Risk of pre-eclampsia after gastric bypass: a matched cohort study.

OBJECTIVE: To investigate whether gastric bypass before pregnancy is associated with reduced risk of pre-eclampsia. DESIGN: Nationwide matched cohort study. SETTING: Swedish national health care. POPULATION: A total of 843 667 singleton pregnancies without pre-pregnancy hypertension were identified in the Swedish Medical Birth Register between 2007 and 2014, of which 2930 had a history of gastric bypass and a pre-surgery weight available from the Scandinavian Obesity Surgery Registry. Two matched control groups (pre-surgery and early-pregnancy body mass index [BMI]) were propensity score matched separately for nulliparous and parous births, to post-gastric bypass pregnancies (npre-surgery-BMI = 2634:2634/nearly-pregnancy-BMI = 2766:2766) on pre-surgery/early-pregnancy BMI, diabetes status (pre-surgery/pre-conception), maternal age, early-pregnancy smoking status, educational level, height, country of birth, delivery year and history of pre-eclampsia. MAIN OUTCOME MEASURES: Pre-eclampsia categorised into any, preterm onset (<37+0 weeks) and term onset (≥37+0 weeks). RESULTS: In post-gastric bypass pregnancies, mean pre-surgery BMI was 42.9 kg/m2 and mean BMI loss between surgery and early pregnancy was 14.0 kg/m2 (39 kg). Post-gastric bypass pregnancies had lower risk of pre-eclampsia compared with pre-surgery BMI-matched controls (1.7 versus 9.7 per 100 pregnancies; hazard ratio [HR] 0.21, 95% CI 0.15-0.28) and early-pregnancy BMI-matched controls (1.9 versus 5.0 per 100 pregnancies; HR 0.44, 95% CI 0.33-0.60). Although relative risks for pre-eclampsia for post-gastric bypass pregnancies versus pre-surgery matched controls was similar, absolute risk differences (RD) were significantly greater for nulliparous women (RD -13.6 per 100 pregnancies, 95% CI -16.1 to -11.2) versus parous women (RD -4.4 per 100 pregnancies, 95% CI -5.7 to -3.1). CONCLUSION: We found that gastric bypass was associated with lower risk of pre-eclampsia, with the largest absolute risk reduction among nulliparous women. TWEETABLE ABSTRACT: In this large study including two comparison groups matched for pre-surgery or early-pregnancy BMI, gastric bypass was associated with lower risk of pre-eclampsia.

SARS-CoV-2 and pregnancy outcomes under universal and non-universal testing in Sweden: register-based nationwide cohort study.

OBJECTIVE: To assess associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes considering testing policy and test-positivity-to-delivery interval. DESIGN: Nationwide cohort study. SETTING: Sweden. POPULATION: From the Pregnancy-Register we identified 88 593 singleton births, 11 March 2020-31 January 2021, linked to data on SARS-CoV-2-positivity from the Public Health Agency, and information on neonatal care admission from the Neonatal Quality Register. Adjusted odds ratios (aORs) were estimated stratified by testing-policy and test-positivity-to-delivery interval. MAIN OUTCOME MEASURES: Five-minute Apgar score, neonatal care admission, stillbirth and preterm birth. RESULTS: During pregnancy, SARS-CoV-2 test-positivity was 5.4% (794/14 665) under universal testing and 1.9% (1402/73 928) under non-universal testing. There were generally lower risks associated with SARS-CoV-2 under universal than non-universal testing. In women testing positive >10 days from delivery, generally no significant differences in risk were observed under either testing policy. Neonatal care admission was more common (15.3% versus 8.0%; aOR 2.24, 95% CI 1.62-3.11) in women testing positive ≤10 days before delivery under universal testing. There was no significant association with 5-minute Apgar score below 7 (1.0% versus 1.7%; aOR 0.64, 95% CI 0.24-1.72) or stillbirth (0.3% versus 0.4%; aOR 0.72, 95% CI 0.10-5.20). Compared with term births (2.1%), test-positivity was higher in medically indicated preterm birth (5.7%; aOR 2.70, 95% CI 1.60-4.58) but not significantly increased in spontaneous preterm birth (2.3%; aOR 1.12, 95% CI 0.62-2.02). CONCLUSIONS: Testing policy and timing of test-positivity impact associations between SARS-CoV-2-positivity and pregnancy outcomes. Under non-universal testing, women with complications near delivery are more likely to be tested than women without complications, thereby inflating any association with adverse pregnancy outcomes compared with findings under universal testing. TWEETABLE ABSTRACT: Testing policy and time from SARS-CoV-2 infection to delivery influence the association with pregnancy outcomes.

Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men.

BACKGROUND: Whilst tall stature has been related to lower risk of vascular disease, it has been proposed as a risk factor for atrial fibrillation. Little is known about other anthropometric measures and their joint effects on risk of atrial fibrillation. OBJECTIVES: We aim to investigate associations and potential joint effects of height, weight, body surface area (BSA) and body mass index (BMI) with risk of atrial fibrillation. METHODS: In a cohort covering 1 153 151 18-year-old men participating in the Swedish military conscription (1972-1995), Cox regression was used to investigate associations of height, weight, BSA and BMI with risk of atrial fibrillation. RESULTS: During a median of 26.3 years of follow-up, higher height was associated with higher risk of atrial fibrillation (hazard ratio [HR] 2.80; 95% CI 2.63-2.98; for 5th vs. 1st quintile) and so was larger BSA (HR 3.05; 95% CI 2.82-3.28; for 5th vs. 1st quintile). Higher weight and BMI were to a lesser extent associated with risk of atrial fibrillation (BMI: 1.42; 95% CI 1.33-1.52, for 5th vs. 1st quintile). We found a multiplicative joint effect of height and weight. Adjusting for muscle strength, exercise capacity and diseases related to atrial fibrillation attenuated these measures. CONCLUSIONS: Higher height and weight are strongly associated with higher risk of atrial fibrillation. These associations are multiplicative and independent of each other and are summarized in a strong association of body surface area with risk of atrial fibrillation. The mechanisms remain unknown but may involve increased atrial volume load with larger body size.

Predictors of work disability after start of anti-TNF therapy in a national cohort of Swedish patients with rheumatoid arthritis: does early anti-TNF therapy bring patients back to work?

OBJECTIVES: To examine predictors of work ability gain and loss after anti-tumour necrosis factor (TNF) start, respectively, in working-age patients with rheumatoid arthritis (RA) with a special focus on disease duration. METHODS: Patients with RA, aged 19-62 years, starting their first TNF inhibitor 2006-2009 with full work ability (0 sick leave/disability pension days during 3 months before bio-start; n=1048) or no work ability (90 days; n=753) were identified in the Swedish biologics register (Anti-Rheumatic Treatment In Sweden, ARTIS) and sick leave/disability pension days retrieved from the Social Insurance Agency. Outcome was defined as work ability gain ≥50% for patients without work ability at bio-start and work ability loss ≥50% for patients with full work ability, and survival analyses conducted. Baseline predictors including disease duration, age, sex, education level, employment, Health Assessment Questionnaire, Disease Activity Score 28 and relevant comorbidities were estimated using Cox regression. RESULTS: During 3 years after anti-TNF start, the probability of regaining work ability for totally work-disabled patients was 35% for those with disease duration <5 years and 14% for disease duration ≥5 years (adjusted HR 2.1 (95% CI 1.4 to 3.2)). For patients with full work ability at bio-start, disease duration did not predict work ability loss. Baseline disability pension was also a strong predictor of work ability gain after treatment start. CONCLUSIONS: A substantial proportion of work-disabled patients with RA who start anti-TNF therapy regain work ability. Those initiating treatment within 5 years of symptom onset have a more than doubled 3-year probability of regaining work ability compared with later treatment starts. This effect seems largely due to the impact of disease duration on disability pension status.

Prevalence of paediatric inflammatory bowel disease in Sweden: a nationwide population-based register study.

BACKGROUND: We evaluated the impact of different case definition algorithms on the prevalence of paediatric inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) and to compare the occurrence of certain diseases compared to matched controls. METHODS: Paediatric patients (<18 years) were identified via ICD codes for UC and CD in Swedish registers between 1993 and 2010 (n = 1432). Prevalence was defined as ≥2 IBD-related visits. Prevalence of treated children in 2010 was defined as ≥2 IBD-related visits with one visit and ≥1 dispensed IBD-related drug prescription in 2010. To test the robustness of the estimates, prevalence was also calculated according to alternative case definitions. The presence of rheumatic, hepatobiliary, pancreatic, and dermatologic diseases were compared with age-/sex-/county-of-residence-matched general population controls. RESULTS: The IBD prevalence was 75/100,000 (CD: 29/100,000; UC: 30/100,000; patients with IBD-U: 16/100,000). Prevalence of treated disease in 2010 was 62/100,000 (CD: 23/100,000; UC: 25/100,000; patients with IBD-U: 13/100,000). When age restrictions were employed, the prevalence estimate decreased (<17y: 61/100,000, <16y: 49/100,000 and <15y: 38/100,000). Compared to general population controls (n = 8583), children with IBD had a higher prevalence of dermatologic (4.7% vs. 0.6%), hepatobiliary (including primary sclerosing cholangitis) (5.5% vs. 0.1%), pancreatic (1.7% vs. 0%) and rheumatic diseases (7.2% vs. 1.2%; all P < 0.01). CONCLUSIONS: The overall prevalence of paediatric IBD in Sweden was similar to that in earlier regional cohorts. IBD patients had a higher prevalence of comorbid conditions than matched general population controls.

Cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis.

OBJECTIVE: To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. DESIGN: Model based on a population-based cohort study. SETTING: The Swedish health service. POPULATION: Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010-2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008-2009 when standard care did not include RAADP (n = 7099). METHODS: Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. MAIN OUTCOME MEASURE: Additional cost per RhD immunisation averted. RESULTS: Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. CONCLUSION: Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. TWEETABLE ABSTRACT: Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP.

Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalimumab, etanercept and infliximab.

OBJECTIVE: To compare drug survival on adalimumab, etanercept and infliximab in patients with rheumatoid arthritis (RA). METHODS: Patients with RA (n=9139; 76% women; mean age 56 years) starting their first tumour necrosis factor (TNF) inhibitor between 2003 and 2011 were identified in the Swedish Biologics Register (ARTIS). Data were collected through 31 December 2011. Drug survival over up to 5 years of follow-up was compared overall and by period of treatment start (2003-2005/2006-2009; n=3168/4184) with adjustment for age, sex, education, period, health assessment questionnaire (HAQ), disease duration, concomitant disease modifying antirheumatic drug (DMARD) treatment and general frailty (using hospitalisation history as proxy). RESULTS: During 20 198 person-years (mean/median 2.2/1.7 years) of follow-up, 3782 patients discontinued their first biological (19/100 person-years; 51% due to inefficacy, 36% due to adverse events). Compared with etanercept, infliximab (adjusted HR 1.63, 95% CI 1.51 to 1.77) and adalimumab initiators had higher discontinuation rates (1.26, 95% CI 1.16 to 1.37), and infliximab had a higher discontinuation rate than adalimumab (1.28, 95% CI 1.18 to 1.40). These findings were consistent across periods, but were modified by time for adalimumab versus etanercept (p<0.001; between-drug difference highest the 1st year in both periods). The discontinuation rate was higher for starters in 2006-2009 than 2003-2005 (adjusted HR 1.12, 95% CI 1.04 to 1.20). The composition of 1-year discontinuations also changed from 2003-2005 vs 2006-2009: adverse events decreased from 45% to 35%, while inefficacy increased from 43% to 53% (p<0.001). CONCLUSIONS: Discontinuation rates were higher for infliximab compared with adalimumab and etanercept initiators, and for adalimumab versus etanercept during the 1st year. Discontinuation rates increased with calendar period, as did the percentage discontinuations due to inefficacy.

Risk of disability pension in patients following rectal cancer treatment and surgery.

BACKGROUND: Aspects of survivorship, such as long-term ability to work, are increasingly relevant owing to the improved survival of patients with rectal cancer. The aim of this study was to assess risk and determinants of disability pension (DP) in this patient group. METHODS: Using Swedish national clinical and population-based registers, patients with stage I-III rectal cancer aged 18-61 years in 1995-2009 were identified at diagnosis and matched with population comparators. Prospectively registered records of DP during follow-up were retrieved up to 2013. Non-proportional and proportional hazards models were used to estimate the incidence rate ratio (IRR) for DP annually and overall. Potential variations in risk by demographic and clinical factors were calculated, with relapse as a time-varying exposure. RESULTS: A total of 2815 patients were identified and compared with 13 465 population comparators. During a median follow-up of 6·0 (range 0-10) years, 23·3 per cent of the relapse-free patients and 10·3 per cent of the population comparators received DP (IRR 2·40, 95 per cent c.i. 2·17 to 2·65). An increased annual risk of DP was evident almost every year until the tenth year of follow-up. Abdominoperineal resection was associated with an increased DP risk compared with anterior resection (IRR 1·44, 1·19 to 1·75). Surgical complications (IRR 1·33, 1·10 to 1·62) and reoperation (IRR 1·42, 1·09 to 1·84), but not radiotherapy or chemotherapy, were associated with risk of DP. CONCLUSION: Relapse-free patients with rectal cancer of working age are at risk of disability pension.

How good is the coverage and how accurate are exposure data in the Swedish Biologics Register (ARTIS)?

OBJECTIVES: To assess the coverage of the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden, ARTIS) across indications, and the accuracy of the registered information on treatment with biologics. METHOD: Through cross-reference of ARTIS to almost complete national health registers on prescriptions (adalimumab and etanercept), outpatient visits, and death/residency during 2008-2010, we assessed: the treatment coverage of ARTIS for each treatment indication, the validity of the registered start and stop dates, ARTIS treatments with no corresponding drug dispensations, and the accuracy of the registered information on concomitant anti-rheumatic therapies. RESULTS: According to the national health registers, 3945 individuals with a spondyloarthropathy (SpA) and 8032 patients with rheumatoid arthritis (RA) had filled at least one adalimumab or etanercept prescription during the study period. Of these, 86% of those with SpAs and 95% of patients with RA were also found in ARTIS with the corresponding treatment. Tumour necrosis factor (TNF) inhibitor prescriptions had been filled by 95% of patients between the ARTIS start and stop dates (allowing a 90-day window). More than 60 days before and more than 60 days after the registered start date in ARTIS, 5% and 4% respectively of patients had filled their first TNF inhibitor prescription. More than 90 days after the registered stop date in ARTIS, 8% of patients had filled one or more TNF inhibitor prescriptions. CONCLUSIONS: We observed a high coverage and accuracy of ARTIS data on biologics exposure, for both SpAs and RA. The combination of data from clinical registers such as ARTIS with data from national health registers offers a high quality measurement of actual treatment.

Pregnancy and perinatal outcomes in women with polycystic ovary syndrome and twin births: a population-based cohort study.

OBJECTIVE: To investigate pregnancy and perinatal outcomes in twin births among women with and without polycystic ovary syndrome (PCOS) diagnosis. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: We identified 20,965 women with twin births between 1995 and 2009 of whom 226 had a PCOS diagnosis through linkage between the Swedish Medical Birth Register and the Swedish National Patient Register. METHODS: Calculating risk ratios (RR) with 95% confidence intervals (CI) using a log-binomial regression model and hazard ratios (HR) with 95% CI for preterm birth. MAIN OUTCOME MEASURES: Preterm birth, low birthweight, caesarean section, pre-eclampsia, Apgar score <7 at 5 minutes and perinatal mortality. RESULTS: PCOS diagnosis in twin pregnancy was associated with increased risk of preterm delivery (51% versus 43%, RR 1.18 [95% CI 1.03-1.37]), particularly spontaneous preterm delivery (37% versus 28%; RR 1.30 [95% CI 1.09-1.55]) and very preterm birth (<32 weeks) (14% versus 8%, RR 1.62 [95% CI 1.10-2.37]). Twins of PCOS mothers had more often low birthweight (48% versus 39%, adjusted RR 1.40 [95% CI 1.09-1.80]). This difference disappeared when adjusting for gestational age. No risk difference was found for caesarean section, pre-eclampsia, low 5-minute Apgar score or perinatal mortality. CONCLUSIONS: The risk of preterm delivery in twin pregnancies is increased by having a PCOS diagnosis. This should be considered in risk estimation and antenatal follow-up of twin pregnancies.

Risk of symptomatic gallstones and cholecystectomy after a very-low-calorie diet or low-calorie diet in a commercial weight loss program: 1-year matched cohort study.

BACKGROUND: Concern exists regarding gallstones as an adverse event of very-low-calorie diets (VLCDs; <800 kcal per day). OBJECTIVE: To assess the risk of symptomatic gallstones requiring hospital care and/or cholecystectomy in a commercial weight loss program using VLCD or low-calorie diet (LCD). DESIGN: A 1-year matched cohort study of consecutively enrolled adults in a commercial weight loss program conducted at 28 Swedish centers between 2006 and 2009. A 3-month weight loss phase of VLCD (500 kcal per day) or LCD (1200-1500 kcal per day) was followed by a 9-month weight maintenance phase. Matching (1:1) was performed by age, sex, body mass index, waist circumference and gallstone history (n=3320:3320). Gallstone and cholecystectomy data were retrieved from the Swedish National Patient Register. RESULTS: One-year weight loss was greater in the VLCD than in the LCD group (-11.1 versus -8.1 kg; adjusted difference, -2.8 kg, 95% CI -3.1 to -2.4; P<0.001). During 6361 person-years, 48 and 14 gallstones requiring hospital care occurred in the VLCD and LCD groups, respectively, (152 versus 44/10 000 person-years; hazard ratio, 3.4, 95% CI 1.8-6.3; P<0.001; number-needed-to-harm, 92, 95% CI 63-168; P<0.001). Of the 62 gallstone events, 38 (61%) resulted in cholecystectomy (29 versus 9; hazard ratio, 3.2, 95% CI 1.5-6.8; P=0.003; number-needed-to-harm, 151, 95% CI 94-377; P<0.001). Adjusting for 3-month weight loss attenuated the hazard ratios, but the risk remained higher with VLCD than LCD for gallstones (2.5, 95% CI 1.3-5.1; P=0.009) and became borderline for cholecystectomy (2.2, 95% CI 0.9-5.2; P=0.08). CONCLUSION: The risk of symptomatic gallstones requiring hospitalization or cholecystectomy, albeit low, was 3-fold greater with VLCD than LCD during the 1-year commercial weight loss program.

IgA deficiency and mortality: a population-based cohort study.

IgA deficiency has been linked to increased morbidity but data on mortality is lacking. In this population-based prospective cohort study we examined mortality in patients with IgA deficiency compared with the general population. Through six university hospitals in Sweden we identified 2,495 individuals with IgA deficiency (IgA deficiency ≤0.07 mg/L) diagnosed between 1980 and 2012. Each patient with IgA deficiency was matched on age, sex, place of residence, and year of diagnosis with up to 10 general population controls (n = 24,509). Data on education level and emigration status were obtained from Statistics Sweden. Our main outcome measure was all-cause mortality retrieved from the nationwide Causes of Death Register, which includes >99 % of all deaths in Sweden. We used Cox regression to estimate mortality hazard ratios conditioned on the matching factors and adjusted for education level. During 25,367 person-years of follow-up (median 8.3), there were 260 deaths in the IgA deficiency group versus 1,599 deaths during 257,219 person-years (median 8.6) in the general population controls (102 versus 62 deaths per 10,000 person-years; incidence rate difference, 40, 95%CI 28­53, P < .001). This corresponded to a conditional mortality hazard ratio of 1.8 (95%CI 1.6­2.1, P < .001). Relative mortality varied by follow-up time (P < .001) from a hazard ratio of 3.6 (95%CI 2.5­5.3; P < .001) during the first year to 1.9 (95%CI 1.5­2.4; P < .001) year 1­4; 1.9 (95%CI 1.4­2.4; P < .001) year 5-9; 1.5 (1.0­2.2; P = .054) year 10­14.9; and 1.1 (0.7­1.6; P = .66) year 15­25. Effect modification was also seen by age in each stratum of follow-up time, with higher relative mortality in younger than older patients (P < .001). In conclusion, patients with IgA deficiency are at increased risk of death in the first 10 to 15 years after diagnosis.

Sick leave and disability pension before and after initiation of antirheumatic therapies in clinical practice.

OBJECTIVE: To investigate sick leave and disability pension in rheumatoid arthritis (RA) in relation to the initiation of biological and non-biological antirheumatic therapies in clinical practice. METHODS: Patients aged 19-60 years initiating non-biological mono (n=2796) or combination disease-modifying antirheumatic drug (DMARD) therapy (n=973), or biological agents (n=4787) were identified in the Swedish Rheumatology Quality Register between 1999 and 2007. Sick leave and disability pension data (1995-2010) were retrieved from national registers. RESULTS: During the year before the start of mono DMARD, combination DMARD and biological treatment, 10%, 12% and 43% of patients received disability pension benefits, respectively. The corresponding combined annual sick leave and disability pension days were 78 (54+25), 132 (105+27) and 190 (79+111). Irrespective of treatment type, initiators were characterised by a history of increasing sick leave and disability pension. Treatment start was associated with a break in this trajectory: sick leave decreased while disability pension increased, resulting in a net stabilisation of total days. Higher levels of days on sick leave and disability pension at treatment start were observed in patients initiating biologics in 1999 (236 days/year) compared with 2007 (150 days/year; p<0.001), but the trajectory thereafter remained largely similar and contrasted markedly with the level in the general population. CONCLUSION: Sick leave and disability pension increased rapidly before the initiation of antirheumatic therapy, which was associated with a halt but not a reversal of this development. Work ability is a metric of importance for clinical practice, signalling large remaining needs in the RA population, and the need for intervention earlier in the disease process.

Generalisability of clinical registers used for drug safety and comparative effectiveness research: coverage of the Swedish Biologics Register.

OBJECTIVE: To determine coverage and generalisability of data in the Swedish Biologics Register ARTIS. METHODS: Patients with adult onset rheumatoid arthritis (RA) were identified in the National Patient Register and the Swedish Rheumatology Quality Register, including the ARTIS cohort of patients exposed to biological agents. Exposure to etanercept and adalimumab between 2006 and 2008 was determined by register linkage to the Prescribed Drug Register which contains patient-level data on >99% of all etanercept and adalimumab use in Sweden. RESULTS: Of 62 897 patients with RA, 6510 had received treatment with etanercept or adalimumab according to the Prescribed Drug Register. Of these, 5673 were also registered in ARTIS, resulting in a national coverage of 87%. The regional variation was small with >85% coverage in 18 of 21 counties. In multivariable analysis, ARTIS-registered and non-registered patients did not differ by age (p=0.62), sex (p=0.84) or education level (p=0.24). CONCLUSION: Nationwide drug dispensing and demographic data may function as quality metrics for coverage and generalisability assessments. Using such data, the coverage of ARTIS was estimated at 87% with no indications of compromised external generalisability regarding demography.

Small-area variations in sales of TNF inhibitors in Sweden between 2000 and 2009.

OBJECTIVE: To measure small-area variations in sales per capita of tumour necrosis factor (TNF) inhibitors. METHODS: For 2000-2009, sales data on etanercept, infliximab, and adalimumab were retrieved from the Swedish National Corporation of Pharmacies, which keeps data on drugs dispensed in ambulatory care and hospitals. As points of reference, data were retrieved on all drugs, non-biologic treatments for chronic inflammatory disorders (sulfasalazine, methotrexate, azathioprine), and for a biologic used in a different therapeutic area (trastuzumab). As a corollary measure to sales per capita, penetration of biologics in the rheumatoid arthritis (RA) population was calculated using nationwide registers. Small areas were defined as the 21 counties of Sweden. RESULTS: From 2000 to 2009, annual TNF inhibitor sales increased 9-fold from 195 to 1779 million SEK (0.7-5.0% of total drug expenditure). The county variation in sales per capita, initially 6.2-fold (coefficient of variation 42%), decreased to 2.3-fold in 2009 (24%). During the same period, total drug expenditure per capita remained at a 1.2-fold county variation (4-6%). Sales per capita variations of non-biologic treatments against chronic inflammatory diseases ranged from 1.5 to 1.8 (12-16%). For trastuzumab, a 3.2-fold variation (30%) was observed in 2009. At the patient level, there was a 2-fold county variation (from 10% to 21%) in biologic penetration in RA. County-specific sales per capita were associated with mean RA duration (r = -0.52, p = 0.015) and C-reactive protein at treatment initiation (r = -0.49, p = 0.025), while pain was borderline significant (r = -0.43, p = 0.055). CONCLUSIONS: Despite universal access to treatment, substantial but decreasing small-area variations were observed. Although geographic variations are anticipated initially, their persistence calls for investigation of patient equity and treatment appropriateness as counties seem to have different initiation thresholds.

Juvenile idiopathic arthritis and risk of cancer: a nationwide cohort study.

OBJECTIVE: Reports of therapy-related adverse events suggest an elevated rate of malignancy in patients with juvenile idiopathic arthritis (JIA) treated with biologic therapies. However, the scarcity of data on the underlying risk of malignancy in JIA hampers interpretation of these signals. Therefore, the aim of this study was to determine the risk of cancer in patients with JIA as compared with that in the general population. METHODS: Through linkage with a national database, the Swedish Patient Register (comprising inpatient discharges in 1969-2007 and specialist outpatient visits in 2001-2007 in Sweden), a national JIA cohort (n = 9,027) was identified, and each JIA case was matched with 5 general population comparators. Using data from the Swedish Cancer, Census, Death, and Biologics Registers, the occurrence of cancer, vital status, and start of a biologic therapy were identified. The relative risk (RR) of first occurrence of a primary cancer in patients who had not been treated with biologics (biologics-naive patients with JIA) was estimated using Poisson regression, stratified a priori by year of earliest identification of JIA (before 1987 versus 1987 and thereafter). In sensitivity analyses, the data were followed up to 1999, when biologics first became available. RESULTS: In this biologics-naive JIA cohort, 60 malignancies were observed during 131,144 person-years of followup, compared with 266 cancers observed during 661,758 person-years in the general population comparator (0.46 cases/1,000 person-years versus 0.40 cases/1,000 person-years; RR 1.1, 95% confidence interval [95% CI] 0.9-1.5). Patients with JIA identified before 1987 were not at increased risk of cancer, whereas JIA identified in 1987 and thereafter was significantly associated with incident lymphoproliferative malignancies (RR 4.2, 95% CI 1.7-10.7) and cancers overall (RR 2.3, 95% CI 1.2-4.4). Sensitivity analyses did not reveal any ready explanation for this heterogeneity. CONCLUSION: Although absolute risks were low, an elevated risk of malignancy was observed among biologics-naive patients in whom the diagnosis of JIA was made in the past 20 years, which may have implications for the interpretation of cancer signals in patients with JIA treated with newer therapies.

Obesity status and risk of disability pension due to psychiatric disorders.

OBJECTIVE: The aim of this study was to investigate associations between underweight, overweight and obesity in young adult men and risk of disability pension (DP) due to psychiatric disorders. DESIGN AND SUBJECTS: In this nationwide study of 1 110 139 Swedish men (mean age 18.3+/-0.5 years), weight, height and muscular strength were measured at mandatory military conscription testing (1969-1994). Information on DP (1971-2006), residential area, parental socioeconomic position and education and preexisting psychiatric disorders was obtained by record linkage of national registers. RESULTS: During 26 million person-years of follow-up, 19 684 men received DP due to psychiatric disorders. After adjustment, hazard ratios (HRs) due to any psychiatric disorder were 1.20 (95% CI: 1.15-1.26) for underweight, 1.14 (95% CI: 1.08-1.21) for overweight and 1.43 (95% CI: 1.28-1.60) for obesity compared to normal weight. For affective disorders, HRs were elevated for underweight (1.24, 95% CI: 1.16-1.32), overweight (1.19, 95% CI: 1.10-1.28) and obesity (1.55, 95% CI: 1.33-1.81), whereas for substance abuse increased risks were seen only for underweight (1.41, 95% CI: 1.23-1.61) and obesity (1.50, 95% CI: 1.07-2.12). For nonaffective disorders (including schizophrenia) overweight (HR=0.87, 95% CI: 0.76-1.00) and obesity (HR=0.79, 95% CI: 0.57-1.10) seemed to be protective, although not statistically significant. HRs for personality disorders were increased for underweight (1.18, 95% CI: 1.04-1.34), overweight (1.16, 95% CI: 1.00-1.30) and obesity (1.40, 95% CI: 1.03-1.90). CONCLUSION: Underweight and overweight were associated with small risk increases, whereas higher risks for DP were generally found for obesity.

The combined effects of overweight and smoking in late adolescence on subsequent disability pension: a nationwide cohort study.

BACKGROUND: Smoking and obesity are two of the most important risk factors for chronic disease today. Their combined effect on the risk of disability pension is not known. METHODS: A nationwide cohort of 45 920 Swedish men (18.7 + or - 0.5 years) were followed for 38 years. The body mass index (BMI), based on measured height and weight, was used to define underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9) and obesity (> or = 30.0). The hazard ratios (HRs) associated with BMI and smoking status at baseline for receiving disability pension were adjusted for socio-economic index (SEI), muscular strength, geographic region and place of residence. RESULTS: During 1.6 million person-years, 4631 disability pensions and 2897 deaths occurred. After adjustment, overweight (HR 1.34, 95% CI 1.19-1.51) and obesity (HR 1.55, 1.18-2.05) were associated with an increased risk of disability pension, independent of smoking, whereas underweight (18.5; HR 1.07, 0.97-1.17) was not compared with normal weight. Similarly, smoking 1-10 (HR 1.37, 1.27-1.49) or >10 cigarettes per day (HR 2.01, 1.86-2.17) showed independent risk increases versus non-smoking. Although obese individuals smoking >10 daily cigarettes were at greatly increased risk (HR 2.98, 1.98-4.47), no evidence of interaction between the two risk factors could be detected. CONCLUSIONS: Both increased adiposity and smoking are strong and independent predictors of disability pension, but they do not act synergistically.

Patients with rheumatoid arthritis treated with tumour necrosis factor antagonists increase their participation in the workforce: potential for significant long-term indirect cost gains (data from a population-based registry).

OBJECTIVE: To investigate the effect of tumour necrosis factor (TNF) antagonist treatment on workforce participation in patients with rheumatoid arthritis (RA). METHODS: Data from the Stockholm anti-TNFalpha follow-up registry (STURE) were used in this observational study. Patients with RA (n = 594) aged 18-55 years, (mean (SD) 40 (9) years) followed for up to 5 years were included with hours worked/week as the main outcome measure. Analyses were performed unadjusted and adjusted for baseline age, disease duration, Health Assessment Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28) and pain score. RESULTS: At baseline patients worked a mean 20 h/week (SD 18). In unadjusted analyses, significant improvements in hours worked/week could already be observed in patients at 6 months (mean, 95% CI) +2.4 h (1.3 to 3.5), with further increases compared to baseline at 1-year (+4.0 h, 2.4 to 5.6) and 2-year follow-up (+6.3 h, 4.2 to 8.4). The trajectory appeared to stabilise at the 3-year (+6.3 h, 3.6 to 8.9), 4-year (+5.3 h, 2.3 to 8.4) and 5-year follow-up (+6.6 h, 3.3 to 10.0). In a mixed piecewise linear regression model, adjusted for age, sex, baseline disease activity, function and pain, an improvement of +4.2 h/week was estimated for the first year followed by an added improvement of +0.5 h/week annually during the years thereafter. Over 5 years of treatment, the expected indirect cost gain corresponded to 40% of the annual anti-TNF drug cost in patients continuing treatment. CONCLUSION: Data from this population-based registry indicate that biological therapy is associated with increases in workforce participation in a group typically expected to experience progressively deteriorating ability to work. This could result in significant indirect cost benefits to society.

Increased physical activity in abdominally obese women through support for changed commuting habits: a randomized clinical trial.

BACKGROUND: Abdominally obese women can reduce their health risk through regular physical activity. There is, however, little evidence on the effectiveness of interventions that promote physical activity long-term, such as cycling and walking to and from work. METHODS: This intervention focused on physically active commuting (cycling and walking) in middle-aged (30-60 years), abdominally obese (waist circumference > or = 88 cm) women (n=120), recruited by newspaper advertisement. The intervention group was a moderate-intensity programme with physician meetings, physical activity prescriptions, group counselling and bicycles. The control group was a low-intensity group support programme with pedometers. We used a randomized, controlled, 2-armed design with 18 months duration and intention-to-treat analysis (data collection 2005-2006). Treatment success was defined as bicycling > or = 2 km/d (primary) or walking 10,000 steps per day (secondary). RESULTS: At baseline, mean (s.d.) age was 48.2 years (7.4), waist circumference 103.8 cm (7.8), walking 8471 steps per day (2646), bicycling 0 km per day. Attrition at 18 months was 10% for the intervention group and 25% in the control group (P=0.03). The intervention group was more likely to achieve treatment success for cycling than controls: 38.7 vs 8.9% (odds ratio (OR)=7.8 (95% confidence interval=4.0 to 15.0, P<0.001)), but with no difference for compliance with the walking recommendation: 45.7 vs 39.3% (OR=1.2 (95% CI=0.7 to 2.0, P=0.50)). Commuting by car and public transport were reduced by 34% (P<0.01) and 37% (P<0.001), respectively, with no differences between groups. Both groups attained similar waist reductions (-2.1 and -2.6 cm, P=0.72). CONCLUSIONS: Abdominally obese women can increase PA long-term through moderate-intensity behavioural support aimed at changing commuting habits.