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Objective: Although off‐label use of rituximab is a common alternative to disease‐modifying therapies (DMTs) approved for multiple sclerosis (MS) in several countries, the impact of this on treatment cost‐effectiveness is not well known. Methods: We evaluated the relative cost‐effectiveness of rituximab and MS‐approved DMTs in a register‐based cohort study of Swedish residents with relapsing–remitting MS, aged 18–65 years, starting treatment with rituximab, natalizumab, fingolimod, or dimethyl fumarate between January 2010 and July 2016, and followed through July 2021 (n = 5,924). By linking the population‐based Swedish MS register to several Swedish health care and demographic registers, we estimated health care costs in relation to number of relapses, over 5 years from treatment start. Differences between treatments were estimated in inverse probability of treatment‐weighted regression models, adjusting for a broad range of potential confounders covering demographics, medical history, and MS‐related clinical characteristics. Results: Off‐label rituximab was associated with both lower total health care costs (mean cost savings ranged $35,000–$66,000 vs. each approved DMT), and fewer relapses (mean number of prevented relapses ranged 0.12–0.22), per started therapy over 5 years. Results were robust to variations in discounting and pricing of health care visits, with the main driver of cost‐savings being the price of the index drug itself. Interpretation: The cost‐effectiveness of rituximab dominated the MS‐approved alternatives. Off‐label, low‐dose rituximab should be considered for persons with MS and could reduce barriers to treatment, especially in resource‐limited settings. ANN NEUROL 2024;95:1099–1111 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study examines the pregnancy outcomes of individuals infected with SARS-CoV-2 and those uninfected at a hospital in Sweden. [ABSTRACT FROM AUTHOR]

I Background: i A recent Danish study reported that the rate of extremely preterm birth was reduced during the lockdown period of the coronavirus disease 2019 (COVID-19) pandemic; the odds ratio (OR) was 0.09 (95% CI, 0.01 to 0.40) compared with previous years ([1]). A study from the United Kingdom reported that stillbirth was more common during the pandemic; the difference was 6.93 (CI, 1.83 to 12.0) cases per 1000 births, corresponding to a 4-fold risk increase ([2]). [Extracted from the article]

Background: Maternal type 1 diabetes (T1D) has been linked to preterm birth and other adverse pregnancy outcomes. How these risks vary with glycated hemoglobin (or hemoglobin A1c [HbA1c]) levels is unclear.Objective: To examine preterm birth risk according to periconceptional HbA1c levels in women with T1D.Design: Population-based cohort study.Setting: Sweden, 2003 to 2014.Patients: 2474 singletons born to women with T1D and 1 165 216 reference infants born to women without diabetes.Measurements: Risk for preterm birth (<37 gestational weeks). Secondary outcomes were neonatal death, large for gestational age, macrosomia, infant birth injury, hypoglycemia, respiratory distress, 5-minute Apgar score less than 7, and stillbirth.Results: Preterm birth occurred in 552 (22.3%) of 2474 infants born to mothers with T1D versus 54 287 (4.7%) in 1 165 216 infants born to mothers without diabetes. The incidence of preterm birth was 13.2% in women with a periconceptional HbA1c level below 6.5% (adjusted risk ratio [aRR] vs. women without T1D, 2.83 [95% CI, 2.28 to 3.52]), 20.6% in those with a level from 6.5% to less than 7.8% (aRR, 4.22 [CI, 3.74 to 4.75]), 28.3% in those with a level from 7.8% to less than 9.1% (aRR, 5.56 [CI, 4.84 to 6.38]), and 37.5% in those with a level of 9.1% or higher (aRR, 6.91 [CI, 5.85 to 8.17]). The corresponding aRRs for medically indicated preterm birth (n = 320) were 5.26 (CI, 3.83 to 7.22), 7.42 (CI, 6.21 to 8.86), 11.75 (CI, 9.72 to 14.20), and 17.51 (CI, 14.14 to 21.69), respectively. The corresponding aRRs for spontaneous preterm birth (n = 223) were 1.81 (CI, 1.31 to 2.52), 2.86 (CI, 2.38 to 3.44), 2.88 (CI, 2.23 to 3.71), and 2.80 (CI, 1.94 to 4.03), respectively. Increasing HbA1c levels were associated with the study's secondary outcomes: large for gestational age, hypoglycemia, respiratory distress, low Apgar score, neonatal death, and stillbirth.Limitation: Because HbA1c levels were registered annually at routine visits, they were not available for all pregnant women with T1D.Conclusion: The risk for preterm birth was strongly linked to periconceptional HbA1c levels. Women with HbA1c levels consistent with recommended target levels also were at increased risk.Primary Funding Source: Swedish Diabetes Foundation. [ABSTRACT FROM AUTHOR]

This cohort study uses Swedish Medical Birth Register data to investigate risk of birth defects in infants born to women who had Roux-en-Y bariatric surgery between 2007 and 2014. [ABSTRACT FROM AUTHOR]

Purpose: To explore the risk of infections in individuals with IgA deficiency compared to general population controls. Methods: In this nationwide prospective population-based cohort study, we used data on IgA levels (<0.07 g/L) from six university hospitals in Sweden to identify 2100 individuals with IgA deficiency. Individuals were diagnosed between 1980 and 2010. For each patient with IgA deficiency we identified 10 controls from the general population, matched on age, sex, and place of residence ( n = 18,653). Data on infections were obtained from the Swedish National Patient Register (including inpatient and hospital-based outpatient care) between 2001 and 2010. We defined infections as having a record of a relevant international classification of disease (ICD) code. Prevalences and prevalence ratios (PRs) were calculated. Results: Individuals with IgA deficiency were more likely to have a record of any infection (36.1 vs. 18.8 % in controls) corresponding to a PR of 2.4 (95%CI 2.2-2.6). We also noted statistically significant associations with IgA deficiency (all P-values <0.05) and respiratory tract infections (17.8 vs. 6.3 % in controls; PR = 3.2), gastrointestinal infections (6.0 vs. 1.8 % in controls; PR = 3.5), skin infections (4.1 vs. 2.2 % in controls; PR = 1.9), joint infections (0.48 vs. 0.24 % in controls; PR = 2.0; P = 0.052), sepsis (1.5 vs. 0.45 % in controls; PR = 3.4), meningitis (0.38 vs. 0.12 %, PR = 3.2), mastoiditis/otitis (2.1 vs. 1.1 % in controls; PR = 2.0), and urinary tract infections (6.1 vs. 3.4 % in controls; PR = 1.8). Conclusions: Individuals with IgA deficiency are at an increased risk of infections requiring hospital care. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the risk of cancer in individuals with IgA deficiency compared with the general population. Methods: Prospective nationwide population-based cohort study. We identified 2320 individuals with IgA deficiency (IgA levels < 0.07 g/L) diagnosed between 1980 and 2010 in six Swedish university hospitals. Individuals with IgA deficiency were then matched on age, sex, place of residence, and year of diagnosis with up to 10 general population controls ( n = 23,130). Through linkage with the Swedish Cancer Register we calculated conditional hazard ratios (HRs) for cancer diagnosed after IgA deficiency diagnosis in patients without a previous cancer diagnosis. Results: During follow-up, 125 individuals with IgA deficiency (61/10,000 person-years) and 984 controls (47/10,000 person-years) developed cancer (HR 1.31; 95%CI = 1.09-1.58). In cause-specific analyses, we found an increased risk of any gastrointestinal cancer (HR = 1.64; 95%CI = 1.07-2.50), but not for lymphoproliferative malignancy (HR 1.68; 95%CI = 0.89-3.19). Relative risk estimates for overall cancer were very high in the first year of follow-up (overall: HR = 2.80; 95%CI = 1.74-4.49), but failed to reach statistical significance thereafter. IgA deficiency diagnosed in childhood ( n = 487) was not associated with overall cancer (HR = 3.26; 0.88-12.03). Conclusions: Individuals with IgA deficiency are at a moderately increased risk of cancer, with excess risks of gastrointestinal cancer. This excess risk is highest just after diagnosis suggesting a degree of surveillance bias. Children with IgA deficiency were at no increased risk of cancer but the statistical power was limited in subanalyses. [ABSTRACT FROM AUTHOR]

Background: Several autoimmune disorders have been linked to adverse pregnancy outcome. IgA deficiency shares many autoimmune traits, but its association with pregnancy outcome is unknown. Methods: Prospective population-based cohort study in Sweden of 613 mothers with IgA deficiency (IgA levels < .07 g/L) diagnosed in 1980-2010 in six university hospitals. In 1973-2010, these women delivered 1,172 singleton infants registered in the Swedish Medical Birth Register. Each delivery to a woman with IgA deficiency was matched on maternal age, parity, early pregnancy smoking status, education level, and delivery year with up to 5 control births ( n = 5,758). Results: Offspring to women with IgA deficiency had 79 g lower birth weight than controls (mean ± SD: 3,457 ± 559 vs 3,537 ± 553 g, P < 0.001), and 1.4 days shorter gestational age (mean ± SD: 278 ± 13 vs 280 ± 14 days, P = 0.001). No difference in preterm birth (<37 weeks) could be detected in deliveries to women with IgA deficiency vs control deliveries (5.8 % vs 5.2 %; odds ratio (OR) = 1.13, 95%CI = 0.85-1.49), but small for gestational age birth was more common (4.3 % vs 2.8 %; OR = 1.48, 95%CI = 1.04-2.10). Women with IgA deficiency also delivered more often by caesarean section (16.9 % vs 11.9 %; OR = 1.51, 95%CI = 1.26-1.82), while no difference was observed regarding low Apgar score (<7 at 5 min; 1.1 % vs 1.0 %; OR = 1.18; 95%CI = 0.62-2.27). When excluding women with autoimmune diseases, the excess risks of adverse pregnancy outcome diminished. Conclusion: There is a small excess risk of certain adverse delivery and perinatal outcomes among offspring to women with IgA deficiency. These excess risks are attenuated when considering the presence of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Purpose: To examine autoimmune disorders in patients with IgA deficiency compared with the general population. Methods: Nationwide prospective population-based cohort study. Through six university hospitals in Sweden we identified 2100 individuals with IgA deficiency (IgA levels < .07 g/L) diagnosed between 1980 and 2011. 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 = 18,653). Data on nine autoimmune disorders were retrieved from the Swedish National Patient Register (including inpatient and non-primary outpatient care). Autoimmune disorders were defined as having at least two visits listing the relevant international classification of disease (ICD) code as main diagnosis. Prevalences and prevalence ratios (PRs) were calculated. Results: Individuals with IgA deficiency more often had celiac disease (6.7 % vs. 0.19 % in controls) and type 1 diabetes (5.9 % vs. 0.57 %) corresponding to a 35-fold higher PR for celiac disease and 10-fold higher for type 1 diabetes. Also for the other autoimmune diseases did we see statistically significantly elevated prevalences and PRs (juvenile idiopathic arthritis (0.76 % vs. 0.09 % in controls, PR = 8.9), systemic lupus erythematosus (0.57 % vs. 0.06 %; PR = 8.9), inflammatory bowel disease (3.9 % vs. 0.81 %; PR = 5.0; specifically Crohn's disease (2.4 % vs. 0.42 %; PR = 5.7) and ulcerative colitis (1.7 % vs. 0.46 %; PR = 3.9)), hypothyreosis (0.76 % vs. 0.16 %; PR = 4.6), rheumatoid arthritis (2.2 % vs. 0.50 %; PR = 4.5), and hyperthyreosis (1.7 % vs. 0.43 %; PR = 3.9), but not with myasthenia gravis (0.05 % vs. 0.02 %; PR = 3.0). Conclusions: Individuals with IgA deficiency have a higher prevalence of several other autoimmune disorders. [ABSTRACT FROM AUTHOR]

Objective To determine whether the differences in the modes of action and safety profiles of individual tumor necrosis factor inhibitors (TNFi) translate into differential mortality risks, as investigated in etanercept, infliximab, and adalimumab. Methods Data on patients with rheumatoid arthritis (RA) identified in the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden [ARTIS]) in whom first-ever treatment with a biologic agent (etanercept [n = 2,686], infliximab [n = 2,027], or adalimumab [n = 1,609]) was initiated between 2003 and 2008 were linked to national Swedish registers to get information on deaths from any cause, demographic features, RA characteristics, comorbid conditions, and concurrent treatment at the start of TNFi treatment. Hazard ratios (HRs) were modeled using multivariable adjusted and weighted Cox models. Results During 19,118 person-years of followup, 211 patients died (3.3%; 1.1 deaths per 100 person-years); 85% of the deaths occurred among patients who had been exposed to only one TNFi. We found no statistically significant difference in overall mortality rates across the exposure groups, regardless of adjustment and modeling approach (for infliximab versus etanercept, HR 1.1 [95% confidence interval (95% CI) 0.7-1.7], and for adalimumab versus etanercept, HR 1.3 [95% CI 0.9-2.0]). Conclusion Overall, we noted no statistically significant difference in mortality rates between the 3 TNF inhibitors under study. Further studies need to examine whether certain subsets of patients are at increased risk of death with specific TNFi. [ABSTRACT FROM AUTHOR]

The article informs about a population based cohort study related to the estimation of risks for venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA) including the relation of these risks to disease period and hospitalization. It mentions that incident RA cohorts and prevalent RA cohorts from Sweden are used in the study using Swedish Population Register. It includes that primary outcome was first-time hospitalization for VTE and secondary outcomes were deep vein thrombosis (DVT) and pulmonary embolism separately. It adds that follow-up studies were employed in the cohort study. According to the study, patients with RA are at increased risk of VTE and that the risk of VTE increases shortly after RA diagnosis and remains stable over the first 10 years after diagnosis.

The article presents information about a research conducted for assessing the health care use over 20 years in obese patients who have been treated conventionally or with bariatric surgery. The research employed the Swedish obese subjects study in an ongoing, prospective, nonrandomized, controlled intervention study at the Swedish health care system which included 2010 adults who underwent bariatric surgery. The inclusion criteria were age 37 to 60 years of age and body mass index of 34 or higher in men and 38 or higher in women.

Background: Sick-leave is an important source of productivity losses to society. The objective of this study was to investigate the association between body mass index (BMI) status in young adulthood and future sick-leave. Methods: A nation-wide cohort of 43 989 Swedish men (18.7 ± 0.5 years) performing military conscription tests in 1969–70 were followed between 1986 and 2005 regarding sick-leave. BMI was used to define underweight (<18.5), normal weight (18.5–24.9), overweight (25.0–29.9) and obesity (&geq;30.0). Relative risks of sick-leave were estimated with Cox proportional hazards models adjusted for smoking, socio-economic index and muscular strength, using normal weight as the reference. Results: During 803 684 person-years of follow-up, 488 570 sick-leave episodes were recorded. On average, one short-term (&leq;7 days) episode occurred every eight person-months, one intermediate-term (8–30 days) every five person-years and one long-term (>30 days) episode every 15 person-years. Overweight was associated with 20% and obesity with >30% risk elevation for episodes ranging from 8 to 30 days [hazard ratio (HR) 1.20; 95% CI 1.15–1.24 and HR 1.35; 95% CI 1.24–1.47, respectively] as well as for episodes >30 days (HR 1.19; 95% CI 1.15–1.23 and HR 1.34; 95% CI 1.24–1.47, respectively) compared to normal weight. Obesity was also associated with an increased risk of sick-leave episodes &leq;7 days (HR 1.13; 95% CI 1.09–1.16), but the corresponding risk increase for overweight was very small (HR 1.02; 95% CI 1.00–1.03). Underweight showed increased risk only for short-term episodes (HR 1.05; 95% CI 1.04–1.07). Discussion: Overweight and obesity are associated with increased risk for sick-leave compared to normal weight, especially for sick-leave episodes of longer duration. [ABSTRACT FROM PUBLISHER]

Aim: To limit further comparisons between the two fasting indices Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI), and to examine their robustness in assessing insulin sensitivity. Methods: A total of 191 obese children and adolescents (age 13.9 ± 2.9 years, BMI SDS 6.1 ± 1.6), who had undergone a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), were included. Receiver operating characteristic curve (ROC) analysis was used to compare indices in detecting insulin resistance and Bland-Altman plots to investigate agreement between three consecutive fasting samples when compared to using single samples. Results: ROC analysis showed that the diagnostic accuracy was identical for QUICKI and HOMA-IR [area under the curve (AUC) boys 0.80, 95%CI 0.70-0.89; girls 0.80, 0.71-0.88], while insulin had a nonsignificantly lower AUC (boys 0.76, 0.66-0.87; girls 0.75, 0.66-0.84). Glucose did not perform better than chance as a diagnostic test (boys 0.47, 0.34-0.60; girls 0.57, 0.46-0.68). Indices varied with consecutive sampling, mainly attributable to fasting insulin variations (mean maximum difference in HOMA-IR −0.8; −0.9 to −0.7). Conclusions: Using both HOMA-IR and QUICKI in further studies is superfluous as these indices function equally well as predictors of the FSIVGTT sensitivity index. Focus should be on establishing a general standard for research and clinical purposes. [ABSTRACT FROM AUTHOR]

Objective. Early detection and treatment of local oral fungal infection (OFI) minimize the risk of overgrowth and more serious complications such as invasive infections. Generalized fungal infection increases both morbidity and mortality in end-stage renal disease (ESRD) patients. This study reports the prevalence of ongoing OFI in patients with ESRD and presents correlations with dental microbial plaque formation and mouth dryness. It also describes how oral fungal growth correlates with oral lesions associated with fungal infection. Material and methods. From March 2007 to October 2008, 93 ESRD patients and 45 age- and gender-matched controls were consecutively asked to participate in the study. In total, 34 patients were treated with peritoneal dialysis (PD) and 59 with haemodialysis (HD). OFI was diagnosed by taking two smear layers from the buccal mucosa. The samples from each side of the mouth were stained with the periodic acid Schiff (PAS) method. The associations between histological findings, age, gender, type of dialysis treatment, tobacco habits, self-experienced mouth dryness, taste disturbances, dental plaque and gingivitis were investigated. The presence of erythematous oral stomatitis, membranous candidiasis and angular cheilitis was noted to clarify how the presence of fungal hyphae correlate with oral lesions associated with OFI. Results. OFI was found in 32% of the ESRD patients and 11% of the controls (p=0.007). An extensive OFI, defined as frequent fungal hyphae formations in oral mucosal smear layers, was found in 3% of the PD and 17% of the HD patients. Oral lesions, defined as clinical signs associated with OFI such as erythematous oral stomatitis, membranous candidiasis or angular cheilitis, were found in 37% of the patients with OFI, while 5% of the patients without findings of fungal infection presented oral lesions associated with OFI (p=0.0002). Furthermore, patients with self-reported mouth dryness were three times more likely (p=0.02) to be diagnosed with OFI. Conclusions. ESRD patients are found to have significantly more OFI than controls. Patients with ESRD experiencing mouth dryness and dental plaque formation also seem to be at risk of developing OFI. Detection of oral lesions associated with OFI should be combined with a histopathological diagnosis before antifungal treatment. [ABSTRACT FROM AUTHOR]

Objective. Early detection of oral infections plays an important role for dental referral during progression of renal disease and during dialysis treatment in uraemic patients. This study investigated how oral health is related to uraemia in a group of uraemic patients in Stockholm, Sweden. Material and methods. This cross-sectional study assessed oral diseases in chronic kidney disease (CKD) patients in different stages (n=93) compared with healthy age- and gender-matched controls. Differences in multiple oral outcomes, assessed by a dentist, were investigated in multivariate analyses, adjusted for tobacco habits, diabetes mellitus and uraemia status (predialysis, peritonealdialysis or haemodialysis). Results. Compared with healthy controls, uraemic patients had significantly worse dental status regarding the decayed, missing, filled teeth (DMFT) index (3.3, p=0.003), periodontal loss of attachment (0.9, p=0.00002) and periapical lesions (0.6, p=0.002). For haemodialysis patients DMFT (6.5, p=0.01), periodontal loss of attachment (2.2, p=0.007) and periapical lesions (1.0, p=0.01) were worse compared with controls. The differences between uraemic patients and controls remained after adjustment for age, gender, tobacco habits and diabetes (p<0.05 for all outcomes). Conclusions. Objective measurements showed that uraemic patients have more dental problems than healthy controls and the patients seem to develop their problems before they have progressed to dialysis. Therefore greater attention to dental problems may be warranted during the progression of uraemia to prevent deterioration of oral health. [ABSTRACT FROM AUTHOR]

Objective To investigate the combined effects on adult mortality of overweight and smoking in late adolescence. Design Record linkage study with Cox proportional hazard ratios adjusted for muscle strength, socioeconomic position, and age. Setting Swedish military service conscription register, cause of death register, and census data. Participants45 920 Swedish men (mean age 18.7, SD0.5) followed for 38 years. Main outcome measures Body mass index (underweight (BMI <18.5), normal weight (18.5-24.9), overweight (25-29.9), and obesity (230)), muscle strength, and self reported smoking (non-smoker, light smoker (1-10 cigarettes/day), heavy smoker (>10/day)) at mandatory military conscription tests in 1969-70. AH cause mortality. Results Over 1.7 million person years, 2897 men died. Compared with normal weight men (incidence rate 17/10 000 person years, 95% confidence interval 16 to 18), risk of mortality was increased in overweight (hazard ratio 1.33,1.15 to 1.53; incidence rate 23, 20 to 26) and obese men (hazard ratio 2.14,1.61 to 2.85; incidence rate 38, 27 to 48), with similar relative estimates in separate analyses of smokers and non-smokers. No increased risk was detected in underweight men (hazard ratio 0.97,0.86 to 1.08; incidence rate 18,16 to 19), though extreme underweight (BMI <17) was associated with increased mortality (hazard ratio 1.33,1.07 to 1.64; incidence rate 24,19 to 29). The relative excess risk due to interaction between BMI and smoking status was not significant in any stratum. Furthermore, all estimates of interaction were of small magnitude, except for the combination of obesity and heavy smoking (relative excess risk 1.5, -0.7 to 3.7). Compared with non-smokers (incidence rate 14,13 to 15), risk was increased in both light (hazard ratio 1.54, Î.41 to 1.70; incidence rate 15,14 to 16) and heavy smokers (hazard ratio 2.11,1.92 to 2.31; incidence rate 26, 24 to 27). Conclusions Regardless of smoking status, overweight and obesity in late adolescence increases the risk of adult mortality. Obesity and overweight were as hazardous as heavy and light smoking, respectively, but there was no interaction between BMI and smoking status. The global obesity epidemic and smoking among adolescents remain important targets for intensified public health initiatives. [ABSTRACT FROM AUTHOR]

The article focuses on the integration of dual x-ray absorptiometry (DXA) and bioelectrical impedance (BIA) for detecting accuracy of fat mass from fat-freem mass among individuals in Great Britain. It stresses that such DXA uses a total-body scanner that highlights the calculation of percent body fat (%BF) through dividing fat soft-tissue mass with entire body mass and the application of the software supplied by the manufacturer. Further, it reveals that such BIA is a double indirect method that measures body fat through proper estimation of the total body water and then conversion of %BF through the prediction equation.

OBJECTIVE -- To validate fasting indexes against minimal model analysis (MMOD) of the frequently sampled intravenous glucose tolerance test (FSIVGTT) in an obese pediatric population. RESEARCH DESIGN AND METHODS -- FSIVGTT-MMOD results were compared with homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin with the sample stratified by sex, puberty, and sensitivity index (Si) median in 191 children (82 males and 109 females, 13.9 ± 2.9 years of age, BMI 36.9 ± 6.2 kg/m², BMI SD score 6.1 ± 1.6). RESULTS -- Across pubertal groups, correlation coefficients between Si, and HOMA-IR ranged from -0.43 to -0.78 in males and from -0.53 to -0.57 in females (age and BMI adjusted, P < 0.05 in all instances). Similar results were seen for fasting insulin. In females, the relationship was significantly weaker in more-insulin-resistant subjects. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

A response by Julia F. Simard and colleagues to a letter to the editor about the article "Mortality rates in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: drug-specific comparisons in the Swedish Biologics Register" is presented.

The article discusses research which investigated perinatal outcomes in women with history of bariatric surgery. It acknowledges increased risk of women who previously undergone bariatric surgery for preterm and small for gestational age births. It offers brief details about study procedures which include selection of participants and data analysis. A chart listing information on preterm birth and fetal growth outcomes recorded is also presented.

The article describes a study which investigated the association between blood pressure and subsequent mortality in Swedish adolescent men. The researchers examined whether systolic and diastolic blood pressures in late adolescence contribute to risk of death. The study revealed a stronger association between diastolic blood pressure and mortality, than systolic blood pressure.

The article discusses a randomised controlled trial that investigated the effect of weight loss on mild obstructive sleep apnoea in obese men. For treatment allocation, the researchers used a blocked randomisation procedure. The study involved sixty-three obese men who are suffering from severe obstructive sleep apnoea treated with continuous positive airway pressure. Study physicians suggested that there was a link between eight adverse events and very low energy diet. The article also mentions reasons for caution concerning the study.

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

Objectives To compare trajectories of marriage and parenthood in individuals with JIA vs the general population. Methods Patients with JIA (n  = 4399) were identified in the Swedish National Patient Register (2001–2016) and individually matched to up to five general population comparators on birthyear, sex and residence county (n  = 21 981). Marriage and parenthood data were retrieved from the Total Population Register from age 18 y, and parenthood from the Multigeneration Register from age 15 y, respectively. Hazard ratios (HRs) were estimated using Cox regression adjusted for parental education, parental marital status and number of siblings. Results During a median of 6.3 years of follow-up, 362 patients with JIA and 1744 comparators got married (12.9 vs. 12.5 per 1000 person-years; HR 1.03, 95%CI 0.93-1.15). During a median of 8.8 years of follow-up, 680 patients with JIA and 3477 matched comparators became parents (17.1 vs 17.8 per 1000 person-years; HR 0.94, 95%CI 0.87-1.01). In the subgroup of patients with systemic onset JIA (SJIA), the adjusted hazard ratios for marriage and parenthood were 0.79 (95%CI 0.53-1.17) and 0.73 (95%CI 0.55-0.97), respectively. Conclusion The times to first marriage and first parenthood are similar for patients with JIA and the general population, suggesting that adolescents with JIA transition into family life along a trajectory resembling their community peers. One exception is the subgroup of patients with systemic onset JIA, who become parents for the first time at a lower rate than general population comparators. [ABSTRACT FROM AUTHOR]

Objective Tumor necrosis factor (TNF) may affect tumor development and spreading. While data on the incidence of cancer following anti-TNF therapy have been published, the purpose of this study was to examine the clinical presentation and outcome of cancers that develop during or after anti-TNF therapy. Methods By linking data from Swedish clinical registries of rheumatoid arthritis (RA) patients, including Anti-Rheumatic Therapy in Sweden (ARTIS), the Swedish Biologics Register, with nationwide data on hospitalizations and outpatient visits for RA, we assembled a cohort of 78,483 RA patients who were alive in 1999 or who entered the cohort thereafter. Of these, 8,562 patients started therapy with a biologic agent (98% started an anti-TNF) during the period from January 1, 1999 to December 31, 2007. Linkage to the Swedish Cancer Register and other registers identified first primary cancers occurring during 1999-2007 as well as post-cancer survival through March 31, 2009. Through this linkage, we identified 314 cancers in patients who were undergoing, or had a history of, treatment with biologic agents and 4,650 cancers in patients who were biologics-naive at the time of cancer diagnosis. The distributions of tumor stage among the biologics-exposed and the biologics-naive patients were compared. The relative risk of death among the biologics-exposed versus the 586 matched biologics-naive cancer cases were assessed by Cox regression analyses. Through chart review in a defined subset, we gathered additional clinical information and validated the diagnoses. Results For all cancers combined, the distribution of cancer stages at the time of cancer diagnosis was largely similar between those in the biologics-exposed and the matched biologics-naive groups. Based on the total of 113 deaths among those with cancer in the biologics-exposed group versus the 256 deaths among those with cancer in the biologics-naive group, the relative risk of death following cancer associated with exposure to anti-TNF was 1.1 (95% confidence interval 0.8-1.6). Conclusion During routine care, cancers that occur following anti-TNF therapy are not characterized by any markedly altered stage at presentation or by altered post-cancer survival rates. [ABSTRACT FROM AUTHOR]

Abstract: Previous research has been inconclusive as to whether high peak bone mineral density (BMD, g/cm2) resulting from previous physical activity is retained with reduced activity later in life. The aim of this 12-year longitudinal study was to investigate the association between BMD loss and reduced physical activity (h/wk) at trabecular and cortical bone sites in men. Three groups with a mean age of 17 years at baseline were investigated: i) 51 athletes who discontinued their active careers during the follow-up period (former athletes), ii) 16 athletes who were active throughout the follow-up period (active athletes), and iii) 25 controls. BMD loss at the hip, spine, and pelvis (mainly trabecular bone) was compared to BMD loss at femur, humerus, and legs (mainly cortical bone) during a 12-year follow-up period. Across the total follow-up period in the total cohort, reduced physical activity was more strongly associated with changes at trabecular BMD sites, i.e. hip, spine, and pelvis (B =0.008–0.005 g/cm2 per weekly hour physical activity (h), p <0.001), than at cortical bone sites, i.e. humerus, legs (B =0.002–0.003 g/cm2/h, p <0.05), and femur (p >0.05). At the final follow-up, former athletes showed higher BMD than controls only at the cortical bone sites of the humerus, legs, and femur (difference 0.05–0.10 g/cm2, p <0.05). In conclusion, this study indicates that predominantly trabecular bone is lost with reduced physical activity levels in young men. Benefits were still evident at the more cortical sites eight years after the discontinuation of an active sports career. [Copyright &y& Elsevier]

It is unclear whether the high fracture incidence in Sweden compared with other countries is related to low bone mass. We present and compare bone mineral density (BMD, g/cm2) at the femoral neck in a mainly osteoporotic referral population consisting of 2,031 men and 6,932 women with that of previous population-based cohorts. BMD measurements were collected at a single study center in Sweden, and data on validated hip fractures were collected from the corresponding health-care district and the cohort investigated. The BMD values of our cohort were similar to those of population-based cohorts from other countries. In contrast, the total incidence of hip fractures in 80-year-old women and men in the health-care district where our BMD measurements were performed was high (1.8% and 0.9%, respectively). The correlation between age and BMD was more negative in men aged 20–49 years than in women of the same age group (–0.011 vs. –0.006 g/cm2 yearly, P < 0.001). In contrast, at 50–80 years of age, more negative regression coefficients were seen in women (–0.007 vs. –0.004 g/cm2 yearly, P < 0.001 for comparison). In conclusion, a low BMD may not be the key factor explaining Sweden’s comparatively high fracture incidence. In our cross-sectional data, age trends in BMD at the femoral neck differ between men and women. It would be highly interesting to further study the underlying causes of the global variations in fracture incidence rates. [ABSTRACT FROM AUTHOR]

Objective To compare mortality risk over up to 14 years of follow-up in methotrexate-refractory patients with early RA randomized to a strategy starting with addition of infliximab vs addition of SSZ and HCQ. Methods Data was from the two-arm, parallel, randomized, active-controlled, open-label Swefot trial in which patients with early RA (symptom duration <1 y) were recruited from 15 rheumatology clinics in Sweden (2002–2005). Patients who did not achieve low disease activity after 3–4 months of MTX were randomized to addition of infliximab (n  = 128) or SSZ and HCQ (n  = 130). Participants were followed until death, emigration, or end of follow-up, whichever came first. Analyses were by intention-to-treat. Results Over an average follow-up of 13 years, there were 13 and 16 deaths, respectively [8.8 vs 10.6 deaths per 1000 person-years; mortality hazard ratio 1.2 (95% CI: 0.6, 2.5); P  =0.62]. The 1-year mortality was 0.8% in both treatment arms, the 5-year mortality was 2.3% for the infliximab arm compared with 1.5% for the conventional combination treatment arm, while the 10-year mortality was 7.8% and 7.7%, respectively. After 5 years, ∼50% of patients in the conventional combination therapy arm had switched to biologic treatment, and 50% in the biologic arm had discontinued treatment with a biologic DMARD. Conclusion No difference in mortality risk could be observed over up to 14 years of follow-up between treatment strategy groups. At 5 years (3 years after trial cessation), 50% of patients remained on their assigned therapy, reflecting that DMARD combination is an adequate treatment strategy in 50% of patients. Trial registration clinicaltrials.gov, identifier: NCT00764725. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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 5 187,542). 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 costswere $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 difference5$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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence of violent crime conviction among Swedish military veterans after deployment to Afghanistan versus non-deployed comparators. The main outcome was first conviction of a violent crime, retrieved from the Swedish National Council for Crime Prevention Register until December 31, 2013.Methods: This was a cohort study of military veterans identified through personnel registers regarding deployment to Afghanistan between 2002 and 2013 (n = 5894). To each military veteran, up to five non-deployed comparators identified via the Military Service Conscription Register were matched by age, sex, conscription year, cognitive ability, psychological assessment, self-reported mental health, body mass index, antidepressants/anxiolytics prescriptions and self-harm (fully matched comparators; n = 28 895). Multivariable adjustment was made for substance abuse and previous health care visits with psychiatric diagnoses. An additional comparator group matched only for age, sex and conscription year was also used (age-sex-matched comparators; n = 29 410).Results: During 21 898 person-years of follow-up (median = 3.6 years) there were 26 events among deployed military veterans compared with 98 in non-deployed fully matched comparators [12 vs 9 per 10 000 person-years, adjusted hazard ratio (aHR) 1.36; 95% confidence interval (CI) 0.88-2.10]. Among non-deployed age-sex-matched comparators there were 170 violent crime convictions (16 per 10 000 person-years; aHR 0.85; 95% CI 0.56-1.29). Factors associated with greater risk of violent crime convictions were younger age, lower scores on cognitive ability tests and psychological assessment, and convictions preceding deployment.Conclusion: The violent crime conviction rate after returning from military deployment to Afghanistan was not different compared with non-deployed comparators in individuals without history of violent crime convictions. [ABSTRACT FROM AUTHOR]

Aim: To investigate the probability of marriage and divorce among Swedish military veterans deployed to Afghanistan relative to non-deployed matched comparators. Study design and setting: Matched cohort study in Sweden. Participants: Military veterans were identified through Swedish military personnel registers regarding foreign deployments, and comparators from the Military Service Conscription Register (1969–2013). Of 1,882,411 eligible conscripts, 7041 had served in Afghanistan at some point in time between 2002 and 2013. To each military veteran, up to 5 non-deployed comparators who underwent conscription were matched by age, sex, psychological assessment, cognitive ability, psychiatric history and social characteristics. After matching there were 4896 (82%) unmarried and 1069 (18%) married deployed military veterans. The main outcome was marriage or divorce after deployment to Afghanistan. Data on marital status were retrieved from Statistics Sweden until December 31, 2014. Results: During a median follow-up of 4.1 years after deployment of married individuals, 124 divorces were observed among deployed military veterans and 399 in the matched non-deployed comparator cohort (277 vs. 178 per 10,000 person-years; adjusted hazard ratio 1.61, 95%CI 1.31–1.97). During a median follow-up of 4.7 years after deployment in the unmarried cohort, 827 new marriages were observed among deployed military veterans and 4363 in the matched non-deployed comparators cohort (399 vs. 444 per 10,000 person-years; adjusted hazard ratio 0.89, 95%CI 0.83–0.96). Conclusion: Military veterans were more likely to divorce and less likely to marry after deployment compared with matched non-deployed comparators. [ABSTRACT FROM AUTHOR]

Background: Obesity increases the risk of adverse delivery outcomes. Whether weight loss induced by bariatric surgery influences these risks remains to be determined. The objective was to investigate the risk of adverse delivery outcomes among post-surgery women compared with women without bariatric surgery history but with similar characteristics.Methods and Findings: We identified 801,443 singleton live-born term births (≥37 gestational weeks) in the Swedish Medical Birth Register between 1 January 2006 and 31 December 2013, of which 1,929 were in women with a history of bariatric surgery and a pre-surgery weight available from the Scandinavian Obesity Surgery Registry. For each post-surgery delivery, up to 5 control deliveries were matched by maternal pre-surgery BMI (early-pregnancy BMI used for controls), age, parity, smoking, education, height, country of birth, and delivery year (N post-surgery deliveries:matched controls = 1,431:4,476). The main outcome measures were mode of delivery, induction of labor, post-term pregnancy (≥42 + 0 gestational weeks), epidural analgesia, fetal distress, labor dystocia, peripartum infection, obstetric anal sphincter injury (perineal tear grade III-IV), and postpartum hemorrhage. Among the women with a history of bariatric surgery, the mean pre-surgery BMI was 42.6 kg/m2, the median surgery-to-conception interval was 1.4 years, and the mean BMI loss between surgery and early pregnancy was 13.5 kg/m2 (38 kg). Compared to matched control women, post-surgery women were less likely to have cesarean delivery (18.2% versus 25.0%, risk ratio [RR] 0.70, 95% CI 0.60-0.80), especially emergency cesarean (6.8% versus 15.1%, RR 0.40, 95% CI 0.31-0.51). Post-surgery women also had lower risks of instrumental delivery (5.0% versus 6.5%, RR 0.73, 95% CI 0.53-0.98), induction of labor (23.4% versus 34.0%, RR 0.68, 95% CI 0.59-0.78), post-term pregnancy (4.2% versus 10.3%, RR 0.40, 95% CI 0.30-0.53), obstetric anal sphincter injury (1.5% versus 2.9%, RR 0.46, 95% CI 0.25-0.81), and postpartum hemorrhage (4.6% versus 8.0%, RR 0.58, 95% CI 0.44-0.76). Since this study was not randomized, a limitation is the possibility of selection bias, despite our efforts using careful matching.Conclusions: Bariatric-surgery-induced weight loss was associated with lower risks for adverse delivery outcomes in term births. [ABSTRACT FROM AUTHOR]

Aim A population-based cohort and four randomized trials enriched with long-term register data were used to clarify if radiotherapy in combination with rectal cancer surgery is associated with increased risks of cardiovascular disease (CVD). Methods We identified 14,901 rectal cancer patients diagnosed 1995–2009 in Swedish nationwide registers, of whom 9227 were treated with preoperative radiotherapy. Also, we investigated 2675 patients with rectal cancer previously randomized to preoperative radiotherapy or not followed by surgery in trials conducted 1980–1999. Risks of CVD overall and subtypes were estimated based on prospectively recorded hospital visits during relapse-free follow-up using multivariable Cox regression. Maximum follow-up was 18 and 33 years in the register and trials, respectively. Results We found no association between preoperative radiotherapy and overall CVD risk in the register (Incidence Rate Ratio, IRR = 0.99, 95% confidence interval (CI) 0.92–1.06) or in the pooled trials (IRR = 1.07, 95% CI 0.93–1.24). We noted an increased risk of venous thromboembolism among irradiated patients in both cohorts (IRR register  = 1.41, 95% CI 1.15–2.72; IRR trials  = 1.41, 95% CI 0.97–2.04), that remained during the first 6 months following surgery among patients treated 2006–2009, after the introduction of antithrombotic treatment (IRR 6 months  = 2.30, 95% CI 1.01–5.21). However, the absolute rate difference of venous thromboembolism attributed to RT was low (10 cases per 1000 patients and year). Discussion Preoperative radiotherapy did not affect rectal cancer patients’ risk of CVD overall. Although an excess risk of short-term venous thromboembolism was noted, the small increase in absolute numbers does not call for general changes in routine prophylactic treatment, but might do so for patients already at high risk of venous thromboembolism. [ABSTRACT FROM AUTHOR]

The clear dose-dependent weight loss effect that we found in our study2 strongly supports the importance of gastric-bypass-induced weight loss on pre-eclampsia risk. I Sir, i We find it unlikely that the effect of calcium and vitamin D supplementation would be large enough to be equal to/compete with the metabolic and weight loss effects of gastric bypass in severely obese women and thereby, as van Gelder et al.1 put it, make it 'challenging to distinguish between the effect of gastric bypass itself and the effect of vitamin D and calcium supplementation'. Although calcium and vitamin D supplementation could have contributed to the substantial risk reduction of pre-eclampsia in the gastric bypass group, we do not agree with van Gelder et al. SP 1 sp that stating 'gastric bypass in itself is effective in the prevention of pre-eclampsia may still be considered premature'. [Extracted from the article]

Background: Associations of obesity with incidence of heart failure have been observed, but the causality is uncertain. We hypothesized that gastric bypass surgery leads to a lower incidence of heart failure compared with intensive lifestyle modification in obese people.Methods: We included obese people without previous heart failure from a Swedish nationwide registry of people treated with a structured intensive lifestyle program and the Scandinavian Obesity Surgery Registry. All analyses used inverse probability weights based on baseline body mass index and a propensity score estimated from baseline variables. Treatment groups were well balanced in terms of weight, body mass index, and most potential confounders. Associations of treatment with heart failure incidence, as defined in the National Patient Register, were analyzed with Cox regression.Results: The 25 804 gastric bypass surgery patients had on average lost 18.8 kg more weight after 1 year and 22.6 kg more after 2 years than the 13 701 lifestyle modification patients. During a median of 4.1 years, surgery patients had lower heart failure incidence than lifestyle modification patients (hazard ratio, 0.54; 95% confidence interval, 0.36-0.82). A 10-kg achieved weight loss after 1 year was related to a hazard ratio for heart failure of 0.77 (95% confidence interval, 0.60-0.97) in both treatment groups combined. Results were robust in sensitivity analyses.Conclusions: Gastric bypass surgery was associated with approximately one half the incidence of heart failure compared with intensive lifestyle modification in this study of 2 large nationwide registries. We also observed a graded association between increasing weight loss and decreasing risk of heart failure. [ABSTRACT FROM AUTHOR]

Importance: Maternal overweight and obesity are associated with increased risks of preterm delivery, asphyxia-related neonatal complications, and congenital malformations, which in turn are associated with increased risks of cerebral palsy. It is uncertain whether risk of cerebral palsy in offspring increases with maternal overweight and obesity severity and what could be possible mechanisms.Objective: To study the associations between early pregnancy body mass index (BMI) and rates of cerebral palsy by gestational age and to identify potential mediators of these associations.Design, Setting, and Participants: Population-based retrospective cohort study of women with singleton children born in Sweden from 1997 through 2011. Using national registries, children were followed for a cerebral palsy diagnosis through 2012.Exposures: Early pregnancy BMI.Main Outcomes and Measures: Incidence rates of cerebral palsy and hazard ratios (HRs) with 95% CIs, adjusted for maternal age, country of origin, education level, cohabitation with a partner, height, smoking during pregnancy, and year of delivery.Results: Of 1 423 929 children included (mean gestational age, 39.8 weeks [SD, 1.8]; 51.4% male), 3029 were diagnosed with cerebral palsy over a median 7.8 years of follow-up (risk, 2.13 per 1000 live births; rate, 2.63/10 000 child-years). The percentages of mothers in BMI categories were 2.4% at BMI less than 18.5 (underweight), 61.8% at BMI of 18.5 to 24.9 (normal weight), 24.8% at BMI of 25 to 29.9 (overweight), 7.8% at BMI of 30 to 34.9 (obesity grade 1), 2.4% at BMI of 35 to 39.9 (obesity grade 2), and 0.8% at BMI 40 or greater (obesity grade 3). The number of cerebral palsy cases in each BMI category was 64, 1487, 728, 239, 88, and 38; and the rates per 10 000 child-years were 2.58, 2.35, 2.92, 3.15, 4.00, and 5.19, respectively. Compared with children of normal-weight mothers, adjusted HR of cerebral palsy were 1.22 (95% CI, 1.11-1.33) for overweight, 1.28 (95% CI, 1.11-1.47) for obesity grade 1, 1.54 (95% CI, 1.24, 1.93) for obesity grade 2, and 2.02 (95% CI, 1.46-2.79) for obesity grade 3. Results were statistically significant for children born at full term, who comprised 71% of all children with cerebral palsy, but not for preterm infants. An estimated 45% of the association between maternal BMI and rates of cerebral palsy in full-term children was mediated through asphyxia-related neonatal morbidity.Conclusions and Relevance: Among Swedish women with singleton children, maternal overweight and obesity were significantly associated with the rate of cerebral palsy. The association was limited to children born at full term and was partly mediated through asphyxia-related neonatal complications. [ABSTRACT FROM AUTHOR]

Objective. To compare work-loss in RA patients starting their first biologic with high vs moderate disease activity. Methods. We identified all RA patients aged 20-63 years in the Swedish Biologics Register who started their first biologic 2007-09 with high disease activity (DAS28 >5.1; n = 868) or moderate disease activity (DAS28 3.2-5.1; n = 854). Work days lost, defined as sick leave and disability pension days from the Swedish Social Insurance Agency, were assessed over 5 years after first bio-start. We estimated be-tween-group mean differences adjusted for age, sex, calendar year, education level, disease duration, comorbidities and work-loss the month before bio-start. Results. During 5 years after anti-TNF start, mean monthly work days lost declined from 16.0 to 9.2 (42%; P< 0.001) in patients with high disease activity at baseline and from 12.0 to 7.2 (40%; P< 0.001) in patients with moderate disease activity, with no between-group difference (adjusted mean difference 0.81; 95% CI-0.44, 2.05). Accumulated 5-year work-loss was, however, higher in the high activity group (724 vs 548 days; adjusted mean difference 70; 95% CI 20, 120), but after stratification on baseline disability pension status, no differences in accumulated work-loss were detected. Conclusion. Substantial work-loss was seen in both patients with high and patients with moderate disease activity at anti-TNF start, with a 5-year decline in mean monthly work days lost by ~40% in both groups and no between-group difference. Accumulated work-loss over 5 years was higher in the high-activity group, which may be explained by differences in baseline disability pension status. [ABSTRACT FROM AUTHOR]

Purpose.To investigate if testicular cancer survivors (TCSs) have a higher incidence of work loss compared with the population, accounting for stage, treatment and relapse. Material and methods.A cohort of 2146 Swedish TCSs diagnosed 1995–2007 (seminoma n = 926, non-seminoma n = 1220) was identified in the SWENOTECA (Swedish-Norwegian Testicular Cancer Group) register, and matched 1:4 to population comparators. Prospectively recorded work loss data (both before and after diagnosis) were obtained from national registers through September 2013. Adjusted relative risks (RR) and 95% confidence intervals (CI) of sick leave and/or disability pension were calculated annually and overall with Poisson- and Cox regression, censoring at relapse. The mean number of annual work days lost was also estimated. Results.TCSs were at a modestly increased annual risk of work loss up to the third year of follow-up (RR3rd year1.25, 95% CI 1.08, 1.43), attributed to a more pronounced risk among extensively treated patients (4 chemotherapy courses: RR3rd year1.60, 95% CI 1.19, 2.15; > 4 courses: RR3rd year3.70, 95% CI 2.25, 6.11). Patients on surveillance or limited treatment (radiotherapy, 1–3 chemotherapy courses) did not have an increased risk of work loss beyond the first year. TCSs receiving > 4 chemotherapy courses had higher mean number of annual days of work loss up to the 10th year post-diagnosis, and a five-fold risk of disability pension (RR 5.16, 95% CI 2.00, 10.3). Conclusion.Extensively treated TCSs, but not those on surveillance or limited treatment, are at increased risk of work loss long-term, not explained by relapse. These patients may benefit from early rehabilitation initiatives. [ABSTRACT FROM PUBLISHER]

Objective. To investigate whether disease activity at baseline influences health care costs in patients with RA initiating biologic treatment. Methods. In the Swedish Biologics Register, we identified patients with RA with baseline 28-joint DAS (DAS28) recorded and starting their first biologic in 2007-11 [n = 1638 with moderate disease activity (DAS28 3.2-5.1) and n = 1870 with high disease activity (DAS28>5.1)]. Data on inpatient and outpatient care and prescription drugs were retrieved from nationwide registers. Mean cost differences were estimated adjusted for age, sex and costs the year before treatment start. Results. Patients with high (vs moderate) disease activity were older (60 vs 56 years; P < 0.001), but did not differ in sex distribution (75 vs 74% women; P = 0.99) or disease duration (10 vs 10 years; P=0.13). The year after initiation of biologics, patients with high (vs moderate) baseline disease activity accumulated 9% higher health care costs, but the difference was not statistically significant after adjustment [E19333 vs E17810; adjusted difference E870 (95% CI -2, 1742)]. In the subgroup of patients with up to 4 years of follow-up data, decreasing costs were observed over the follow-up time, but no difference was found between patients with high compared with moderate baseline disease activity [E13 704 vs E12 349; adjusted difference 878 (95% CI -364, 2120)]. Irrespective of baseline disease activity, health care costs were approximately three times higher the year after initiation of biologics than the year before due to increased drug costs. Conclusion. Over up to 4 years of follow-up, no difference in health care costs was found after adjustment in patients starting their first biologic treatment with high vs moderate baseline disease activity. [ABSTRACT FROM AUTHOR]

This pharmacoepidemiology study uses Norwegian registry data to investigate associations between fluconazole use during pregnancy and subsequent stillbirth and neonatal death. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Outcomes of Pregnancy after Bariatric Surgery" in the February 26, 2015 issue is presented.