to investigate obstetric factors contributing to adhesion formation after caesarean section (CS). Longitudinal population-based register study. Sweden. Women undergoing benign hysterectomy and/or adnexal surgery in Sweden, 2000-2014, with a previous delivery during 1973-2013 (n=15479). Information about abdominal adhesions during gynaecological surgery, prior medical history, pregnancies and deliveries were retrieved from Swedish National Health and Quality registers. Adhesions. In women with previous CS, adhesions were present in 37%, compared with 10% of women with no previous CS [odds ratio (OR): 5.18, 95% confidence interval (CI): 4.70-5.71]. Adhesions increased with the number of caesarean sections: 32% after one CS; 42% after two CS and 59% after three or more CS (P<0.001). Regardless of the number of CS, factors at CS such as age ≥35years (aOR: 1.28, 95% CI: 1.05-1.55), body mass index (BMI) ≥30 [adjusted OR (aOR): 1.91, 95% CI: 1.49-2.45] and postpartum infection (aOR: 1.55, 95% CI: 1.05-2.30) increased the risk of adhesions. Presence of adhesions in abdominal gynaecological surgery is associated with women's personal history of caesarean delivery. The number of caesarean sections was the important predictor of adhesions; advanced age, obesity and postpartum infection further increased the incidence. Repeat caesarean, age, obesity and infection increased the risk of pelvic adhesions after caesarean section.

Dog Exposure During the First Year of Life and Type 1 Diabetes in Childhood

The association between early exposure to animals and type 1 diabetes in childhood is not clear. To determine whether exposure to dogs during the first year of life is associated with the development of type 1 diabetes in childhood. A nationwide cohort study utilizing high-quality Swedish national demographic and health registers was conducted. A total of 840 593 children born in Sweden from January 1, 2001, to December 31, 2010, were evaluated. Type 1 diabetes was identified using diagnosis codes from hospitals and dispensed prescriptions of insulin. Cox proportional hazards regression models were used to assess the association between exposure to dogs and risk of type 1 diabetes in childhood. The possible association was further investigated by performing dose-response and breed group-specific analyses. The cohort was followed up until September 30, 2012. Data analysis was conducted from October 15, 2015, to February 8, 2017. Having a parent who was registered as a dog owner during the child's first year of life. Childhood-onset type 1 diabetes. Of the 840 593 children reviewed, 408 272 (48.6%) were girls; mean (SD) age at diagnosis of type 1 diabetes was 5.1 (2.6) years. Dog exposure was identified in 102 035 children (12.1%). Follow-up started at age 1 year, and the children were followed up for as long as 10.7 years (median, 5.5 years). During follow-up, 1999 children developed type 1 diabetes. No association was found between exposure to dogs (adjusted hazard ratio [HR], 1.00; 95% CI, 0.86-1.16) and type 1 diabetes in childhood. The size of the dog (adjusted HR per 10-cm increase in height, 0.96; 95% CI, 0.86-1.06) or number of dogs in the household (1 dog: adjusted HR, 1.07; 95% CI, 0.91-1.26; 2 dogs: 0.79; 95% CI, 0.54-1.15; ≥3 dogs: 0.50; 95% CI, 0.23-1.12; compared with nonexposed children) also was not associated with type 1 diabetes risk. An analysis of children whose parent had type 1 diabetes (210 events) yielded an adjusted HR of 0.71 (95% CI, 0.43-1.17) for dog exposure. In a nationwide study, no evidence supporting an association of register-derived measures of dog exposure with childhood type 1 diabetes was identified.

Management of Acute Myocardial Infarction in Patients With Dementia: Data From SveDem, the Swedish Dementia Registry

ObjectivesWe aimed to (1) study factors that determine the use of invasive procedures in the management of acute myocardial infarction (AMI) in patients with dementia and (2) determine whether the use of invasive procedures was associated with their better survival. DesignCohort study based on patients registered in the Swedish Dementia Registry (SveDem), 2007–2012. Median follow-up time was 228 days. SettingPatients diagnosed with dementia in specialist memory clinics and primary care units in Sweden. ParticipantsA total of 525 patients with dementia who suffered AMI (mean age 89 years, 54% women). MeasurementsInformation on AMI and use of invasive procedures (coronary angiography and percutaneous coronary intervention) was obtained from Swedish national health registers. Binary logistic regression was applied to study associations of patients’ characteristics with the use of invasive procedures; odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Survival was analyzed with Kaplan-Meier curves; log-rank test was used to compare survival of patients who received an invasive procedure versus those who did not receive it. Cox regression was applied to study association of the invasive procedures with all-cause mortality; hazard ratios (HRs) with 95% CIs were calculated. ResultsOne hundred ten patients (21%) with dementia received an invasive procedure in the management of AMI. After multivariate adjustment, lower age and higher global cognitive status were associated with the use of invasive procedures. The invasively managed patients survived longer (P = .001). The use of invasive procedures was associated with a lower risk of all-cause mortality, adjusting for type of AMI and dementia disorder, age, gender, registration unit, history of AMI and comorbidity score (HR 0.35, 95% CI 0.21–0.59), or total number of drugs (HR 0.34, 95% CI 0.20–0.58). ConclusionAge and cognitive status determine the use of invasive procedures in patients with dementia. This study suggests that the invasive management of AMI has a benefit for survival of patients with dementia.

Injuries before and after diagnosis of cancer: nationwide register based study.

To examine the relative risks of iatrogenic and non-iatrogenic injuries during the period shortly before and after a diagnosis of cancer. Nationwide register based study. Swedish national population and health registers. 720 901 patients with diagnosis of cancer, 1991-2009, in Sweden. All hospital admissions in patients with cancer with a main discharge diagnosis of iatrogenic (from medical complications) or non-iatrogenic injuries in 1990-2010 identified from the Swedish patient register. Conditional Poisson regression was used to compare the incidence rate of injuries during the "diagnostic period" (16 weeks before to 16 weeks after diagnosis) with the incidence rate during a "pre-diagnostic period" (the same 32 weeks one year before diagnosis) among the same patients. During the diagnostic period, there were 7306 iatrogenic (incidence rate 0.60 per 1000 person months) and 8331 non-iatrogenic injuries (incidence rate 0.69 per 1000 person months). For iatrogenic injuries, the incidence rate ratio was 7.0 (95% confidence interval 6.6 to 7.4) during the diagnostic period compared with the pre-diagnostic period. The increase in risk started two weeks before cancer diagnosis and peaked during the two weeks after diagnosis (48.6, 37.3 to 63.5). For non-iatrogenic injuries, the incidence rate ratio was 1.9 (1.8 to 2.0) during the diagnostic period compared with the pre-diagnostic period. The increase in risk began four weeks before diagnosis and peaked during the two weeks before diagnosis (5.3, 4.6 to 6.1). There were increased risks of both types of injury during the diagnostic period for all common cancers, with the smallest risk increase noted for non-melanoma skin cancer. Patients with cancer have highly increased risks of both iatrogenic and non-iatrogenic injuries requiring inpatient care : shortly before and after their diagnosis. These findings shed further light on the total burden of medical complications and call for prevention of intentional and unintentional injuries during the diagnostic process of cancer.

Characteristics of the Offspring of Women with a History of Malignancy, Excluding Congenital Malformations.

To study the characteristics (except congenital malformations) of offspring born to women with a history of malignancy. Data were obtained by linkage between four different Swedish national health registers. We compared the offspring born between 1994 and 2011 of women with a history of malignancy with all other infants. Survival of the infants was followed up through 2013. Adjusting for confounders was performed using Mantel-Haenszel methodology. We identified 7315 infants born to women with a history of a malignancy diagnosed at least 1 year before delivery. The total number of deliveries in Sweden in these years was 1 746 870, with 1780 112 infants being born. We assessed rates of intrauterine death, preterm birth, low birth weight, and the nature of intrauterine growth. We also examined neonatal diagnoses (asphyxia, chronic respiratory condition, intracranial hemorrhage, jaundice, hypoglycemia, CNS symptoms) and infant death. In women with a history of malignancy, we found no significantly increased risk for stillbirth or infant death. There were elevated rates of preterm birth (OR 1.50, 95% CI 1.37 to 1.64), very preterm birth (OR 1.89, 95% CI 1.54 to 2.32), and low birth weight (OR 1.50, 95% CI 1.34 to 1.68). There was a significantly increased risk of birth asphyxia, jaundice, hypoglycemia, and low Apgar score among infants born to women with a history of malignancy (OR 1.24, 95% CI 1.15 to 1.33), and this risk was maintained after excluding infants born after IVF. We found an increased risk of preterm birth and low birth weight among infants of women with a history of malignancy, and as a result, found an increased risk of neonatal morbidity. No significant increase in risk of intrauterine or postnatal death was noted.

Preterm birth in women with inflammatory bowel disease – the association with disease activity and drug treatment

Background: The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) have been associated with an increased risk of preterm birth.Material and methods: We identified all 246 singleton preterm births among women with IBD between July 2006 and December 2010 as cases and an equal number of controls with IBD from the Swedish national health registers, matched by maternal age, parity and IBD diagnosis (CD/UC). From register data and medical charts, we obtained information on reproductive history, comorbidity, disease activity and drug treatment (corticosteroids, 5-aminosalicylates, sulfasalazine, thiopurines and anti-TNF) as risk factors for preterm birth. Associations were estimated using conditional logistic regression and results were presented as odds ratios (OR) with 95% confidence intervals (CI).Results: Previous preterm birth was more common among cases, OR 6.13 (95%CI: 2.51–15.01). Significant activity at any time during pregnancy (OR: 2.20; 95%CI: 1.37–3.53), and in particular both in early and in late pregnancy, was more common for cases (OR: 4.78 95%; CI: 2.10–10.9). The OR for immunosuppressive treatment with thiopurines or anti-TNF was 1.88 (1.04–3.39) without significant activity and 12.78 (95%CI: 3.68–44.72) with. The risk for women who discontinued thiopurines was 6.56 (1.44–29.82).Conclusions: Significant activity and immunosuppressive treatment was associated with preterm birth, particularly in women with both. The existing recommendations to aim at maintaining quiescent disease during pregnancy, even if it means continuing immunosuppressive treatment, are rational.

Deliveries After Malignant Disease Before Pregnancy: Maternal Characteristics, Pregnancy, and Delivery Complications.

Survival after cancer has increased, and the question of risks in later pregnancies has become important. A previous malignancy may affect pregnancy outcome. Comparison of women with malignant disease before pregnancy with all other women giving birth during 1994-2011. Data were obtained by linkage between Swedish national health registers. Subfertility, evaluated as time to pregnancy, and in vitro fertilization (IVF) before the relevant delivery were studied. The following delivery diagnoses were studied: gestational diabetes, preeclampsia, placenta previa, placenta abruption, placenta retention, bleeding around delivery, and premature rupture of membranes. The rates of cesarean section and vacuum extraction or forceps delivery were also studied. We identified 3931 women with 7176 deliveries and with a malignancy diagnosed at least 1 year before the delivery. The total number of deliveries in Sweden in these years was 1,746,870. Overall, an increased risk of subfertility (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.07-1.28), use of IVF (OR = 1.36, CI 1.21-1.53), delivery complications (OR = 1.17, 95% CI 1.10-1.24), and rate of caesarean sections (OR = 1.27, 95% CI 1.20-1.34) was observed among women with a history of malignancy compared with other women. We found an increased risk of subfertility, pregnancy, and delivery complications in women with a history of malignant disease. Further studies are needed to evaluate the risks of specific treatments and to provide these women with reliable information that could affect their family planning.

Depression in amyotrophic lateral sclerosis.

To examine the relative risk of depression among patients with amyotrophic lateral sclerosis (ALS), both in terms of depression diagnosis and use of antidepressant drugs, before and after diagnosis. We conducted a nested case-control study including 1,752 patients with ALS diagnosed from July 2005 to December 2010 and 8,760 controls based on the Swedish national health and population registers, to assess the associations of depression diagnosis and use of antidepressant drugs with a subsequent risk of ALS. We further followed the patients with ALS after diagnosis to estimate the association of an ALS diagnosis with the subsequent risk of depression and use of antidepressant drugs. Before diagnosis, patients with ALS were at higher risk of receiving a clinical diagnosis of depression compared to controls (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.3-2.3), and the highest risk increase was noted during the year before diagnosis (OR 3.5, 95% CI 2.1-5.6). Patients with ALS also had a highly increased risk of depression within the first year after diagnosis (hazard ratio 7.9, 95% CI 4.4-14.3). Antidepressant use was more common in patients with ALS than in controls, especially during the year before (OR 5.8, 95% CI 4.5-7.5) and the year after (hazard ratio 16.1, 95% CI 11.5-22.6) diagnosis. Patients with ALS are at higher risk of depression diagnosis and use of antidepressant drugs both immediately before and after diagnosis.

Risk factors for the rapid increase in risk of acute coronary events in patients with new-onset rheumatoid arthritis: a nested case-control study.

To investigate risk factors for acute coronary syndrome (ACS) in patients with new-onset rheumatoid arthritis (RA). We performed a nested case-control study of patients with incident RA included in the Epidemiological Investigation of RA study. Cases with ACS were identified using Swedish national health registers and matched with up to 5 controls without ACS, based on incidence density-based sampling. Information on potential exposures (clinical disease activity, serologic features, genetic markers, comorbidities, pharmacotherapies, and sick leave) was collected from medical charts and register-based sources. We identified 138 cases and 624 controls. Smoking, history of myocardial infarction, and >50 days of sick leave the year following RA onset were associated with an increased risk of ACS. Area under the curve measurements of C-reactive protein level, erythrocyte sedimentation rate, Disease Activity Score in 28 joints (DAS28), and global health in the upper tertile during the first year and the complete followup period were both strongly associated with an increased risk of ACS. Treatment with disease-modifying antirheumatic drugs did not alter the ACS risk, nor did the presence of rheumatoid factor (RF) or shared epitope alleles, whereas high anti-citrullinated protein antibody (ACPA) levels were borderline significantly associated with ACS risk. In this study of risk factors for ACS in incident RA, clinical markers of inflammatory activity, disease activity, and total number of days of sick leave and disability pension during the first year following RA onset were identified as ACS risk factors. We found no association with RF, which was previously linked to cardiovascular disease risk in RA, but there was a borderline significant association with high ACPA levels.

Associations of Rhesus and non-Rhesus maternal red blood cell alloimmunization with stillbirth and preterm birth.

Although the risks of adverse pregnancy outcomes associated with anti-D antibodies are well-recognized, much less is known concerning alloimmunization with other red blood cell antibodies detected during routine maternal screening. To date, most reports of adverse pregnancy outcomes associated with non-anti-D antibodies have been from small case studies. The aim of this study was to examine the associations of maternal alloimmunization with specific red blood cell antibodies and the risks of preterm birth and stillbirth in the Swedish population. All antibody screening, outcome and covariate data were obtained through linkages of Swedish national health and data registers. Follow-up in these population-based registers was available up to 31 December 2002. The final study sample consisted of 1,022,569 singleton births from 668,952 mothers during 1987-2002. In total, 1.3% of the 1,022,569 study pregnancies were alloimmunized. In adjusted logistic regression models, compared with having no antibodies, alloimmunization with anti-D, anti-E, anti-C and anti-c was associated with increased risk of both stillbirth and preterm birth. In addition, anti-Kell was associated with increased risk of preterm birth and anti-Lea with increased risk of stillbirth. Compared with firstborn children, risk of preterm birth associated with alloimmunization was greater in subsequent births In the largest study to date, alloimmunization with Rhesus, K- and -Lea red blood cell antibodies increased the risk of preterm birth and/or stillbirth. The association of anti-Lea with stillbirth was an unexpected finding. Further study of the consequences of non-anti-D alloimmunization is warranted.

Congenital Malformations in the Offspring when Drugs for Functional Gastrointestinal Disease were used during Early Pregnancy

Background: Little is known about the risk for congenital malformations among infants born of women who are treated for functional gastrointestinal diseases during early pregnancy. Material and methods: Data from the Swedish national health registers were used to investigate possible associations between different drugs used at functional gastrointestinal diseases and occurrence of congenital malformations in the offspring. Drug use was ascertained by midwife interviews in early pregnancy recorded in the Medical Birth Register and the presence of congenital malformations by the use of three national health registers. Risk estimates were made with Mantel-Haenszel methodology and confidence interval estimates with Miettinen’s method. The effect of maternal characteristics and concomitant drug use was controlled. Women using drugs for inflammatory bowel disease were excluded from the analysis. Results: Among 1.5 million women 1282 (1301 infants) reported the use of drugs for functional gastrointestinal diseases in early pregnancy, 1048 (1062 infants) reported the use of antipropulsives, 3579 (3635 infants) the use of laxatives, and 13103 (13332 infants) the use of drugs for GERD. An increased risk for congenital malformations was found after the use of drugs for functional gastrointestinal diseases or of antipropulsives which could not be explained by concomitant drug use or maternal characteristics. It is unclear if it is a direct drug effect or is due to underlying disease. A specific effect was seen of dimethicone and of loperamide. No certain teratogenic effect was seen from laxatives or from most drugs used for GERD. An association between the use of sucralfate and congenital malformations was seen, however. Further independent data on these specific drugs are needed. Conclusion: A small risk for congenital malformations is associated with maternal use of drugs for functional gastrointestinal diseases, if due to drug effects or to underlying pathology is unclear.

Autism and Mental Retardation Among Offspring Born After In Vitro Fertilization

Between 1978 and 2010, approximately 5 million infants were born after in vitro fertilization (IVF) treatments. Yet limited information on neurodevelopment after IVF exists, especially after the first year of life. To examine the association between use of any IVF and different IVF procedures and the risk of autistic disorder and mental retardation in the offspring. A population-based, prospective cohort study using Swedish national health registers. Offspring born between 1982 and 2007 were followed up for a clinical diagnosis of autistic disorder or mental retardation until December 31, 2009. The exposure of interest was IVF, categorized according to whether intracytoplasmic sperm injection (ICSI) for male infertility was used and whether embryos were fresh or frozen. For ICSI, whether sperm were ejaculated or surgically extracted was also considered. Relative risks (RRs) for autistic disorder and mental retardation and rates per 100,000 person-years, comparing spontaneously conceived offspring with those born after an IVF procedure and comparing 5 IVF procedures used in Sweden vs IVF without ICSI with fresh embryo transfer, the most common treatment. We also analyzed the subgroup restricted to singletons. Of the more than 2.5 million infants born, 30,959 (1.2%) were conceived by IVF and were followed up for a mean 10 (SD, 6) years. Overall, 103 of 6959 children (1.5%) with autistic disorder and 180 of 15,830 (1.1%) with mental retardation were conceived by IVF. The RR for autistic disorder after any procedure compared with spontaneous conception was 1.14 (95% CI, 0.94-1.39; 19.0 vs 15.6 per 100,000 person-years). The RR for mental retardation was 1.18 (95% CI, 1.01-1.36; 46.3 vs 39.8 per 100,000 person-years). For both outcomes, there was no statistically significant association when restricting analysis to singletons. Compared with IVF without ICSI with fresh embryo transfer, there were statistically significantly increased risks of autistic disorder following ICSI using surgically extracted sperm and fresh embryos (RR, 4.60 [95% CI, 2.14-9.88]; 135.7 vs 29.3 per 100,000 person-years); for mental retardation following ICSI using surgically extracted sperm and fresh embryos (RR, 2.35 [95% CI, 1.01-5.45]; 144.1 vs 60.8 per 100,000 person-years); and following ICSI using ejaculated sperm and fresh embryos (RR, 1.47 [95% CI, 1.03-2.09]; 90.6 vs 60.8 per 100,000 person-years). When restricting the analysis to singletons, the risks of autistic disorder associated with ICSI using surgically extracted sperm were not statistically significant, but the risks associated with ICSI using frozen embryos were significant for mental retardation (with frozen embryos, RR, 2.36 [95% CI, 1.04-5.36], 118.4 vs 50.6 per 100,000 person-years]; with fresh embryos, RR, 1.60 [95% CI, 1.00-2.57], 80.0 vs 50.6 per 100,000 person-years). Compared with spontaneous conception, IVF treatment overall was not associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation. For specific procedures, IVF with ICSI for paternal infertility was associated with a small increase in the RR for autistic disorder and mental retardation compared with IVF without ICSI. The prevalence of these disorders was low, and the increase in absolute risk associated with IVF was small.

Accuracy and Sensitivity of Parkinsonian Disorder Diagnoses in Two Swedish National Health Registers

Background: Swedish population-based national health registers are widely used data sources in epidemiological research. Register-based diagnoses of Parkinson’s disease have not been validated against clinical information. Methods: Parkinson’s disease (PD) and other parkinsonian disorder diagnoses were ascertained in two registers, i.e. the National Patient Register (NPR) and the Cause of Death Register (CDR). Diagnoses were validated in terms of accuracy (positive predictive value) and sensitivity against data from a population-based study of PD in 1998–2004 that screened more than 35,000 persons and identified 194 cases of parkinsonian disorders including 132 PD cases (the gold standard for the purposes of this study). Results: Accuracy for any parkinsonian disorder diagnoses was 88.0% in the NPR and 94.4% in the CDR. Accuracy of PD diagnoses was 70.8% in the NPR and 66.7% in the CDR. Misclassification between differential parkinsonian diagnoses was common. The accuracy of PD diagnoses in the NPR improved to 83.0% by restricting the definition to primary diagnoses only. The sensitivity of PD diagnoses in the NPR and CDR combined was 83.1%, with a mean time to detection of 6.9 years. Conclusions: Population-based national health registers are valid data sources in epidemiological studies of PD or parkinsonian disorder etiology but are less suitable in studies of incidence or prevalence.

Treatment and overall survival (OS) in metastatic renal cell carcinoma (mRCC): A Swedish population-based study (2000–2008).

389 Background: This retrospective register study assessed OS in all mRCC patients in Sweden diagnosed before (2000–2005) and after (2006–2008) the introduction of targeted therapies, plus factors and treatment options influencing OS. Methods: Three Swedish national health registers were used: the Swedish Cancer register (diagnosis and death), the National Patient Register (in-/out-patient data), and the Swedish Prescribed Drug Register. From 2000-2008, 3,243 patients were identified with mRCC; 602 were recorded as receiving 1st-line treatment. Cox proportional hazards regression analysis, including estimation of adjusted OS, was used in three models with the covariates: diagnosis period, age, gender, institution size, nephrectomy status, geographic region (all models); mRCC treatments, defined as any tyrosine kinase inhibitor (TKI; Model 1; n=417); sunitinib (SU), sorafenib (SO), and interferon-alfa (IFN-α) in the 1st-line setting (Model 2; n=602 [SU=244, SO=110, IFN-α=248]); and variations of these drugs as 1st- and 2nd-line treatment sequences (Model 3; n=602). Results: Amongst mRCC patients diagnosed from 2006–2008 compared with 2000–2005, median adjusted OS was 16.1 vs. 10.9 months, respectively (HR=0.76, 95% CI: 0.69, 0.83; P&lt;0.001). In all three models, factors independently associated with significantly improved OS included female gender, large institution, and prior nephrectomy. Prescription of any TKI (Model 1: HR=0.82, 95% CI: 0.73, 0.93; P=0.002) and 1st-line SU treatment (Model 2: HR=0.79, 95% CI: 0.67, 0.94; P=0.007) were associated with significantly improved OS compared with other or no treatments. A similar significant improvement in OS was also confirmed for patients treated with SU only in Model 3; however, due to a low number of observations, the model had insufficient statistical power to be appropriate for all sequences. Conclusions: An improved OS for mRCC patients was demonstrated for the period 2006-2008 compared with 2000-2005. Although the observed survival advantage is multifactorial in origin, contribution of targeted therapies is highly probable. Of the drugs studied, given design limitations, only SU was associated with improved OS.

Antipsychotics During Pregnancy

Knowledge about the effects of exposure to the newer antipsychotics during pregnancy is limited. To investigate the effects of maternal use of antipsychotics during pregnancy on gestational diabetes and fetal growth. Population-based cohort study comparing women exposed and not exposed to antipsychotics during pregnancy. Exposure was defined as prescriptions filled. Swedish national health registers. All women giving birth in Sweden from July 1, 2005, through December 31, 2009, grouped by filled prescriptions for (1) olanzapine and/or clozapine, the most obesogenic and diabetogenic antipsychotics (n = 169), (2) other antipsychotics (n = 338), or (3) no antipsychotics (n = 357,696). Odds ratios (ORs) with 95% CIs for gestational diabetes and being small for gestational age (SGA) and large for gestational age for birth weight, birth length, and head circumference. Exposure to other antipsychotics was associated with an increased risk of gestational diabetes (adjusted OR, 1.77 [95% CI, 1.04-3.03]). The risk increase with olanzapine and/or clozapine was of similar magnitude but not statistical significance (adjusted OR, 1.94 [95% CI, 0.97-3.91]). Infants exposed to either group of antipsychotics had increased risks of being SGA on birth weight, whereas only exposure to other antipsychotics yielded increased risks of being SGA for birth length and head circumference. None of the risks for SGA measurements remained significant after adjusting for maternal factors. There were no increased risks of being large for gestational age for birth weight or birth length after exposure to olanzapine and/or clozapine, but the risk increased for head circumference (OR, 3.02 [95% CI, 1.60-5.71]). Women who used antipsychotics during pregnancy had increased risks of gestational diabetes. The increased risks of giving birth to an SGA infant seemed to be an effect of confounders, such as smoking. Except for macrocephaly, olanzapine and/or clozapine exposure was not associated with anabolic fetal growth.

A nationwide survey of the prevalence of multiple sclerosis in immigrant populations of Sweden

Background: In 2008, immigrants constituted 14% of the population of Sweden, a high-risk area for multiple sclerosis (MS). We investigated the largest Swedish immigrant populations for the prevalence of MS. Method: Data on foreign-born MS patients were retrieved from Swedish national health and population registers. We calculated observed versus expected numbers of MS patients and gender- and age-specific prevalence ratios (PR) between immigrant populations and the general population of Sweden and, where possible, of the countries of birth. Results: The 19 largest immigrant populations included 1327 MS patients. The global variation in MS prevalence was reflected in Sweden. The prevalence in immigrant populations who had moved to Sweden from countries with a lower MS risk was however higher than in their countries of birth. Notably, the MS prevalence in the population born in Iran was at least as high as in the general population of Sweden (men: PR = 1.10, 95% CI 0.81–1.46, p = 0.537, women: PR = 1.18, 95% CI 0.97–1.44, p = 0.855) and more than twice as high as in Isfahan, Iran (men: PR = 3.06 (95% CI 2.26–4.06), p <0.001, women: PR = 2.21 (95% CI 1.81–2.68), p <0.001). Conclusions: The MS prevalence increased in migrants who moved to Sweden from countries with a lower MS risk. In the Iranian immigrant population the prevalence exceeded that in the general population of Sweden. This indicates that Iranians carry genetic factors that contribute to a higher MS risk when environmental–lifestyle MS risk factors change.

Risk of tuberculosis in a large sample of patients with coeliac disease - a nationwide cohort study

Research suggests a positive association between coeliac disease and tuberculosis (TB), but that research has often been limited to in-patients and small sample size. We examined the relationship between TB and coeliac disease. To examine the association of TB and coeliac disease. We collected biopsy data from all pathology departments in Sweden (n=28) to identify individuals who were diagnosed with coeliac disease between 1969 and 2007 (Marsh 3: villous atrophy; n=29,026 unique individuals). Population-based sex- and age-matched controls were selected from the Total Population Register. Using Cox regression, we calculated hazard ratios (HRs) for TB from data in the Swedish national health registers. Individuals with coeliac disease were at increased risk of TB (HR=2.0; 95% CI=1.3-3.0) (during follow-up, 31 individuals with coeliac disease and 74 reference individuals had a diagnosis of TB). The absolute risk of TB in patients with coeliac disease was 10/100,000 person-years with an excess risk of 5/100,000. Risk estimates were the highest in the first year. Restricting our outcome to a diagnosis of TB confirmed by (I) a record of TB medication (HR=2.9; 95% CI=1.0-8.3), (II) data in the National Surveillance System for Infectious Diseases in Sweden (HR=2.6; 95% CI=1.3-5.2) or (III) positive TB cultivation (HR=3.3; 95% CI=1.6-6.8) increased risk estimates. The positive association between coeliac disease and TB was also observed before the coeliac disease diagnosis (odds ratio=1.6; 95% CI=1.2-2.1). We found a moderately increased risk of tuberculosis in patients with coeliac disease.

The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research

Swedish health care and national health registers are dependent on the presence of a unique identifier. This paper describes the Swedish personal identity number (PIN) and explores ethical issues of its use in medical research. A ten-digit-PIN is maintained by the National Tax Board for all individuals that have resided in Sweden since 1947. Until January 2008, an estimated 75,638 individuals have changed PIN. The most common reasons for change of PIN are incorrect recording of date of birth or sex among immigrants or newborns. Although uncommon, change of sex always leads to change of PIN since the PIN is sex-specific. The most common reasons for re-use of PIN (n = 15,887), is when immigrants are assigned a PIN that has previously been assigned to someone else. This is sometimes necessary since there is a shortage of certain PIN combinations referring to dates of birth in the 1950s and 1960s. Several ethical issues can be raised pro and con the use of PIN in medical research. The Swedish PIN is a useful tool for linkages between medical registers and allows for virtually 100% coverage of the Swedish health care system. We suggest that matching of registers through PIN and matching of national health registers without the explicit approval of the individual patient is to the benefit for both the individual patient and for society.