Adolescent Cardiorespiratory Fitness and Risk of Cancer in Late Adulthood: Nationwide Sibling-Controlled Cohort Study.

Objective: To investigate whether the higher risks of certain cancers associated with high cardiorespiratory fitness can be explained by increased detection and unobserved confounders. Design: Nationwide sibling-controlled cohort study of adolescents. Setting: Sweden. Participants: 1 124 049 men of which 477 453 were full siblings, who underwent mandatory military conscription examinations between 1972 and 1995 at a mean age of 18.3 years. Main outcome measures: Hazard ratios (HR) and 95% confidence intervals (CI) of overall cancer diagnosis and cancer mortality, and 14 site-specific cancers (diagnosis or death), as recorded in the Swedish National Patient Register or Cause of Death Register until 31 December 2023, modelled using flexible parametric regressions. Results: Participants were followed until a median (maximum) age of 55.9 (73.5) years, during which 98 410 were diagnosed with cancer and 16 789 had a cancer-related death (41 293 and 6908 among full siblings respectively). The most common cancers were non-melanoma skin (27 105 diagnoses & 227 deaths) and prostate cancer (24 211 diagnoses & 869 deaths). In cohort analysis, those in the highest quartile of cardiorespiratory fitness had a higher risk of prostate (adjusted HR 1.10; 95% CI: 1.05 to 1.16) and skin cancer (e.g., non-melanoma HR 1.44; 1.37 to 1.50) compared to those in the lowest quartile, which led to a higher risk of any type of cancer diagnosis (HR 1.08; 1.06 to 1.11). However, those in the highest quartile had a lower risk of cancer mortality (HR 0.71; 0.67 to 0.76). When comparing full siblings, and thereby controlling for all behavioural, environmental, and genetic factors they share, the excess risk of prostate (HR 1.01; 0.90 to 1.13) and skin cancer (e.g., non-melanoma HR 1.09; 0.99 to 1.20) attenuated to the null. In contrast, the lower risk of overall cancer mortality was still statistically significant after control for such shared confounders (HR 0.78; 0.68 to 0.89). For other site-specific cancers, the influence of such confounding tended to vary, but none showed the same excess risk as prostate and non-melanoma skin cancer. Conclusions: The association between high levels of adolescent cardiorespiratory fitness and excess risk of some cancers, such as prostate and non-melanoma skin cancer, appears to be fully explained by unobserved confounders shared between full siblings. However, the protective association with cancer mortality persists even after control for such confounding. Summary box: What is already known on this topic Adolescent physical activity and cardiorespiratory fitness are considered important factors for the prevention of cancer based on evidence from observational studies.Observational studies are, however, vulnerable to unobserved confounders and bias processes, including health-seeking behaviours and genetic and environmental confounders.These biases could explain why prior studies have found that high adolescent cardiorespiratory fitness is associated with higher risks of some cancers, typically low-mortality cancers such as prostate and non-melanoma skin cancer. What this study adds This nationwide cohort study of 1.1 million male adolescents showed that while higher cardiorespiratory fitness was associated with excess risk of the most common cancers - prostate and non-melanoma skin - these associations attenuated to the null when accounting for behavioural, environmental, and genetic confounders shared between full siblings.In contrast, high adolescent cardiorespiratory fitness was associated with a lower risk of overall cancer mortality, which remained after controlling for unobserved confounders shared between full siblings.

Long-term prescribed drug use in stage I-III rectal cancer patients in Sweden, with a focus on bowel-regulating drugs after surgical and oncological treatment.

PURPOSE: To describe long-term prescribed drug use after rectal cancer treatment. METHODS: We identified 12,871 rectal cancer patients without distant metastasis between 2005 and 2016 and 64,341 matched population comparators using CRCBaSe (a Swedish nationwide register linkage of colorectal cancer patients). Mean defined daily doses (DDDs) of drug dispensing during relapse-free follow-up were calculated by Anatomical Therapeutic Chemical drug categories. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) from negative binomial regression were used to compare drug dispensing between patients and comparators. RESULTS: The overall pattern of drug dispensing was similar among cancer survivors and comparators, although patients had higher mean DDDs of drugs regulating the digestive system. Excess dispensing of drugs for constipation (IRR, 3.35; 95% CI, 3.12-3.61), diarrhea (IRR, 6.43; 95% CI, 5.72-7.22), functional gastrointestinal disorders (IRR, 3.78; 95% CI, 3.15-4.54), and vitamin and mineral supplements (IRR, 1.37; 95% CI, 1.24-1.50) was observed up to 10 years after surgery. Treatment with Hartmann's procedure was associated with higher dispensing rates of digestive drugs compared to surgery with anterior resection and abdominoperineal resection but the association was attributed to higher use of diabetic drugs. Additionally, excess digestive drug dispensing was associated with more advanced cancer stage but not with (chemo)radiotherapy treatment. CONCLUSIONS: Excess drug use after rectal cancer is primarily driven by bowel-regulating drugs and is not modified by surgical or oncological treatment. IMPLICATIONS FOR CANCER SURVIVORS: The excess use of bowel-regulating drugs after rectal cancer indicated long-standing postsurgical gastrointestinal morbidity and need of prophylaxis. Reassuringly, no excess use of other drug classes was noted long term.

Comparison of Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass: A Randomized Clinical Trial.

Importance: Laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) are widely used bariatric procedures for which comparative efficacy and safety remain unclear. Objective: To compare perioperative outcomes in SG and RYGB. Design, Setting, and Participants: In this registry-based, multicenter randomized clinical trial (Bypass Equipoise Sleeve Trial), baseline and perioperative data for patients undergoing bariatric surgery from October 6, 2015, to March 31, 2022, were analyzed. Patients were from university, regional, county, and private hospitals in Sweden (n = 20) and Norway (n = 3). Adults (aged ≥18 years) eligible for bariatric surgery with body mass indexes (BMIs; calculated as weight in kilograms divided by height in meters squared) of 35 to 50 were studied. Interventions: Laparoscopic SG or RYGB. Main Outcomes and Measures: Perioperative complications were analyzed as all adverse events and serious adverse events (Clavien-Dindo grade >IIIb). Ninety-day mortality was also assessed. Results: A total of 1735 of 14 182 eligible patients (12%; 1282 [73.9%] female; mean (SD) age, 42.9 [11.1] years; mean [SD] BMI, 40.8 [3.7]) were included in the study. Patients were randomized and underwent SG (n = 878) or RYGB (n = 857). The mean (SD) operating time was shorter in those undergoing SG vs RYGB (47 [18] vs 68 [25] minutes; P < .001). The median (IQR) postoperative hospital stay was 1 (1-1) day in both groups. The 30-day readmission rate was 3.1% after SG and 4.0% after RYGB (P = .33). There was no 90-day mortality. The 30-day incidence of any adverse event was 40 (4.6%) and 54 (6.3%) in the SG and RYGB groups, respectively (odds ratio, 0.71; 95% CI, 0.47-1.08; P = .11). Corresponding figures for serious adverse events were 15 (1.7%) for the SG group and 23 (2.7%) for the RYGB group (odds ratio, 0.63; 95% CI, 0.33-1.22; P = .19). Conclusions and Relevance: This randomized clinical trial of 1735 patients undergoing primary bariatric surgery found that both SG and RYGB were performed with a low perioperative risk without clinically significant differences between groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02767505.

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

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

Pregnancy Weight Gain After Gastric Bypass or Sleeve Gastrectomy.

Importance: Pregnancy weight gain may affect the association of bariatric surgery with postsurgery pregnancy outcomes. However, the association of pregnancy weight gain with bariatric surgery is unclear. Objective: To compare pregnancy weight gain among women with a history of bariatric surgery vs those without and to investigate whether pregnancy weight gain differs by surgical procedure, surgery-to-conception interval, and/or surgery-to-conception weight loss. Design, Setting, and Participants: This nationwide, population-based matched cohort study was conducted in Sweden from 2014 to 2021. Singleton pregnancies with a history of bariatric surgery were propensity score matched (1:1) to pregnancies without such a history according to early-pregnancy body mass index (BMI), prepregnancy diabetes, prepregnancy hypertension, maternal age, smoking status, education level, height, country of birth, and delivery year. In addition, post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy. Data analysis was performed from November 2022 to May 2023. Exposure: History of bariatric surgery. Main Outcomes and Measures: Pregnancy weight gain was standardized by gestational age into early-pregnancy BMI-specific z scores. Results: This study included 12 776 pregnancies, of which 6388 had a history of bariatric surgery and 6388 were matched controls. The mean (SD) age was 31.6 (4.9) years for the surgery group and 31.4 (5.2) for the matched controls, with an early-pregnancy mean (SD) BMI of 29.4 (5.2) in both groups. Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls. The differences in pregnancy weight gain z score values between the 2 groups were -0.33 (95% CI, -0.43 to -0.23) for normal weight, -0.33 (95% CI, -0.40 to -0.27) for overweight, -0.21 (95% CI, -0.29 to -0.13) for obese class I, -0.16 (95% CI, -0.29 to -0.03) for obese class II, and -0.08 (95% CI, -0.28 to 0.13) for obese class III. Pregnancy weight gain did not differ by surgical procedure. A shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss was associated with lower pregnancy weight gain. Conclusions and Relevance: In this nationwide matched cohort study, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls with similar early-pregnancy characteristics. Pregnancy weight gain was lower in those with a shorter surgery-to-conception interval or lower surgery-to-conception weight loss, but did not differ by surgical procedure.

Increasing healthcare costs in inflammatory bowel disease 2007-2020 in Sweden.

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

Earnings and work loss from 5 years before to 5 years after bariatric surgery: A cohort study.

BACKGROUND: The personal economic impact of bariatric surgery is not well-described. OBJECTIVES: To examine earnings and work loss from 5 years before to 5 years after bariatric surgery compared with the general population. SETTING: Nationwide matched cohort study in the Swedish health care system. METHODS: Patients undergoing primary bariatric surgery (n = 15,828) and an equal number of comparators from the Swedish general population were identified and matched on age, sex, place of residence, and educational level. Annual taxable earnings (primary outcome) and annual work loss (secondary outcome combining months with sick leave and disability pension) were retrieved from Statistics Sweden. Participants were included in the analysis until the year of study end, emigration or death. RESULTS: From 5 years before to 5 years after bariatric surgery, earnings increased for patients overall and in subgroups defined by education level and sex, while work loss remained relatively constant. Bariatric patients and matched comparators from the general population increased their earnings in a near parallel fashion, from 5 years before (mean difference -$3,489 [95%CI -3,918 to -3,060]) to 5 years after surgery (-$4,164 [-4,709 to -3,619]). Work loss was relatively stable within both groups but with large absolute differences both at 5 years before (1.09 months, [95%CI 1.01 to 1.17]) and 5 years after surgery (1.25 months, [1.11 to 1.40]). CONCLUSIONS: Five years after treatment, bariatric surgery had not reduced the gap in earnings and work loss between surgery patients and matched comparators from the general population.

Metabolic and bariatric surgery versus intensive non-surgical treatment for adolescents with severe obesity (AMOS2): a multicentre, randomised, controlled trial in Sweden.

BACKGROUND: Severe obesity in adolescents has a profound impact on current and future health. Metabolic and bariatric surgery (MBS) is increasingly used in adolescents internationally. However, to our knowledge, there are no randomised trials examining the currently most used surgical techniques. Our aim was to evaluate changes in BMI and secondary health and safety outcomes after MBS. METHODS: The Adolescent Morbid Obesity Surgery 2 (AMOS2) study is a randomised, open-label, multicentre trial done at three university hospitals in Sweden (located in Stockholm, Gothenburg, and Malmö). Adolescents aged 13-16 years with a BMI of at least 35 kg/m2, who had attended treatment for obesity for at least 1 year, passed assessments from a paediatric psychologist and a paediatrician, and had a Tanner pubertal stage of at least 3, were randomly assigned (1:1) to MBS or intensive non-surgical treatment. Exclusion criteria included monogenic or syndromic obesity, major psychiatric illness, and regular self-induced vomiting. Computerised randomisation was stratified for sex and recruitment site. Allocation was concealed for both staff and participants until the end of the inclusion day, and then all participants were unmasked to treatment intervention. One group underwent MBS (primarily gastric bypass), while the other group received intensive non-surgical treatment starting with 8 weeks of low-calorie diet. The primary outcome was 2-year change in BMI, analysed as intention-to-treat. The trial is registered at ClinicalTrials.gov, NCT02378259. FINDINGS: 500 people were assessed for eligibility between Aug 27, 2014, and June 7, 2017. 450 participants were excluded (397 did not meet inclusion criteria, 39 declined to participate, and 14 were excluded for various other reasons). Of the 50 remaining participants, 25 (19 females and six males) were randomly assigned to receive MBS and 25 (18 females and seven males) were assigned to intensive non-surgical treatment. Three participants (6%; one in the MBS group and two in the intensive non-surgical treatment group) did not participate in the 2-year follow-up, and in total 47 (94%) participants were assessed for the primary endpoint. Mean age of participants was 15·8 years (SD 0·9) and mean BMI at baseline was 42·6 kg/m2 (SD 5·2). After 2 years, BMI change was -12·6 kg/m2 (-35·9 kg; n=24) among adolescents undergoing MBS (Roux-en-Y gastric bypass [n=23], sleeve gastrectomy [n=2]) and -0·2 kg/m2 (0·4 kg; [n=23]) among participants in the intensive non-surgical treatment group (mean difference -12·4 kg/m2 [95% CI -15·5 to -9·3]; p<0·0001). Five (20%) patients in the intensive non-surgical group crossed over to MBS during the second year. Adverse events (n=4) after MBS were mild but included one cholecystectomy. Regarding safety outcomes, surgical patients had a reduction in bone mineral density, while controls were unchanged after 2 years (z-score change mean difference -0·9 [95% CI -1·2 to -0·6]). There were no significant differences between the groups in vitamin and mineral levels, gastrointestinal symptoms (except less reflux in the surgical group), or in mental health at the 2-year follow-up. INTERPRETATION: MBS is an effective and well tolerated treatment for adolescents with severe obesity resulting in substantial weight loss and improvements in several aspects of metabolic health and physical quality of life over 2 years, and should be considered in adolescents with severe obesity. FUNDING: Sweden's Innovation Agency, Swedish Research Council Health.

Opioid Use After Gastric Bypass, Sleeve Gastrectomy or Intensive Lifestyle Intervention.

OBJECTIVE: To compare opioid use in patients with obesity treated with bariatric surgery versus adults with obesity who underwent intensive lifestyle modification. SUMMARY OF BACKGROUND DATA: Previous studies of opioid use after bariatric surgery have been limited by small sample sizes, short follow-up, and lack of control groups. METHODS: Nationwide matched cohort study including individuals from the Scandinavian Obesity Surgery Registry and the Itrim health database with individuals undergoing structured intensive lifestyle modification, between August 1, 2007 and September 30, 2015. Participants were matched on Body Mass Index, age, sex, education, previous opioid use, diabetes, cardiovascular disease, and psychiatric status (n = 30,359:21,356). Dispensed opioids were retrieved from the Swedish Prescribed Drug Register from 2 years before to up to 8 years after intervention. RESULTS: During the 2-year period before treatment, prevalence of individuals receiving ≥1 opioid prescription was identical in the surgery and lifestyle group. At 3 years, the prevalence of opioid prescriptions was 14.7% versus 8.9% in the surgery and lifestyle groups (mean difference 5.9%, 95% confidence interval 5.3-6.4) and at 8 years 16.9% versus 9.0% (7.9%, 6.8-9.0). The difference in mean daily dose also increased over time and was 3.55 mg in the surgery group versus 1.17 mg in the lifestyle group at 8 years (mean difference [adjusted for baseline dose] 2.30 mg, 95% confidence interval 1.61-2.98). CONCLUSIONS: Bariatric surgery was associated with a higher proportion of opioid users and larger total opioid dose, compared to actively treated obese individuals. These trends were especially evident in patients who received additional surgery during follow-up.

Comparison of Sleeve Gastrectomy vs Intensive Lifestyle Modification in Patients With a BMI of 30 to Less Than 35.

Importance: There is a lack of studies evaluating sleeve gastrectomy compared with intensive lifestyle treatment in patients with class 1 obesity (body mass index [BMI] 30 to <35 [calculated as weight in kilograms divided by height in meters squared]). Objective: To compare outcomes and safety of sleeve gastrectomy compared with intensive nonoperative obesity treatment in patients with class 1 obesity. Design, Setting, and Participants: This matched, nationwide cohort study included patients with class 1 obesity who underwent a sleeve gastrectomy or intensive lifestyle treatment between January 1, 2012, and December 31, 2017, and who were registered in the Scandinavian Obesity Surgery Registry or the Itrim health database. Participants with class 1 obesity were matched 1:2 using a propensity score including age, sex, BMI, treatment year, education level, income, cardiovascular disease, and use of antibiotic drugs, antidepressants, and anxiolytics. Interventions: Sleeve gastrectomy or intensive lifestyle treatment. Main Outcomes and Measures: Outcomes included weight loss after intervention, changes in metabolic comorbidities, substance use disorders, self-harm, and major cardiovascular events retrieved from the National Patient Register, Prescribed Drug Register, and Cause of Death Register as well as the Scandinavian Obesity Surgery Registry and the Itrim health database. Data were analyzed from December 1, 2021 until May 31, 2022. Results: The study included 1216 surgery patients and 2432 lifestyle participants with similar mean (SD) BMI (32.8 [1.4] vs 32.9 [1.4]), mean (SD) age (42.4 [9.7] vs 42.6 [12.7] years), and sex (1091 [89.7%] vs 2191 [90.1%] women). Surgery patients had greater 1-year weight loss compared with controls (22.9 kg vs 11.9 kg; mean difference, 10.7 kg; 95% CI, 10.0-11.5 kg; P < .001). Over a median follow-up of 5.1 years (IQR, 3.9-6.2 years), surgery patients had a lower risk of incident use of diabetes drugs (59.7 vs 100.4 events per 10 000 person-years; hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02) and greater 2-year diabetes drug remission (48.4% vs 22.0%; risk difference 26.4%; 95% CI, 11.7%-41.0%; P < .001), but higher risk for substance use disorder (94 vs 50 events per 10 000 person-years; HR, 1.86; 95% CI, 1.30-2.67; P < .001) and self-harm (45 vs 25 events per 10 000 person-years; HR, 1.81; 95% CI, 1.09-3.01; P = .02). No between-group difference in occurrence of major cardiovascular events was observed (23.4 vs 24.8 events per 10 000 person-years; HR, 0.96; 95% CI, 0.49-1.91; P = .92). Conclusions and Relevance: In this cohort study, compared with intensive nonoperative obesity treatment, sleeve gastrectomy in patients with class 1 obesity was associated with greater weight loss, diabetes prevention, and diabetes remission but a higher incidence of substance use disorder and self-harm.

Pooled analysis of all-cause and cause-specific mortality among Nordic military veterans following international deployment.

OBJECTIVES: To investigate all-cause and cause-specific mortality risks, including deaths from external, cardiovascular and cancer causes, among deployed Nordic military veterans in comparison to the general population in each country. DESIGN: Pooled analysis. SETTING: Denmark, Norway, Finland and Sweden. PARTICIPANTS: Military veterans deployed between 1990 and 2010 were followed via nationwide registers and compared with age-sex-calendar-year-specific rates in the general population using pooled standardised mortality ratios (SMRs). MAIN OUTCOMES: All-cause and cause-specific mortality retrieved from each country's Causes of Death Register, including deaths from external, cardiovascular and cancer causes. RESULTS: Among 83 584 veterans 1152 deaths occurred of which 343 were from external causes (including 203 suicides and 129 traffic/transport accidents), 134 from cardiovascular causes and 297 from neoplasms. Veterans had a lower risk of death from any cause (pooled SMR 0.58, 95% CI 0.52 to 0.64), external causes (0.71, 95% CI 0.64 to 0.79), suicide (0.77, 95% CI 0.67 to 0.89), cardiovascular causes (0.54, 95% CI 0.46 to 0.64) and neoplasms (0.78, 95% CI 0.70 to 0.88). There was no difference regarding traffic/transport accidents for the whole period (1.10, 95% CI 0.92 to 1.31) but the pooled point estimate was elevated, though not statistically significant, during the first 5 years (1.17, 95% CI 0.89 to 1.53) but not thereafter (1.01, 95% CI 0.77 to 1.34). For all other causes of death, except suicide, statistically significantly lower risk among veterans was observed both during the first 5 years and thereafter. For suicide, no difference was observed beyond 5 years. Judged from the country-specific SMR estimates, there was a high degree of consistency although statistically significant heterogeneity was found for all-cause mortality. CONCLUSIONS: Nordic military veterans had lower overall and cause-specific mortality than the general population for most outcomes, as expected given the predeployment selection process. Though uncommon, fatal traffic/transport accidents were an exception with no difference between deployed military veterans and the general population.

Work Loss in Patients With Celiac Disease: A Population-based Longitudinal Study.

BACKGROUND & AIMS: Celiac disease (CD) affects around 1% of the population worldwide. Data on work disability in patients with CD remain scarce. We estimated work loss in patients with CD, including its temporal relationship to diagnosis. METHODS: Through biopsy reports from Sweden's 28 pathology departments, we identified 16,005 working-aged patients with prevalent CD (villus atrophy) as of January 1, 2015, and 4936 incident patients diagnosed with CD in 2008 to 2015. Each patient was matched to up to 5 general-population comparators. Using nationwide social insurance registers, we retrieved prospectively recorded data on compensation for sick leave and disability leave to assess work loss in patients and comparators. RESULTS: In 2015, patients with prevalent CD had a mean of 42.5 lost work days as compared with 28.6 in comparators (mean difference, 14.7; 95% confidence interval [CI], 13.2-16.2), corresponding to a relative increase of 49%. More than one-half of the work loss (60.1%) in patients with CD was derived from a small subgroup (7%), whereas 75.4% had no work loss. Among incident patients, the annual mean difference between patients and comparators was 8.0 days (range, 5.4-10.6 days) of lost work 5 years before CD diagnosis, which grew to 13.7 days (range, 9.1-18.3 days) 5 years after diagnosis. No difference in work loss was observed between patients with or without mucosal healing at follow-up. CONCLUSIONS: Patients with CD lost more work days than comparators before their diagnosis, and this loss increased after diagnosis. Identifying patients with an increased risk of work loss may serve as a target to mitigate work disability, and thereby reduce work loss, in patients with CD.

Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates.

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.

Long-term risk of anaemia after bariatric surgery: results from the Swedish Obese Subjects study.

BACKGROUND: Nutritional deficiencies, such as iron and vitamin B12 deficiencies, are potential adverse consequences of bariatric surgery. Long-term data on anaemia after bariatric surgery are largely lacking. We aimed to investigate the risk of anaemia, iron and vitamin B12 deficiency anaemia, and vitamin B12 deficiency over 20 years in individuals who had bariatric surgery or received usual obesity care. METHODS: The prospective, controlled Swedish Obese Subjects study recruited people with obesity via recruitment campaigns in the mass media and at primary health-care centres, and was done at 480 primary health-care centres and in 25 surgical departments in Sweden. Eligible participants were aged 37-60 years and had a BMI of either 34 kg/m2 or more (for men) or 38 kg/m2 or more (for women). Participants were excluded if they had undergone previous bariatric surgery or had contraindicating conditions. Two main groups were formed: those who chose bariatric surgery, the type of which was determined by the operating surgeon, and a contemporaneously matched control group, created by use of 18 matching variables, who received usual non-surgical obesity care that ranged from lifestyle advice to no treatment. Haemoglobin concentration was measured during examination visits at baseline and at 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years of follow-up. Anaemia was defined as a haemoglobin concentration of less than 120 g/L for women and 130 g/L for men. The primary, non-specified outcome was the incidence of anaemia, and was assessed in the as-treated population, which comprised only patients who received the actual treatment. The associations between treatment type and anaemia are expressed as unadjusted hazard ratios (HRs) and HRs adjusted for age, sex, BMI, menopausal status, education, diabetes, and hypertension, with 95% CIs. This study is registered in ClinicalTrials.gov, NCT01479452, and is closed to new participants, with follow-up ongoing. FINDINGS: Between Sept 1, 1987, and Jan 31, 2001, 6905 individuals were assessed for eligibility, of whom 5335 were eligible. Of these, we included 2007 patients who chose bariatric surgery (266 in the gastric bypass group, 1365 in the vertical-banded gastroplasty group, and 376 in the gastric banding group) and 2040 matched controls who received usual obesity care. During a maximum of 20 years and a median of 10 years (IQR 3-20) of follow-up, there were 133 anaemia events in the gastric bypass group, 359 in the vertical-banded gastroplasty group, 101 in the gastric banding group, and 261 in the control group. Compared with the control group (13 cases per 1000 person-years, 95% CI 11-14), the incidence of anaemia was higher in the gastric bypass group (64 cases per 1000 person-years, 53-74; HR 5·05, 95% CI 3·94-6·48; p<0·0001), the vertical-banded gastroplasty group (23 cases per 1000 person-years, 21-26; 2·67, 2·25-3·18; p<0·0001), and the gastric banding group (26 per 1000 person-years, 21-31; 2·76, 2·15-3·52; p<0·0001). These associations remained after adjustment. INTERPRETATION: Our findings highlight the increased risk of anaemia after bariatric surgery and the importance of long-term compliance to nutritional supplementation and monitoring to enable prevention and early detection of serious nutritional deficiencies after bariatric surgery. FUNDING: Swedish Research Council, the Swedish state under the agreement between the Swedish Government and the county councils, the Swedish Diabetes Foundation, the Swedish Heart-Lung Foundation, and the Novo Nordisk Foundation.

Earnings and employment for women after bariatric surgery: a matched cohort study.

BACKGROUND/OBJECTIVES: Bariatric surgery induces durable weight loss and improves health and quality of life. Less is known about how bariatric surgery affects labour market outcomes. This study examined the development of earnings and employment status among women with obesity who underwent bariatric surgery versus matched comparators. SUBJECTS/METHODS: This study included two cohorts of women in Sweden who gave birth between 1992 and 2014: a cohort with bariatric patients and their full sisters (sister cohort) and a cohort with bariatric patients and comparators matched on BMI, education, birth year, and previous cardiovascular, psychiatric, and musculoskeletal inpatient care diagnoses (BMI-matched cohort). Taxable annual earnings were retrieved from the Swedish Income Tax Register from 2 years before to 5 years after surgery. Employment status was measured dichotomously (employed/not employed) based on earnings data. Adjusted mean and prevalence differences were estimated for earnings and employment by ordinary least squares regression. RESULTS: The sister cohort included 1400 patient-sister pairs. At baseline, patients and their sisters were of similar age (38.3 vs. 38.6 years) but had different BMI (37.3 vs. 26.7 kg/m2). The BMI-matched cohort included 2967 patient-comparator pairs with similar age (36.1 vs. 36.2 years) and BMI (37.1 vs. 37.0 kg/m2) before surgery. During follow-up, similar developments of earnings and employment status were observed between bariatric patients and the comparators in both cohorts. When comparing absolute levels of earnings in the sister cohort, the difference in earnings at 2 years before surgery [mean difference -$4137 (95% CI -5245 to -3028)] was similar to the difference in earnings at 5 years after surgery [-$5620 (-7024 to -4215)]. Similar results were found in the BMI-matched cohort, but of smaller magnitude. CONCLUSIONS: Bariatric surgery had little influence on the development of annual earnings and employment for women with obesity in Sweden over 5 years after surgery.

Healthcare use, work loss and total costs in incident and prevalent Crohn's disease and ulcerative colitis: results from a nationwide study in Sweden.

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

Costs and Use of Health Care in Patients With Celiac Disease: A Population-Based Longitudinal Study.

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

Adult height in patients with childhood-onset inflammatory bowel disease: a nationwide population-based cohort study.

BACKGROUND: Growth retardation is well described in childhood-onset inflammatory bowel disease (IBD). AIMS: To study if childhood-onset IBD is associated with reduced final adult height. METHODS: We identified 4201 individuals diagnosed with childhood-onset IBD 1990-2014 (Crohn's disease: n = 1640; ulcerative colitis: n = 2201 and IBD-unclassified = 360) in the Swedish National Patient Register. RESULTS: Patients with IBD attained a lower adult height compared to reference individuals (adjusted mean height difference [AMHD] -0.9 cm [95% CI -1.1 to -0.7]) and to their healthy siblings (AMHD -0.8 cm [-1.0 to -0.6]). Patients with Crohn's disease (CD) were slightly shorter than patients with ulcerative colitis (UC; -1.3 cm vs -0.6 cm). Lower adult height was more often seen in patients with pre-pubertal disease onset (AMHD -1.6 cm [-2.0 to -1.2]), and in patients with a more severe disease course (AMHD -1.9 cm, [-2.4 to -1.4]). Some 5.0% of CD and 4.3% of UC patients were classified as growth retarded vs 2.5% of matched reference individuals (OR 2.42 [95% CI 1.85-3.17] and 1.74 [1.36-2.22] respectively). CONCLUSION: Patients with childhood-onset IBD on average attain a slightly lower adult height than their healthy peers. Adult height was more reduced in patients with pre-pubertal onset of disease and in those with a more severe disease course.

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.