Search

Summary: Background: Inflammatory bowel disease has been linked to increasing healthcare costs, but longitudinal data on other societal costs are scarce. Aim: To assess costs, including productivity losses, in patients with prevalent Crohn's disease (CD) or ulcerative colitis (UC) in Sweden between 2007 and 2020. Methods: We linked data from national registers on all patients with CD or UC and a matched (sex, birthyear, healthcare region and education) reference population. We assessed mean costs/year in Euros, inflation‐adjusted to 2020, for hospitalisations, out‐patient visits, medications, sick leave and disability pension. We defined excess costs as the mean difference between patients and matched comparators. Results: Between 2007 and 2020, absolute mean annual societal costs in working‐age (18–64 years) individuals decreased by 17% in CD (−24% in the comparators) and by 20% in UC (−27% in comparators), due to decreasing costs from sick leave and disability, a consequence of stricter sick leave regulations. Excess costs in 2007 were dominated by productivity losses. In 2020, excess costs were mostly healthcare costs. Absolute and excess costs increased in paediatric and elderly patients. Overall, costs for TNF inhibitors/targeted therapies increased by 274% in CD and 638% in UC, and the proportion treated increased from 5% to 26% in CD, and from 1% to 10% in UC. Conclusion: Between 2007 and 2020, excess costs shifted from productivity losses to direct healthcare costs; that is, the patients' compensation for sickness absence decreased, while society increased its spending on medications. Medication costs were driven both by expanding use of TNF inhibitors and by high costs for newer targeted therapies. [ABSTRACT FROM AUTHOR]

Background: There are little data on positioning biologics in Crohn's disease (CD). Aims: We aimed to assess the comparative effectiveness and safety of ustekinumab vs tumour necrosis factor-alpha (anti-TNF) agents after first-line treatment with anti-TNF in CD. Methods: We used Swedish nationwide registers to identify patients with CD, exposed to anti-TNF who initiated second-line biologic treatment with ustekinumab or second-line anti-TNF therapy. Nearest neighbour 1:1 propensity score matching (PSM) was used to balance the groups. The primary outcome was 3-year drug survival used as a proxy for effectiveness. Secondary outcomes included drug survival without hospital admission, CD-related surgery, antibiotics, hospitalization due to infection and exposure to corticosteroids. Results: Some 312 patients remained after PSM. Drug survival at 3 years was 35% (95% CI 26–44%) in ustekinumab compared to 36% (95% CI 28–44%) in anti-TNF-treated patients (p = 0.72). No statistically significant differences were observed between the groups in 3-year survival without hospital admission (72% vs 70%, p = 0.99), surgery (87% vs 92%, p = 0.17), hospital admission due to infection (92% vs 92%, p = 0.31) or prescription of antibiotics (49% vs 50%, p = 0.56). The proportion of patients continuing second-line biologic therapy did not differ by reason for ending first-line anti-TNF (lack of response vs intolerance) or by type of first-line anti-TNF (adalimumab vs infliximab). Conclusion: Based on data from Swedish routine care, no clinically relevant differences in effectiveness or safety of second-line ustekinumab vs anti-TNF treatment were observed in patients with CD with prior exposure to anti-TNF. [ABSTRACT FROM AUTHOR]

Background: Both testicular germ cell tumours (TGCT) and neurodevelopmental disorders are associated with urogenital malformations. Few studies have investigated the association between psychiatric disorders and TGCT. We investigated whether history of any psychiatric or neurodevelopmental disorder is associated with increased risk or mortality of TGCT. Method: This is a nested case–control study including 6166 TGCT patients diagnosed during 1992–2014, individually matched for age and calendar period to 61,660 controls. We calculated odds ratios (ORs) for the association between type of psychiatric diagnoses and TGCT risk. Among the cases, we used a cohort design and calculated hazard ratios (HRs) of the association between psychiatric diagnose and all-cause and TGCT-specific death. Results: History of a neurodevelopmental disorder (attention deficit hyperactivity disorder, autism spectrum disorder and intellectual disabilities) was associated with an increased risk of seminoma (OR: 1.54; 1.09–2.19). Seminoma patients with neurodevelopmental disorders were younger (34 versus 38 years, p = 0.004) and had more stage IV disease (5.4% versus 1.2%) than those without. Psychiatric history overall was not associated with TGCT. Patient history of any psychiatric disorder was associated with an increased all-cause and TGCT-specific death. Conclusions: We report an association between neurodevelopmental disorders and testicular seminoma, and an increased TGCT-specific mortality for TGCT patients with psychiatric disorders. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To determine the risk of inflammatory bowel disease (IBD) in patients with celiac disease (CeD) (and vice versa) compared with general-population comparators. METHODS: Using Swedish histopathology and healthcare register data, we identified 48,551 patients with CeD and 83,529 with IBD diagnosed in 1969–2016. Each patient was compared with age- and sex-matched general-population comparators (CeD: n = 240,136; IBD: n = 408,195). Cox regression estimated hazard ratios (HRs) for IBD in patients with CeD and vice versa. Our main analyses were limited to events beyond the first year of follow-up to reduce potential surveillance bias. RESULTS: During follow-up, 784 (1.6%) patients with CeD were diagnosed with IBD compared with 1,015 (0.4%) matched comparators. In patients with CeD, the HR for IBD was 3.91 (95% confidence interval [CI] 3.56–4.31), with largely similar HRs for Crohn's disease (4.36; 3.72–5.11) and ulcerative colitis (3.40; 3.00–3.85). During follow-up, 644 (0.8%) patients with IBD and 597 (0.1%) comparators were diagnosed with CeD. The HR for CeD in patients with IBD was 5.49 (95% CI 4.90–6.16), with the highest risk estimates seen in ulcerative colitis (HR = 6.99; 6.07–8.05), and the HR for Crohn's disease was 3.31 (2.69–4.06). In patients with CeD and IBD, the diagnostic interval was usually <1 year; however, HRs of 3–4 were seen even after 10 years of follow-up. During 20 years of follow-up, 2.5% of patients with CeD developed incident IBD, and 1.3% of patients with IBD developed CeD. DISCUSSION: The bidirectional association between CeD diagnosis and IBD warrants attention in the initial assessment and follow-up of these conditions. Their co-occurrence, independent of temporal sequence, suggests shared etiology. [ABSTRACT FROM AUTHOR]

Introduction: A revised intrapartum cardiotocography (CTG) classification was introduced in Sweden in 2017. The aims of the revision were to adapt to the international guideline published in 2015 and to adjust the classification of CTG patterns to current evidence regarding intrapartum fetal physiology. This study aimed to investigate adverse neonatal outcomes before and after implementation of the revised CTG classification. Material and Methods: A before‐and‐after design was used. Cohort I (n = 160 210) included births from June 1, 2014 through May 31, 2016 using the former CTG classification, and cohort II (n = 166 558) included births from June 1, 2018 through May 31, 2020 with the revised classification. Data were collected from the Swedish Pregnancy and Neonatal Registers. The primary outcome was moderate to severe neonatal hypoxic ischemic encephalopathy (HIE 2–3). Secondary outcomes were birth acidemia (umbilical artery pH <7.05 and base excess < −12 mmol/L or pH <7.00), A‐criteria for neonatal hypothermia treatment, 5‐min Apgar scores <4 and <7, neonatal seizures, meconium aspiration, neonatal mortality and delivery mode. Logistic regression was used (period II vs period I), and results are presented as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs). Results: There were no statistically significant differences in HIE 2–3 (aOR 1.27; 95% CI 0.97–1.66), proportion of neonates meeting A‐criteria for hypothermia treatment (aOR 0.96; 95% CI 0.89–1.04) or neonatal mortality (aOR 0.68; 95% CI 0.39–1.18) between the cohorts. Birth acidemia (aOR 1.36; 95% CI 1.25–1.48), 5‐min Apgar scores <7 (aOR 1.27; 95% CI 1.18–1.36) and <4 (aOR 1.40; 95% CI 1.17–1.66) occurred more often in cohort II. The absolute risk difference for HIE 2–3 was 0.02% (95% CI 0.00–0.04). Operative delivery (vacuum or cesarean) rates were lower in cohort II (aOR 0.82; 95% CI 0.80–0.85 and aOR 0.94; 95% CI 0.91–0.97, respectively). Conclusions: Although not statistically significant, a small increase in the incidence of HIE 2–3 after implementation of the revised CTG classification cannot be excluded. Operative deliveries were fewer but incidences of acidemia and low Apgar scores were higher in the latter cohort. This warrants further in‐depth analyses before a full re‐evaluation of the revised classification can be made. [ABSTRACT FROM AUTHOR]

It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/− one year and within +/− three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005–2008, 2009–2012, and 2013–2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4–81.7) were ever captured in the PDR/NPR in. A time window of +/− one year or +/− three months reduced the sensitivity to 63.3% (95% CI: 61.3–65.3) and 52.6% (95% CI: 50.5–54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG. [ABSTRACT FROM AUTHOR]

Background: Use of tumor necrosis factor inhibitors (TNFi) in patients with a history of cancer remains a clinical dilemma.Objective: To investigate whether TNFi treatment in rheumatoid arthritis (RA) is associated with increased risk for cancer recurrence.Design: Population-based cohort study based on linkage of nationwide registers.Setting: Sweden.Participants: Patients with RA who started TNFi treatment between 2001 and 2015, after being diagnosed with cancer, and matched patients with RA and a history of the same cancer who had never received biologics.Measurements: The primary outcome was the first recurrence of cancer. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs), taking into account time, cancer type, and whether the cancer was invasive or in situ (or tumor, node, metastasis [TNM] classification system stage in a subset of patients).Results: Among 467 patients who started TNFi treatment (mean time after cancer diagnosis, 7.9 years), 42 had cancer recurrences (9.0%; mean follow-up, 5.3 years); among 2164 matched patients with the same cancer history, 155 had recurrences (7.2%; mean follow-up, 4.3 years) (HR, 1.06 [95% CI, 0.73 to 1.54). Hazard ratios were close to 1 in analyses of patient subsets matched on cancer stage or with similar time from index cancer diagnosis to the start of TNFi treatment, as well as in unmatched analyses. Several CIs had upper limits close to 2.Limitation: The outcome algorithm was partly nonvalidated, and channeling bias was possible if patients with a better index cancer prognosis were more likely to receive TNFi.Conclusion: The findings suggest that TNFi treatment is not associated with increased risk for cancer recurrence in patients with RA, although meaningful risk increases could not be ruled out completely.Primary Funding Source: ALF (an agreement in Stockholm County Council concerning medical education and research in health and medical care), the Swedish Cancer Society, the Swedish Foundation for Strategic Research, and the Swedish Research Council. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Celiac disease (CD) affects 1% of the population. Its effect on healthcare cost, however, is barely understood. We estimated healthcare use and cost in CD, including their temporal relationship to diagnosis. METHODS: Through biopsy reports from Sweden's 28 pathology departments, we identified 40,951 prevalent patients with CD (villous atrophy) as of January 1, 2015, and 15,086 incident patients with CD diagnosed in 2008-2015, including 2,663 who underwent a follow-up biopsy to document mucosal healing. Each patient was compared with age- and sex-matched general population comparators (n 5 187,542). Using nationwide health registers, we retrieved data on all inpatient and nonprimary outpatient care, prescribed diets, and drugs. RESULTS: Compared with comparators, healthcare costs in 2015 were, on average, $1,075 (95% confidence interval, $864-1,278) higher in prevalent patients with CD aged <18 years, $715 ($632-803) in ages 18-64 years, and $1,010 ($799-1,230) in ages 65 years. Half of all costs were attributed to 5% of the prevalent patients. Annual healthcare costswere $391 higher 5 years before diagnosis and increased until 1 year after diagnosis; costs then declined but remained 75% higher than those of comparators 5 years postdiagnosis (annual difference5$1,044). Although hospitalizations, nonprimary outpatient visits, and medication use were all more common with CD, excess costs were largely unrelated to the prescription of gluten-free staples and follow-up visits for CD. Mucosal healing in CD did not reduce the healthcare costs. DISCUSSION: The use and costs of health care are increased in CD, not only before, but for years after diagnosis. Mucosal healing does not seem to lower the healthcare costs. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does exposure to mRNA COVID-19 vaccination during pregnancy increase the risk of adverse events in newborn infants? Findings: In this population-based cohort study from Sweden and Norway that included 94 303 infants exposed to COVID-19 vaccination during pregnancy and 102 167 control infants born between June 2021 and January 2023, vaccination during pregnancy was associated with lower odds of neonatal intracranial hemorrhage, cerebral ischemia and hypoxic-ischemic encephalopathy, and neonatal mortality. Meaning: In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants. Importance: Better knowledge about neonatal adverse events after COVID-19 vaccination during pregnancy could help address concerns about vaccine safety. Objective: To evaluate the risks of neonatal adverse events after exposure to COVID-19 vaccination during pregnancy. Design, Setting, and Participants: Population-based cohort study including all infants in Sweden and Norway born from June 2021 to January 2023. Unique personal identity numbers were used to link individual information from different national registers. Exposure: Administration of any mRNA vaccine against COVID-19 during pregnancy, irrespective of previous vaccination, number of doses during pregnancy, or vaccine manufacturer. Main Outcomes and Measures: Outcomes were neonatal conditions with bleeding/thrombosis or inflammation/infection; disorders of the central nervous system; circulatory, respiratory, or gastrointestinal problems; and neonatal mortality. Statistical methods included logistic regression adjusted for characteristics of the pregnant individuals, with additional restricted and stratified analyses. Results: Of 196 470 newborn infants included (51.3% male, 93.8% born at term, 62.5% born in Sweden), 94 303 (48.0%) were exposed to COVID-19 vaccination during pregnancy. Exposed infants exhibited no increased odds of adverse neonatal outcomes, and they exhibited lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1000; adjusted odds ratio [aOR], 0.78 [95% CI, 0.61-0.99]), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73 [95% CI, 0.55-0.96]), and neonatal mortality (0.9 vs 1.8/1000; aOR, 0.68 [95% CI, 0.50-0.91]). Subgroup analyses found a similar association between vaccination during pregnancy and lower neonatal mortality; subgroups were restricted to infants delivered by individuals unvaccinated before pregnancy, individuals vaccinated before pregnancy, individuals vaccinated after a general recommendation of vaccination during pregnancy was issued, and individuals without COVID-19 infection during pregnancy. Analyses restricted to term infants, singleton births, or infants without birth defects yielded similar results. Stratifying the analysis by vaccine manufacturer did not attenuate the association between vaccination and low neonatal mortality. Conclusions and Relevance: In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants. This cohort study evaluates the risks of neonatal adverse events after exposure to COVID-19 vaccination during pregnancy. [ABSTRACT FROM AUTHOR]

Summary: Background: The microbiome plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Antibiotic use can fundamentally alter gut microbial ecology. We examined the association of antibiotic use with IBS in a large population‐based investigation. Methods: A case–control study with prospectively collected data on 29,111 adult patients diagnosed with IBS in Sweden between 2007 and 2016 matched with 135,172 controls. Using a comprehensive histopathology cohort, the Swedish Patient Register, and the Prescribed Drug Register, we identified all consecutive cases of IBS in addition to cumulative antibiotic dispensations accrued until 1 year prior to IBS (exclusionary period) for cases and time of matching for up to five general population controls matched on the basis of age, sex, country and calendar year. Conditional logistic regression estimated multivariable‐adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of IBS. Results: Patients with IBS (n = 29,111) were more likely than controls (n = 135,172) to have used antibiotics up to 1 year prior to diagnosis (74.9% vs. 57.8%). After multivariable adjustment, this translated to a more than twofold increased odds of IBS (OR 2.21, 95% CI 2.14–2.28) that did not differ according to age, sex, year of IBS diagnosis or IBS subtype. Compared to none, 1–2 (OR 1.67, 95% CI 1.61–1.73) and ≥3 antibiotics dispensations (OR 3.36, 95% CI 3.24–3.49) were associated with increased odds of IBS (p for trend <0.001) regardless of the antibiotic class. Conclusions: Prior antibiotics use was associated with an increased odds of IBS with the highest risk among people with multiple antibiotics dispensations. [ABSTRACT FROM AUTHOR]

Introduction: A detailed understanding of respiratory support patterns in preterm infants is lacking. The aim was to explore and visualize this practice in Sweden. Methods: Preterm infants with gestational ages of 22–31 weeks, admitted to neonatal units reporting daily to the Swedish Neonatal Quality Register and discharged alive in November 2015–April 2022, were included in this descriptive cohort study. Proportions receiving mechanical ventilation, noninvasive support, or supplemental oxygen were calculated and graphically displayed for each gestational week and postnatal day (range 0–97) up to hospital discharge or 36 weeks of postmenstrual age. Results: Respiratory support in 148,515 days of care (3,368 infants; 54% males; median [interquartile range] birthweight = 1,215 [900–1,525] g) was evaluated. Trajectories showed distinct nonlinear patterns for each category of respiratory support, but differences in respiratory support over the gestational age range were linear: the proportion of infants on mechanical ventilation decreased by −11.7 to −7.3% (variability in estimates related to the postnatal day chosen for regression analysis) for each week higher gestational age (r = −0.99 to −0.87, p ≤ 0.001). The corresponding proportions of infants with supplemental oxygen decreased by −12.4% to −4.5% for each week higher gestational age (r = −0.98 to −0.94, p < 0.001). At 36 weeks of postmenstrual age, dependencies on mechanical ventilation, noninvasive support, and supplemental oxygen varied from 3%, 84%, and 94% at 22 weeks to 0%, 3%, and 5% at 31 weeks of gestational age, respectively. Conclusions: Respiratory support patterns in very preterm infants follow nonlinear, gestational age-specific postnatal trajectories in a dose-response-related fashion. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with celiac disease (CD) have an increased risk of encapsulated bacterial infections. Less is known about other serious infections in CD, especially in patients diagnosed in the 21st century. METHODS: We contacted all 28 pathology departments in Sweden through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort study and identified 20,088 individuals with CD (defined as villous atrophy) diagnosed in 2002–2017. Patients were matched for sex, age, and calendar year to 80,152 general population comparators and followed up until December 31, 2019. Serious infections were defined as having a hospital-based (inpatient and outpatient) diagnosis in the National Patient Register. Cox regression yielded adjusted hazard ratios (aHR) controlling for education, country of birth, and comorbidities. RESULTS: During 173,695 person-years of follow-up, 6,167 individuals with CD (35.5/1,000 person-years) had a serious infection. This was compared with 19,131 infections during 743,260 person-years (25.7/1,000 person-years) in matched comparators, corresponding to an aHR of 1.29 (95% confidence interval [CI] = 1.25–1.33). aHR were similar when restricted to infection requiring hospital admission (1.23; 95% CI = 1.17–1.29). The excess risk of serious infections also persisted beyond the first year after CD diagnosis (aHR = 1.24; 95% CI = 1.20–1.29). Patients with CD were at risk of sepsis (aHR = 1.26; 95% CI = 1.09–1.45) and gastrointestinal infections (1.60; 95% CI = 1.47–1.74). Mucosal healing during CD follow-up did not influence the risk of subsequent serious infections. DISCUSSION: This nationwide study of patients with celiac disease diagnosed in the 21st century revealed a significantly increased risk of serious infections. While absolute risks were modest, vaccinations should be considered during CD follow-up care. [ABSTRACT FROM AUTHOR]

Summary: Background: IBD with onset during childhood seems to represent a severe disease phenotype with increased morbidity. We have previously demonstrated that children with IBD have significantly lower final grades in compulsory school compared to healthy peers. Aim: To evaluate the association of childhood‐onset IBD with a later professional career and subsequent earnings Methods: We identified 5404 individuals diagnosed with childhood‐onset (<18 years) IBD between 1990 and 2014 (2818 with ulcerative colitis and 2328 with Crohn's disease) in the Swedish National Patient Register. Patients were matched with 10 general population reference individuals by sex, birth year, and place of residence (n = 51,295). Data on earnings during 1992–2017 were obtained through the longitudinal integration database for health insurance and labour market studies. Earnings were converted into Euros (inflation‐adjusted to 2019). The differences in earnings between patients and general population reference individuals were calculated through quantile regression. Results: Patients with childhood‐onset IBD had significantly lower annual taxable earnings from ages 20 to 30 (adjusted median annual income difference (AMAID) at age 30: −5.4% [95% CI −9.1% to −1.8%]). In particular, annual taxable earnings through early adult age were lower in patients who, during childhood, had had surgery or long‐term inpatient treatment for IBD (AMAID at age 30: −16.3% [95% CI ‐24.7% to −7.9%]). Conclusions: Overall, the negative influence of disease on earnings in early adult age was modest for patients with childhood‐onset IBD. The markedly larger negative income gap from ages 20 to 30 in patients with more severe IBD during childhood should be recognised. [ABSTRACT FROM AUTHOR]

The objectives of the current study were to identify risk factors for SARS-CoV-2 positivity, and to address how different testing strategies, choice of comparison group, and population background characteristics may influence observed associations. National registries data for 107,627 pregnant women in Sweden and 81,195 in Norway, were used to identify risk factors for SARS-CoV-2, separately for women under non-universal testing (testing by indication) and universal testing (testing of all pregnant women in contact with a delivery ward). We also investigated underlying characteristics associated with testing for SARS-CoV-2. Overall, 2.1% of pregnant women in Sweden and 1.1% in Norway were test-positive during the pandemic's first 18 months. We show that the choice of test strategy for SARS-CoV-2 provided different associations with risk factors for the disease; for instance, women who were overweight, obese or had gestational diabetes had increased odds of being test-positive under non-universal testing, but not under universal testing. Nevertheless, a consistent pattern of association between being born in the Middle East and Africa and test-positivity was found independent of test strategy and in both countries. These women were also less likely to get tested. Our results are useful to consider for surveillance and clinical recommendations for pregnant women during the current and future pandemics. [ABSTRACT FROM AUTHOR]

Aim: Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it. Method: We performed a nationwide register‐based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first‐line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. Results: We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09–1.46; p = 0.002). Conclusion: Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more. [ABSTRACT FROM AUTHOR]

• Symptoms of irritable bowel syndrome (IBS) are common reasons for endoscopic procedures. • We examined the yield of colonoscopy and upper endoscopy in IBS in a large cohort. • Inflammatory bowel disease, precancerous polyps, colorectal cancer, and celiac disease were all less common in IBS compared to controls. • Microscopic colitis was more common in IBS patients. • The yield of upper endoscopy and colonoscopy for organic disease is low in patients with a first-time diagnosis of IBS. : Symptoms of irritable bowel syndrome (IBS) are common reasons for endoscopic procedures. We examined the yield of colonoscopy and upper endoscopy in IBS for several organic diseases. : Matched population-based prevalence study in Sweden. We identified 21,944 participants diagnosed with IBS from 1987 to 2016 undergoing colonoscopy with a biopsy from all of Sweden's 28 pathology departments within 6 months of diagnosis. We compared prevalence of histopathology-proven diagnoses of inflammatory bowel disease (IBD), colorectal cancer, precancerous polyps, and microscopic colitis between patients recently diagnosed with IBS and matched controls without IBS (n = 81,101) undergoing colonoscopy. We also compared prevalence of celiac disease between patients diagnosed with IBS (n = 9,965) and matched controls (n = 45,584) undergoing upper endoscopy with biopsy. IBS patients were also compared to their siblings. Conditioned logistic regression estimated adjusted odds ratios (aORs). : Biopsy-proven IBD was seen in 1.6% of IBS and in 5.9% of controls (aOR=0.21; 95%CI=0.19–0.24). The prevalence of precancerous polyps was 4.1% vs. 13.0% (aOR=0.28; 95%CI=0.26–0.30), colorectal cancer 0.8% vs. 6.3% (aOR=0.17; 95%CI=0.14–0.20) and celiac disease 1.9% vs. 3.4% (aOR=0.54; 95%CI=0.47–0.63). Conversely, the prevalence of microscopic colitis was 2.9% vs. 1.7% (aOR=1.77; 95%CI=1.61–1.95), with higher prevalence in older patients and patients with IBS with diarrhea. Yield of colonoscopy for precancerous polyps, colorectal cancer, and microscopic colitis increased by age. Our findings were consistent using unaffected siblings as the comparator group. : The diagnostic yield of upper endoscopy and colonoscopy for organic disease is low in patients with a first-time diagnosis of IBS, though increases with age. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Data suggest atherosclerotic-related inflammation may play a role in the pathogenesis of inflammatory bowel disease (IBD), but large-scale studies are missing. METHODS: In this nationwide case-control study, we used the Swedish Patient Register and the Epidemiology Strengthened by histoPathology Reports in Sweden cohort to identify adult cases of incident IBD between 2002 and 2021, with each case matched to up to 10 general population controls. We used conditional logistic regression to calculate odds ratios (OR) for exposure to an atherosclerotic-related condition (myocardial infarction, thromboembolic stroke, or atherosclerosis itself) before being diagnosed with IBD. RESULTS: There were a total of 56,212 individuals with IBD and 531,014 controls. Of them, 2,334 (4.2%) cases and 18,222 (3.4%) controls had a prior diagnosis of an atherosclerotic-related condition, corresponding to an OR of 1.30 (95% confidence interval [CI] 1.24-1.37). Results were statistically significant for both Crohn's disease (OR 1.37, 95% CI 1.26-1.48) and ulcerative colitis (OR 1.27, 95% CI 1.20-1.35) and for individuals who developed IBD at 40-59 years of age and 60 years or older. In addition, associations persisted when adjusting for underlying comorbidities, including the presence of immune-mediated diseases and prior aspirin and/or statin use. The highest odds of an atherosclerotic-related condition were seen in the 6-12 months before IBD diagnosis, though odds were increased even ≥5 years before. A higher magnitude of odds was also observed when having 2 or more atherosclerotic-related conditions when compared with having only 1 condition. DISCUSSION: A history of an atherosclerotic-related condition is associated with increased odds of developing IBD, particularly among older adults. Future studies should investigate whether drugs targeting atherosclerotic-related inflammation may prevent IBD in higher-risk individuals. [ABSTRACT FROM AUTHOR]

Importance: The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear.Objective: To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy.Design, Setting, and Participants: Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants.Exposures: Maternal test positivity for SARS-CoV-2 in pregnancy.Main Outcomes and Measures: In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2.Results: Of 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia.Conclusions and Relevance: In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Mortality concern is a frequent driver of care seeking in patients with irritable bowel syndrome (IBS). Data on mortality in IBS are scarce, and population-based studies have been limited in size. We examined mortality in IBS. METHODS: A nationwide, matched, population-based cohort study was conducted in Sweden. We identified 45,524 patients undergoing a colorectal biopsy at any of Sweden's 28 pathology departments and with a diagnosis of IBS from 2002 to 2016 according to the National Patient Register, a nationwide registry of inpatient and outpatient specialty care. We compared the mortality risk between these individuals with IBS and age- and sex-matched reference individuals (n = 217,316) from the general population and siblings (n = 53,228). In separate analyses, we examined the role of mucosal appearance for mortality in IBS. Finally, we examined mortality in 41,427 patients with IBS not undergoing a colorectal biopsy. Cox regression estimated hazard ratios (HRs) for death. RESULTS: During follow-up, there were 3,290 deaths in individuals with IBS (9.4/1,000 person-years) compared with 13,255 deaths in reference individuals (7.9/1,000 person-years), resulting in an HR of 1.10 (95% confidence interval [CI] = 1.05-1.14). After adjustment for confounders, IBS was not linked to mortality (HR = 0.96; 95% CI = 0.92-1.00). The risk estimates were neutral when patients with IBS were compared with their siblings. The underlying mucosal appearance on biopsy had only a marginal impact on mortality, and patients with IBS not undergoing a colorectal biopsy were at no increased risk of death (HR = 1.02; 95% CI = 0.99-1.06). DISCUSSION: IBS does not seem to confer an increased risk of death. [ABSTRACT FROM AUTHOR]

Importance: Celiac disease may be associated with a modest but persistent increased long-term mortality risk. It is uncertain whether this risk has changed in the era of wider diagnosis rates, less severe clinical disease, and more widespread availability of gluten-free food.Objective: To evaluate the association between celiac disease and mortality risk in a population-based cohort in Sweden.Design, Setting, and Participants: All individuals in Sweden with celiac disease diagnosed between 1969 and 2017 were identified through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort. Participants (n = 49 829) were observed starting on the day of the biopsy. The final date of follow-up was December 31, 2017.Exposures: Celiac disease was defined by the presence of small intestinal villus atrophy on histopathology specimens during the years 1969-2017 from Sweden's 28 pathology departments. Each individual was matched with as many as 5 control participants in the general population by age, sex, county, and calendar period.Main Outcomes and Measures: The primary outcome was all-cause mortality, and the secondary outcome was cause-specific mortality. Patients with celiac disease were compared with controls using stratified Cox proportional modeling, stratifying by year of diagnosis.Results: There were 49 829 patients with celiac disease, including 24% who were diagnosed between the years 2010 and 2017. The mean (SD) age at diagnosis was 32.2 (25.2) years and 62.4% were women. During a median follow-up time of 12.5 years, 13.2% (n = 6596) died. Compared with controls (n = 246 426), overall mortality was increased in those with celiac disease (9.7 vs 8.6 deaths per 1000 person-years; absolute difference, 1.2 per 1000 person-years; hazard ratio [HR], 1.21 [95% CI, 1.17-1.25]). The relative increase in mortality risk was present in all age groups and was greatest in those diagnosed in the age range of 18 to 39 years (1.9 vs 1.1 per 1000 person-years; HR, 1.69 [95% CI, 1.47-1.94]; P values for heterogeneity comparing 18-39 years with 40-59 years and with ≥60 years were both <.001). Individuals with celiac disease were at increased risk of death from cardiovascular disease (3.5 vs 3.4 per 1000 person-years; HR, 1.08 [95% CI, 1.02-1.13]), cancer (2.7 vs 2.2 per 1000 person-years; HR, 1.29 [95% CI, 1.22-1.36]), and respiratory disease (0.6 vs 0.5 per 1000 person-years; HR, 1.21 [95% CI, 1.08-1.37]). When compared with controls, the overall mortality risk was greatest in the first year after diagnosis (15.3 vs 6.5 per 1000 person-years; HR, 2.34 [95% CI, 2.14-2.55]) but persisted beyond 10 years after diagnosis (10.5 vs 10.1 per 1000 person-years; HR, 1.15 [95% CI, 1.10-1.20]). The mortality risk was likewise present for patients diagnosed during the years 2010-2017 (7.5 vs 5.5 per 1000 person-years; HR, 1.35 [95% CI, 1.21-1.51]).Conclusions and Relevance: In a Swedish population studied between 1969 and 2017, a diagnosis of celiac disease compared with the general population was associated with a small but statistically significant increased mortality risk. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Several earlier studies have indicated an increased risk of cardiac birth defects among infants born to mothers with celiac disease (CeD). Through linking nationwide Swedish health care registries, we aimed to investigate maternal CeD and risk of any or cardiac birth defects in their offspring. METHODS: We performed a retrospective cohort study of infants born between 2002 and 2016 to women with biopsy-proven CeD (villous atrophy, Marsh III) matched to infants born to nonceliac women from the general population. Conditional logistic regression with odds ratios (OR) and their 95% confidence intervals (CI) was used to determine the association between maternal CeD and birth defects. To minimize the impact of intrafamilial confounding, we also compared infants born to mothers with CeD with infants born to their nonaffected sisters. RESULTS: A total of 6,990 infants were born to mothers with diagnosed CeD compared with 34,643 infants born to reference mothers. Any birth defect was seen in 234 (33 per 1,000 infants) and 1,244 (36/1,000) reference infants corresponding to an OR of 0.93 (95% CI 0.81-1.08). Cardiac birth defects were seen in 113 (16/1,000) vs 569 (16/1,000) infants (OR 0.98, 95% CI 0.80-1.20). Similar OR for any and cardiac birth defects were also seen in sibling comparisons. DISCUSSION: We found no statistically significant risk of any or cardiac birth defects in infants born to mothers with diagnosed CeD compared with the general population and to their nonaffected sisters. [ABSTRACT FROM AUTHOR]

I Background: i A recent Danish study reported that the rate of extremely preterm birth was reduced during the lockdown period of the coronavirus disease 2019 (COVID-19) pandemic; the odds ratio (OR) was 0.09 (95% CI, 0.01 to 0.40) compared with previous years ([1]). A study from the United Kingdom reported that stillbirth was more common during the pandemic; the difference was 6.93 (CI, 1.83 to 12.0) cases per 1000 births, corresponding to a 4-fold risk increase ([2]). [Extracted from the article]

Background: Maternal type 1 diabetes (T1D) has been linked to preterm birth and other adverse pregnancy outcomes. How these risks vary with glycated hemoglobin (or hemoglobin A1c [HbA1c]) levels is unclear.Objective: To examine preterm birth risk according to periconceptional HbA1c levels in women with T1D.Design: Population-based cohort study.Setting: Sweden, 2003 to 2014.Patients: 2474 singletons born to women with T1D and 1 165 216 reference infants born to women without diabetes.Measurements: Risk for preterm birth (<37 gestational weeks). Secondary outcomes were neonatal death, large for gestational age, macrosomia, infant birth injury, hypoglycemia, respiratory distress, 5-minute Apgar score less than 7, and stillbirth.Results: Preterm birth occurred in 552 (22.3%) of 2474 infants born to mothers with T1D versus 54 287 (4.7%) in 1 165 216 infants born to mothers without diabetes. The incidence of preterm birth was 13.2% in women with a periconceptional HbA1c level below 6.5% (adjusted risk ratio [aRR] vs. women without T1D, 2.83 [95% CI, 2.28 to 3.52]), 20.6% in those with a level from 6.5% to less than 7.8% (aRR, 4.22 [CI, 3.74 to 4.75]), 28.3% in those with a level from 7.8% to less than 9.1% (aRR, 5.56 [CI, 4.84 to 6.38]), and 37.5% in those with a level of 9.1% or higher (aRR, 6.91 [CI, 5.85 to 8.17]). The corresponding aRRs for medically indicated preterm birth (n = 320) were 5.26 (CI, 3.83 to 7.22), 7.42 (CI, 6.21 to 8.86), 11.75 (CI, 9.72 to 14.20), and 17.51 (CI, 14.14 to 21.69), respectively. The corresponding aRRs for spontaneous preterm birth (n = 223) were 1.81 (CI, 1.31 to 2.52), 2.86 (CI, 2.38 to 3.44), 2.88 (CI, 2.23 to 3.71), and 2.80 (CI, 1.94 to 4.03), respectively. Increasing HbA1c levels were associated with the study's secondary outcomes: large for gestational age, hypoglycemia, respiratory distress, low Apgar score, neonatal death, and stillbirth.Limitation: Because HbA1c levels were registered annually at routine visits, they were not available for all pregnant women with T1D.Conclusion: The risk for preterm birth was strongly linked to periconceptional HbA1c levels. Women with HbA1c levels consistent with recommended target levels also were at increased risk.Primary Funding Source: Swedish Diabetes Foundation. [ABSTRACT FROM AUTHOR]

Background: Obesity increases the risk of adverse delivery outcomes. Whether weight loss induced by bariatric surgery influences these risks remains to be determined. The objective was to investigate the risk of adverse delivery outcomes among post-surgery women compared with women without bariatric surgery history but with similar characteristics.Methods and Findings: We identified 801,443 singleton live-born term births (≥37 gestational weeks) in the Swedish Medical Birth Register between 1 January 2006 and 31 December 2013, of which 1,929 were in women with a history of bariatric surgery and a pre-surgery weight available from the Scandinavian Obesity Surgery Registry. For each post-surgery delivery, up to 5 control deliveries were matched by maternal pre-surgery BMI (early-pregnancy BMI used for controls), age, parity, smoking, education, height, country of birth, and delivery year (N post-surgery deliveries:matched controls = 1,431:4,476). The main outcome measures were mode of delivery, induction of labor, post-term pregnancy (≥42 + 0 gestational weeks), epidural analgesia, fetal distress, labor dystocia, peripartum infection, obstetric anal sphincter injury (perineal tear grade III-IV), and postpartum hemorrhage. Among the women with a history of bariatric surgery, the mean pre-surgery BMI was 42.6 kg/m2, the median surgery-to-conception interval was 1.4 years, and the mean BMI loss between surgery and early pregnancy was 13.5 kg/m2 (38 kg). Compared to matched control women, post-surgery women were less likely to have cesarean delivery (18.2% versus 25.0%, risk ratio [RR] 0.70, 95% CI 0.60-0.80), especially emergency cesarean (6.8% versus 15.1%, RR 0.40, 95% CI 0.31-0.51). Post-surgery women also had lower risks of instrumental delivery (5.0% versus 6.5%, RR 0.73, 95% CI 0.53-0.98), induction of labor (23.4% versus 34.0%, RR 0.68, 95% CI 0.59-0.78), post-term pregnancy (4.2% versus 10.3%, RR 0.40, 95% CI 0.30-0.53), obstetric anal sphincter injury (1.5% versus 2.9%, RR 0.46, 95% CI 0.25-0.81), and postpartum hemorrhage (4.6% versus 8.0%, RR 0.58, 95% CI 0.44-0.76). Since this study was not randomized, a limitation is the possibility of selection bias, despite our efforts using careful matching.Conclusions: Bariatric-surgery-induced weight loss was associated with lower risks for adverse delivery outcomes in term births. [ABSTRACT FROM AUTHOR]

The clear dose-dependent weight loss effect that we found in our study2 strongly supports the importance of gastric-bypass-induced weight loss on pre-eclampsia risk. I Sir, i We find it unlikely that the effect of calcium and vitamin D supplementation would be large enough to be equal to/compete with the metabolic and weight loss effects of gastric bypass in severely obese women and thereby, as van Gelder et al.1 put it, make it 'challenging to distinguish between the effect of gastric bypass itself and the effect of vitamin D and calcium supplementation'. Although calcium and vitamin D supplementation could have contributed to the substantial risk reduction of pre-eclampsia in the gastric bypass group, we do not agree with van Gelder et al. SP 1 sp that stating 'gastric bypass in itself is effective in the prevention of pre-eclampsia may still be considered premature'. [Extracted from the article]

INTRODUCTION: Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort. METHODS: We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged <18 and of RA in individuals with CD aged ≥18. RESULTS: We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82–3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36–2.12) over a follow-up of 8.8 years. DISCUSSION: Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA. [ABSTRACT FROM AUTHOR]

Introduction: Our objective was to compare neonatal outcomes and resource use of neonates born to mothers with SARS-CoV-2 positivity during pregnancy with neonates born to mothers without SARS-CoV-2 positivity. Methods: We conducted a two-country cohort study of neonates admitted between January 1, 2020, and September 15, 2021, to tertiary neonatal intensive care unit (NICU) in Canada and Sweden. Neonates from mothers who were SARS-CoV-2 positive during pregnancy were compared with three randomly selected NICU neonates of mothers who were not test-positive, matched on gestational age, sex, and birth weight (±0.25 SD). Subgroup analyses were conducted for neonates born <33 weeks' gestation and mothers who were SARS-CoV-2 positive ≤10 days prior to birth. Primary outcome was duration of respiratory support. Secondary outcomes were in-hospital mortality, neonatal morbidity, late-onset sepsis, receipt of breast milk at discharge, and length of stay. Results: There were 163 exposed and 468 matched neonates in Canada, and 303 exposed and 903 matched neonates in Sweden. There was no statistically significant difference in invasive or noninvasive respiratory support durations, mortality, respiratory and other neonatal morbidities, or resource utilizations between two groups in both countries in entire cohort and in subgroup analyses. Receipt of breast milk at discharge was lower in the Canadian neonates of mothers who were SARS-CoV-2 positive ≤10 days before birth (risk ratio 0.68, 95% CI: 0.57–0.82). Conclusion: Maternal SARS-CoV-2 positivity was not associated with increased durations of respiratory support, morbidities, mortality, or length of hospital stay in Canada and Sweden among neonates admitted to tertiary NICU. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) is a highly prevalent condition and a significant contributor to global disability. The vast majority of MDD is handled by primary care, but most real‐life studies on MDD only include data from secondary care. The aim of this study was therefore to estimate the total clinical and societal burden of incident MDD including data from all healthcare levels in a large well‐defined western European healthcare region. Methods: Population‐wide observational study included healthcare data from Region Stockholm, Sweden's largest region with approximately 2.4 million inhabitants. All patients in Region Stockholm having their first unipolar MDD episode between January 1, 2012, and December 31, 2018, were included. The sample also included matched study population controls. Outcomes were psychiatric and non‐psychiatric comorbid conditions, antidepressant therapy use, healthcare resource utilization, work loss, and all‐cause mortality. Results: In the study period, 137,822 patients in Region Stockholm were diagnosed with their first unipolar MDD episode. Compared with matched controls, MDD patients had a higher burden of non‐psychiatric and psychiatric comorbid conditions, 3.2 times higher outpatient healthcare resource utilization and 8.6 times more work loss. MDD was also associated with a doubled all‐cause mortality compared with matched controls (HR: 2.2 [95% CI: 2.0–2.4]). Conclusions: The high mortality, morbidity, healthcare resource utilization, and work loss found in this study confirms that MDD is associated with individual suffering and low functioning leading to substantial costs for patients and society. These findings should motivate additional efforts in improving outcomes for MDD patients. [ABSTRACT FROM AUTHOR]

We aimed to determine the risk of incident cancer in autoimmune hepatitis (AIH) compared with the general population and siblings. AIH was defined by the presence of a medical diagnosis of AIH and results of examination of a liver biopsy specimen in a nationwide Swedish population-based cohort study. We identified 5,268 adults with AIH diagnosed during 1969–2016 and 22,996 matched, general population, reference individuals and 4,170 sibling comparators. Using Cox regression, hazard ratios were determined for any incident cancer, and subtypes were determined from the Swedish Cancer Register. During follow-up, a cancer diagnosis was made in 1,119 individuals with AIH (17.2 per 1,000 person-years) and 4,450 reference individuals (12.0 per 1,000 person-years). This corresponded to a hazard ratio of 1.53 (95% confidence interval: 1.42, 1.66). Cancer risk was highest in those with cirrhosis. There was a 29.18-fold increased risk of hepatocellular carcinoma (HCC) (95% confidence interval: 17.52, 48.61). The annual incidence risk of HCC in individuals with AIH who had cirrhosis was 1.1% per year. AIH was also linked to nonmelanoma skin cancer (hazard ratio (HR) = 2.69) and lymphoma (HR = 1.89). Sibling analyses yielded similar risk estimates for any cancer (HR = 1.84) and HCC (HR = 23.10). AIH is associated with an increased risk of any cancer, in particular, HCC and extrahepatic malignancies. The highest risk for cancer, especially HCC, is in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Celiac disease (CeD) has been linked to an increased risk of other autoimmune diseases, yet the impact of delayed CeD diagnosis on risk of developing additional autoimmune diseases remains uncertain. We investigated this through a nationwide matched case-control study. Using the ESPRESSO cohort with histophatology data from Sweden's 28 pathology departments, we assessed 46,575 biopsy-confirmed CeD cases from 1964 to 2017. We extracted 225,295 matched controls without histopathology information from the Swedish Total Population Register. Autoimmune disease was defined through diagnostic codes in the National Patient Register. Through conditional logistic regression we estimated odds ratio (OR) of autoimmune disease up until CeD diagnosis/matching date comparing CeD cases to controls across different age strata. A total of 3059 (6.6 %) CeD patients and 4076 (1.8 %) controls had earlier autoimmune disease. The overall OR for autoimmune disease in CeD was 3.50 (95%CI 3.32–3.70). The risk of autoimmune disease did not escalate with increasing age at CeD diagnosis. Compared with controls, the OR of autoimmune disease in CeD patients was 7.70 (95%CI 4.71–12.57) in those diagnosed with CeD in 0–4 years, 19.02 (95%CI 13.80–26.23) in 5–9 years, 6.18 (95%CI 5.14–7.44) in 10–14 years, 4.80 (95%CI 3.97–5.79) in 15–19 years, 4.24 (95%CI 3.55–5.07) in 20–29 years, 4.65 (95%CI 3.93–5.51) in 30–39 years, 3.67 (95%CI 3.30–4.09) in 40–59 years, and 1.67 (95%CI 1.50–1.85) in ≥60 years. This study revealed an increased risk of autoimmune disease among CeD patients compared with controls. However, older age at CeD diagnosis did not seem to escalate the risk of autoimmune diseases. • The diagnosis of celiac disease peaked at age 2 and subsequently declined as age progresses. • Celiac disease patients exhibited a higher prevalence of autoimmune diseases compared to their controls. • The risk of autoimmune disease did not escalate with increasing age at the celiac disease diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Some, but not all, prior studies have suggested that patients with chronic liver disease are at increased risk of contracting COVID-19 and developing more severe disease. However, nationwide data are lacking from well-phenotyped cohorts with liver histology and comparisons to matched general population controls.Methods: We conducted a nationwide cohort study of all Swedish adults with chronic liver disease (CLD) confirmed by liver biopsy between 1966 and 2017 (n = 42,320), who were alive on February 1, 2020. CLD cases were matched to ≤ 5 population comparators by age, sex, calendar year and county (n = 182,147). Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 hospitalization and severe COVID-19 (intensive care admission or death due to COVID-19).Results: Between February 1 and July 31, 2020, 161 (0.38%) CLD patients and 435 (0.24%) general population controls were hospitalized with COVID-19 (aHR = 1.36, 95% CI = 1.11-1.66), while 65 (0.15%) CLD patients and 191 (0.10%) controls developed severe COVID-19 (aHR = 1.08, 95% CI = 0.79-1.48). Results were similar in patients with CLD due to alcohol use, nonalcoholic fatty liver disease, viral hepatitis, autoimmune hepatitis, and other etiologies. Among patients with cirrhosis (n = 2549), the aHRs for COVID-19 hospitalization and for severe COVID-19 were 1.08 (95% CI 0.48-2.40) and 1.23 (95% CI = 0.37-4.04), respectively, compared to controls. Moreover, among all patients diagnosed with COVID-19, the presence of underlying CLD was not associated with increased mortality (aHR = 0.85, 95% CI = 0.61-1.19).Conclusions: In this nationwide cohort, patients with CLD had a higher risk of hospitalization for COVID-19 compared to the general population, but they did not have an increased risk of developing severe COVID-19. [ABSTRACT FROM AUTHOR]

Aims : The purpose of this research was to describe the current prevalence and historic trends in overweight, obesity and severe obesity in Sweden. Methods : Data on BMI, age, gender, education and geographic region were obtained in n =447,925 Swedish adults through a nationwide screening test (1995–2017). To account for sampling variations, we quantified prevalence estimates and time trends using standardized values (direct method) to all 18–74-year-old Swedes, using nationwide databases. Rates of overweight (BMI ⩾25 kg/m2), obesity (BMI ⩾30 kg/m2) and severe obesity (BMI ⩾35 kg/m2) were calculated across gender, age, education and geographic categories. Years were grouped into two-year sampling periods (except the first period where we used three years) for increased power. We used multivariable logistic regression to quantify independent associations between age, gender, education and region with obesity development and current prevalence rates. Results : In 2016/17 the unstandardized prevalence of overweight, obesity and severe obesity were 55.1%, 16.6% and 4.2%, respectively. Factors associated with a higher obesity prevalence were male gender, older age, lower education and residing in a rural region (all P <0.001). Between 1995 and 2017 the prevalence of severe obesity increased by 153%, compared to obesity (+86%) and overweight (+23%). While there were similar increases in obesity across gender and age groups, people with low education (vs high) and rural areas (vs urban) had a higher prevalence increase (both P <0.001). Conclusions : Rates of overweight, obesity and severe obesity have increased markedly in Swedish adults since 1995. Priority groups for prevention efforts include individuals with low education and those living in rural areas. [ABSTRACT FROM AUTHOR]

Objective To compare mortality risk over up to 14 years of follow-up in methotrexate-refractory patients with early RA randomized to a strategy starting with addition of infliximab vs addition of SSZ and HCQ. Methods Data was from the two-arm, parallel, randomized, active-controlled, open-label Swefot trial in which patients with early RA (symptom duration <1 y) were recruited from 15 rheumatology clinics in Sweden (2002–2005). Patients who did not achieve low disease activity after 3–4 months of MTX were randomized to addition of infliximab (n  = 128) or SSZ and HCQ (n  = 130). Participants were followed until death, emigration, or end of follow-up, whichever came first. Analyses were by intention-to-treat. Results Over an average follow-up of 13 years, there were 13 and 16 deaths, respectively [8.8 vs 10.6 deaths per 1000 person-years; mortality hazard ratio 1.2 (95% CI: 0.6, 2.5); P  =0.62]. The 1-year mortality was 0.8% in both treatment arms, the 5-year mortality was 2.3% for the infliximab arm compared with 1.5% for the conventional combination treatment arm, while the 10-year mortality was 7.8% and 7.7%, respectively. After 5 years, ∼50% of patients in the conventional combination therapy arm had switched to biologic treatment, and 50% in the biologic arm had discontinued treatment with a biologic DMARD. Conclusion No difference in mortality risk could be observed over up to 14 years of follow-up between treatment strategy groups. At 5 years (3 years after trial cessation), 50% of patients remained on their assigned therapy, reflecting that DMARD combination is an adequate treatment strategy in 50% of patients. Trial registration clinicaltrials.gov, identifier: NCT00764725. [ABSTRACT FROM AUTHOR]

This study examines the pregnancy outcomes of individuals infected with SARS-CoV-2 and those uninfected at a hospital in Sweden. [ABSTRACT FROM AUTHOR]

Summary: Background: There are limited data on population‐wide assessment of cost in Crohn's disease (CD) and ulcerative colitis (UC). Aim: To estimate the societal cost of actively treated CD and UC in Sweden. Methods: We identified 10 117 prevalent CD and 19 762 prevalent UC patients, aged ≥18 years on 1 January 2014 and 4028 adult incident CD cases and 8659 adult incident UC cases (2010‐2013) from Swedish Patient Register. Each case was matched to five population comparators. Healthcare costs were calculated from medications, outpatient visits, hospitalisations and surgery. Cost of productivity losses was derived from disability pension and sick leave. Results: The mean annual societal costs per working‐age patient (18‐64 years) with CD and UC were $22 813 (vs $7533 per comparator) and $14 136 (vs $7351 per comparator), respectively. In patients aged ≥65 years, the mean annual costs of CD and UC were $9726 and $8072 vs $3875 and $4016 per comparator, respectively. The majority of cost for both CD (56%) and UC (59%) patients originated from productivity losses. Higher societal cost of working‐age CD patients as compared to UC patients was related to greater utilisation of anti‐TNF (22.2% vs 7.4%) and increased annual disability pension (44 days vs 25 days). Among incident CD and UC patients, the mean total cost over the first year per patient was over three times higher than comparators. Conclusion: In Sweden, the societal cost of incident and prevalent CD and UC patients was consistently two to three times higher than the general population. [ABSTRACT FROM AUTHOR]

The aim was to investigate sex- and age-specific associations between cardiorespiratory fitness, all-cause and cause-specific mortality, and cardiovascular disease (CVD) morbidity. 266.109 participants (47% women, 18-74 years) free from CVD, participating in occupational health service screenings in 1995-2015 were included. CRF was assessed as estimated maximal oxygen consumption (estVO2max) using a submaximal cycle test. Incident cases of first-time CVD event and death from any cause were ascertained through national registers. There were 4244 CVD events and 2750 cases of all-cause mortality during mean 7.6 years follow-up. Male gender, higher age and lower estVO2max were associated with higher all-cause mortality and CVD morbidity incidence rates. Risk reductions with increasing estVO2max were present in all age-groups of men and women. No obvious levelling off in risk was identified in the total cohort. However, women and older age-groups showed no further reduction in higher aggregated estVO2max levels. CVD specific mortality was more associated with estVO2max compared to tumor specific mortality. The risk for all-cause mortality and CVD morbidity decreased by 2.3% and 2.6% per increase in 1 ml·min-1·kg-1 with no significant sex-differences but more pronounced in the three lower estVO2max categories for all-cause mortality (9.1%, 3.8% and 3.3%, respectively). High compared to lower levels of estVO2max was not related to a significantly elevated mortality or morbidity. In this large cohort study, CVD morbidity and all-cause mortality were inversely related to estVO2max in both men and women of all age-groups. Increasing cardiorespiratory fitness is a clear public health priority. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence of violent crime conviction among Swedish military veterans after deployment to Afghanistan versus non-deployed comparators. The main outcome was first conviction of a violent crime, retrieved from the Swedish National Council for Crime Prevention Register until December 31, 2013.Methods: This was a cohort study of military veterans identified through personnel registers regarding deployment to Afghanistan between 2002 and 2013 (n = 5894). To each military veteran, up to five non-deployed comparators identified via the Military Service Conscription Register were matched by age, sex, conscription year, cognitive ability, psychological assessment, self-reported mental health, body mass index, antidepressants/anxiolytics prescriptions and self-harm (fully matched comparators; n = 28 895). Multivariable adjustment was made for substance abuse and previous health care visits with psychiatric diagnoses. An additional comparator group matched only for age, sex and conscription year was also used (age-sex-matched comparators; n = 29 410).Results: During 21 898 person-years of follow-up (median = 3.6 years) there were 26 events among deployed military veterans compared with 98 in non-deployed fully matched comparators [12 vs 9 per 10 000 person-years, adjusted hazard ratio (aHR) 1.36; 95% confidence interval (CI) 0.88-2.10]. Among non-deployed age-sex-matched comparators there were 170 violent crime convictions (16 per 10 000 person-years; aHR 0.85; 95% CI 0.56-1.29). Factors associated with greater risk of violent crime convictions were younger age, lower scores on cognitive ability tests and psychological assessment, and convictions preceding deployment.Conclusion: The violent crime conviction rate after returning from military deployment to Afghanistan was not different compared with non-deployed comparators in individuals without history of violent crime convictions. [ABSTRACT FROM AUTHOR]

Background: Long‐term trend analyses of cardiorespiratory fitness (VO2max) in the general population are limited. Objectives: To describe trends in VO2max from 1995 to 2017 in the Swedish working force and to study developments across categories of sex, age, education, and geographic regions. Methods: A total of 354 277 participants (44% women, 18‐74 years) who participated in a nationwide occupational health service screening between 1995 and 2017 were included. Changes in standardized mean values of absolute (L/min) and relative (mL/min/kg) VO2max, and the proportion with low (<32) relative VO2max are reported. VO2max was estimated using a submaximal cycle test. Results: Absolute VO2max decreased by −6.7% (−0.19 L/min) in the total population. Relative VO2max decreased by −10.8% (−4.2 mL/min/kg) with approximately one‐third explained by a simultaneous increase in body mass. Decreases in absolute fitness were more pronounced in men vs women (8.7% vs 5.3%), in younger vs older (6.5% vs 2.3%), in short (11.4%) vs long (4.5%) education, and in rural vs urban regions (6.5% vs 3.5%), all P < 0.001. The proportions with low VO2max increased from 27% to 46% (P < 0.001). Conclusion: Between 1995 and 2017, there was a steady and pronounced decline in mean cardiorespiratory fitness in Swedish adults. Male gender, young age, short education, and living in a rural area were predictive of greater reductions. The proportion with low cardiorespiratory fitness almost doubled. Given the strong associations between cardiorespiratory fitness and multiple morbidities and mortality, preventing further decreases is a clear public health priority, especially for vulnerable groups. [ABSTRACT FROM AUTHOR]

Aim: To investigate the probability of marriage and divorce among Swedish military veterans deployed to Afghanistan relative to non-deployed matched comparators. Study design and setting: Matched cohort study in Sweden. Participants: Military veterans were identified through Swedish military personnel registers regarding foreign deployments, and comparators from the Military Service Conscription Register (1969–2013). Of 1,882,411 eligible conscripts, 7041 had served in Afghanistan at some point in time between 2002 and 2013. To each military veteran, up to 5 non-deployed comparators who underwent conscription were matched by age, sex, psychological assessment, cognitive ability, psychiatric history and social characteristics. After matching there were 4896 (82%) unmarried and 1069 (18%) married deployed military veterans. The main outcome was marriage or divorce after deployment to Afghanistan. Data on marital status were retrieved from Statistics Sweden until December 31, 2014. Results: During a median follow-up of 4.1 years after deployment of married individuals, 124 divorces were observed among deployed military veterans and 399 in the matched non-deployed comparator cohort (277 vs. 178 per 10,000 person-years; adjusted hazard ratio 1.61, 95%CI 1.31–1.97). During a median follow-up of 4.7 years after deployment in the unmarried cohort, 827 new marriages were observed among deployed military veterans and 4363 in the matched non-deployed comparators cohort (399 vs. 444 per 10,000 person-years; adjusted hazard ratio 0.89, 95%CI 0.83–0.96). Conclusion: Military veterans were more likely to divorce and less likely to marry after deployment compared with matched non-deployed comparators. [ABSTRACT FROM AUTHOR]

This cohort study uses Swedish Medical Birth Register data to investigate risk of birth defects in infants born to women who had Roux-en-Y bariatric surgery between 2007 and 2014. [ABSTRACT FROM AUTHOR]