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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]

Aim: To validate child‐adapted shortened versions of the Irritable Bowel Syndrome‐Behavioural Responses Questionnaire (IBS‐BRQ; short scale denoted BRQ‐C) and the Visceral Sensitivity Index (VSI; short scale denoted VSI‐C) for children with functional abdominal pain disorders (FAPDs). Methods: A child psychologist supervised by a child gastroenterologist was responsible for shortening the scales (BRQ‐C, 11 items; and VSI‐C, 7 items). Then, a sample of 89 children aged 8–12 years with FAPDs was used in the validation. Construct validity was assessed with correlations. Measures included gastrointestinal symptoms, quality of life, pain intensity and anxiety. Also, internal consistency, test–retest reliability, administration time and factor structure were assessed. Results: Internal consistency for the BRQ‐C and the VSI‐C was α = 0.84 and α = 0.80, respectively. Correlations with related scales were similar between child‐adapted scales and original scales, indicating construct validity equivalence. Correlations between short scales and original scales were high. Mean administration time was reduced by 47% (BRQ‐C) and 42% (VSI‐C), compared with original scales. Test–retest reliability was r = 0.72 for BRQ‐C and r = 0.83 for VSI‐C. BRQ‐C had two factors (Avoidance and Bowel control). VSI‐C had a unifactorial structure. Conclusion: The BRQ‐C and the VSI‐C were found to be time‐saving, reliable and valid for children with FAPDs. [ABSTRACT FROM AUTHOR]

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

INTRODUCTION: 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]

Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96–99)% for Crohn's disease, 98 (97–100)% for ulcerative colitis, and 8 (4–11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32–40)% for colonic Crohn's disease (L2), 61 (56–65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78–87)% for perianal disease. Correspondingly, the PPV was 80 (71–89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance paradigms, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account, such as by assessing CRC incidence by tumour stage, or stage-adjusted mortality from CRC. We aimed to compare both overall and country-specific risks of CRC mortality and incident CRC among patients with UC.Methods: In this population-based cohort study of 96 447 patients with UC in Denmark (n=32 919) and Sweden (n=63 528), patients were followed up for CRC incidence and CRC mortality between Jan 1, 1969, and Dec 31, 2017, and compared with matched reference individuals from the general population (n=949 207). Patients with UC were selected from national registers and included in the analysis if they had two or more records with a relevant International Classification of Disease in the patient register (in the country in question) or one such record plus a colorectal biopsy report with a morphology code suggestive of inflammatory bowel disease. For every patient with UC, we selected matched reference individuals from the total population registers of Denmark and Sweden, who were matched for sex, age, birth year, and place of residence. We used Cox regression to compute hazard ratios (HRs) for incident CRC, and for CRC mortality, taking tumour stage into account.Findings: During follow-up, we observed 1336 incident CRCs in the UC cohort (1·29 per 1000 person-years) and 9544 incident CRCs in reference individuals (0·82 per 1000 person-years; HR 1·66, 95% CI 1·57-1·76). In the UC cohort, 639 patients died from CRC (0·55 per 1000 person-years), compared with 4451 reference individuals (0·38 per 1000 person-years; HR 1·59, 95% CI 1·46-1·72) during the same time period. The CRC stage distribution in people with UC was less advanced (p<0·0001) than in matched reference individuals, but taking tumour stage into account, patients with UC and CRC remained at increased risk of CRC death (HR 1·54, 95% CI 1·33-1·78). The excess risks declined over calendar periods: during the last 5 years of follow-up (2013-17, Sweden only), the HR for incident CRC in people with UC was 1·38 (95% CI 1·20-1·60, or one additional case per 1058 patients with UC per 5 years) and the HR for death from CRC was 1·25 (95% CI 1·03-1·51, or one additional case per 3041 patients with UC per 5 years).Interpretation: Compared with those without UC, individuals with UC are at increased risk of developing CRC, are diagnosed with less advanced CRC, and are at increased risk of dying from CRC, although these excess risks have declined substantially over time. There still seems to be room for improvement in international surveillance guidelines.Funding: The Swedish Medical Society, Karolinska Institutet, Stockholm County Council, Swedish Research Council, Swedish Foundation for Strategic Research, Independent Research Fund Denmark, Forte Foundation, Swedish Cancer Foundation. [ABSTRACT FROM AUTHOR]

The Swedish National Patient Register (SNPR) is frequently used in studies of colonic diverticular disease (DD). Despite this, the validity of the coding for this specific disease in the register has not been studied. From SNPR, 650 admissions were randomly identified encoded with ICD 10, K572-K579. From the years 2002 and 2010, 323 and 327 patients respectively were included in the validation study. Patients were excluded prior to, or up to 2 years after a diagnosis with IBD, Celiac disease, IBS, all forms of colorectal cancer (primary and secondary), and anal cancer. Medical records were collected and data on clinical findings with assessments, X-ray examinations, endoscopies and laboratory results were reviewed. The basis of coding was compared with internationally accepted definitions for colonic diverticular disease. Positive predictive values (PPV) were calculated. The overall PPV for all diagnoses and both years was 95% (95% CI: 93–96). The PPV for the year 2010 was slightly higher 98% (95% CI: 95–99) than in the year 2002, 91% (95% CI: (87–94) which may be due to the increasing use of computed tomography (CT). The validity of DD in SNPR is high, making the SNPR a good source for population-based studies on DD. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Everhov et al papers. To view these articles, visit https://doi.org/10.1111/apt.17175 and https://doi.org/10.1111/apt.17207 [ABSTRACT FROM AUTHOR]

Functional abdominal pain (FAP) and functional dyspepsia (FD) are common in adolescents and associated with low quality of life. Exposure-based cognitive-behavioral therapy (CBT) is efficient for adult and adolescent irritable bowel syndrome (IBS), but has never been evaluated for adolescent FAP/FD. The aim of this study was to evaluate the feasibility and potential efficacy of a novel disorder-specific Internet-delivered CBT (Internet-CBT) for adolescents with FAP or FD, using an uncontrolled open pilot including 31 adolescents. The Internet-CBT consisted of 10 weekly online modules, which focused mainly on exposure to abdominal symptoms. Parents received modules to help them reduce unhelpful parental behaviors. Participants reported the treatment to be credible, and an overall satisfaction with the treatment. Data attrition rate was low (7%) and adherence to treatment was acceptable. We saw a significant and large effect on the primary outcome, pain intensity, at posttreatment (d = 1.20, p < .001) that was further improved after 6 months (d = 1.69, p < .001). Participants also made significant and large improvements on gastrointestinal symptoms (d = 0.84, p < .001) and quality of life (d = 0.84, p < .001) that were sustained or further improved at follow-up 6 months after treatment. This study demonstrated that exposure-based Internet-CBT, tailored for adolescents with FAP or FD, is a feasible treatment that potentially improves pain intensity, gastrointestinal symptoms, and quality of life. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The burden of kidney and urological complications in patients with inflammatory bowel disease (IBD) remains poorly characterized. METHODS: We analyzed association between developing IBD (as a time-varying exposure) and relative risks of receiving diagnoses of chronic kidney disease (CKD), acute kidney injury (AKI), or kidney stones, and experiencing a clinically-relevant decline in estimated glomerular filtration rate (eGFR) (CKD progression; composite of kidney failure oran eGFR decline ≥30%) in 1,682,795 individuals seeking healthcare in Stockholm, Sweden, during 2006-2018. We quantified 5- and 10-year absolute risks of these complications in a parallel matched cohort of IBD cases and random controls matched (1:5) on sex, age, and eGFR. RESULTS: During median 9 years, 10,117 participants developed IBD. Incident IBD was associated with higher risks of kidney-related complications compared with non-IBD periods: hazard ratio (HR) (95% confidence interval) was 1.24 (1.10-1.40) for receiving a CKD diagnosis and 1.11 (1.00-1.24) for CKD progression. For absolute risks, 11.8% IBDcases had a CKD event within 10-year. Of these, 6.4% received a CKD diagnosis, and 7.9% reached CKD progression. The risks of AKI (HR 1.97 [1.70-2.29]; 10-year absolute risk 3.6%) and kidney stones (HR 1.69 [1.48-1.93]; 10-year absolute risk 5.6%) were also elevated. Risks were similar in Crohn's disease and ulcerative colitis. DISCUSSION: Morethan 10% of patients with IBD developed CKD within 10-yearfrom diagnosis, with many not being identified through diagnostic codes. This, together with their elevated AKI and kidney stone risks, highlights the need of established protocols for kidney function monitoring and referral to nephrological/urological care for patients with IBD. [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]

Irritable bowel syndrome (IBS) is common in adolescents with a pronounced negative impact on quality of life. A pattern of avoidance behavior is commonly seen in the IBS population, which is associated with more gastrointestinal (GI) symptoms. Exposure-based cognitive behavior therapy (CBT) targets the avoidance behavior to reduce symptoms, but it is unknown whether reduced avoidance is a mediator of symptom improvement in adolescent IBS. Stress has been suggested to play a key role in worsening GI symptoms and is also a potential mediator of the treatment effect in IBS. This study was based on data from a randomized controlled trial (N = 101) that evaluated exposure-based internet-delivered CBT (Internet-CBT) compared with a wait-list for adolescents with IBS. We investigated whether avoidance behavior and perceived stress mediated the improvement in global GI symptoms due to treatment. We found that a change in avoidance behavior, but not perceived stress, mediated the effect of exposure-based Internet-CBT on GI symptoms. The decrease in avoidance behavior explained a large portion (67%) of the total treatment effect. Moreover, a unidirectional relationship over time was observed between avoidance behavior and GI symptoms. Our conclusion is that exposure-based CBT in adolescent IBS reduces avoidance and, consequently, reduces GI symptoms. [ABSTRACT FROM AUTHOR]

Background: Children with pain-related functional gastrointestinal disorders (P-FGIDs) have an increased risk for school absenteeism, depression, anxiety and low quality of life. Exposure-based cognitive behavior therapy (CBT) has shown large treatment effects in adults with irritable bowel syndrome, but has not been tested for children 8–12 years with P-FGIDs. Aim: The aim of this trial was to test the feasibility, acceptability and potential efficacy of a newly developed exposure-based CBT for children with P-FGIDs. Method: The children (n = 20) with a P-FGID, were referred by their treating physicians. The participants received 10 weekly sessions of exposure-based CBT and were assessed at pre-treatment, post-treatment and 6-month follow-up. Results: Children improved significantly on the primary outcome measure pain intensity at post (Cohen’s d = 0.40, p = 0.049) and at 6-month follow-up (Cohen’s d = 0.85, p = 0.004). Improvements were also seen in pain frequency, gastrointestinal symptoms, quality of life, depression, anxiety, school absenteeism and somatic symptoms. Improvements were maintained or further increased at 6-month follow-up. The children engaged in the exposures and were satisfied with the treatment. Conclusions: Exposure-based CBT for children with P-FGIDs is feasible, acceptable and potentially efficacious. [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]

Objective. To examine the relationship between body mass index (BMI) and an inpatient diagnosis of coeliac disease (CD) in two independent Swedish national registers. Material and methods. Study 1: Cohort study of women. The relationship between (pre-pregnancy) BMI and CD in pregnant women was evaluated (174 undiagnosed CD (at time of pregnancy), 550 diagnosed CD, 787,986 without a diagnosis of CD). The association between BMI and undiagnosed CD was estimated by Cox regression. Study 2: Case-control study of men. The relationship between BMI and CD in male conscripts was evaluated (70 undiagnosed CD, 1,047 diagnosed CD and 6,887 without a diagnosis of CD). The association between BMI and undiagnosed CD was estimated by logistic regression. Prevalence of underweight, normal weight and overweight was compared between diagnosed CD, undiagnosed CD and no diagnosis of CD. Results. The prevalence of underweight (BMI <18.5) in women was: reference individual: 5.2%; undiagnosed CD: 16.7% and prior diagnosis of CD: 6.4%. In men, the corresponding figures were 6.5%; 14.3% and 9.8%, respectively. Underweight was associated with undiagnosed CD (future diagnosis of CD) in both women (hazard ration (HR) = 2.5; 95% CI = 1.6-3.7) and men (odds ratio (OR) = 2.4; 95% CI = 1.2-4.9). In women, overweight was negatively associated with undiagnosed CD (HR = 0.6; 95% CI = 0.4-0.9), but not in men (OR = 1.1; 95% CI = 0.6-2.2). 9.2% of women with undiagnosed CD and 14.3% of men with undiagnosed CD were overweight. Conclusions. Underweight individuals are at increased risk of having undiagnosed CD. However, overweight does not rule out CD. [ABSTRACT FROM AUTHOR]

Objective. Case reports have indicated a link between coeliac disease (CD) and immune thrombocytopenic purpura (ITP). Two national, register-based studies were carried out to investigate a possible association between CD and ITP and vice versa. Material and methods. In a cohort study of 14,347 individuals with inpatient diagnoses of CD and 69,967 reference individuals matched for age, gender, calendar year and county, the Cox regression was used to estimate the risk of subsequent inpatient diagnoses of ITP (of any type or chronic). In a case control design, conditional logistic regression was used to assess the risk of exposure (diagnosis of ITP prior to CD) in 15,382 cases (individuals with diagnoses of CD) and 76,824 matched controls. Diagnoses of CD and ITP were identified through the Swedish National Inpatient Register. Results. Individuals with CD were at increased risk of both subsequent ITP of any type (hazard ratio (HR)=1.91; 95% CI=1.19-3.11; p=0.008) and subsequent chronic ITP (HR 2.77; 95% CI=1.09-7.04; p=0.033). Risk estimates were similar when reference individuals were restricted to inpatients. There was also a positive association between CD and prior ITP of any type (odds ratio (OR)=2.96; 95% CI=1.60-5.50; p=0.001) or with prior chronic ITP (OR=6.00; 95% CI=1.83-19.66; p=0.003). Conclusions. We found a positive association between CD and both ITP of any type and chronic ITP, irrespective of which disease came first, and suggest there should be increased awareness of CD in patients with ITP. [ABSTRACT FROM AUTHOR]

Objective. Previous research has indicated a link between coeliac disease (CD) and urinary tract infection (UTI). The objective of this study was to assess the risk of UTI and repeated episodes of UTI before the current pregnancy in women with diagnosed or undiagnosed CD. Material and methods. A national registry-based cohort study restricted to pregnant women was used in this investigation, with linkage between the Swedish National Medical Birth Registry and the National Inpatient Registry. We analysed the risk of UTI during pregnancy from 1973 to 1989 in 212 pregnancies to women who had received a diagnosis of CD prior to giving birth and in 786 pregnancies to women diagnosed after giving birth. We also assessed the risk of repeated episodes of UTI before the current pregnancy according to data in the national birth records of 1990–2001 in 617 women with CD diagnosed prior to giving birth and 109 women diagnosed after giving birth. Results. UTI during pregnancy: UTI occurred during 19,139/1,678,304 pregnancies to women who had never had a diagnosis of CD, compared with in 12/786 pregnancies to women with undiagnosed CD (adjusted odds ratio (AOR) =1.37; 95% CI =0.78–2.43; p=0.276) and in 0/212 pregnancies to women with diagnosed CD (AOR =0.06; 95% CI =0.00–8.94; p=0.277) (ORs adjusted for maternal age, parity, nationality and calendar period). Repeated episodes of UTI before the current pregnancy: among 692,991 women who had never had a diagnosis of CD, 74,776 reported repeated episodes of UTI, compared with 14/101 women with undiagnosed CD (AOR =1.39; 95% CI =0.79–2.45; p=0.255) and 69/566 women with diagnosed CD (AOR =1.02; 95% CI =0.79–1.32; p=0.864) (ORs adjusted for maternal age, parity, nationality, calendar period and civil status). Adjustment for smoking in a subset of patients with available data did not change the risk estimates. Conclusions. It cannot be ruled out that undiagnosed CD in pregnant women is associated with a small, increased risk of UTI. In pregnant women with diagnosed CD, there seems to be no increased risk of UTI. [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]

Summary: Background: 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. Aim: To assess and compare the risk of ACS between patients with IBD and the general population. Methods: 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). Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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

Summary: Background: Whether long‐term effectiveness differs between anti‐tumour necrosis factor (anti‐TNF) agents is unknown. Aims: To examine drug survival of first‐line anti‐TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti‐TNF. Methods: Biologic‐naïve patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow‐up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Results: In Crohn's disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%‐38%] for infliximab versus 16% [95%CI = 11%‐21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20‐3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26‐3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19‒0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction‐mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28‐0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08‐0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%‐47%] for infliximab versus 37% [95% CI = 21%‐53%] for adalimumab. Disease duration ≥10 years [aHR = 0.25; 95% CI = 0.10‐0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18‒0.84] were associated with lower discontinuation rates. Conclusions: Clinical characterisation of patients may aid decision‐making on anti‐TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohn's disease, suggests a potential difference between the two drugs. [ABSTRACT FROM AUTHOR]

The article presents a reply by the authors to a commentary about their study which claims that Rome III criteria and alarm symptoms can provide high specificity but low sensitivity for functional gastrointestinal disorders in children. Topics discussed include the difficulty of determining whether the cause of recurrent abdominal pain (RAP) in children is organic or functional and the importance of identifying reliable alarm symptoms in the general pediatric population with RAP.

Background: The etiology of irritable bowel syndrome (IBS) is poorly understood. Animal and human data suggest that early life stress may induce long‐term changes in the nociceptive circuitry, but conclusive studies are lacking. Methods: We identified all Swedish children born between 1973 and 1992 in the Swedish Medical Birth Register. We had access to all diagnostic codes for specialized (nonprimary care) outpatient visits 2001‐2009 (the National Patient Register) and identified individuals who were diagnosed with IBS (ICD‐10 code: K58) after 18 years of age. We compared incidence of IBS in individuals with and without pre‐ and perinatal stress using multivariable logistic regression. Key Results: 2 056 430 children were included in the study. After turning 18 years, 14 382 of them were diagnosed with IBS in specialized outpatient care. Neither high, nor low birth weight was a risk factor for IBS in young adults. Preterm birth was associated with lower occurrence of IBS (adjusted OR 0.82 [0.75‐0.90]) and vaginal instrumental delivery and Cesarean delivery were associated with slightly increased odds of IBS (adjusted OR 1.14 [1.06‐1.24] and 1.09 [1.03‐1.16] respectively). Neonatal distress and respiratory distress were not associated with future IBS. Female gender was by far the strongest risk factor for IBS in young adults (adjusted OR 3.48 [3.34‐3.63]). Conclusions & Inferences: In this large population‐based study, we found that mode of delivery was associated with an increased risk for IBS in young adulthood, while other proxies for pre‐ and perinatal stress were not. Female gender remains the most important risk factor for IBS. The etiology of irritable bowel syndrome is poorly understood but previous studies have suggested that early life stress may be an underlying cause. In this large, Swedish register‐based study of neonatal stress, we did not detect any risk factors for irritable bowel syndrome, except mode of delivery. Female gender remains the most important risk factor for irritable bowel syndrome and the underlying causes are yet to be determined. [ABSTRACT FROM AUTHOR]

A wide range of psychological treatments have been found to reduce the symptoms of irritable bowel syndrome (IBS) but their relative effects are unclear. In this systematic review and meta-analysis, we determined the effects of psychological treatments for IBS, including subtypes of cognitive behavior therapy, versus attention controls. We searched 11 databases (March 2022) for studies of psychological treatments for IBS, reported in journal articles, books, dissertations, and conference abstracts. The resulting database comprised 9 outcome domains from 118 studies published in 1983–2022. Using data from 62 studies and 6496 participants, we estimated the effect of treatment type on improvement in composite IBS severity using random-effects meta-regression. In comparison with the attention controls, there was a significant added effect of exposure therapy (g = 0.52, 95% CI = 0.17–0.88) and hypnotherapy (g = 0.36, 95% CI = 0.06–0.67) when controlling for the pre- to post-assessment duration. When additional potential confounders were included, exposure therapy but not hypnotherapy retained a significant added effect. Effects were also larger with a longer duration, individual treatment, questionnaire (non-diary) outcomes, and recruitment outside of routine care. Heterogeneity was substantial. Tentatively, exposure therapy appears to be a particularly promising treatment for IBS. More direct comparisons in randomized controlled trials are needed. OSF.io identifier: 5yh9a. [ABSTRACT FROM AUTHOR]

Background: About 50% of patients with Crohn's disease (CD) and about 20% of those with ulcerative colitis (UC) undergo surgery at some point during the course of the disease. The diagnostic validity of the Swedish National Patient Register (NPR) has previously been shown to be high for inflammatory bowel disease (IBD), but there are little data on the validity of IBD-related surgical procedure codes.Methods: Using patient chart data as the gold standard, surgical procedure codes registered between 1966 and 2014 in the NPR were abstracted and validated in 262 randomly selected patients with a medical diagnosis of IBD. Of these, 53 patients had reliable data about IBD-related surgery. The positive predictive value (PPV), sensitivity and specificity of the surgical procedure codes were calculated.Results: In total, 158 surgical procedure codes were registered in the NPR. One hundred fifty-five of these, representing 60 different procedure codes, were also present in the patient charts and validated using a standardized form. Of the validated codes 153/155 were concordant with the patient charts, corresponding to a PPV of 96.8% (95%CI = 93.9-99.1). Stratified in abdominal, perianal and other surgery, the corresponding PPVs were 94.1% (95%CI = 88.7-98.6), 100% (95%CI = 100-100) and 98.1% (95%CI = 93.1-100), respectively. Of 164 surgical procedure codes in the validated patient charts, 155 were registered in the NPR, corresponding to a sensitivity of the surgical procedure codes of 94.5% (95%CI = 89.6-99.3). The specificity of the NPR was 98.5% (95%CI = 97.6-100).Conclusions: Data on IBD-related surgical procedure codes are reliable, with the Swedish National Patient Register showing a high sensitivity and specificity for such surgery. [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]

Purpose: Intussusception has been associated with rotavirus vaccine. The rotavirus vaccine will soon be introduced in the Swedish national immunization program. A validation of the diagnosis of intussusception among Swedish children in the Swedish National Patient Register is needed, as a basis for future vaccine safety surveillance by Swedish registers.Methods: This diagnostic study reviewed the medical admission records of 392 Swedish children with intussusception from 1987 to 2013. The records were randomly selected by The National Board of Health and Welfare from all Sweden and from both pediatric and pediatric surgery care. Positive predictive values (PPV) were calculated to study the concordance between the diagnosis coded in the Swedish Patient Register and the accepted international criteria of case definitions.Results: The PPV for a definitive diagnosis, based on certain radiology findings or surgery, was 84%. When clinically probable cases were added the PPV was 87%. When cases of possible intussusception were added the PPV was 89%. The PPV for the 240 children under 1 year was 88%.Conclusion: Swedish health care registers can be used in the evaluation of incidences of intussusception when rotavirus vaccine will be introduced, due to a high validity of the diagnosis of intussusception in the registers. [ABSTRACT FROM AUTHOR]

Aim: To investigate inflammatory bowel disease (IBD) register-based subtype classifications over a patient's disease course and over time. Methods: We examined International Classification of Diseases coding in patients with ≥2 IBD diagnostic listings in the National Patient Register 2002-2014 (n = 44,302). Results: 18% of the patients changed diagnosis (17% of adults, 29% of children) during a median follow-up of 3.8 years. Of visits with diagnoses of Crohn's disease (CD) or ulcerative colitis (UC), 97% were followed by the same diagnosis, whereas 67% of visits with diagnosis IBD-unclassified (IBD-U) were followed by another IBD-U diagnosis. Patients with any diagnostic change changed mostly once (47%) or twice (31%), 39% from UC to CD, 33% from CD to UC and 30% to or from IBD-U. Using a classification algorithm based on the first two diagnoses ('incident classification'), suited for prospective cohort studies, the proportion adult patients with CD, UC, and IBD-U 2002-2014 were 29%, 62%, and 10% (43%, 45%, and 12% in children). A classification model incorporating additional information from surgeries and giving weight to the last 5 years of visits ('prevalent classification'), suited for description of a study population at end of follow-up, classified 31% of adult cases as CD, 58% as UC and 11% as IBD-U (44%, 38%, and 18% in children). Conclusions: IBD subtype changed in 18% during follow-up. The proportion with CD increased and UC decreased from definition at start to end of follow-up. IBD-U was more common in children. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is a diagnosis which relies on histopathologic criteria. This report examines the validity of having a diagnosis of MC in Swedish pathology registers. METHODS: We reviewed patient charts from 215 randomly selected individuals from 15 pathology departments in five healthcare regions in Sweden with a relevant histopathology code for MC on colon biopsies. Information on clinical symptoms and laboratory data were obtained from medical chart review. We obtained sufficient data on 211 individuals for calculating positive predictive values (PPVs) for MC. RESULTS: In total, 200/211 patients with a histopathology diagnosis of MC were confirmed as also having a clinical diagnosis of MC after chart review, yielding a PPV of 95% (95%CI =91-97%). The PPV for CC was 95% (95%CI =87-98%) and 85% for LC (95%CI =78-90%). The median age at biopsy was 67 years (range 17-90 years), and 72% (n=154) were women. The most common symptoms in patients with MC histopathology were diarrhea (96% of patients), weight loss (24%) and abdominal pain (13%). Four percent (4/111) of patients with available data on stool culture were positive for gastrointestinal pathogens (none had Clostridium difficile). In 81 patients with available celiac serology, five (6%) were positive. Twenty-six percent of all patients had at least one other autoimmune disease, the most frequent being hypothyroidism (8%) and celiac disease (6%). CONCLUSIONS: This study found a high validity for MC as recorded in Swedish pathology registers. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to validate the Rome III criteria and alarm symptoms with regard to their ability to discriminate between organic and functional diagnoses in children with gastrointestinal complaints.Methods: We recruited 258 children aged four years to 17 years who consulted a paediatrician in secondary or tertiary care in Stockholm from January 2013 to May 2014 due to gastrointestinal complaints. A symptom questionnaire based on the official Questionnaire on Pediatric Gastrointestinal Symptoms Rome III, including questions on alarm symptoms, was used. A diagnostic review of their medical records was also carried out.Results: The reference diagnoses were organic (16%), pain-predominant functional gastrointestinal disorders (54%) and other functional diseases (30%). When the reported symptoms that fulfilled the Rome III criteria for pain-predominant functional gastrointestinal disorders were combined with an absence of alarm symptoms, they had a high specificity (0.90) for a functional diagnosis, but a low sensitivity (0.15). Alarm symptoms were equally common in patients with organic (83%) and functional diseases (80%, p = 0.66).Conclusions: Combining the Rome III criteria and an absence of alarm symptoms from patient questionnaires had high specificity but low sensitivity when diagnosing pain-predominant functional gastrointestinal disorders in children seeking medical care for gastrointestinal complaints. [ABSTRACT FROM AUTHOR]

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

National patient registers are valuable in epidemiological studies. To ensure high-quality data for studies of irritable bowel syndrome (IBS), this study aimed to validate the ICD-10 code for IBS in the Swedish National Patient Register. The positive predictive values (PPV) for IBS defined by the Rome criteria were calculated based on a review of medical records of randomly selected individuals with a first-ever diagnostic listing of IBS in the Swedish National Patient register in the year 2005 (Rome II criteria) or 2010 (Rome III criteria). 340 medical records were reviewed (172 from 2005 and 168 from 2010). The majority of patients were females (74%), and the mean age was 42 years. IBS used in any type of department had a PPV of 76% (95% confidence interval 71–80%), which increased to 80% (76–84%) when we included individuals likely to have IBS but where information about some aspects of the Rome criteria was lacking in the medical record. Two highly specialized gastroenterological departments had the best PPV, 96%, while departments of internal medicine in general had a PPV of 82% (80–95%). The PPV for the IBS subtype was 62% (55–67%). The PPVs were not significantly different comparing the two time periods investigated. The validity of a register-based definition of IBS in the Swedish National Patient register is high and can be used to identify patients with IBS in observational research. The data source, i.e., type of hospital and department, influences reliability. [ABSTRACT FROM AUTHOR]

Background:Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown. Methods:Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohn’s disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated. Results:For cases with ≥2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87–97) for any IBD, 79% (66–88) for UC and 72% (60–82) for CD. In UC patients with ≥2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77–97). The PPV for CD in patients with ≥2 CD diagnoses but never a UC diagnosis was 81% (67–91)). Combining data from SWIBREG (≥1 record) and the NPR (≥1 record), the PPV was 99% for any IBD (97–100), 96% (89–99) for UC, and 90% (82–96) for CD. Conclusion:The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR. [ABSTRACT FROM PUBLISHER]

Background: Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce. Aims: To assess the long-term effectiveness of ustekinumab in patients with active Crohn's disease (CD). Methods: This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey–Bradshaw Index (HBI) ≤ 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (≥ 3-point-decrease in HBI among patients with initial HBI ≥ 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures. Results: Of 114 included patients, 107 (94%) had previously failed ≥ 1 and 58 (51%) ≥ 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed. Conclusions: In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care. [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: 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]

Summary: Background: Previous research indicates that the increased relative risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) is limited to young‐onset IBD. Aim: To estimate risks of incident CRC and death from CRC in elderly‐onset IBD Methods: Patients diagnosed with IBD at age ≥ 60 years between 1969 and 2017 were identified using Danish and Swedish National Patient Registers and histopathology data. We linked data to Cancer and Causes of Death Registers and used Cox regression to estimate hazard ratios (HRs) for CRC diagnosis and death compared to matched (by sex, age, and region) IBD‐free individuals. Results: Among 7869 patients with Crohn's disease followed for 54,220 person‐years, and 21,224 patients with ulcerative colitis (UC) followed for 142,635 person‐years, 2.10% and 1.90% were diagnosed with CRC, compared to 2.26% and 2.34% of reference individuals (median follow‐up 6 and 7 years). The incidence of CRC was elevated during the first year after IBD diagnosis: 4.36 (95% CI = 3.33–5.71) in Crohn's disease and 2.48 (95% CI = 2.03–3.02) in UC, but decreased after the first year of follow‐up: 0.69 (95% CI = 0.56–0.86) and 0.78 (95% CI = 0.69–0.88). Once diagnosed with CRC, the risk of CRC death was similar for IBD patients and the general population. Conclusion: The excess risk of CRC in elderly‐onset IBD was probably due to bias and not observed beyond the first year. From 2010, the HR for CRC diagnosis more than 1 year after initial IBD diagnosis was lower than in the largely unscreened reference population, supporting the benefit of endoscopic screening and surveillance in patients with IBD. [ABSTRACT FROM AUTHOR]

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

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]

Summary: Background and Aims: To estimate familial aggregation of inflammatory bowel disease (IBD), we performed a nationwide, case–control study and examined the odds for patients with IBD (vs controls) to have a first‐degree relative (FDR) with IBD, by age of diagnosis, type of family history and IBD subtype. To assess the incidence of future IBD in relatives of incident IBD patients, we performed a cohort study. Methods: Individuals diagnosed with IBD (N = 50,667) between 2003 and 2017 with at least one FDR were identified from Swedish national registers and compared to general population controls (N = 506,720) with at least one FDR. We used logistic regression to calculate adjusted odds ratios (ORs) and Cox regression to estimate hazard ratios (HRs). Results: Compared to controls, IBD cases more often had a mother (3.0% vs 0.9%, OR = 3.5; 95% CI: 3.3–3.7), father (2.9% vs 0.8%, OR = 3.5; 95% CI: 3.3–3.7), full sibling (5.3% vs 1.5%, OR = 3.6; 95% CI: 3.4–3.8) and child (2.4% vs 0.9%, OR = 2.6; 95% CI: 2.4–2.8) with IBD. The strength of association increased with the number of affected FDRs and was modified by subtype of IBD and age of diagnosis. Highest ORs were observed for paediatric IBD among paediatric‐onset Crohn's disease (OR = 10.6; 95% CI: 8.2–13.5) and paediatric‐onset ulcerative colitis (OR = 8.4; 95% CI: 6.4–10.9) cases. The 10‐year cumulative incidence of IBD was 1.7% in full‐siblings of incident IBD patients vs 0.4% among full‐siblings of reference individuals. Conclusion: The variations in the strength of familial IBD and future risk of IBD in FDRs support differences in genetic predisposition and call for targeted approaches in potential screening programmes. [ABSTRACT FROM AUTHOR]

Objective: A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease.Material and methods: A nation-wide population-based case–control study was performed, including 13,127 cases hospitalised during 2006–2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as “current” or “former” if a statin prescription was last dispensed ≤125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation.Results: A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17–1.30]; fully adjusted OR 1.00 [0.94–1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73–1.08]; fully adjusted OR 0.70 [0.55–0.89]).Conclusions: The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for diverticular disease. [ABSTRACT FROM PUBLISHER]

LINKED CONTENT: This article is linked to Visuri et al and Haydek & Scott papers. To view these articles, visit https://doi.org/10.1111/apt.16525 and https://doi.org/10.1111/apt.16555 [ABSTRACT FROM AUTHOR]

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

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]

LINKED CONTENT This article is linked to Mouratidou et al and Hron papers. To view these articles, visit https://doi.org/10.1111/apt.15667 and https://doi.org/10.1111/apt.15828. [ABSTRACT FROM AUTHOR]

To investigate absolute and relative risk of serious infections in adult/elderly inflammatory bowel disease (IBD) diagnosed 2002–2017. Nationwide, register-based cohort study of Swedish patients with IBD compared with general population matched reference individuals with regard to time to first serious infection, equal to hospital admission. Multivariable Cox regression estimated hazard ratios (HRs) for any serious infection. Secondary outcomes included site-specific infections, opportunistic infections and sepsis. We identified 47 798 individuals with IBD. During a follow-up of 329 000 person-years, they had 8752 first serious infections (26.6 per 1000 person-years). This compared with an incidence rate of 10.7 per 1000 person-years in matched reference individuals, corresponding to a 2.53-fold increased hazard of serious infections (95%CI = 2.47–2.59). The HR for serious infection in elderly-onset IBD was 2.01 (95%CI = 1.95–2.08). The relative hazard of serious infection was somewhat higher in Crohn's disease (2.94; 95%CI = 2.81–3.06) than in ulcerative colitis (2.24; 95%CI = 2.17–2.31). The HR for serious infections was high in the first year of follow-up (5.17; 95%CI = 4.93–5.42). Individuals with IBD were at a particularly high relative hazard of gastrointestinal and opportunistic infections. The HR for sepsis was 2.47 (95%CI = 2.32–2.63). The relative rates for serious infections in IBD increased in recent years. Patients with adult-onset IBD are at increased risk of serious infections, particularly gastrointestinal and opportunistic infections. Relative rates were highest just after IBD diagnosis, and seem to have increased in recent years. [ABSTRACT FROM AUTHOR]

Background: Studies on allergy-related diseases in relation to abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) in children are few and results are contradictory. We examined the associations between childhood allergy-related diseases and adolescent AP-FGIDs in general and irritable bowel syndrome (IBS) in particular.Method: Prospective population-based birth cohort study of 4089 children born in Sweden 1994-1996. We analysed data from 2949 children with complete follow-up at 16 years (y) and no diagnosis of inflammatory bowel disease or coeliac disease at 12y or 16y. Asthma, rhinitis, eczema, and food hypersensitivity (FH) were assessed through questionnaires at 1-2y, 4y, 8y, 12y, and 16y. AP-FGIDs and IBS were assessed through questionnaires at 16y and defined according to the Rome III criteria. Associations between childhood allergy-related diseases and any AP-FGID and IBS and 16y respectively were examined using binomial generalized linear models with a log link function and described as relative risk with 95% confidence intervals.Results: The prevalence of any AP-FGID and IBS at 16y were 12.0% and 6.0% respectively. Eczema at 1-2y, 4y, and 8y, and FH at 12y and 16y were associated with an increased risk for any AP-FGID at 16y. Asthma and FH at 12y and 16y were associated with an increased risk for IBS at 16y. The relative risk for IBS at 16y increased with increasing number of concurrent allergy-related diseases at 16y, but linear trend for relative risk was only borderline statistically significant (P for trend = 0.05).Conclusions: This prospective population-based study demonstrated positive associations between childhood allergy-related diseases and adolescent AP-FGIDs, including IBS, implicating shared pathophysiology among these disorders. [ABSTRACT FROM AUTHOR]

Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohn's disease (CD) are still limited. To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (≥3-point-decrease of Harvey–Bradshaw index (HBI)) and remission (HBI ≤4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Of 114 included patients, 107 (94%) had failed ≥ 1 and 58 (51%) ≥ 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p =.006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option. [ABSTRACT FROM AUTHOR]

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