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Background: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is associated with increased risk of liver disease and chronic obstructive pulmonary disease (COPD), but the risk of venous thromboembolism (VTE) is unknown. Our aim was to evaluate the risk of VTE in individuals with severe AATD compared with control subjects from the general population. Methods: Individuals with severe AATD (n = 1577) were recruited from the Swedish national AATD register. Control subjects (n = 5969) were selected from the OLIN (Obstructive Lung Disease in Northern Sweden) studies, that include a random general population sample. Longitudinal data on VTE and diagnoses were obtained from the Swedish National Patient Registry. Associations were analyzed using multivariable Cox regression. Results: At inclusion, 46% of the AATD individuals and 53% of the controls were never-smokers. COPD was present in 46% of the AATD individuals compared with 4% of the controls. During a median follow-up of 18 years, 116 (7%) of the AATD individuals and 89 (1%) of the control subjects developed VTE, unadjusted hazard ratio 6.5 (95% confidence interval 4.9–8.6). Risk factors for incident VTE were male gender, age, COPD, cancer, and liver disease. Adjusting for these factors, the AATD individuals had a significantly higher risk of incident VTE, adjusted hazard ratio 4.2 (95% confidence interval 2.9–6.2) as compared with the controls. Conclusion: Subjects with severe AATD have considerably increased risk of developing VTE compared with the general population, even after accounting for risk factors. This calls for optimized risk factor management and clinical follow-up of this patient group. (Less)

Daily school physical activity (PA) improves musculoskeletal traits. This study evaluates whether the benefits remain 4 years after the intervention. We followed 45 boys and 36 girls who had had 40 min PA/school day during the nine compulsory school years and 21 boys and 22 girls who had had 60 min PA/school week (reference), with measurements at baseline and 4 years after the program terminated. Bone mineral content (BMC; g) and bone mineral density (BMD; g/cm2) were measured by dual-energy X-ray absorptiometry and knee flexion peak torque relative to total body weight (PTflexTBW) at a speed of 180 degrees/second with a computerized dynamometer. Group differences are presented as mean differences (adjusted for sex and duration of follow-up period) with 95% confidence intervals. The total gain bone mass [mean difference in spine BMC +32.0 g (14.6, 49.4) and in arms BMD of +0.06 g/cm2 (0.02, 0.09)] and gain in muscle strength [mean difference in PTflex180TBW +12.1 (2.0, 22.2)] were greater in the intervention than in the control group. There are still 4 years after the intervention indications of benefits in both bone mass and muscle strength gain. Daily school PA may counteract low bone mass and inferior muscle strength in adult life. ClinicalTrials.gov.NCT000633828 retrospectively registered 2008-11-03

Background Distal forearm fracture is the most common pediatric fracture. As studies have indicated time trends in fracture incidence, we wanted to update the epidemiology and estimate time trends between 1950 and 2016 in Malmö, Sweden. Methods The city of Malmö, Sweden, had 318,107 inhabitants (58,585 of the population was aged Results Childhood distal forearm fracture incidence in 2014 to 2016 was 546/100,000 person-years (660 in boys and 427 in girls). The age-adjusted incidence in 2014 to 2016 and in 2005 to 2006 was similar (boys IRR 1.0, 95% CI: 0.9–1.2 and girls IRR 1.1, 95% CI: 0.9–1.3). Time-trend analyses from 1950 to 2016 revealed increasing age-adjusted incidence in both boys (APC +0.9%, 95% CI: 0.7–1.2) and girls (APC +0.6%, 95% CI: 0.3–0.9). Conclusion Distal forearm fracture incidence was similar in 2014 to 2016 and in 2005 to 2006. Age-adjusted incidence had increased in both sexes from 1950 to 2016. Level of Evidence This is a Level III b study.

Background and purpose — We have previously reported on the prosthetic survival of total ankle replacements (TAR) in Sweden performed between 1993 and 2010. Few other reports have been published on 5- and 10-year survival rates. Furthermore, there is a lack of long-term outcome data on modern prosthetic designs. Therefore, we compared early and current prosthetic designs after a mean 7-year follow-up. Patients and methods — On December 31, 2016, 1,230 primary TARs had been reported to the Swedish Ankle Registry. We analyzed prosthetic survival, using exchange or permanent extraction of components as endpoint for 1,226 protheses with mean follow-up of 7 years (0–24). Differences between current (Hintegra, Mobility, CCI, Rebalance, and TM Ankle) and early prosthetic designs (STAR, BP, and AES) were examined by log rank test. Results — 267/1,226 prostheses (22%) had been revised by December 31, 2016. We found an overall prosthetic survival rate at 5 years of 0.85 (95% CI 0.83–0.87), at 10 years 0.74 (CI 0.70–0.77), at 15 years 0.63 (CI 0.58–0.67), and at 20 years 0.58 (CI 0.52–0.65). For early prosthetic designs the 5- and 10-year survival rates were 0.81 (CI 0.78–0.84) and 0.69 (CI 0.64-0.73) respectively, while the corresponding rates for current designs were 0.88 (CI 0.85–0.91) and 0.84 (CI 0.79–0.88). Current prosthetic designs had better survival (log rank test p < 0.001). Interpretation — Our results point to a positive time trend of prosthetic survival in Sweden; use of current prosthetic designs was associated with better prosthetic survival. Improved designs and instrumentation, more experienced surgeons, and improved patient selection may all have contributed to the better outcome.

Daily school physical activity (PA) improves musculoskeletal traits. Whether or not benefits remain in adulthood is debated. We included in this study 131 children that took part in an intervention with 40 minutes of PA per school day (200 minutes per week) from age 6 to 9 years (grade one) to age 14 to 16 years (grade nine), whereas 78 children continued with national recommended school physical education of 60 minutes per week. Measurements were done with dual‐energy X‐ray absorptiometry (bone mineral content [BMC], bone mineral density [BMD], and bone area), and a computerized knee dynamometer (peak torque muscle strength) at study start, at the end of the intervention, and 7 years after the intervention. Group differences from study start and end of the intervention to 7 years thereafter were estimated by analyses of covariance (adjusted for sex and follow‐up time). Musculoskeletal gains from study start to 7 years after termination of the intervention were higher in the intervention group (total body less head BMC +182.5 g [95% confidence interval {CI}, 55.1–309.9] and BMD +0.03 g/cm2 [95% CI, 0.003–0.05], femoral neck area + 0.2 cm2 [95% CI, 0.1–0.4], and knee flexion peak torque muscle strength at 60 degrees per second +9.2 Nm [95% CI, 2.9–15.5]). There was no attenuation during the 7 years that followed termination of the intervention (all group comparisons p > 0.05). Benefits in musculoskeletal gains remain 7 years after termination of a daily school‐based PA program, without attenuation after termination of the program. Daily school PA may counteract low bone mass and inferior muscle strength in adulthood. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Gain from mean age 8 to age 23 in total body less head and femoral neck BMC/BMD, femoral neck area and knee flexion peak torque muscle strength (absolute and relative to body weight) in individuals with daily school physical activity expressed in standard deviations (SD), compared to mean gain in the control group (0.0 SD) with the bars representing the 95 percent confidence intervals.

Screen time and physical inactivity have increased among children. As physical activity is a determinant of bone mass, there is a concern that children today have lower bone mass than earlier. If this is true, fractures may become more common in the future. In 2017–2018, we used single‐photon absorptiometry (SPA) to measure distal forearm bone mineral density (BMD; mg/cm2) in a normative cohort of 238 boys and 204 girls aged 7 to 15 years. We compared these results to BMD in a normative cohort collected in 1979–1981 (55 boys and 61 girls aged 7 to 15 years) measured by the same scanner. To investigate difference between the two cohorts, we used multiple linear regression with age, sex, and cohort as predictors. Predicted bone density at age 16 years was estimated through the slope values. The bone density‐age slope was flatter in the cohort measured in 2017–2018 than in the cohort measured 1979–1981 (−5.6 mg/cm2/yr [95% confidence interval −9.6 to −1.5]). Predicted bone density was at age 16 years in 2017–2018 in boys was 10% lower (−0.9 SD) and in girls 11% lower (−1.1 SD) than in their counterparts measured in 1979–1981. We found indications that children nowadays develop lower bone mass than four decades ago, giving concern that they may have a higher risk of osteoporosis and fragility fractures as they grow old. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Background and aim: The value of the forced expiratory volume in one second (FEV1) is useful in the diagnosis and prognosis of chronic obstructive pulmonary disease (COPD). Previous studies on lung function in individuals with severe alpha-1 antitrypsin deficiency (AATD) have shown a variable annual decline in FEV1 (∆FEV1). The aim of this study was to analyze ∆FEV1 and to identify risk factors for ∆FEV1 in individuals with severe AATD. Material and methods: Data on smoking habits, symptoms, results of lung function tests and exacerbations were obtained from the Swedish AATD Register and the Swedish National Patient Register (SNPR). The ∆FEV1 was analyzed by random-effects modeling and adjusted for age and FEV1 at baseline. Results: One hundred and four (9%) current smokers, 539 (48%) ex-smokers and 489 (43%) never-smokers were included in the study and followed-up from 1991 to 2016. A total of 584 (52%) individuals with severe AATD had COPD at inclusion. The median (IQR) annual severe exacerbation rate was 0.66 (1.4). The adjusted mean ∆FEV1 was significantly higher in the current smokers compared with the ex-smokers and never-smokers (70 [95% CI 56-83] vs 42 [95% CI 36-48] and 32 [95% CI 25-38) mL·yr-1], in the middle-aged individuals compared with the young individuals (48 [95% CI 41-55] vs 32 [95% CI 18-45] mL·yr-1), in the individuals with respiratory symptoms at inclusion compared with the asymptomatic individuals (46 [95% CI 40-52] vs 30 [95% CI 22-38]mL·yr-1), and in the individuals with frequent exacerbations compared with those with infrequent exacerbations (57 [95% CI 47-68] vs 27 [95% CI 17-37] mL·yr-1). Conclusion: Active smoking, age, respiratory symptoms at baseline and repeated severe exacerbations of COPD are factors associated with an accelerated decline of lung function in individuals with severe AATD.

Background The hand is the second most fractured region in children. It is therefore important to update fracture epidemiology to be able to identify time trends for adequate health care planning. This study reports pediatric hand fracture incidence 2014–2016 and, using published data, also long-term time trends in 1950–2016. Patients and methods The Swedish city of Malmö, with 328,494 inhabitants in 2016, has only one hospital. We used the hospital radiological archive, medical charts, and diagnosis registry to identify hand fractures in city residents Results In 2014–2016 phalangeal fractures accounted for 71% of all hand fractures, metacarpal fractures for 24%, and carpal fractures for 5%. We identified 615 hand fractures (419 in boys and 196 in girls) during 181,617 person-years in 2014–2016, resulting in an unadjusted pediatric hand fracture incidence of 339/100,000 person-years (boys 452/100,000 person-years and girls 220/100,000 person-years). The age-adjusted incidence 2014–2016 was similar to 2005–2006, the most recently evaluated period (IRR in boys 0.9; 95% CI 0.8 to 1.01, and in girls 1.0; 95% CI 0.8 to 1.2). Looking at the entire period 1950–2016, we found that age-adjusted incidence increased in 1950–1979, in boys by APC + 3.8%; 95% CI 3.0 to 4.5 and in girls by + 3.9%; 95% CI 2.8 to 5.0, but decreased in 1979–2016, in boys by − 0.7%; 95% CI − 1.4 to − 0.003, and girls by − 1.3%; 95% CI − 2.4 to − 0.1. Conclusions Phalangeal fractures accounted for about three quarters of all hand fractures. The age-adjusted hand fracture incidence increased in both sexes in 1950–1979 and decreased in 1979–2016. Level of evidence III

AIM: To, in children, investigate the associations between serum furin, obesity, overweight, body fat and circulating markers reflecting adipose tissue or systemic inflammation. METHODS: We analysed furin, leptin, adipocyte fatty acid-binding protein, triglycerides, interleukin (IL)-6, IL-8 and C-reactive protein in serum from 166 children in the Pediatric Osteoporosis Prevention (POP) study collected at mean age (SD) 9.9 (0.6) years. Children were classified as low-to-normal weight, overweight or obese. Total body fat mass (kg), trunk fat mass (kg) and total body lean mass (kg) were measured by dual-energy X-ray absorptiometry. Body fat percentage (%) was calculated. RESULTS: We found that circulating furin levels were higher in children with obesity and overweight compared with children with low-to-normal weight (p

Background: Age, sex, and body constitution may affect the shedding of membrane bound angiotensin-converting enzyme 2 (mACE2) and lead to a relative mACE2 deficiency. However, it is unclear if differences, reflected by serum renin levels, exist in the basal renin-angiotensin-system (RAS) between children and adults, boys, and girls as well as young women and young men. Furthermore, it remains to be investigated if renin and soluble ACE2 (sACE2) levels are correlated with body mass index (BMI) in children and young adults. The aim of this observational study was to assess age-and sex differences in serum renin, and the relationship between renin, soluble angiotensin-converting enzyme 2, and body mass index in a prospectively followed population-based cohort of children which were followed into young adulthood.Study Design: We analyzed renin and sACE2 in serum in a prospectively followed population-based cohort at 9.9 (0.6) [mean (SD)] (n = 173), 11.7 (0.6) (n = 156), 14.8 (0.8) (n = 149), 18.8 (0.3) (n = 93), and 23.5 (0.7) (n = 152) years of age. Height (cm) and weight (kg) was measured and body mass index (BMI) was calculated as weight (kg)/height (m)2. Sex-related differences in renin levels were calculated using analysis of covariance, adjusted for age. Correlations were assessed by calculating the correlation coefficient (R2) using a multivariable linear mixed model.Results: Both sexes had low renin levels up to 12 years of age. Thereafter renin levels increased more in boys than in girls. Males from the age of 15 had significantly higher levels than females (p < 0.001). There was a positive linear relationship between renin and sACE2 levels in male and female subjects (p < 0.001), and between sACE2 levels and BMI in males (p < 0.001).Conclusion: Renin levels increase with age, are higher in men than in women since around puberty, and are correlated with sACE2 levels. Furthermore, sACE2 levels are correlated with body mass index in males. These findings indicate that high renin levels in males and females and a high BMI in males may activate pathways which increase the shedding of mACE2, with possible implications for the risk of severe coronavirus disease 2019.

Background and purpose — Arthrodesis is the most common treatment of severe ankle arthritis. Large studies on the occurrence of re-arthrodesis are few, especially with information in terms of risk. We used the National Swedish Ankle Registry to assess incidence and risk factors for re-arthrodesis. Patients and methods — In the Registry, we examined the occurrence of re-arthrodesis in 1,716 patients with a primary ankle arthrodesis. We also analyzed associations between the re-arthrodesis risk and sex, diagnosis, and surgical method. Results — The risk of first re-arthrodesis at 2.5 years was 7.4% and the rate at 9 years 7.8%. The risk following arthroscopic surgery with fixation by screws was 15%, which is statistically significantly higher than the 8% following the gold standard technique with open screw fixation, the 5% following fixation by intramedullary nailing, and the 3% following fixation by plate and screws. Patients with either idiopathic osteoarthritis or posttraumatic arthritis had a higher risk of re-arthrodesis than patients with rheumatoid arthritis. We could not find that the risk of re-arthrodesis was associated with sex. Interpretation — In Sweden, the re-arthrodesis risk varied by primary technique and was especially high after arthroscopic surgery. Reasons are unknown but poor surgical technique and/or surgeon inexperience may contribute, as may patient selection.