Menopausal hormone therapy and risk of sarcoidosis: a population-based nested case-control study in Sweden.

Sarcoidosis incidence peaks in women between 50 and 60 years old, which coincides with menopause, suggesting that certain sex hormones, mainly estrogen, may play a role in disease development. We investigated whether menopausal hormone therapy (MHT) was associated with sarcoidosis risk in women and whether the risk varied by treatment type. We performed a nested case-control study (2007-2020) including incident sarcoidosis cases from the Swedish National Patient Register (n = 2593) and matched (1:10) to general population controls (n = 20,003) on birth year, county, and living in Sweden at the time of sarcoidosis diagnosis. Dispensations of MHT were obtained from the Swedish Prescribed Drug Register before sarcoidosis diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression. Ever MHT use was associated with a 25% higher risk of sarcoidosis compared with never use (aOR 1.25, 95% CI 1.13-1.38). When MHT type and route of administration were considered together, systemic estrogen was associated with the highest risk of sarcoidosis (aOR 1.51, 95% CI 1.23-1.85), followed by local estrogen (aOR 1.25, 95% CI 1.11-1.42), while systemic estrogen-progestogen combined was associated with the lowest risk compared to never users (aOR 1.12, 95% CI 0.96-1.31). The aOR of sarcoidosis did not differ greatly by duration of MHT use. Our findings suggest that a history of MHT use is associated with increased risk of sarcoidosis, with women receiving estrogen administered systemically having the highest risk.

Increasing Risk of Lymphoma Over Time in Crohn's Disease but Not in Ulcerative Colitis: A Scandinavian Cohort Study.

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD. METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation. RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs. CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.

Modifiable lifestyle risk factors for sarcoidosis: a nested case-control study.

Objective: We aimed to investigate whether obesity, tobacco use, alcohol consumption and physical inactivity are associated with sarcoidosis risk. Methods: We conducted a matched case-control study nested within the Northern Sweden Health and Disease Study. Incident sarcoidosis cases (n=165) were identified via medical records and matched to controls (n=660) on sub-cohort, sex, birth and questionnaire date (1:4). Data on lifestyle factors were obtained through questionnaires, and physical measurements of height, weight and waist were collected prior to sarcoidosis diagnosis. Conditional logistic regression estimated adjusted odds ratios with 95% confidence intervals (aOR; 95% CI). Results: Compared with never-smoking, current smoking was associated with lower sarcoidosis odds (aOR 0.48; 95% CI 0.32-0.71), and former smoking with higher odds (aOR 1.33; 95% CI 0.98-1.81). Snus use was not associated with sarcoidosis. There was an increased odds of sarcoidosis associated with obesity (aOR 1.34; 95% CI 0.94-1.92) but not with overweight (aOR 0.99; 95% CI 0.76-1.30). Compared with those who were physically inactive, those who were active had a 25% higher odds of sarcoidosis (aOR 1.25; 95% CI 0.91-1.72). No association was found with moderate alcohol consumption (aOR 0.95; 95% CI 0.56-1.62). All results were similar when cases diagnosed within 5 years after exposure assessment were excluded, except the aOR for former smoking decreased to 1.1. Conclusion: We observed a reduced sarcoidosis risk associated with smoking, which cannot be fully explained by early symptoms of sarcoidosis influencing smoking habits. Results indicate an increased risk associated with obesity, but not overweight, and being physically active.

Flexible evaluation of surrogacy in platform studies.

Trial-level surrogates are useful tools for improving the speed and cost effectiveness of trials but surrogates that have not been properly evaluated can cause misleading results. The evaluation procedure is often contextual and depends on the type of trial setting. There have been many proposed methods for trial-level surrogate evaluation, but none, to our knowledge, for the specific setting of platform studies. As platform studies are becoming more popular, methods for surrogate evaluation using them are needed. These studies also offer a rich data resource for surrogate evaluation that would not normally be possible. However, they also offer a set of statistical issues including heterogeneity of the study population, treatments, implementation, and even potentially the quality of the surrogate. We propose the use of a hierarchical Bayesian semiparametric model for the evaluation of potential surrogates using nonparametric priors for the distribution of true effects based on Dirichlet process mixtures. The motivation for this approach is to flexibly model relationships between the treatment effect on the surrogate and the treatment effect on the outcome and also to identify potential clusters with differential surrogate value in a data-driven manner so that treatment effects on the surrogate can be used to reliably predict treatment effects on the clinical outcome. In simulations, we find that our proposed method is superior to a simple, but fairly standard, hierarchical Bayesian method. We demonstrate how our method can be used in a simulated illustrative example (based on the ProBio trial), in which we are able to identify clusters where the surrogate is, and is not useful. We plan to apply our method to the ProBio trial, once it is completed.

Confirmatory prediction-driven RCTs in comparative effectiveness settings for cancer treatment.

BACKGROUND: Medical advances in the treatment of cancer have allowed the development of multiple approved treatments and prognostic and predictive biomarkers for many types of cancer. Identifying improved treatment strategies among approved treatment options, the study of which is termed comparative effectiveness, using predictive biomarkers is becoming more common. RCTs that incorporate predictive biomarkers into the study design, called prediction-driven RCTs, are needed to rigorously evaluate these treatment strategies. Although researched extensively in the experimental treatment setting, literature is lacking in providing guidance about prediction-driven RCTs in the comparative effectiveness setting. METHODS: Realistic simulations with time-to-event endpoints are used to compare contrasts of clinical utility and provide examples of simulated prediction-driven RCTs in the comparative effectiveness setting. RESULTS: Our proposed contrast for clinical utility accurately estimates the true clinical utility in the comparative effectiveness setting while in some scenarios, the contrast used in current literature does not. DISCUSSION: It is important to properly define contrasts of interest according to the treatment setting. Realistic simulations should be used to choose and evaluate the RCT design(s) able to directly estimate that contrast. In the comparative effectiveness setting, our proposed contrast for clinical utility should be used.

Early Initiation of Antitumor Necrosis Factor Therapy Reduces Postoperative Recurrence of Crohn's Disease Following Ileocecal Resection.

BACKGROUND: Postoperative recurrence (POR) of Crohn's disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR). METHODS: We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (≥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab). RESULTS: We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis. CONCLUSION: Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited.

Postoperative recurrence of Crohn's disease is common after ileocecal resection. In this dual-center study, early initiation of an anti-TNF agent within 4 weeks following an ileocecal resection was associated with a reduction in postoperative recurrence of Crohn's disease.

The association of serum vitamin D with incident diabetes in an African American population.

BACKGROUND: Incident diabetes risk is inversely proportional to 25-hydroxyvitamin D [25(OH)D] levels among non-Hispanic white but is unclear among African American (AA) populations. Serum 25(OH)D2 may be an important component of total 25(OH)D among AA populations due to higher levels of melanin. OBJECTIVE: To assess the association of serum 25(OH)D with incident diabetes among AAs and stratify by detectable 25(OH)D2. DESIGN: Serum 25(OH)D2 and 25(OH)D3 were collected from 2000 to 2004 among AA participants in the Jackson Heart Study. A cosinor model was used to adjust for the seasonality of 25(OH)D3; 25(OH)D3 and 25(OH)D2 were combined to ascertain total 25(OH)D. Incident diabetes (fasting glucose ≥126 mg/dl, use of diabetes drugs, or HbA1c ≥6.5%) was assessed over 12 years among adults without diabetes at baseline. Participants with missing baseline covariates or diabetes follow-up were excluded. Hazard ratios (HR) were estimated using Cox modeling, adjusting for age, sex, education, occupation, smoking, physical activity, alcohol use, aldosterone, and body-mass index. RESULTS: Among 3311 adults (mean age 53.3 years, 63% female) 584 participants developed diabetes over a median of 7.7 years. After adjustment, 25(OH)D ≥20 compared to <12 ng/ml was associated with a HR 0.78 (95% CI: 0.61, 1.00). Among participants with detectable 25(OH)D2 and 25(OH)D3 (n = 1671), 25(OH)D ≥ 20 ng/ml compared to <12 ng/ml was associated with a 35% (HR 0.65, 95% CI: 0.46, 0.91) lower risk of diabetes. CONCLUSIONS: Higher levels of 25(OH)D may be protective against the development of diabetes among AA individuals, particularly among those with detectable 25(OH)D2 and 25(OH)D3.

Confidence bands in survival analysis.

BACKGROUND: Providing estimates of uncertainty for statistical quantities is important for statistical inference. When the statistical quantity of interest is a survival curve, which is a function over time, the appropriate type of uncertainty estimate is a confidence band constructed to account for the correlation between points on the curve, we will call this a simultaneous confidence band. This, however, is not the type of confidence band provided in standard software, which is constructed by joining the confidence intervals at given time points. METHODS: We show that this type of band does not have desirable joint/simultaneous coverage properties in comparison to simultaneous bands. RESULTS: There are different ways of constructing simultaneous confidence bands, and we find that bands based on the likelihood ratio appear to have the most desirable properties. Although there is no standard software available in the three major statistical packages to compute likelihood-based simultaneous bands, we summarise and give code to use available statistical software to construct other simultaneous forms of bands, which we illustrate using a study of colon cancer. CONCLUSIONS: There is a need for more user-friendly statistical software to compute simultaneous confidence bands using the available methods.

Reproductive and hormonal risk factors for sarcoidosis: a nested case-control study.

BACKGROUND: Sarcoidosis incidence peaks in females around the fifth decade of life, which coincides with menopause, suggesting hormonal factors play a role in disease development. We investigated whether longer exposure to reproductive and hormonal factors is associated with reduced sarcoidosis risk. METHODS: We conducted a matched case-control study nested within the Mammography Screening Project. Incident sarcoidosis cases were identified via medical records and matched to controls on birth and questionnaire date (1:4). Information on hormonal factors was obtained through questionnaires prior to sarcoidosis diagnosis. Multilevel modelling was used to estimate adjusted odds ratios with 95% credible intervals (OR; 95% CI). RESULTS: In total, 32 sarcoidosis cases and 124 controls were included. Higher sarcoidosis odds were associated with older age at menarche (OR 1.19: 95% CI 0.92-1.55), natural menopause versus non-natural (OR 1.53: 95% CI 0.80-2.93), later age at first pregnancy (OR 1.11: 95% CI 0.76-1.63) and ever hormone replacement therapy (HRT) use (OR 1.40: 95% CI 0.76-2.59). Lower odds were associated with older age at menopause (OR 0.90: 95% CI 0.52-1.55), longer duration of oral contraceptive use (OR 0.70: 95% CI 0.45-1.07), longer duration of HRT use (OR 0.61: 95% CI 0.22-1.70), ever local estrogen therapy (LET) use (OR 0.83: 95% CI 0.34-2.04) and longer duration of LET use (OR 0.78: 95% CI 0.21-2.81). However, the CIs could not rule out null associations. CONCLUSION: Given the inconsistency and modest magnitude in our estimates, and that the 95% credible intervals included one, it still remains unclear whether longer estrogen exposure is associated with reduced sarcoidosis risk.

Adult-onset inflammatory bowel disease and rate of serious infections compared to the general population: a nationwide register-based cohort study 2002-2017.

OBJECTIVES: To investigate absolute and relative risk of serious infections in adult/elderly inflammatory bowel disease (IBD) diagnosed 2002-2017. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Serious Infections in Pediatric Inflammatory Bowel Disease 2002-2017-A Nationwide Cohort Study.

OBJECTIVE: To assess absolute and relative risks of serious infections (resulting in inpatient care) in children with inflammatory bowel disease (IBD) compared with the general population. STUDY DESIGN: We identified children (<18 years of age) with a first diagnosis of IBD in the Swedish nationwide health registry (2002-2017; n = 5767) and individuals from the general population matched for sex, age, calendar year, and place of residence (reference group; n = 58 418). Hazard ratios (HRs) for serious infections were estimated using Cox regression separately in children with ulcerative colitis (n = 2287), Crohn's disease (n = 2365), and IBD unclassified (n = 1115). RESULTS: During 17 408 person-years of follow-up, 672 serious infections (38.6/1000 person-years) occurred among the children with IBD compared with 778 serious infections in the reference group (4.0/1000 person-years; adjusted HR (95% CI), 9.46 [8.53-10.5]). HRs were increased for children with ulcerative colitis 8.48 (7.21-9.98), Crohn's disease 9.30 (7.86-11.0), and IBD unclassified 12.1 (9.66-16.1). HRs were highest in the first year of follow-up (HR = 12.6 [10.7-14.9]), then decreasing to a 4.8-fold increased risk beyond 10 years of follow-up. Particularly high HRs were also seen in children with IBD undergoing surgery. Apart from a high relative risk of gastrointestinal infections resulting in hospitalization, children with IBD were also at an increased risk of opportunistic infections (HR = 11.8 [6.17-22.5]). CONCLUSIONS: Children with IBD have an increased risk of serious infection requiring hospitalization compared with the general population.

Hepatobiliary Cancer Risk in Patients with Inflammatory Bowel Disease: A Scandinavian Population-Based Cohort Study.

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among patients with IBD. METHODS: This Swedish/Danish population-based cohort study (1969-2017) followed patients with IBD and 1:10 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up. RESULTS: Among the 97,496 patients with ulcerative colitis/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths, and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall hazard ratios (HR) were 1.83 [95% confidence interval (CI), 1.41-2.38] for HCC-, 7.33 (95% CI, 5.81-9.25) for ICC-, and 4.46 (95% CI, 3.49-5.70) for ECC-deaths. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among patients with ulcerative colitis with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 patients with Crohn's disease (median follow-up 11 years), 10-year-mortality from HCC (n = 28), ICC (n = 28), and ECC (n = 24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95% CI, 1.31-2.93), 3.33 (95% CI, 2.19-5.09), and 3.10 (95% CI, 1.97-4.87). One of 28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC. CONCLUSIONS: Risk of HCC-, ICC-, and ECC-deaths was low in patients with IBD and decreased over time. However, a large proportion of deaths occurred after PSC. IMPACT: Guidelines on specific surveillance strategies for patients with IBD with PSC, but not those without PSC, are needed.

Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden.

OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD). DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs). RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32). CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

Drug survival of anti-TNF agents compared with vedolizumab as a second-line biological treatment in inflammatory bowel disease: results from nationwide Swedish registers.

BACKGROUND: Comparisons of second-line anti-tumour necrosis factor (TNF) agents and vedolizumab are sparse. AIM: To evaluate the effectiveness of anti-TNF agents compared to vedolizumab as second-line biologics in inflammatory bowel disease (IBD). METHODS: A propensity score-matched cohort was created using Swedish nationwide registers. Patients with Crohn's disease or ulcerative colitis, exposed to first-line anti-TNF treatment, who initiated a second anti-TNF agent or vedolizumab in 2014-2016 (N = 1363) were included. The primary outcome was drug survival at 12 months. Secondarily, we assessed survival without IBD-related hospitalisation, IBD-related surgery, antibiotics, or hospitalisation because of infection, and also corticosteroid exposure. RESULTS: After 1:1 propensity score matching, 400 patients (Crohn's disease, N = 198; ulcerative colitis, N = 202) remained. For Crohn's disease, drug survival was 73% in the vedolizumab group vs 74% in the anti-TNF group (difference: 1 percentage point; 95% confidence interval [CI]:-11-13; P = 0.87). Survival without IBD-related hospitalisation (82% vs 88%), surgery (82% vs 89%), antibiotics (65% vs 71%), hospitalisation due to infection (95% vs 88%) and corticosteroids (58% vs 48%) were not statistically significantly different between groups. For ulcerative colitis, drug survival was 69% in the vedolizumab group vs 62% in the anti-TNF group (difference: -7 percentage points; 95% CI: -20 to 6; P = 0.30). Vedolizumab-treated patients had lower survival without IBD-related hospitalisation (82% vs 93%, P = 0.02). Survival without colectomy (93% vs 97%), antibiotics (81% vs 70%), hospitalisation due to infection (92% vs 92%) and corticosteroids (58% vs 48%) were not statistically significantly different. CONCLUSIONS: Based on Swedish clinical practice, the effectiveness and safety of second-line anti-TNF and vedolizumab at 12 months appeared largely similar.

Inflammatory bowel disease and pancreatic cancer: a Scandinavian register-based cohort study 1969-2017.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of cancer. AIM: To assess the risk of pancreatic cancer in IBD compared to the general population. METHODS: Patients with incident IBD 1969-2017 were identified in Danish and Swedish National Patient Registers and through biopsy data, and were matched to IBD-free reference individuals by sex, age, place of residence and year of IBD diagnosis. We linked data to Cancer and Causes of Death Registers and examined the absolute and relative risks of pancreatic cancer and pancreatic cancer death. RESULTS: Among 161 926 patients followed for 2 000 951 person years, 442 (0.27%) were diagnosed with pancreatic cancer compared to 3386 (0.21%) of the 1 599 024 reference individuals. The 20-year cumulative incidence was 0.34% (95% confidence interval 0.30-0.38) vs 0.29% (0.28-0.30). The incidence rate was 22.1 (20.1-24.2)/100 000 person years in the patients (excluding the first year of follow-up: 20.8 [18.8-23.0]), and 16.6 (16.0-17.2) in the reference individuals. The hazard ratio (HR) for pancreatic cancer was increased overall: 1.43 (1.30-1.58), in subtypes (Crohn's disease: 1.44 [1.18-1.74]; ulcerative colitis: 1.35 [1.19-1.53]; IBD unclassified: 1.99 [1.50-2.64]) and especially in IBD patients with primary sclerosing cholangitis: 7.55 (4.94-11.5). Patients and reference individuals with pancreatic cancer did not differ in cancer stage (P = 0.17) or pancreatic cancer mortality (HR 1.07 [0.95-1.21]). CONCLUSIONS: Patients with IBD had an excess risk of pancreatic cancer, in particular patients with primary sclerosing cholangitis. However, the cumulative incidence difference after 20 years was small: 0.05%, that is, one extra pancreatic cancer per 2000 IBD patients.

Vagotomy and subsequent risk of inflammatory bowel disease: a nationwide register-based matched cohort study.

BACKGROUND: The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti-inflammatory properties. AIMS: To explore the relationship between vagotomy and the risk of inflammatory bowel disease (IBD) and its major categories: Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A matched cohort comprising 15 637 patients undergoing vagotomy was identified through the Swedish Patient Register from 1964 to 2010. Each vagotomised patient was matched for birth year and gender with 40 nonvagotomised individuals on the date of vagotomy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD using flexible parametric models adjusted for matching variables, year of vagotomy, birth country, chronic obstructive pulmonary disease and comorbidity index. RESULTS: We observed 119 (0.8%) patients with vagotomy developed IBD compared to 3377 (0.5%) IBD cases in nonvagotomised individuals. The crude incidence of IBD (per 1000 person-years) was 0.38 for vagotomised patients and 0.25 for nonvagotomised individuals. We observed a time-dependent elevated risk of IBD associated with vagotomy, for instance, the HR (95% CI) was 1.80 (1.40-2.31) at year 5 and 1.49 (1.14-1.96) at year 10 post-vagotomy. The association appeared to be stronger for truncal than selective vagotomy and limited to CD (HR was 3.63 [1.94-6.80] for truncal and 2.06 [1.49-2.84] for selective vagotomy) but not UC (1.36 [0.71-2.62] for truncal and 1.25 [0.95-1.63] for selective vagotomy). CONCLUSIONS: We found a positive association between vagotomy and later IBD, particularly for CD. The finding indirectly underlines the beneficial role of the vagal tone in IBD.

Work Loss in Relation to Pharmacological and Surgical Treatment for Crohn's Disease: A Population-Based Cohort Study.

PURPOSE: Patients with Crohn's disease have increased work loss. We aimed to describe changes in work ability in relation to pharmacological and surgical treatments. PATIENTS AND METHODS: We linked data from the Swedish National Patient Register, The Swedish Quality Register for Inflammatory Bowel Disease SWIBREG, The Prescribed Drug Register, The Longitudinal Integrated Database for Health Insurance and Labour Market Studies, and the Social Insurance Database. We identified working-age (19-59 years) patients with incident Crohn's disease 2006-2013 and population comparator subjects matched by sex, birth year, region, and education level. We assessed the number of lost workdays due to sick leave and disability pension before and after treatments. RESULTS: Of 3956 patients (median age 34 years, 51% women), 39% were treated with aminosalicylates, 52% with immunomodulators, 22% with TNF inhibitors, and 18% with intestinal surgery during a median follow-up of 5.3 years. Most patients had no work loss during the study period (median=0 days). For all treatments, the mean number of lost workdays increased during the months before treatment initiation, peaked during the first month of treatment and decreased thereafter, and was heavily influenced by sociodemographic factors and amount of work loss before first Crohn's disease diagnosis. The mean increase in work loss days compared to pre-therapeutic level was ~3 days during the first month of treatment for all pharmacological therapies and 11 days for intestinal surgery. Three months after treatment initiation, 88% of patients treated surgically and 90-92% of patients treated pharmacologically had the same amount of work loss as before treatment start. Median time to return to work was 2 months for all treatments. CONCLUSION: In this regular clinical setting, patients treated surgically had more lost workdays than patients treated pharmacologically, but return to work was similar between all treatments.