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More data are needed regarding the long-term impact of the histological progression of non-alcoholic fatty liver disease (NAFLD) on long-term outcomes, including end-stage liver disease (ESLD) and mortality. We included Swedish adults with biopsy-confirmed non-cirrhotic NAFLD and ≥2 liver biopsies >6 months apart (1969-2017; n = 718). NAFLD was categorized at initial biopsy as simple steatosis, non-fibrotic steatohepatitis (NASH), or non-cirrhotic fibrosis. NAFLD progression was defined by histological changes between biopsies (i.e. incident NASH, incident fibrosis, fibrosis progression, cirrhosis). Using Cox regression, we estimated multivariable adjusted hazard ratios (aHRs) and 95% CIs for incident ESLD (i.e. hospitalization for decompensated cirrhosis, hepatocellular carcinoma or liver transplantation) and mortality, according to NAFLD progression vs. stable/regressed disease. At initial biopsy, 497 patients (69.2%) had simple steatosis, 90 (12.5%) had non-fibrotic NASH, and 131 (18.2%) had non-cirrhotic fibrosis. Over a median of 3.4 years between biopsies, 30.4% (218/718) experienced NAFLD progression, including 12.5% (62/497) with incident non-fibrotic NASH, 24.0% (141/587) with incident fibrosis, and 5.6% (40/718) with cirrhosis. Compared to stable/regressed disease, NAFLD progression was associated with significantly higher rates of developing incident ESLD (23.8 vs. 11.4/1,000 person-years [PY]; difference = 12.4/1,000 PY; aHR 1.65, 95% CI 1.17-2.32). While the highest ESLD incidence occurred with progression to cirrhosis (difference vs. stable/regressed disease = 56.3/1,000 PY), significant excess risk was also found with earlier transitions, including from simple steatosis to incident fibrosis (difference vs. stable/regressed disease = 18.9/1,000 PY). In contrast, all-cause mortality rates did not appear to differ when NAFLD progression was compared to stable/regressed disease (difference = 4.7/1,000 PY; aHR 0.99, 95% CI 0.78-1.24). In a nationwide, real-world cohort of patients with paired NAFLD biopsies, histological disease progression contributed to significantly higher rates of developing incident ESLD, but did not appear to impact all-cause mortality. Currently, data are scarce regarding the long-term impact of histological progression or regression of non-alcoholic fatty liver disease (NAFLD) on subsequent risk of adverse clinical outcomes, including the development of end-stage liver disease and mortality. This is particularly important because randomized-controlled trials of NAFLD therapeutics currently focus on short-term histological endpoints as presumed surrogates for those major clinical outcomes. Thus, the results from this study can help inform the optimal design of future NAFLD therapeutic trials, while also providing the necessary evidence base for public health policies focused on preventing the development and progression of NAFLD. [Display omitted] • In adults with NAFLD and paired clinical liver biopsies, a substantial proportion experienced progression between biopsies. • NAFLD progression was associated with a markedly higher incidence of end-stage liver disease. • In contrast, NAFLD progression was not associated with significantly worse overall mortality. [ABSTRACT FROM AUTHOR]

Summary: Background: Microscopic colitis (MC) has been linked to several autoimmune conditions. Results from previous studies on the association with rheumatoid arthritis (RA) have been inconsistent. Aim: To assess the risk of future RA in MC. Methods: We conducted a nationwide matched cohort study in Sweden of 8179 patients with biopsy‐verified MC (diagnosed in 2007–2017), 36,400 matched reference individuals and 8202 siblings without MC, with follow‐up until 2021. Information on MC was obtained from all of Sweden's regional pathology registers (n = 28) through the ESPRESSO cohort. Data on incident RA were collected from the National Patient Register. Using Cox regression, we calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results: During a median follow‐up of 9.1 years (interquartile range = 6.7–11.7), 73 MC patients and 183 reference individuals from the general population were diagnosed with RA (99 vs. 55 events per 100,000 person‐years), equivalent to one extra case of RA in 226 patients with MC followed for 10 years. These rates corresponded to an aHR of 1.83 (95% CI = 1.39–2.41). The aHR was highest during the first year of follow‐up (2.31 [95% CI = 1.08–4.97]) and remained significantly elevated up to 5 years after MC diagnosis (aHR 2.16; 95% CI = 1.42–3.30). Compared to siblings, without MC, the aHR was 2.04 (95% CI = 1.18–3.56). Conclusion: Patients with MC are at a nearly two‐fold risk of developing RA compared to the general population. Knowledge of this increased risk may expedite evaluation for RA in patients with MC presenting with joint symptoms and/or arthralgia, thus preventing delay until RA diagnosis. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Several gastrointestinal diseases have been linked to acute pancreatitis, but the risk of acute pancreatitis in microscopic colitis (MC) has not been studied. METHODS: We conducted a nationwide, population-based, matched cohort study in Sweden of 12,140 patients with biopsy-verified MC (diagnosed in 2003-2017), 57,806 matched reference individuals, and 12,781 siblings without MC with a follow-up until 2021. Data on MC were obtained from all of Sweden's regional pathology registers (n = 28) through the ESPRESSO cohort. Data on acute pancreatitis were collected from the National Patient Register. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were calculated using Cox regression. RESULTS: During a mean follow-up of 9.9 years (SD = 4.3), 146 patients with MC and 437 reference individuals were diagnosed with acute pancreatitis (127.8 vs 80.1 per 100,000 person-years), corresponding to an aHR of 1.57 (95% CI = 1.30-1.90). Moreover, we found a positive association between MC and acute nongallstone-related pancreatitis (aHR 1.99 [95% CI = 1.57-2.51]), but not with acute gallstone-related pancreatitis (aHR 1.08 [95% CI = 0.78-1.49]). Comparing patients with MC with their unaffected siblings yielded an aHR of 1.28 (95% CI = 0.92-1.78). The risk of acute pancreatitis remained elevated also for patients with MC with a follow-up exceeding 10 years (aHR 1.75 [95% CI = 1.14-2.67]). DISCUSSION: This nationwide study of more than 12,000 patients with MC demonstrated an increased risk of acute pancreatitis after MC. Hence, clinicians should have a low threshold for the evaluation of acute pancreatitis in patients with MC. In addition, these patients should receive advice and care aimed at reducing the risk of acute pancreatitis. [ABSTRACT FROM AUTHOR]

Background: Although previous evidence has suggested an increased risk of cardiovascular disease (CVD) in patients with inflammatory bowel disease (IBD), its association with arrhythmias is inconclusive. In this study, we aimed to explore the long-term risk of arrhythmias in patients with IBD. Methods and findings: Through a nationwide histopathology cohort, we identified patients with biopsy-confirmed IBD in Sweden during 1969 to 2017, including Crohn's disease (CD: n = 24,954; median age at diagnosis: 38.4 years; female: 52.2%), ulcerative colitis (UC: n = 46,856; 42.1 years; 46.3%), and IBD-unclassified (IBD-U: n = 12,067; 43.8 years; 49.6%), as well as their matched reference individuals and IBD-free full siblings. Outcomes included overall and specific arrhythmias (e.g., atrial fibrillation/flutter, bradyarrhythmias, other supraventricular arrhythmias, and ventricular arrhythmias/cardiac arrest). Flexible parametric survival models estimated hazard ratios (aHR) with 95% confidence intervals (95% CIs), after adjustment for birth year, sex, county of residence, calendar year, country of birth, educational attainment, number of healthcare visits, and cardiovascular-related comorbidities. Over a median of approximately 10 years of follow-up, 1,904 (7.6%) patients with CD, 4,154 (8.9%) patients with UC, and 990 (8.2%) patients with IBD-U developed arrhythmias, compared with 6.7%, 7.5%, and 6.0% in reference individuals, respectively. Compared with reference individuals, overall arrhythmias were increased in patients with CD [54.6 versus 46.1 per 10,000 person-years; aHR = 1.15 (95% CI [1.09, 1.21], P < 0.001)], patients with UC [64.7 versus 53.3 per 10,000 person-years; aHR = 1.14 (95% CI [1.10, 1.18], P < 0.001)], and patients with IBD-U [78.1 versus 53.5 per 10,000 person-years; aHR = 1.30 (95% CI [1.20, 1.41], P < 0.001)]. The increased risk persisted 25 years after diagnosis, corresponding to 1 extra arrhythmia case per 80 CD, 58 UC, and 29 IBD-U cases over the same period. Patients with IBD also had a significantly increased risk of specific arrhythmias, except for bradyarrhythmias. Sibling comparison analyses confirmed the main findings. Study limitations include lack of clinical data to define IBD activity, not considering the potential role of IBD medications and disease activity, and the potential residual confounding from unmeasured factors for arrhythmias. Conclusions: In this study, we observed that patients with IBD were at an increased risk of developing arrhythmias. The excess risk persisted even 25 years after IBD diagnosis. Our findings indicate a need for awareness of this excess risk among healthcare professionals. In a population-based, sibling-controlled cohort study Jiangwei Sun and colleagues explore the long-term risk of arrhythmias in patients with inflammatory bowel disease. Author summary: Why was this study done?: Although previous studies have explored the associations between inflammatory bowel disease (IBD) and arrhythmias, earlier findings are inconclusive and unaddressed issues remain. For example, except for atrial fibrillation, data on the risk of other specific arrhythmias in patients with IBD is lacking. Until now, the long-term risk of overall and specific arrhythmias in patients with IBD remains unclear. What did the researchers do and find?: In this population-based, sibling-controlled cohort study, we identified patients with biopsy-confirmed IBD in Sweden during 1969 to 2017, including Crohn's disease (CD) (n = 24,954), ulcerative colitis (UC) (n = 46,856), and IBD-unclassified (IBD-U) (n = 12,067), as well as their matched reference individuals and IBD-free full siblings. Patients with IBD were at a higher risk of developing overall arrhythmias than their matched reference individuals; the increased risk may persist even 25 years after IBD diagnosis, corresponding to 1 extra arrhythmia case per 80 CD, 58 UC, and 29 IBD-U cases over the same period. The risks of specific arrhythmias were also increased in patients with IBD, including atrial fibrillation/flutter, other supraventricular arrhythmias, and ventricular arrhythmias/cardiac arrest. What do these findings mean?: Healthcare professionals should be aware of the long-term increased risk of arrhythmias in patients with IBD. For those patients, a risk assessment of modifiable and established cardiovascular disease (CVD) risk factors could be considered. Study limitations include the absence of clinical data to define IBD activity, not considering the potential role of IBD medications and disease activity, and the potential residual confounding from unmeasured factors for arrhythmias. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the preliminary validity of two novel scales, the Fear of Asthma Symptoms scale (FAS) and the Asthma Behavior Checklist (ABC). Methods: Using cross-sectional design, data was collected online from 188 adult participants (Age 18-71 years) with a diagnosis of asthma and self-reported anxiety related to asthma, recruited through social media. Confirmatory factor analysis, internal consistency and test-retest reliability were ascertained to address validity.Results: The confirmatory factor analysis demonstrated convergent validity for both the FAS (average variance extracted; AVE=.57) and the item-reduced ABC-8 (AVE=.61) as well as divergent validity for both scales. Both scales demonstrated high internal consistency (FAS: α = 0.94; ABC-8: α = 0.92). Test-retest reliability assessed after 1 week was good (FAS: r=.85; ABC-8: r=.88).Conclusions: We observed promising psychometric properties of the FAS and the ABC-8. The two novel scales could be useful to identify excessive fear and avoidance in patients with asthma and to investigate putative mechanisms in clinical research on anxiety related to asthma. Further evaluation of psychometric properties in independent samples are needed. [ABSTRACT FROM AUTHOR]

Purpose : Predominant antibody deficiency (PAD) disorders, including common variable immunodeficiency (CVID), have been linked to increased risk of gastrointestinal infections and inflammatory bowel diseases. However, there are limited data on the relationship between PAD, specifically CVID, and risk of microscopic colitis (MC). Methods: We performed a nationwide case–control study of Swedish adults with MC diagnosed between 1997 and 2017 (n = 13,651). Data on biopsy-verified MC were retrieved from all of Sweden's pathology departments through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) study. We defined predominant antibody deficiency using International Union of Immunologic Societies (IUIS) phenotypic classification. Individuals with MC were matched to population controls by age, sex, calendar year, and county. We used logistic regression to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: The prevalence of PAD in MC was 0.4% as compared to 0.05% in controls. After adjustment for potential confounders, this corresponded to an aOR of 7.29 (95%CI 4.64–11.63). The magnitude of the association was higher for CVID (aOR 21.01, 95% 5.48–137.44) compared to other antibody deficiencies (aOR 6.16, 95% CI 3.79–10.14). In exploratory analyses, the association between PAD and MC was particularly strong among males (aOR 31.73, 95% CI 10.82–135.04). Conclusion: In this population-based study, predominant antibody deficiency was associated with increased risk of MC, particularly among males. Clinicians who encounter these patients should consider a detailed infectious history and screening for antibody deficiency. [ABSTRACT FROM AUTHOR]

Longitudinal data are scarce regarding the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD). This nationwide, matched cohort study included all Swedish children and young adults (≤25 years) with biopsy-confirmed NAFLD (1966–2017; n = 718). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, and further categorized as simple steatosis or steatohepatitis (NASH). Patients with NAFLD were matched to ≤5 general population controls by age, sex, calendar year and county (n = 3,457). To account for shared genetic and early-life factors, we also matched patients with NAFLD to full-sibling comparators. Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs) and 95% CIs. Over a median of 15.8 years, 59 patients with NAFLD died (5.5/1,000 person-years [PY]) compared to 36 population controls (0.7/1,000 PY; difference = 4.8/1,000 PY; multivariable aHR 5.88; 95% CI 3.77–9.17), corresponding to 1 additional death per 15 patients with NAFLD, followed for 20 years. The 20-year absolute risk of overall mortality was 7.7% among patients with NAFLD, and 1.1% among controls (difference = 6.6%; 95% CI 4.0–9.2). Findings persisted after excluding those who died within the first 6 months (aHR 4.65; 95% CI 2.92–7.42), and after using full-sibling comparators (aHR 11.72; 95% CI 3.18–43.23). Simple steatosis was associated with a 5.26-fold higher adjusted rate of mortality compared to controls (95% CI 3.05–9.07), and this was amplified with NASH (aHR 11.51, 95% CI 4.77–27.79). Most of the excess mortality was from cancer (1.67 vs. 0.07/1,000PY; aHR 15.60; 95% CI 4.97–48.93), liver disease (0.93 vs. 0.04/1,000PY; aHR 16.46; 95% CI 2.75–98.43) and cardiometabolic disease (1.12 vs. 0.14/1,000PY; aHR 4.32, 95% CI 1.73–10.79). Swedish children and young adults with biopsy-confirmed NAFLD have significantly higher rates of overall, cancer-, liver- and cardiometabolic-specific mortality compared to matched general population controls. Currently, the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) is unknown. This nationwide cohort study compared the risk of all-cause and cause-specific mortality in pediatric and young adult patients in Sweden with biopsy-confirmed NAFLD to matched general population controls. We found that compared to controls, children and young adults with biopsy-confirmed NAFLD and NASH have significantly higher rates of overall, cancer-, liver- and cardiometabolic-specific mortality. [Display omitted] • Biopsy-proven pediatric and young-adult NAFLD contributes to substantial excess mortality. • Mortality is increased with simple steatosis, and further amplified with steatohepatitis. • This excess mortality was primarily from cancer, cardiometabolic disease and liver disease. [ABSTRACT FROM AUTHOR]

Background and purpose: Evidence has accumulated to support the early involvement of altered gastrointestinal (GI) function in neurodegenerative disease. However, risk of Alzheimer disease (AD) and Parkinson disease (PD) among individuals with a GI biopsy of normal mucosa or nonspecific inflammation is unknown. Methods: This matched cohort study included all individuals in Sweden with a GI biopsy of normal mucosa (n = 480,346) or nonspecific inflammation (n = 655,937) during 1965–2016 (exposed group) as well as their individually matched population references and unexposed full siblings. A flexible parametric model and stratified Cox model were used to estimate hazard ratio (HR) and its 95% confidence interval (CI). Results: Individuals with normal mucosa or nonspecific inflammation had a higher risk of AD and PD during the 20 years after biopsy. Compared with the population references, individuals with normal mucosa had an increased risk of AD (incidence rate [IR] difference = 13.53 per 100,000 person‐years, HR [95% CI] = 1.15 [1.11–1.20]) and PD (IR difference = 6.72, HR [95% CI] = 1.16 [1.10–1.23]). Elevated risk was also observed for nonspecific inflammation regarding AD (IR difference = 13.28, HR [95% CI] = 1.11 [1.08–1.14]) and PD (IR difference = 6.83, HR [95% CI] = 1.10 [1.06–1.14]). Similar results were observed in subgroup and sensitivity analyses and when comparing with their unexposed siblings. Conclusions: Individuals with a GI biopsy of normal mucosa or nonspecific inflammation had an increased risk of AD and PD. This adds new evidence of the early involvement of GI dysfunction in neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Using a population‐based matched cohort design, we assessed the association of celiac disease (CeD) with risk of PD by comparing patients with biopsy‐confirmed CeD in Sweden to a biopsy‐free population and their unaffected siblings, separately. No overall association was observed but CeD diagnosed before age 60 associated positively with incident diagnosis of PD (hazard ratio [HR] = 1.29; 95% confidence interval [CI]: 1.02–1.62), which was mainly attributed to the significantly elevated risk detected after 10–15 years since biopsy (HR = 1.68; 95% CI: 1.05–2.68). Our findings imply an increased vulnerability to long‐term PD development among patients with CeD diagnosed before 60s. ANN NEUROL 2023;94:911–916 [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]

Summary: Background and Aims: Microscopic colitis (MC) is a colonic inflammatory condition associated with autoimmune dysfunction. Type 1 diabetes (T1D) is a chronic disease induced by autoimmune destruction of pancreatic β‐cells. We aimed to examine the association between T1D and MC. Methods: A matched case–control study was conducted using the nationwide ESPRESSO cohort as study base. All biopsy‐confirmed MC patients born after 1940 were identified and compared to biopsy‐free individuals matched from the general population for T1D diagnosis using the Swedish National Patient Register. The T1D‐MC association was estimated as odds ratios (ORs) and 95% confidence intervals (CIs) by conditional logistic models, considering differences by sex and MC subtype. Full sibling comparison and adjustment for MC‐associated medications were also performed. Results: We identified 352 (3.7%) and 945 (2.0%) T1D diagnoses from 9,600 MC cases and 47,870 matched population controls, respectively, which corresponded to an overall OR of 1.79 (95% CI: 1.56–2.05). The association was stronger for collagenous colitis (OR, 2.15; 95% CI: 1.70–2.71) than lymphocytic colitis (OR, 1.62; 95% CI: 1.37–1.92) and remained statistically significant in full sibling comparison (OR, 1.46; 95%: 1.18–1.81). Medication adjustment attenuated the association to null among females (OR: 1.02; 95% CI: 0.82–1.27) but not among males (OR: 1.45; 95% CI: 1.11–1.90). Conclusion: T1D diagnosis was almost 80% more prevalent in MC patients compared to general population. This positive association did not seem to be spurious due to residual confounding shared by full siblings but may relate to consumption of medications associated with MC onset. [ABSTRACT FROM AUTHOR]

Abstract: Partial Granger causality was introduced by who showed that it could better eliminate the influence of latent variables and exogenous inputs than conditional G-causality. In the recent literature we can find some reviews and applications of this type of Granger causality (e.g. ). These articles apparently do not take into account a serious flaw in the original work on partial G-causality, being the negative F values that were reported and even proven to be plausible. In our opinion, this undermines the credibility of the obtained results and thus the validity of the approach. Our study is aimed to further validate partial G-causality and to find an answer why negative partial Granger causality estimates were reported. Time series were simulated from the same toy model as used in the original paper and partial and conditional causal measures were compared in the presence of confounding variables. Inference was done parametrically and using non-parametric block bootstrapping. We counter the proof that partial Granger F values can be negative, but the main conclusion of the original article remains. In the presence of unknown latent and exogenous influences, it appears that partial G-causality will better eliminate their influence than conditional G-causality, at least when non-parametric inference is used. [Copyright &y& Elsevier]

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN. Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to ≤5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death. A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34–10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79–7.27)). The most common cause of death in IPMN was pancreatic cancer (n = 14; 45.2% of all deaths). We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal inflammation has been linked with Parkinson's disease (PD). Microscopic colitis (MC) is an intestinal inflammatory disease with unknown relationship with PD.Objective: This study aimed to examine the association of MC with PD risk.Methods: In this nationwide matched cohort study in Sweden, PD incidence was compared between 12,609 patients with histologically confirmed MC and a matched population cohort of 58,879 MC-free individuals and a sibling cohort comprising all unaffected siblings of the MC patients (NMC /NSibling  = 6281/12,351). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models.Results: During a mean follow-up of ~7 years, we identified 449 incident PD diagnoses among the MC patients and the population cohort. Overall, MC was associated with an adjusted HR of 1.76 for PD, but the association attenuated substantially during follow-up. In the time-varying effects model, PD hazard was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals but was not different beyond 5 years after biopsy (HR: 1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted when comparing MC patients to their siblings. In a post hoc case-control analysis, we also detected a strong association between MC and preexisting PD (odds ratio: 3.46; 95% CI: 2.91, 4.12).Conclusions: Our findings suggest that MC may not be a risk factor for PD; instead, it may co-occur with PD as a comorbidity or develop after a diagnosis of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Evidence has accumulated to support the involvement of gastrointestinal (GI) dysfunction, possibly via gut microbial dysbiosis and alterations in the enteric nervous system, in the pathophysiology of different neurodegenerative diseases. However, whether patients with GI dysfunction have altered risk of amyotrophic lateral sclerosis (ALS) remains unknown. Methods: Based on a historical nationwide cohort study—ESPRESSO—in Sweden, we compared the risk of ALS among individuals with a previous GI biopsy finding of normal mucosa or non-specific inflammation, as two conditions of GI dysfunction, to that of individuals without any GI biopsy. We identified all individuals with a GI biopsy result of either normal mucosa (n = 483,442) or non-specific inflammation (n = 566,663) during 1965–2016 in Sweden as the exposed groups. For each exposed individual, we randomly selected up to five controls from the general Swedish population after individual matching by age and sex. Both the exposed and unexposed individuals were followed from date of biopsy (exposed individuals) or date of selection (unexposed individuals) until ALS diagnosis, emigration out of Sweden, death, or 31 December 2016, whichever came first. Stratified Cox regression models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs). Results: Compared to individuals without GI biopsy, individuals with a GI biopsy result of normal mucosa had an increased risk of ALS (HR = 1.22; 95%CI: 1.04–1.42) after excluding the first 2 years of follow-up to alleviate concern of surveillance bias. This increased risk was noted among male (HR = 1.20; 95%CI: 0.94–1.51) and female (HR = 1.23; 95%CI: 1.01–1.50), as well as among younger (<60 years; HR = 1.17; 95%CI: 0.94–1.44) and older (≥60 years; HR = 1.24; 95%CI: 0.99–1.56) individuals. In contrast, no association was observed for a GI biopsy result of non-specific inflammation (HR = 1.00; 95%CI: 0.88–1.15). Neither of the GI biopsy results was related to the mortality risk after ALS diagnosis. Conclusions: Individuals with a GI biopsy result of normal mucosa—representing potentially a distinct type of GI dysfunction—had a higher future risk of ALS. No association was however noted for a GI biopsy result of non-specific inflammation. Further studies are needed to validate this finding and to understand the underlying reasons for the contrasting result pattern. [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]

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown. This nationwide multigenerational cohort study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969−2017), and matched general population comparators. Using the Swedish Multi-generation Register, we identified 38,018 first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 spouses of patients with MASLD, as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality. Over a median of 17.6 years, the rate of the primary outcome HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36−2.37). The HCC risk was further increased in FDRs of individuals with liver fibrosis/cirrhosis (aHR 2.14, 95% CI 1.07−4.27; P Heterogeneity = 0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000 PY; aHR 1.52, 95% CI 1.36−1.69) and liver-related mortality (20 vs. 11/100,000 PY; aHR 2.14, 95% CI 1.67−2.74). MASLD FDRs with any concomitant chronic liver condition experienced accelerated progression of liver disease (aHR 1.47, 95% CI 1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000 PY; aHR 1.23, 95% CI 1.01−1.51) and liver-related mortality (25 vs. 19/100,000 PY; aHR 1.93, 95% CI 1.15−3.23), but not of HCC (aHR 1.43, 95% CI 0.87−2.35). There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD, with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low. Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigenerational cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of hepatocellular carcinoma in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality. [Display omitted] • Nationwide multigenerational study of 292,274 family members of people with biopsy-confirmed MASLD and comparators. • MASLD first-degree relatives had increased hazards of HCC, major adverse liver outcomes and liver-related mortality. • The absolute risk of HCC was low, with only one extra case per 900 first-degree relatives over 20 years of follow-up. • Spouses of individuals with MASLD also had a higher relative risk of developing major adverse liver outcomes. • Liver disease progressed more rapidly in MASLD first-degree relatives with concomitant liver diseases. [ABSTRACT FROM AUTHOR]

Background: There is a lack of knowledge about mortality in eosinophilic esophagitis (EoE). Therefore, this study aimed to examine the mortality in EoE. Methods: A nationwide, population-based matched cohort study was conducted of all EoE patients in Sweden diagnosed between July 2005 and December 2017. Individuals with EoE (n = 1,625) were identified through prospectively recorded histopathology codes from all gastrointestinal pathology reports in Sweden, representing 28 pathology departments (the ESPRESSO study). Each individual with EoE was then matched with up to five reference individuals from the general population (n = 8,003) for age, sex, year of birth, and place of residence. We used the Cox proportional hazard modeling to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) while adjusting for other potential confounders. In sensitivity analyses, mortality in EoE patients was compared with mortality in their siblings. Results: Through December 2017, 34 deaths were confirmed in EoE patients (4.60 per 1,000 person-years) compared with 165 in reference individuals (4.57 per 1,000 person-years). This rate corresponds to an aHR of 0.97 (95% CI = 0.67-1.40). HRs were similar in males (aHR = 1.00 [0.66-1.51]) and females (aHR = 0.92 [0.38-2.18]). We observed no increased risk in mortality due to esophageal or other gastrointestinal cancers in patients with EoE (aHR = 1.02 [0.51-2.02]). Mortality was similar in EoE patients and their siblings (aHR = 0.91 [0.44-1.85]). Conclusion: In this nationwide, population-based matched cohort study in Sweden, there was no increased risk of death in patients with EoE compared with their siblings and the general population. [ABSTRACT FROM AUTHOR]

Background and Aims: Antibiotics affect the gut microbiome. Preclinical studies suggest a role of gut dysbiosis in the development of nonalcoholic fatty liver disease (NAFLD), but data from large cohorts with liver histology are lacking. Methods: In this nationwide case–control study, Swedish adults with histologically confirmed early‐stage NAFLD (total n = 2584; simple steatosis n = 1435; steatohepatitis (NASH) n = 383; non‐cirrhotic fibrosis n = 766) diagnosed January 2007–April 2017 were included and matched to ≤5 population controls (n = 12 646) for age, sex, calendar year and county of residence. Data for cumulative antibiotic dispensations and defined daily doses were accrued until 1 year before the matching date. Using conditional logistic regression, multivariable‐adjusted odds ratios (aORs) were calculated. In a secondary analysis, NAFLD patients were compared with their full siblings (n = 2837). Results: Previous antibiotic use was seen in 1748 (68%) NAFLD patients versus 7001 (55%) controls, corresponding to 1.35‐fold increased odds of NAFLD (95% CI = 1.21–1.51) in a dose‐dependent manner (pfor trend <.001). Estimates were comparable for all histologic stages (p >.05). The highest risk of NAFLD was observed after treatment with fluoroquinolones (aOR 1.38; 95% CI = 1.17–1.59). Associations remained robust when patients were compared with their full siblings (aOR 1.29; 95% CI = 1.08–1.55). Antibiotic treatment was only linked to NAFLD in patients without metabolic syndrome (aOR 1.63; 95% CI = 1.35–1.91) but not in those with metabolic syndrome (aOR 1.09; 95% CI = 0.88–1.30). Conclusions: Antibiotic use may be a risk factor for incident NAFLD, especially in individuals without the metabolic syndrome. The risk was highest for fluoroquinolones and remained robust in sibling comparisons with whom individuals share genetic and early environmental susceptibilities. [ABSTRACT FROM AUTHOR]

Background: Although evidence suggests a persistently decreased risk of colorectal cancer for up to 10 years among individuals with a negative endoscopic biopsy result (i.e., normal mucosa), concerns have been raised about other long-term health outcomes among these individuals. In this study, we aimed to explore the long-term risk of inflammatory bowel disease (IBD) after an endoscopic biopsy with normal mucosa. Methods and findings: In the present nationwide cohort study, we identified all individuals in Sweden with a lower or upper gastrointestinal (GI) biopsy of normal mucosa during 1965 to 2016 (exposed, n = 200,495 and 257,192 for lower and upper GI biopsy, respectively), their individually matched population references (n = 989,484 and 1,268,897), and unexposed full siblings (n = 221,179 and 274,529). Flexible parametric model estimated hazard ratio (HR) as an estimate of the association between a GI biopsy of normal mucosa and IBD as well as cumulative incidence of IBD, with 95% confidence interval (CI). The first 6 months after GI biopsy were excluded to avoid detection bias, surveillance bias, or reverse causation. During a median follow-up time of approximately 10 years, 4,853 individuals with a lower GI biopsy of normal mucosa developed IBD (2.4%) compared to 0.4% of the population references. This corresponded to an incidence rate (IR) of 20.39 and 3.39 per 10,000 person-years in the respective groups or 1 extra estimated IBD case among 37 exposed individuals during the 30 years after normal GI biopsy. The exposed individuals had a persistently higher risk of overall IBD (average HR = 5.56; 95% CI: 5.28 to 5.85), ulcerative colitis (UC, average HR = 5.20; 95% CI: 4.85 to 5.59) and Crohn's disease (CD, average HR = 6.99; 95% CI: 6.38 to 7.66) than their matched population references. In the sibling comparison, average HRs were 3.27 (3.05 to 3.51) for overall IBD, 3.27 (2.96 to 3.61) for UC, and 3.77 (3.34 to 4.26) for CD. For individuals with an upper GI biopsy of normal mucosa, the average HR of CD was 2.93 (2.68 to 3.21) and 2.39 (2.10 to 2.73), compared with population references and unexposed full siblings, respectively. The increased risk of IBD persisted at least 30 years after cohort entry. Study limitations include lack of data on indications for biopsy and potential residual confounding from unmeasured risk or protective factors for IBD. Conclusions: Endoscopic biopsy with normal mucosa was associated with an elevated IBD incidence for at least 30 years. This may suggest a substantial symptomatic period of IBD and incomplete diagnostic examinations in patients with early IBD. Jiangwei Sun and colleagues investigate the long-term risk of inflammatory bowel disease after endoscopic biopsy with normal mucosa in a Swedish cohort. Author summary: Why was this study done?: As the most frequent gastrointestinal (GI) histologic finding on endoscopy, a negative endoscopic result (i.e., normal mucosa) has been associated with a persistently decreased risk of colorectal cancer for up to 10 years. However, concerns have been raised about other long-term health outcomes among these individuals. We aimed to explore the long-term risk of inflammatory bowel disease (IBD) after an endoscopic biopsy with normal mucosa. What did the researchers find?: In this population-based, sibling-controlled cohort study, we identified individuals with a lower (n = 200,495) or upper (n = 257,192) GI biopsy of normal mucosa, their individually matched general population references (n = 989,484 and 1,268,897, respectively), and unexposed full siblings (n = 221,179 and 274,529, respectively). Compared with population references and unexposed full siblings, individuals with a lower GI biopsy of normal mucosa had a persistently higher risk of overall IBD (average HR = 5.56 and 3.27, respectively), ulcerative colitis (UC, average HR = 5.20 and 3.27, respectively), and Crohn's disease (CD, average HR = 6.99 and 3.77, respectively). Individuals with an upper GI biopsy of normal mucosa were also at an increased risk of CD (average HR = 2.93 and 2.39, respectively). The elevated risk of IBD persisted at least 30 years after a biopsy with normal mucosa. What do these findings mean?: Our findings suggest a substantial symptomatic period before IBD diagnosis. Clinicians should be aware of the long-term increased risk of IBD in those with symptoms requiring GI investigation but with a finding of histologically normal mucosa. [ABSTRACT FROM AUTHOR]

Background There are little data on diverticular disease and cancer development other than colorectal cancer. Methods We conducted a population-based, matched cohort study with linkage of nationwide registers to the Epidemiology Strengthened by histoPathology Reports in Sweden histopathology cohort. We included 75 704 patients with a diagnosis of diverticular disease and colorectal histopathology and 313 480 reference individuals from the general population matched on age, sex, calendar year, and county. Cox proportional hazards models estimated multivariable-adjusted hazard ratios (HRs) for associations between diverticular disease and overall cancer and specific cancers. Results Over a median follow-up of 6 years, we documented 12 846 incident cancers among patients with diverticular disease and 43 354 incident cancers among reference individuals from the general population. Compared with reference individuals, patients with diverticular disease had statistically significantly increased overall cancer incidence (24.5 vs 18.1 per 1000 person-years), equivalent to 1 extra cancer case in 16 individuals with diverticular disease followed-up for 10 years. After adjusting for covariates, having a diagnosis of diverticular disease was associated with a 33% increased risk of overall cancer (95% confidence interval [CI] = 1.31 to 1.36). The risk increases also persisted compared with siblings as secondary comparators (HR = 1.26, 95% CI = 1.21 to 1.32). Patients with diverticular disease also had an increased risk of specific cancers, including colon cancer (HR = 1.71, 95% CI = 1.60 to 1.82), liver cancer (HR = 1.72, 95% CI = 1.41 to 2.10), pancreatic cancer (HR = 1.62, 95% CI = 1.42 to 1.84), and lung cancer (HR = 1.50, 95% CI = 1.39 to 1.61). The increase in colorectal cancer risk was primarily restricted to the first year of follow-up, and especially early cancer stages. Conclusions Patients with diverticular disease who have colorectal histopathology have an increased risk of overall incident cancer. [ABSTRACT FROM AUTHOR]

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: There are limited population cohort data on overall and cause-specific mortality in colonic diverticular disease.Objective: To measure overall and cause-specific mortality in colonic diverticular disease, compared to matched reference individuals and siblings.Methods: Population-based cohort study ("the ESPRESSO study") in Sweden. There were 97,850 cases with a medical diagnosis of diverticular disease (defined by international classification of disease codes) and colorectal histology identified in 1987-2017 from histopathology reports. The mortality risk between individuals with colonic diverticular disease and matched reference individuals (n = 453/634) from the general population was determined. Cox regression models adjusted for comorbidity estimated hazard ratios (HRs) for all-cause mortality.Results: During follow-up, there were 32,959 deaths in individuals with colonic diverticular disease (44/1000 person-years) compared with 127,153 in matched reference individuals (34/1000 person-years), resulting in an HR of 1.27 (95%CI 1.25-1.29). Also compared to siblings, colonic diverticular disease patients were at increased risk of death, HR 1.39 (95%CI 1.33-1.45). Mortality risks were further increased in colonic diverticular disease patients with a colorectal biopsy showing any mucosal inflammation HR 1.36; (95%CI 1.33-1.38), with the most significant increase during the first year after diagnosis HR 2.18; (95%CI 2.05-2.32).Conclusions: Mortality in colonic diverticular disease is increased over reference individuals in the general population. The presence of mucosal inflammation on colorectal biopsies is a predictor of increased risk of mortality. [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]

Background: Eosinophilic gastrointestinal disorders (EGIDs) include inflammatory conditions with enteric infiltration of eosinophils and resulting symptoms. This study aims to examine a population-based sample of patients for prevalence, mortality, and cancer risk in EGIDs distal to the esophagus.Methods: Nationwide, population-based cohort study. EGID was identified through relevant biopsy codes from Sweden's all 28 pathology departments through the ESPRESSO cohort. Individuals with EGID were then matched to general population reference individuals with similar age and sex. Study participants were linked to Swedish healthcare registers. Through Cox regression, we calculated adjusted hazard ratios (aHRs) adjusting for sex, age, county, calendar period, and education.Results: In total, 2429 patients (56% female) were found to have EGID distal to the esophagus, representing a prevalence of about 1/4800 in the Swedish population. Mean age was 44 years with 11% children at the time of diagnosis. Mortality was increased 17% in patients with EGIDs compared to reference individuals (aHR = 1.17; 95%CI = 1.04-1.33). Excess mortality was seen in gastric and small bowel eosinophilic disease, but not colonic disease (aHR = 1.81; 95%CI = 1.32-2.48, aHR = 1.50; 95%CI = 1.18-1.89, and aHR = 0.99; 95%CI = 0.85-1.16, respectively). Cause specific mortality was driven by cancer-related death (aHR = 1.33; 95%CI = 1.05-1.69). However, this study failed to show an increase in incident cancers (aHR = 1.14; 95%CI = 0.96-1.35). Comparison of EGID individuals with their siblings yielded similar aHRs.Conclusions: This study found an increased risk of death in patients with EGIDs distal to the esophagus, with cancer death driving the increase. Proximal gut disease seems to confer the greatest risk. There was no increase in incident cancers. [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]

Background: While individuals with normal gastrointestinal (GI) mucosa on endoscopy have a lower risk of colorectal cancer, risks of other cancers remain unexplored.Methods: Through Sweden's 28 pathology departments, we identified 415,092 individuals with a first GI biopsy with histologically normal mucosa during 1965-2016 and no prior cancer. These individuals were compared to 1,939,215 matched reference individuals from the general population. Follow-up began 6 months after biopsy, and incident cancer data were retrieved from the Swedish Cancer Register. Flexible parametric model was applied to estimate cumulative incidences and hazard ratios (HRs) for cancers. We also used full siblings (n = 441,534) as a secondary comparison group.Results: During a median follow-up of 10.9 years, 40,935 individuals with normal mucosa (incidence rate: 82.74 per 10,000 person-years) and 177,350 reference individuals (incidence rate: 75.26) developed cancer. Restricting the data to individuals where follow-up revealed no cancer in the first 6 months, we still observed an increased risk of any cancer in those with a histologically normal mucosa (average HR = 1.07; 95%CI = 1.06-1.09). Although the HR for any and specific cancers decreased shortly after biopsy, we observed a long-term excess risk of any cancer, with an HR of 1.08 (95%CI = 1.05-1.12) and a cumulative incidence difference of 0.93% (95%CI = 0.61%-1.25%) at 30 years after biopsy. An elevated risk of gastric cancer, lung cancer, and hematological malignancy (including lymphoproliferative malignancy) was also observed at 20 or 30 years since biopsy. Sibling analyses confirmed the above findings.Conclusion: Individuals with a histologically normal mucosa at biopsy and where follow-up revealed no cancer in the first 6 months, may still be at increased risk of cancer, although excess risks are small. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Several gastrointestinal and allergic diseases have been linked to psychiatric disease, but there are limited data on psychiatric disease in eosinophilic esophagitis (EoE). Our aim was to study the association between EoE and later psychiatric disorders. METHODS: This was a population-based nationwide cohort study. Individuals with EoE diagnosed during 1989–2017 in Sweden (n = 1,458) were identified through the ESPRESSO histopathology cohort that represents all gastrointestinal biopsy reports in Sweden's 28 pathology departments. Individuals with EoE were matched with up to 5 reference individuals on sex, age, county, and calendar year (n = 6,436). Cox proportional hazard modeling estimated adjusted hazard ratios (HRs). In a secondary analysis, we compared individuals with EoE with their siblings to adjust for intrafamilial confounding. RESULTS: The median age at EoE diagnosis was 39 years, and 76% of the enrolled individuals with EoE were male. During a median follow-up of 4 years, 106 individuals with EoE (15.96/1,000 person-years) developed a psychiatric disorder compared with 331 reference individuals (10.93/1,000 person-years), corresponding to an HR of 1.50 (95% confidence interval = 1.20–1.87). The increased risk was seen in the first 5 years of follow-up, but not thereafter. The highest relative risks were seen in individuals diagnosed with EoE in childhood. Compared with siblings, individuals with EoE were at an increased risk of psychiatric disease (HR = 1.62; 95% confidence interval = 1.14–2.31). EoE was linked to mood disorders, anxiety disorder, and attention-deficit hyperactivity disorder. DISCUSSION: Individuals with EoE may be at greater risk of psychiatric disease than their siblings and the general population. This risk needs to be considered in clinical care to detect, prevent, and treat comorbidity. [ABSTRACT FROM AUTHOR]

Summary: Background: Epidemiological studies have shown inconsistent incidence rates (IRs) for inflammatory bowel disease (IBD). Aim: To assess the incidence and temporal trends of IBD in Sweden. Methods: Nationwide cohort study based on diagnostic codes for IBD and biopsy reports registered through the ESPRESSO cohort in 1990‐2014. Age‐specific and age‐standardised IRs and cumulative incidence were calculated. Results: Overall, we identified 65 908 cases of incident IBD: ulcerative colitis (UC, n = 38 261, 58%), Crohn's disease (CD, n = 18 577, 28%) and IBD‐U (n = 9070, 14%). During 1990‐2014, the overall IRs per 100 000 person‐years were 29.0 (95% CI: 27.3‐30.7) for IBD, 16.9 (15.9‐17.9) for UC, and 8.1 (7.7‐8.6) for CD. For IBD‐U, the IR was 5.2 (4.9‐5.6) in 2002‐2014. The annual incidence of IBD, UC and CD increased by approximately 7% per year between 1990 and 2001 (P < 0.001) and then decreased by 1%‐2% per year from 2002 onwards (P < 0.001). IRs for IBD, UC and IBD‐U were higher in males while the IR for CD was higher in females. The lifetime risk of IBD was about 2.5% for both sexes. Conclusions: In Sweden, the incidence of IBD in all subtypes increased in 1990‐2001 but has since declined. One in 40 individuals is expected to be diagnosed with IBD during their lifetime. [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]

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]

Lexical bias is the tendency for phonological errors to form existing words at a rate above chance. This effect has been observed in experiments and corpus analyses in Germanic languages, but S. del Viso, J. M. Igoa, and J. E. García-Albea (1991) found no effect in a Spanish corpus study. Because lexical bias plays an important role in the debate on interactivity in language production, the authors reconsidered its absence in Spanish. A corpus analysis, which considered relatively many errors and which used a method of estimating chance rate that is relatively independent of total error number, and a speech-error elicitation experiment provided converging evidence for lexical bias in Spanish. The authors conclude that the processing mechanisms underlying this effect hold cross-linguistically. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Endoscopic screening reduces colorectal cancer (CRC) incidence and mortality. Individuals with a negative result are recommended to undergo rescreening within a 10-year interval, but evidence supporting this advice is limited. METHODS: We performed a matched cohort study using prospectively collected data from 88,798 individuals in Sweden with normal mucosa at the first colorectal biopsy (aged ≥50 years) in the nationwide gastrointestinal epidemiology strengthened by histopathology reports (ESPRESSO) (1965-2016) and 424,150 matched reference individuals from the general population. Cox proportional hazards regression estimated multivariable hazard ratios and 95% confidence intervals (CIs) of CRC incidence and mortality of incident CRCs up to 44 years of follow-up. RESULTS: In the normal biopsy and reference groups, respectively, the 20-year incidences of CRC were 3.03%and 4.53%and the 20-year mortalities of incident CRC were 0.89% and 1.54%. The multivariable hazard ratio comparing the normal biopsy and reference groups was 0.62 for CRC incidence (95% CI = 0.58-0.66, P < 0.001) and 0.56 formortality of incident CRC (95% CI = 0.49-0.64, P < 0.001). When assessed by time interval after biopsy, lower CRC incidence and mortality were observed throughout the follow-up. The association seemed weaker for proximal colon cancer than for rectal and distal colon cancer. DISCUSSION: A normal colorectal biopsy was associated with lower CRC incidence and mortality for at least 20 years after the examination. Our findings confirm previous data and suggest that the screening intervals after a normal colonoscopy could be longer than the commonly recommended 10 years. It may be time to open the discussion for a revision of the international guidelines. [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]

This study examines the reliability and convergent validity of 2 versions of the Social Cognition and Object Relations Scale (SCORS), one for use with Thematic Apperception Test narratives (SCORS–TAT; Westen, 1990) and one for use with clinical interview data (SCORS–CDI; Westen, Barends, Leigh, Mendel, & Silbert, 1990). Four SCORS dimensions were evaluated. Data were collected in a psychiatric sample (N = 74). Results show that although interrater reliability was good for all dimensions, internal consistency was low, especially for the affective dimensions. Structural equation modeling, in which a model with 2 factors (i.e., SCORS–TAT and SCORS–CDI) and 4 dimensions each was tested, indicated low convergence between corresponding dimensions of SCORS–TAT and SCORS–CDI. Correlational analyses suggested that this was due to a strong method factor. Regression analyses, however, revealed that the presence of a personality disorder operated as a moderator for convergence between corresponding cognitive-structural dimensions. [ABSTRACT FROM PUBLISHER]