Preterm birth has been linked with increased risk of autism spectrum disorder (ASD); however, potential causality, sex-specific differences, and association with early term birth are unclear. We ...examined whether preterm and early term birth are associated with ASD in a large population-based cohort.
A national cohort study was conducted of all 4 061 795 singleton infants born in Sweden during 1973-2013 who survived to age 1 year, who were followed-up for ASD identified from nationwide outpatient and inpatient diagnoses through 2015. Poisson regression was used to determine prevalence ratios for ASD associated with gestational age at birth, adjusting for confounders. Cosibling analyses were used to assess the influence of unmeasured shared familial (genetic and/or environmental) factors.
ASD prevalences by gestational age at birth were 6.1% for extremely preterm (22-27 weeks), 2.6% for very to moderate preterm (28-33 weeks), 1.9% for late preterm (34-36 weeks), 2.1% for all preterm (<37 weeks), 1.6% for early term (37-38 weeks), and 1.4% for term (39-41 weeks). The adjusted prevalence ratios comparing extremely preterm, all preterm, or early term versus term, respectively, were 3.72 (95% confidence interval, 3.27-4.23), 1.35 (1.30-1.40), and 1.11 (1.08-1.13) among boys and 4.19 (3.45-5.09), 1.53 (1.45-1.62), and 1.16 (1.12-1.20) among girls (
< .001 for each). These associations were only slightly attenuated after controlling for shared familial factors.
In this national cohort, preterm and early term birth were associated with increased risk of ASD in boys and girls. These associations were largely independent of covariates and shared familial factors, consistent with a potential causal relationship.
Polypharmacy is becoming a global health problem. The aims of this study were to evaluate the temporal trends in the prevalence of polypharmacy in Sweden and to explore polypharmacy disparities by ...age, gender, education, and immigration status.
Polypharmacy and excessive polypharmacy were evaluated using data extracted from the Swedish Prescribed Drug Register between 2006 and 2014. Polypharmacy was defined as being exposed to five or more drugs and excessive polypharmacy was defined as being exposed to 10 or more drugs during 1 month respectively. Average annual percent change (AAPC) was calculated using Joinpoint Statistical Software.
The prevalence of polypharmacy increased from 16.9% in 2006 to 19.0% in 2014 with an AAPC of 1.3; the prevalence of excess polypharmacy increased from 3.8% in 2006 to 5.1% in 2014 with an AAPC of 3.4. The prevalence of polypharmacy and excessive polypharmacy increased dramatically with age and peaked up to 79.6% and 36.4% in individuals aged 90 and above respectively. Females and individuals with lower education level were associated with a higher rate of polypharmacy and excessive polypharmacy. Immigrants from Middle-Eastern countries had the highest rate of polypharmacy and excessive polypharmacy, whereas individuals from Western Europe countries had the lowest rate.
The prevalence of polypharmacy has increased gradually in Sweden during the past decade. Individuals with older age, female sex, or lower education have a higher rate of polypharmacy and excessive polypharmacy. Immigrants from Middle-Eastern countries showed a higher rate of polypharmacy.
Preterm birth has previously been linked with cardiovascular disease (CVD) in adulthood. However, associations with lipid disorders (e.g., high cholesterol or triglycerides), which are major risk ...factors for CVD, have seldom been examined and are conflicting. Clinicians will increasingly encounter adult survivors of preterm birth and will need to understand the long-term health sequelae. We conducted the first large population-based study to determine whether preterm birth is associated with an increased risk of lipid disorders.
A retrospective national cohort study was conducted of all 2,235,012 persons born as singletons in Sweden during 1973 to 1995 (48.6% women), who were followed up for lipid disorders identified from nationwide inpatient, outpatient, and pharmacy data through 2016 (maximum age 44 years). Cox regression was used to adjust for other perinatal and maternal factors, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and/or environmental) factors. A total of 25,050 (1.1%) persons were identified with lipid disorders in 30.3 million person-years of follow-up. Each additional 5 weeks of gestation were associated with a 14% reduction in risk of lipid disorders (adjusted hazard ratio HR, 0.86; 95% CI, 0.83-0.89; P < 0.001). Relative to full-term birth (gestational age 39-41 weeks), the adjusted HR associated with preterm birth (<37 weeks) was 1.23 (95% CI, 1.16-1.29; P < 0.001), and further stratified was 2.00 (1.41-2.85; P < 0.001) for extremely preterm (22-27 weeks), 1.33 (1.19-1.49; P < 0.001) for very preterm (28-33 weeks), and 1.19 (1.12-1.26; P < 0.001) for late preterm (34-36 weeks). These findings were similar in men and women (e.g., preterm versus full-term, men: HR, 1.22; 95% CI, 1.14-1.31; P < 0.001; women: HR, 1.23; 1.12-1.32; P < 0.001). Co-sibling analyses suggested that they were substantially though not completely explained by shared genetic or environmental factors in families. The main study limitation was the unavailability of laboratory data to assess specific types or severity of lipid disorders.
In this large national cohort, preterm birth was associated with an increased risk of lipid disorders in early- to midadulthood. Persons born prematurely may need early preventive evaluation and long-term monitoring for lipid disorders to reduce their future cardiovascular risks.
Colorectal cancer (CRC) incidence is increasing among young adults below screening age, despite the effectiveness of screening in older populations. Individuals with diabetes mellitus are at ...increased risk of early-onset CRC. We aimed to determine how many years earlier than the general population patients with diabetes with/without family history of CRC reach the threshold risk at which CRC screening is recommended to the general population.
A nationwide cohort study (follow-up:1964-2015) involving all Swedish residents born after 1931 and their parents was carried out using record linkage of Swedish Population Register, Cancer Registry, National Patient Register, and Multi-Generation Register. Of 12,614,256 individuals who were followed between 1964 and 2015 (51% men; age range at baseline 0-107 years), 162,226 developed CRC, and 559,375 developed diabetes. Age-specific 10-year cumulative risk curves were used to draw conclusions about how many years earlier patients with diabetes reach the 10-year cumulative risks of CRC in 50-year-old men and women (most common age of first screening), which were 0.44% and 0.41%, respectively. Diabetic patients attained the screening level of CRC risk earlier than the general Swedish population. Men with diabetes reached 0.44% risk at age 45 (5 years earlier than the recommended age of screening). In women with diabetes, the risk advancement was 4 years. Risk was more pronounced for those with additional family history of CRC (12-21 years earlier depending on sex and benchmark starting age of screening). The study limitations include lack of detailed information on diabetes type, lifestyle factors, and colonoscopy data.
Using high-quality registers, this study is, to our knowledge, the first one that provides novel evidence-based information for risk-adapted starting ages of CRC screening for patients with diabetes, who are at higher risk of early-onset CRC than the general population.
The overall aim of this study is to present descriptive data regarding the treated prevalence of nine common psychiatric and substance use disorders in the first Primary Care Registry (PCR) in ...Sweden: Major Depression (MD), Anxiety Disorders (AD), Obsessive-Compulsive Disorder (OCD), Adjustment Disorder (AdjD), Eating Disorders (ED), Personality Disorder (PD), Attention Deficit Hyperactivity Disorder (ADHD), Alcohol Use Disorder (AUD) and Drug Abuse (DA).
We selected 5,397,675 individuals aged ≥18. We examined patterns of comorbidity among these disorders and explored the association between diagnoses in the PCR and diagnoses obtained from Hospital and Specialist care. We explored the proportion of patients with these nine disorders that are only treated in primary health care.
For four of our disorders, 80% or more of the cases were present only in the PCR: AdjD, DA, AD and MD. For two disorders (OCD and ED), 65-70% of cases were only found in the PCR. For three disorders (PD, AUD, and ADHD), 45-55% of the patients were only present in the PCR.
The PCR will, in the future, likely prove to be an important tool for studies in psychiatric epidemiology.
Summary Background Some autoimmune disorders have been linked to venous thromboembolism. We examined whether there is an association between autoimmune disorders and risk of pulmonary embolism. ...Methods We followed up all individuals in Sweden without previous hospital admission for venous thromboembolism and with a primary or secondary diagnosis of an autoimmune disorder between Jan 1, 1964, and Dec 31, 2008, for hospital admission for pulmonary embolism. We obtained data from the MigMed2 database , which has individual-level information about all registered residents of Sweden. The reference population was the total population of Sweden. We calculated standardised incidence ratios (SIRs) for pulmonary embolism, adjusted for individual variables, including age and sex. Findings 535 538 individuals were admitted to hospital because of an autoimmune disorder. Overall risk of pulmonary embolism during the first year after admission for an autoimmune disorder was 6·38 (95% CI 6·19–6·57). All the 33 autoimmune disorders were associated with a significantly increased risk of pulmonary embolism during the first year after admission. However, some had a particularly high risk—eg, immune thrombocytopenic purpura (10·79, 95% CI 7·98–14·28), polyarteritis nodosa (13·26, 9·33–18·29), polymyositis or dermatomyositis (16·44, 11·57–22·69), and systemic lupus erythematosus (10·23, 8·31–12·45). Overall risk decreased over time, from 1·53 (1·48–1·57) at 1–5 years, to 1·15 (1·11–1·20) at 5–10 years, and 1·04 (1·00–1·07) at 10 years and later. The risk was increased for both sexes and all age groups. Interpretation Autoimmune disorders are associated with a high risk of pulmonary embolism in the first year after hospital admission. Our findings suggest that these disorders in general should be regarded as hypercoagulable disorders. Funding Swedish Research Council, Swedish Council for Working Life and Social Research, Swedish Research Council Formas, Region Skåne.
Abstract
Phosphodiesterase-5 (PDE5) inhibitors are suggested to have anti-tumor effects and to inhibit surgery-induced immunosuppression. We aimed to explore whether post-diagnostic use of PDE5 ...inhibitors was associated with a better prognosis among male patients with colorectal cancer (CRC) and the role of open surgery in the association. Here we show that post-diagnostic use of PDE5 inhibitors is associated with a decreased risk of CRC-specific mortality (adjusted HR = 0.82, 95% CI 0.67-0.99) as well as a decreased risk of metastasis (adjusted HR = 0.85, 95% CI 0.74-0.98). Specifically, post-operative use of PDE5 inhibitors has a strong anti-cancer effect. The reduced risk of metastasis is mainly due to distant metastasis but not regional lymphatic metastasis. PDE5 inhibitors have the potential to be an adjuvant drug for patients with CRC to improve prognosis, especially those who have undergone open surgery.
Preterm birth is the leading cause of infant mortality in developed countries, but the association between gestational age at birth and mortality in adulthood remains unknown.
To examine the ...association between gestational age at birth and mortality in young adulthood.
National cohort study of 674,820 individuals born as singletons in Sweden in 1973 through 1979 who survived to age 1 year, including 27,979 born preterm (gestational age <37 weeks), followed up to 2008 (ages 29-36 years).
All-cause and cause-specific mortality.
A total of 7095 deaths occurred in 20.8 million person-years of follow-up. Among individuals still alive at the beginning of each age range, a strong inverse association was found between gestational age at birth and mortality in early childhood (ages 1-5 years: adjusted hazard ratio aHR for each additional week of gestation, 0.92; 95% CI, 0.89-0.94; P < .001), which disappeared in late childhood (ages 6-12 years: aHR, 0.99; 95% CI, 0.95-1.03; P = .61) and adolescence (ages 13-17 years: aHR, 0.99; 95% CI, 0.95-1.03; P = .64) and then reappeared in young adulthood (ages 18-36 years: aHR, 0.96; 95% CI, 0.94-0.97; P < .001). In young adulthood, mortality rates (per 1000 person-years) by gestational age at birth were 0.94 for 22 to 27 weeks, 0.86 for 28 to 33 weeks, 0.65 for 34 to 36 weeks, 0.46 for 37 to 42 weeks (full-term), and 0.54 for 43 or more weeks. Preterm birth was associated with increased mortality in young adulthood even among individuals born late preterm (34-36 weeks, aHR, 1.31; 95% CI, 1.13-1.50; P < .001), relative to those born full-term. In young adulthood, gestational age at birth had the strongest inverse association with mortality from congenital anomalies and respiratory, endocrine, and cardiovascular disorders and was not associated with mortality from neurological disorders, cancer, or injury.
After excluding earlier deaths, low gestational age at birth was independently associated with increased mortality in early childhood and young adulthood.
Certain immune-mediated diseases (IMDs) have been associated with increased risk for cardiovascular disorders. The aim of the present study was to examine whether there is an association between 32 ...different IMDs and first hospitalization for ischemic or hemorrhagic stroke.
All individuals in Sweden hospitalized with a main diagnosis of IMD (without previous or coexisting stroke), between January 1, 1987 and December 31, 2008 (n = 216,291), were followed for first hospitalization for ischemic or hemorrhagic stroke. The reference population was the total population of Sweden. Adjusted standardized incidence ratios (SIRs) for ischemic and hemorrhagic stroke were calculated.
Totally 20 and 15 of the 32 IMDs studied, respectively, were associated with an increased risk of ischemic and hemorrhagic stroke during the follow-up. The overall risks of ischemic and hemorrhagic stroke during the first year after hospitalization for IMD were 2.02 (95% CI 1.90-2.14) and 2.65 (95% CI 2.27-3.08), respectively. The overall risk of ischemic or hemorrhagic stroke decreased over time, to 1.50 (95% CI 1.46-1.55) and 1.83 (95% CI 1.69-1.98), respectively, after 1-5 years, and 1.29 (95% CI 1.23-1.35) and 1.47 (95% CI 1.31-1.65), respectively, after 10+ years. The risk of hemorrhagic stroke was ≥2 during the first year after hospitalization for seven IMDs: ankylosing spondylitis (SIR = 8.11), immune thrombocytopenic purpura (SIR = 8.60), polymyalgia rheumatica (SIR = 2.06), psoriasis (SIR = 2.88), rheumatoid arthritis (SIR = 3.27), systemic lupus erythematosus (SIR = 8.65), and Wegener's granulomatosis (SIR = 5.83). The risk of ischemic stroke was ≥2 during the first year after hospitalization for twelve IMDs: Addison's disease (SIR = 2.71), Crohn's disease (SIR = 2.15), Grave's disease (SIR = 2.15), Hashimoto's thyroiditis (SIR = 2.99), immune thrombocytopenic purpura (SIR = 2.35), multiple sclerosis (SIR = 3.05), polymyositis/dermatomyositis (SIR = 3.46), rheumatic fever (SIR = 3.91), rheumatoid arthritis (SIR = 2.08), Sjögren's syndrome (SIR = 2.57), systemic lupus erythematosus (SIR = 2.21), and ulcerative colitis (SIR = 2.15).
Hospitalization for many IMDs is associated with increased risk of ischemic or hemorrhagic stroke. The findings suggest that several IMDs are linked to cerebrovascular disease.
Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based ...studies are lacking.
We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified incidence of each VHD and adjusted comorbidity profiles were assessed.
In the Swedish population (n=10 164 211), the incidence of VHD was 63.9 per 100 000 person-years, with aortic stenosis (AS; 47.2%), mitral regurgitation (MR; 24.2%) and aortic regurgitation (AR; 18.0%) contributing most of the VHD diagnoses. The majority of VHDs were diagnosed in the elderly (68.9% in subjects aged ≥65 years), but pulmonary valve disease incidence peaked in newborns. Incidences of AR, AS and MR were higher in men who were also more frequently diagnosed at an earlier age. Mitral stenosis (MS) incidence was higher in women. Rheumatic fever was rare. Half of AS cases had concomitant atherosclerotic vascular disease (48.4%), whereas concomitant heart failure and atrial fibrillation were common in mitral valve disease and tricuspid regurgitation. Other common comorbidities were thoracic aortic aneurysms in AR (10.3%), autoimmune disorders in MS (24.5%) and abdominal hernias or prolapse in MR (10.7%) and TR (10.3%).
Clinically diagnosed VHD was primarily a disease of the elderly. Rheumatic fever was rare in Sweden, but specific VHDs showed a range of different comorbidity profiles . Pronounced sex-specific patterns were observed for AR and MS, for which the mechanisms remain incompletely understood.
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