Nationwide Swedish Cohort Study Research Articles

Early-Life Factors Associated With Adult-Onset Type 1 Diabetes: A Swedish Nationwide Cohort and Family-Based Study.

Childhood-onset type 1 diabetes (T1D) is associated with perinatal factors, but data related to adult-onset T1D are scarce. This study aimed at investigating the association between early-life factors and adult-onset T1D in a Swedish nationwide cohort and family-based study. We included 1,813,415 individuals aged ≥18 years, born in Sweden 1983 to 2002, followed until 2020. T1D diagnosis (n = 3,283) was identified from the National Diabetes, Patient and Prescribed Drugs Registers, and perinatal exposures were obtained from the Medical Birth Register. We performed Cox proportional hazard (hazard ratio [95% CI]) regression with mutual adjustment for perinatal exposures, sex, birth year, and parental sociodemographic background and history of diabetes. We also compared T1D risks among siblings' groups identified from the Multiple Generation Register. The incidence rate of adult-onset T1D was 18.8 per 100,000 person-years. Year of birth (1.06 [1.01-1.10], per five additional years) and history of maternal (4.10 [3.09-5.43]) and paternal (6.24 [5.10-7.64]) T1D were associated with a higher incidence of adult-onset T1D, whereas female sex (0.69 [0.64-0.74]) and having parents born outside Sweden were associated with a lower incidence. Regarding perinatal exposures, only non-full-term birth (<39 weeks vs. ≥39 weeks) was associated with a higher incidence of adult-onset T1D (1.12 [1.04-1.22]). The sibling cohort results were consistent with the full cohort analysis. Perinatal factors seem to play a minor role in the development of adult-onset T1D compared with childhood-onset T1D, suggesting that triggers or accelerators of autoimmunity occurring later in life are more significant.

#2576 Effect of dialysis versus conservative care on all-cause mortality in older patients with advanced CKD: nationwide Swedish cohort study

Abstract Background and Aims Conservative care is emerging as an alternative to dialysis in older patients with advanced chronic kidney disease (CKD). However, high-quality evidence comparing the effect of dialysis versus conservative care on patient survival is lacking. Previous observational studies suffered from avoidable biases, such as immortal time bias and lead time bias, and adjusted for limited confounders. This study aimed to assess the effects of dialysis versus conservative care on mortality in older patients with advanced CKD. Method The target trial emulation framework was used to design and analyze this observational study. We conducted a nationwide observational cohort study using data from the Swedish Renal Registry between 2007-2021. We included all nephrologist-referred patients with eGFR &amp;lt; 20 ml/min/1.73 m2 who had a registered decision for dialysis or conservative care. Eligible patients were required to be ≥ 65 years with a Davies Comorbidity Score ≥ 2 or ≥ 80 years. The primary endpoint was 5-year all-cause mortality. Inverse probability of treatment weighting was used to adjust for 50 baseline confounders, including demographics, comorbidities, medication use, blood pressure, laboratory measurements, hospitalizations, and calendar year. Patients in the non-overlapping region of the propensity score distribution were excluded since they had an absolute indication for dialysis or conservative care. Cox proportional hazards regression was used to estimate intention-to-treat hazard ratios (HRs) with 95% confidence intervals (CIs), and the Kaplan-Meier estimator was used to estimate absolute risks. Additionally, we calculated the 5-year restricted mean survival times (RMST) and the 5-year RMST difference between dialysis and conservative care arms. To test the robustness and consistency of our main results, we performed a subgroup analysis in patients aged ≥80. Results Of 2834 eligible patients, 1903 had a registered choice for dialysis and 931 for conservative care. The median age was 81 years, 36.1% were female and median eGFR was 13.1 ml/min/1.73 m2. During the 5-year follow-up period, 29 conservative care patients started dialysis and 430 patients died before starting dialysis. After weighting, all confounders were balanced (standardized mean difference &amp;lt; 0.10). Compared to dialysis, conservative care was associated with a higher absolute 5-year risk of death (91.8% vs. 74.1%), corresponding with an absolute risk difference of 17.6% (95% CI 13.3%-21.9%) (Fig. 1). The adjusted hazard ratio for conservative care vs. dialysis was 2.3 (95% CI 2.0-2.6). The 5-year restricted mean survival times were 34.8 (95% CI 33.2-37.3) months for dialysis and 21.5 (95% CI 19.4-23.6) months for conservative care groups. The 5-year RMST difference was 13.3 months (95% CI 10.8-16.6), meaning that dialysis patients would live on average 13.3 months longer over a 5-year follow-up period than conservative care patients (Table 1). The results were consistent among people ≥ 80 years (adjusted HR 2.2, 95% CI 1.9-2.5; 5-year RMST difference 9.4 months, 95% CI 7.2-13.9). Conclusion In older patients with advanced CKD under nephrologist care, conservative care was associated with a higher risk of mortality than dialysis. These findings could improve the shared decision-making process with patients on the choice of kidney failure treatment.

Risk of Kidney Failure in Patients With Inflammatory Bowel Disease Undergoing Colectomy: A Nationwide Cohort Study

Inflammatory bowel disease (IBD) is frequently accompanied by kidney complications. Potential triggers or subpopulations at high-risk of kidney problems are not well-elucidated. We hypothesized that surgical interventions, specifically colectomy, might in part explain this risk. This study was a nationwide Swedish cohort study comprising 82,051 individuals with biopsy-proven IBD diagnosed during 1965 to 2017, with follow-up until 2019. We investigated the association between incident colectomy (time-varying exposure) and future risk of acute kidney injury (AKI) and kidney failure (diagnosis of end-stage kidney disease or death due to chronic kidney disease) using Cox proportional hazard models. We also examined the impact of partial vs total colectomy and the presence/duration of a stoma. Covariates included demographics, education level, and selected comorbidities. Over a median follow-up of 14 years, 16,479 individuals underwent colectomy, and 2556 AKI and 1146 kidney failure events occurred. Colectomy was associated with an increased relative risk of both AKI (adjusted hazard ratio, 2.37; 95% confidence interval, 2.17-2.58) and kidney failure (adjusted hazard ratio, 1.54; 95% confidence interval, 1.34-1.76). Compared with pre-colectomy periods, undergoing total colectomy and colectomy with prolonged stoma showed higher risks of both kidney outcomes versus partial colectomy or colectomy with a temporary stoma, respectively. Subgroup analyses suggested higher risks in patients with ulcerative colitis. In people with IBD, rates of AKI and kidney failure are higher among those undergoing colectomy, particularly among those following total colectomy, or colectomy with a prolonged stoma. This study identifies a high-risk population that may benefit from established protocols for kidney function monitoring/surveillance and referral to nephrologist care.

Antipsychotic Use and Psychiatric Hospitalization in First-Episode Non-affective Psychosis and Cannabis Use Disorder: A Swedish Nationwide Cohort Study.

There is a paucity of research on treatment outcomes of patients with psychosis and cannabis use disorder (CUD). We aimed to compare the effectiveness of antipsychotics in reducing the risk of hospitalization in patients with first-episode psychosis (FEP) and co-occurring CUD. We utilized a nationwide Swedish cohort of patients with longitudinal register data from the year 2006 to 2021. Participants were patients with FEP and co-occurring CUD (n = 1820, 84.73% men, mean age 26.80 years, SD 8.25 years). The main outcome was hospitalization due to psychotic relapse. Hospitalization due to any psychiatric disorder or substance use disorder (SUD) were examined as secondary outcomes. Within-individual Cox regression models were used to study these associations. Use of any antipsychotic was associated with a 33% risk reduction of psychotic relapse (aHR = 0.67; 95% CI 0.60-0.75). Clozapine (0.43; 0.29-0.64), long-acting injectable (LAI) formulations of risperidone (0.40; 0.22-0.71), aripiprazole (0.42; 0.27-0.65), and paliperidone (0.46; 0.30-0.69) were associated with the lowest risk of relapse. The association between the LAI formulation of olanzapine and hospitalization due to psychosis was statistically non-significant (0.61; 0.35-1.05). Clozapine was associated with an 86% risk reduction of hospitalization due to SUD (0.14; 0.05-0.44). Of oral non-clozapine antipsychotics, aripiprazole was associated with the lowest risk of hospitalization due to psychotic relapse (0.61; 0.45-0.83). These findings support the use of clozapine, LAI formulations of second-generation antipsychotics other than olanzapine, or oral aripiprazole to prevent hospitalization in FEP and co-occurring CUD.

Long-Term Survival After Single-Ventricle Palliation: A Swedish Nationwide Cohort Study.

Long-term survival after single-ventricle palliation and the effect of dominant ventricle morphology in large, unselected series of patients are scarcely reported. This nationwide cohort study included all children undergoing operation with single-ventricle palliation during their first year of life in Sweden between January 1994 and December 2019. Data were obtained from institutional records and assessment of underlying cardiac anomaly and dominant ventricular morphology was based on complete review of medical records, surgical reports, and echocardiographic examinations. Data on vital status and date of death were retrieved from the Swedish Cause of Death Register, allowing for complete data on survival. Among 766 included patients, 333 patients (43.5%) were classified as having left or biventricular dominance, and 432 patients (56.4%) as having right ventricular (RV) dominance (of whom 231 patients had hypoplastic left heart syndrome). Follow-up was 98.7% complete (10 patients emigrated). Mean follow-up was 11.3 years (maximum, 26.7 years). Long-term survival was significantly higher in patients with left ventricular compared with RV dominance (10-year survival: 91.0% [95% CI, 87.3%-93.6%] versus 71.1% [95% CI, 66.4%-75.2%]). RV dominance had a significant impact on outcomes after first-stage palliation but was also associated with impaired survival after completed total cavopulmonary connection. In total, 34 (4.4%) patients underwent heart transplantation. Of these 34 patients, 25 (73.5%) had predominant RV morphology. This study provides clinically relevant knowledge about the long-term prognosis in patients with different underlying cardiac anomalies undergoing single-ventricle palliation. RV dominance had a significant impact on outcomes after initial surgical treatment but was also associated with impaired survival after completed Fontan circulation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356574.

Recurrence of Atrial Fibrillation in Patients With New-Onset Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting

New-onset postoperative atrial fibrillation (POAF) occurs in approximately 30% of patients undergoing coronary artery bypass grafting (CABG). It is unknown whether early recurrence is associated with worse outcomes. To test the hypothesis that early AF recurrence in patients with POAF after CABG is associated with worse outcomes. This Swedish nationwide cohort study used prospectively collected data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry and 3 other mandatory national registries. The study included patients who underwent isolated first-time CABG between January 1, 2007, and December 31, 2020, and developed POAF. Data analysis was performed between March 6 and September 16, 2023. Early AF recurrence defined as an episode of AF leading to hospital care within 3 months after discharge. The primary outcome was all-cause mortality. Secondary outcomes included ischemic stroke, any thromboembolism, heart failure hospitalization, and major bleeding within 2 years after discharge. The groups were compared with multivariable Cox regression models, with early AF recurrence as a time-dependent covariate. The hypothesis tested was formulated after data collection. Of the 35 329 patients identified, 10 609 (30.0%) developed POAF after CABG and were included in this study. Their median age was 71 (IQR, 66-76) years. The median follow-up was 7.1 (IQR, 2.9-9.0) years, and most patients (81.6%) were men. Early AF recurrence occurred in 6.7% of patients. Event rates (95% CIs) per 100 patient-years with vs without early AF recurrence were 2.21 (1.49-3.24) vs 2.03 (1.83-2.25) for all-cause mortality, 3.94 (2.92-5.28) vs 2.79 (2.56-3.05) for heart failure hospitalization, and 3.97 (2.95-5.30) vs 2.74 (2.51-2.99) for major bleeding. No association between early AF recurrence and all-cause mortality was observed (adjusted hazard ratio [AHR], 1.17 [95% CI, 0.80-1.74]; P = .41). In exploratory analyses, there was an association with heart failure hospitalization (AHR, 1.80 [95% CI, 1.32-2.45]; P = .001) and major bleeding (AHR, 1.92 [1.42-2.61]; P < .001). In this cohort study of early AF recurrence after POAF in patients who underwent CABG, no association was found between early AF recurrence and all-cause mortality. Exploratory analyses showed associations between AF recurrence and heart failure hospitalization, oral anticoagulation, and major bleeding.

Impact of inflammatory bowel disease on the risk of acute coronary syndrome: A Swedish Nationwide Cohort Study.

There are conflicting data on the risk of acute coronary syndrome (ACS) in patients with inflammatory bowel disease (IBD). Only a few previous reports include patients diagnosed during the last decade. To assess and compare the risk of ACS between patients with IBD and the general population. In this cohort study, we used nationwide registers to identify patients diagnosed with IBD in Sweden 2003-2021. Every patient was matched by birth year, sex, calendar year and area of residence with up to 10 general population comparators. The primary outcome was incident ACS. We used semi-parametric Cox proportional hazard models to estimate hazard ratios (HRs). We identified 76,517 patients with IBD (Crohn's disease [CD], N = 22,732; ulcerative colitis [UC], N = 42,194 and IBD-unclassified, N = 11,591) and 757,141 comparators. During a median follow-up of 8 years, 2546 patients with IBD (37.5/10,000 person-years) were diagnosed with ACS compared with 19,598 (28.0/10,000 person-years) among comparators (HR 1.30; 95% confidence interval 1.24-1.35) after adjustments for confounding factors, and approximately one extra case of ACS in 100 IBD patients followed for 10 years. The highest HRs for ACS were in patients with elderly onset IBD (≥60 years) and among patients with CD or UC with extra-intestinal manifestations. No increased HRs were observed in patients diagnosed with IBD before the age of 40. In this contemporary cohort of patients with IBD, exposed to modern IBD care, there was an increased risk for ACS compared with individuals from the general population.

Maternal origin matters: Country of birth as a risk factor for obstetric anal sphincter injuries.

Obstetric anal sphincter injuries (OASIS) are severe complications to vaginal births with potential long-term consequences. Maternal origin has been proposed to affect the overall risk, but the association and underlying explanation are uncertain. The objective was to assess the association between maternal country of birth and OASIS. A Swedish nationwide cohort study including singleton term vaginal births during 2005-2016. Data were extracted from the Swedish Medical Birth Registry and Statistics Sweden. Modified Poisson regression analyses were performed to obtain crude and adjusted risk ratios (RRs). Adjustments were made in four cumulative steps. Sub-analyses were performed to investigate the risk of OASIS associated with female genital circumcision (FGC). In all, 988 804 births were included. The rate of OASIS in Swedish-born women was 3.5%. Women from East/Southeast Asia had an increased risk of OASIS (adjusted RR [aRR] 1.71, 95% confidence interval [CI] 1.60-1.83), as did women born in Sub-Saharan Africa (aRR 1.60, 95% CI 1.49-1.72). The risk remained significantly increased also after adjustment for maternal height. By contrast, women from South/Central America had a decreased risk of OASIS (aRR 0.65, 95% CI 0.56-0.76). FGC was associated with an increased risk of OASIS (aRR 3.05, 95% CI 2.60-3.58). Episiotomy appeared to have an overall protective effect (aRR 0.95, 95% CI 0.92-0.98), but not significantly more protective among women with female genital mutilation. Country of birth plays an important role in the risk of OASIS. Women from East/Southeast Asia and Sub-Saharan Africa are at significantly increased risk as compared with Swedish-born women, whereas women from South/Central America are at lower risk. FGC is also a significant risk factor for OASIS.

Risk of stillbirth after a previous caesarean delivery: A Swedish nationwide cohort study.

To investigate the risk of stillbirth in relation to (1) a previous caesarean delivery (CD) compared with those following a vaginal birth (VB); and (2) vaginal birth after caesarean (VBAC) compared with a repeat CD. Population-based cohort study. The Swedish Medical Birth registry. Women with their first and second singletons between 1982 and 2012. Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) of the association between CD in the first pregnancy and stillbirth in the second pregnancy and the association between VBAC and stillbirth. Sub-group analyses were performed by types of CD and timing of stillbirth (antepartum and intrapartum). Stillbirth (antepartum and intrapartum fetal death). Of the 1 771 700 singleton births from 885 850 women, 117 114 (13.2%) women had a CD in the first pregnancy, and 51 755 had VBAC in the second pregnancy. We found a 37% increased odds of stillbirth (aOR 1.37; 95% CI 1.23-1.52) in women with a previous CD compared with VB. The odds of intrapartum stillbirth were higher in the previous pre-labour CD group (aOR 2.72; 95% CI 1.51-4.91) and in the previous in-labour CD group (aOR 1.35; 95% CI 0.76-2.40), although not statistically significant in the latter case. No increased odds were found for intrapartum stillbirth in women who had VBAC (aOR 0.99; 95% CI 0.48-2.06) compared with women who had a repeat CD. This study confirms that a CD is associated with an increased risk of subsequent stillbirth, with a greater risk among pre-labour CD. This association is not solely mediated by increases in intrapartum asphyxia, uterine rupture or attempted VBAC. Further research is needed to understand this association, but these findings might help healthcare providers to reach optimal decisions regarding mode of birth, particularly when CD is unnecessary.

DOP51 Risk of kidney failure in patients with Inflammatory Bowel Disease undergoing colectomy: a nationwide cohort study

Abstract Background Inflammatory bowel disease (IBD) is frequently accompanied by kidney complications. Potential triggers or subpopulations at high-risk of kidney problems are not well elucidated. We hypothesized that surgical interventions, specifically colectomy, might in part explain this risk. Methods A nationwide Swedish cohort study comprising 82,052 individuals with biopsy-proven IBD diagnosed during 1965-2017, with follow-up until 2019. We investigated the association between incident colectomy (time-varying exposure) and future risk of kidney failure (diagnosis of end-stage kidney disease or death due to chronic kidney disease) using Cox proportional hazard models. We also examined the impact of partial vs. total colectomy and the presence of a stoma. Covariates included age, sex, education level, and selected comorbidities. Results Over a median follow-up of 14 years, 15,922 individuals underwent colectomy, and 952 kidney failure events occurred. Colectomy was associated with an increased relative risk of kidney failure (adjusted hazard ratio [aHR] 1.60; 95% CI 1.39-1.84). Compared to periods without colectomy, undergoing total colectomy (aHR 1.82; 95% CI 1.54-2.15) and colectomy with the presence of a stoma (aHR 2.40; 95% CI 1.75-3.28) showed higher risks versus partial colectomy or colectomy without a stoma, respectively. Subgroup analyses revealed higher kidney failure risk in patients with ulcerative colitis and those aged ≥40 years at IBD diagnosis. In absolute risks, at 30-year after colectomy, 8.9% of patients with IBD had kidney failure, with an absolute risk difference of 4.5% (95% CI 1.9-7.0%). Conclusion In people with IBD, rates of kidney failure are higher among those undergoing colectomy, particularly following total colectomy or colectomy with a stoma. This study identifies a high-risk population that may benefit from established protocols for kidney function monitoring/surveillance and referral to nephrologist care.

P1073 Opioid use Before and After First Diagnosis of Crohn’s Disease: A Swedish Nationwide Cohort Study 2008-2020

Abstract Background The ongoing opioid misuse epidemic, initially sparked by over-prescription, presents challenges in managing severe pain in Crohn’s disease (CD). Despite associated negative effects, such as narcotic bowel syndrome and susceptibility to chronic use, opioids are frequently prescribed for CD patients. However, data on the evolution of opioid use before and after the initial CD diagnosis in a European context are limited. Methods This nationwide cohort study utilized the Swedish Patient Register to identify adults with a first CD diagnosis between 1 January 2008 and 31 December 2017, residing in Sweden at least two years before and three years after the diagnosis. For each CD patient, we included up to 10 reference individuals from the general population matched on birth year, sex, calendar year, and place of residence. Data on dispensed opioid prescriptions were retrieved from the National Prescribed Drug Register. Opioid use history was categorized into non-users (no dispensations), intermittent users (≥1 dispensation in 1–3 periods), and chronic users (≥1 dispensation in all periods) based on the four preceding six-month periods before the first CD diagnosis. Opioid use per six-month period was estimated from two years before to five years following CD diagnosis (corresponding index date for matched reference individuals) and coarsened exact matching was employed to account for confounding (birth year, sex, education, and history of psychiatric disorders and cancer). Results We included 12,539 incident CD patients and 116,073 matched reference individuals. During the two years before the first CD diagnosis, CD patients (and 3.9% vs 10.4% and 1.4%, respectively) were more often intermittent (22.3% vs 10.4%) or chronic (3.9% vs 1.4%) opioid users than matched reference individuals. Prior to diagnosis, opioid use per six-month period was twice as common among CD patients than in reference individuals. Following a peak in the first year after the diagnosis, the prevalence of dispensed opioids per six-month period stabilized at a three-fold level among CD patients (13.6%; 95% CI: 13.0, 14.3) compared with the reference individuals (5.5%; 95% CI: 5.4, 5.7) (Figure 1). The 6-month prevalence of opioid use five years after CD diagnosis was 7.6% (95% CI: 7.0, 8.2), 22.9% (95% CI: 21.1, 24.6), and 79.5.4% (95% CI: 73.2, 85.7) for CD patients classified as non-users, intermittent, or chronic users two years before diagnosis, respectively. Conclusion CD patients exhibited elevated opioid use two years before their initial diagnosis, which persisted at a three-fold level compared to matched reference individuals for five years post-diagnosis. This pattern persisted despite publicly-funded healthcare and modern CD therapy accessibility.

P827 Has opioid use increased among adults with Crohn’s disease? A Swedish Nationwide cohort Study 2008-2020

Abstract Background Chronic opioid use has turned into a global health challenge. Crohn’s disease (CD) patients may experience severe pain requiring opioids which could exacerbate CD symptoms and pose a risk of chronic use. The use of opioids among CD patients has not been explored on a national level. We compared the secular trends of opioid use among prevalent CD patients and matched reference individuals in Sweden. Methods This nationwide cohort study included adults with a prevalent CD diagnosis who lived in Sweden for at least 12 consecutive months at some point between 1 January 2008 and 31 December 2020. For each patient, up to 10 reference individuals from the general population were matched on birth year, sex, calendar year, and place of residence. We retrieved the data on dispensed opioid prescriptions (opioid use) from the National Prescribed Drug Register. We defined opioid use as ≥1 filled prescription per calendar year. We also estimated the annual prevalence of ≥1 dispensation of weak (codeine combinations, tramadol, and Dextropropoxifen) and/or strong opioids (Oxycodone, Morphine, Hydromorphone, Fentanyl, Buprenorphine, Tapentadol, and Petidin). Results We identified 43,155 adult CD patients and 418,218 reference individuals (Table 1). The prevalence of opioid use was stable from 2008-2016. However, between 2017 and 2020 it decreased from 19.7% (95% CI: 19.2, 20.2) to 16.9% (95% CI: 16.2, 17.7) and from 8.5% (95% CI: 8.4, 8.7) to 6.9% (95% CI: 6.7, 7.1) among CD patients and reference individuals, respectively (Figure 1a). However, between 2008 and 2020, the prescription of strong opioids more than doubled among both CD patients (increasing from 4.3% [95% CI: 4.1, 4.6] to 11.5% [95% CI: 11.1, 11.8]), and reference individuals (increasing from 1.3% [95% CI: 1.3, 1.4] to 5.4% [95% CI: 5.3, 5.5]) (Figure 1b). In 2020, the last year of the observation, compared with males, both female CD patients (20.3% [19.7, 20.8] vs 9.3% [9.2, 9.5]) and their matched reference individuals (15.3% [14.8, 15.9] vs 7.1% [6.9, 7.2]) had a higher prevalence of annual opioid use. The secular trends of overall opioid use and increasing use of strong opioids were similar for males and females (data not shown). Conclusion Annual opioid use among prevalent CD patients in Sweden, a country with publicly-funded healthcare and access to modern CD treatment, was two-fold higher than in the general population in the last 13 years. The annual opioid use remained stable from 2008-2016 and slightly decreased from 2017-2020 for CD patients and reference individuals. During the same period, the use of strong opioids more than doubled for CD patients and the general population.

P1089 Disease characteristics at time of diagnosis of adult onset inflammatory bowel disease and the risk of venous thromboembolism in the modern era – A Swedish nationwide cohort study 2007-2021

Abstract Background Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics. Methods Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression. Results The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal manifestations and perianal disease. HRs for VTE were persistently elevated across follow-up time, but was higher during the first year of follow-up (Figure 1). Conclusion The risk of VTE was doubled in these modern-day data and remained elevated across follow-up time. Disease characteristics associated with higher inflammatory burden at diagnosis and older age are markers of increased risk. This underscores the importance of continuous vigilance and individual assessment of risk factors for VTE in patients with IBD.

Mental health from 5 years before to 10 years after bariatric surgery in adolescents with severe obesity: a Swedish nationwide cohort study with matched population controls

The long-term effects of bariatric surgery on the mental health of adolescents with severe obesity remain uncertain. We aimed to describe the prevalence of psychiatric health-care visits and filled prescription psychiatric drugs among adolescents with severe obesity undergoing bariatric surgery in the 5 years preceding surgery and throughout the first 10 years after surgery, and to draw comparisons with matched adolescents in the general population. Adolescents with severe obesity and who underwent bariatric surgery were identified through the Scandinavian Obesity Surgery Registry. We included adolescents who had bariatric surgery between 2007 and 2017 and were younger than 21 years at time of surgery. Each adolescent patient was matched with ten adolescents from the general population by age, sex, and county of residence. Specialist psychiatric care and filled psychiatric prescriptions were retrieved from nationwide data registers. 1554 adolescents (<21 years) with severe obesity underwent bariatric surgery between 2007 and 2017, 1169 (75%) of whom were female. At time of surgery, the mean age was 19·0 years [SD 1·0], and the mean BMI was 43·7 kg/m2 (SD 5·5). 15 540 adolescents from the general population were matched with adolescents in the surgery group. 5 years before the matched index date, 95 (6·2%) of 1535 surgery patients and 370 (2·5%) of 14 643 matched adolescents had a psychiatric health-care visit (prevalence difference 3·7%; 95% CI 2·4-4·9), whereas 127 (9·8%) of 1295 surgery patients and 445 (3·6%) of 12 211 matched adolescents filled a psychiatric drug prescription (prevalence difference 6·2%; 95% CI 4·5-7·8). The year before the matched index date, 208 (13·4%) of 1551 surgery patients and 844 (5·5%) of 15 308 matched adolescents had a psychiatric health-care visit (prevalence difference 7·9%; 95% CI 6·2-9·6), whereas 319 (20·6%) of 1551 surgery patients and 1306 (8·5%) of 15 308 matched adolescents filled a psychiatric drug prescription (prevalence difference 12·0%; 10·0-14·1). The prevalence difference in psychiatric health-care visits peaked 9 years after the matched index date (12·0%; 95% CI 9·0-14·9), when 119 (17·6%) of 675 surgery patients and 377 (5·7%) of 6669 matched adolescents had a psychiatric health-care visit. The prevalence difference in filled psychiatric drug prescription was highest 10 years after the matched index date (20·4%; 15·9-24·9), when 171 (36·5%) of 469 surgery patients and 739 (16·0%) of 4607 matched adolescents filled a psychiatric drug prescription. The year before the matched index date, 19 (1·2%) of 1551 surgery patients and 155 (1·0%) of 15304 matched adolescents had a health-care visit associated with a substance use disorder diagnosis (mean difference 0·2%, 95% CI -0·4 to 0·8). 10 years after the matched index date, the prevalence difference had increased to 4·3% (95% CI 2·3-6·4), when 24 (5·1%) of 467 surgery patients and 37 (0·8%) of 4582 matched adolescents had a health-care visit associated with a substance use disorder diagnosis. Psychiatric diagnoses and psychiatric drug prescriptions were more common among adolescents with severe obesity who would later undergo bariatric surgery than among matched adolescents from the general population. Both groups showed an increase in prevalence in psychiatric diagnoses and psychiatric drug prescriptions leading up to the time of surgery, but the rate of increase in the prevalence was higher among adolescents with severe obesity than among matched adolescents. With the exception of health-care visits for substance use disorders, these prevalence trajectories continued in the 10 years of follow-up. Realistic expectations regarding mental health outcomes should be set preoperatively. Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare.

The association between BCG treatment in patients with bladder cancer and subsequent risk of developing Alzheimer and other dementia.—A Swedish nationwide cohort study from 1997 to 2019

Background Alzheimer’s disease (AD) affects 50 million people worldwide. The immune system plays a major role in the pathogenesis of AD. Several retrospective analyses have reported a decreased risk of AD and other dementias in bladder cancer patients treated with immunotherapy in the form of Bacillus Calmette-Guerin (BCG) bladder instillations. We tested this hypothesis in a Swedish population-based prospective cohort of patients with non-muscle invasive bladder cancer (NMIBC). Methods and findings We utilized the BladderBaSe 2.0 database, which contains tumor-specific, health-related, and socio-demographic information for patients diagnosed with NMIBC between 1997 and 2019. The database also includes a matched comparison cohort sampled from the general population, consisting of individuals free from urinary tract cancer at the time of the index case’s diagnosis. Five controls were randomly selected for each index case without replacement on the date of the index case’s diagnosis. Our inclusion criteria identified participants diagnosed with NMIBC who had received BCG as primary treatment, along with their corresponding comparison cohort. We excluded those diagnosed with dementia before or within 6 months of NMIBC diagnosis. To compare the NMIBC cohort with their matched comparison cohort, we used a stratified Cox model, treating each case with its controls as a stratum. We identified 38,934 patients in the NMIBC cohort, with 6,496 receiving BCG after primary diagnosis (cases). AD/dementia was diagnosed during follow-up in 6.1% of cases and 7.4% of controls. Cases had a slightly lower risk of dementia than controls, with a hazard ratio (HR) of 0.88 (95% confidence interval [CI] 0.780–0.991), and a HR of 0.89 (CI 0.703–1.119) for AD. Subgroup analysis for dementia showed that age over 75 years had an HR of 0.73 (CI 0.616–0.863), and female gender had an HR of 0.73 (CI 0.552–0.971). The associations were similar for AD specifically, but not statistically significant. Similar to previous studies, we analyzed bladder cancer patients treated with and without BCG therapy. Multivariate Cox analysis indicated that those treated with BCG had a lower risk of dementia (HR 0.81, 95% CI 0.71–0.92), and an HR of 0.98 (95% CI 0.75–1.27) for AD specifically. High age was a significant risk modifier; the HR was 3.8 (CI 3.44–4.11) for dementia and 3.1 (CI 2.59–3.73) for AD. Even patients not receiving BCG had a significantly lower risk for AD than controls (HR 0.86, CI 0.77–0.96). Conclusions This study observed a marginally decreased risk of developing AD/dementia associated with earlier intravesical BCG treatment in NMIBC patients. This small benefit was most pronounced in those with high age and female gender. The disparity from previous highly positive studies underscores the importance of using an appropriate control cohort.

Effects of education, income and employment on ICU and post-ICU survival - A nationwide Swedish cohort study of individual-level data with 1-year follow up

PurposeThe aim of this study was to examine relationships between education, income, and employment (socioeconomic status, SES) and intensive care unit (ICU) survival and survival 1 year after discharge from ICU (Post-ICU survival). MethodsIndividual data from ICU patients were linked to register data of education level, disposable income, employment status, civil status, foreign background, comorbidities, and vital status. Associations between SES, ICU survival and 1-year post-ICU survival was analysed using Cox's regression. ResultsWe included 58,279 adults (59% men, median length of stay in ICU 4.0 days, median SAPS3 score 61). Survival rates at discharge from ICU and one year after discharge were 88% and 63%, respectively. Risk of ICU death (Hazard ratios, HR) was significantly higher in unemployed and retired compared to patients who worked prior to admission (1.20; 95% CI: 1.10–1.30 and 1.15; (1.07–1.24), respectively. There was no consistent association between education, income and ICU death. Risk of post-ICU death decreased with greater income and was roughly 16% lower in the highest compared to lowest income quintile (HR 0.84; 0.79–0.88). Higher education levels appeared to be associated with reduced risk of death during the first year after ICU discharge. ConclusionsSignificant relationships between low SES in the critically ill and increased risk of death indicate that it is important to identify and support patients with low SES to improve survival after intensive care. Studies of survival after critical illness need to account for participants SES.

Maternal and pregnancy predictive risk factors for having a compensated maternal injury claim: a Swedish nationwide cohort study

To describe trends and identify maternal and pregnancy predictive risk factors for having a compensated claim for a maternal injury during delivery, as a proxy for having received suboptimal care. This nationwide retrospective cohort study included 1 754 869 births in Sweden between 2000 and 2016, including 4488 maternal injury claims filed with The National Swedish Patient Insurance Company (Löf), of which 1637 were compensated. Descriptive statistics on maternal and pregnancy characteristics, trends in filed/compensated claims over time, and distribution of compensated claims by clinical classification are presented. Characteristics associated with suboptimal care were identified using multivariable logistic regression, with mutual adjustment in the final model. Compensated claims were sorted into 14 clinical classifications (ICD-10 codes for main condition, injury, and causality). Overall, there was a two-fold increase in filed claims from 2000 to 2016, peaking in 2014. The rate of compensated claims only increased marginally, and 36.5% of filed claims were deemed avoidable. Perineal and pelvic floor injuries, as well as medical and diagnostic errors, were responsible for the majority of compensated claims. Women with a previous caesarean section, post term delivery, chronic or gestational disease, > 13 antenatal visits, or a multiple pregnancy had increased risk of having a compensated claim for a maternal injury during delivery. Understanding the risk factors for having a compensated maternal injury claim may guide health workers and maternity wards in improving the quality and organisation of care to reduce the risk of childbirth related injuries.

Very low risk of short bowel after Roux-en-Y gastric bypass – a large nationwide Swedish cohort study

BackgroundRoux-en-Y gastric bypass (RYGB) is one of the most common bariatric procedures. Internal herniation may lead to small bowel ischemia requiring small bowel resection, resulting in short bowel syndrome. ObjectiveTo determine the incidence of extensive small bowel resection in patients operated with RYGB. We also aimed to look for early clinical warning signs among patients requiring extensive small bowel resection. SettingCohort from national quality registers. MethodsAll patients having undergone RYGB between January 2007 to June 2019 were analyzed in the Scandinavian Obesity Surgery Registry (SOReg). We identified patients with small bowel obstruction (SBO) for whom small bowel resection was necessary. Additionally, we assessed clinical signs in these patients. ResultsThe study included 57,255 patients having undergone RYGB. Closure of the mesenteric openings was performed in 78%. Surgery for SBO was required in 3659 (6%) of patients, and small bowel resection in 188 (.3%). Extensive small bowel resection, resulting in less than 1.5 meters of remaining small bowel, was required in 7 patients (.01%). All patients with extensive small bowel resection presented with abdominal pain and had confirmed internal herniation as the cause of the small bowel resection, and 2 of 7 patients died. Closure of mesenteric defects was not associated with a reduction in overall small bowel resection rates (P = .89) ConclusionSurgery for SBO after RYGB was common (6%). The risk of extensive small bowel resection leading to short bowel was low (.01%). Patients with abdominal pain after RYGB should be assessed for internal hernia, as it can be devastating.

Pregnancy outcomes for women with myasthenia gravis and their newborns: A nationwide register-based cohort study.

Few large-scale studies examine whether maternal myasthenia gravis (MG) is a risk factor for complications during pregnancy and childbirth. This study evaluated whether maternal MG is associated with an increased risk of adverse pregnancy, delivery, and neonatal outcomes. We conducted a nationwide Swedish register-based cohort study of women who gave birth to singleton infants (≥22 gestational weeks) during 1987-2019. Exposed women were diagnosed with MG before or during the index pregnancy (N = 443). Unexposed women comprised 4249 women without a diagnosis of MG, matched for age, parity, hospital, and year of childbirth. The risks of adverse pregnancy, delivery, and neonatal outcomes for women with MG were estimated using regression modeling and presented as adjusted odds ratios (aOR). There was no increased risk of pregnancy complications in women with MG. Women with MG had a spontaneous onset of labor less often than women without MG (69.8% vs. 79.5%; aOR 0.59; p < 0.001) as well as higher labor induction rates and elective cesarean section deliveries (16.0% vs. 12.3%, aOR 1.42; p = 0.02 and 12.0% vs. 8.1%, aOR 1.59; p = 0.009). Infants of women with MG were born on average 2 days earlier (p = 0.002); however, these infants did not have a higher risk of having low APGAR, being small for gestational age, or having a congenital malformation. This first nationwide study of pregnancy in women with MG in Sweden demonstrates reassuring results overall, suggesting generally safe pregnancy outcomes for women with MG and their infants.

External Causes of Death From Death Certificates in Patients With Dementia.

We aim to analyze the risk of death from specific external causes, including falls, complications of medical and surgical care, unintentional injuries, and suicide, in dementia patients. Swedish nationwide cohort study integrating 6 registers from May 1, 2007, through December 31, 2018, including the Swedish Registry for Cognitive/Dementia Disorders (SveDem). Population-based study. Patients diagnosed with dementia from 2007 to 2018 and up to 4 controls matched on year of birth (±3years), sex, and region of residence. The exposures of this study were diagnosis of dementia and dementia subtypes. Number of deaths and causes of mortality were obtained from death certificates compiled into the Cause of Death Register. Hazard ratios (HRs) and 95% CIs were estimated using Cox and flexible models, adjusted for sociodemographics and medical and psychiatric disorders. The study population included 235,085 patients with dementia [96,760 men (41.2%); mean age 81.5 (SD 8.5) years] and 771,019 control participants [341,994 men (44.4%); mean age 79.9 (SD 8.6) years], over 3,721,687 person-years. Compared with control participants, patients with dementia presented increased risk for unintentional injuries (HR 3.30, 95% CI 3.19-3.40) and falls (HR 2.67, 95% CI 2.54-2.80) during old age (≥75y), and suicide (HR 1.56, 95% CI 1.02-2.39) in middle age (<65y). Suicide risk was 5.04 times higher (HR 6.04, 95% CI 4.22-8.66) in patients with both dementia and 2 or more psychiatric disorders relative to controls (incidence rate per person-years, 1.6 vs 0.3). For dementia subtypes, frontotemporal dementia had the highest risks of unintentional injuries (HR 4.28, 95% CI 2.80-6.52) and falls (HR 3.83, 95% CI 1.98-7.41), whereas subjects with mixed dementia were less likely to die from suicide (HR 0.11, 95% CI 0.03-0.46) and complications of medical and surgical care (HR 0.53, 95% CI 0.40-0.70) compared to controls. Suicide risk screening and psychiatric disorders management in early-onset dementia and early interventions for unintentional injuries and falls prevention in older dementia patients should be provided.