Prospective risk of Type 2 diabetes in 99 892 Nordic women with polycystic ovary syndrome and 446 055 controls: national cohort study from Denmark, Finland, and Sweden.

STUDY QUESTION: What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls? SUMMARY ANSWER: A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries. WHAT IS KNOWN ALREADY: The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited. STUDY DESIGN, SIZE, DURATION: This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort included women originating from Denmark (PCOS Denmark, N = 27 016; controls, N = 133 994), Finland (PCOS Finland, N = 20 467; controls, N = 58 051), and Sweden (PCOS Sweden, N = 52 409; controls, N = 254 010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0-14.8), 9.8 (5.1-15.1), and 6.0 (2.0-10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education. MAIN RESULTS AND THE ROLE OF CHANCE: The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98-4.60) in Denmark, 3.40 (3.11-3.74) in Finland, and 5.68 (5.20-6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs <25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99 892; controls, N = 446 055), the crude HR for T2D in PCOS was 4.64 (3.40-5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32-3.51). LIMITATIONS, REASONS FOR CAUTION: Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2. STUDY FUNDING/COMPETING INTEREST(S): Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Mortality after major lower extremity amputation and association with index level: a cohort study based on 11,205 first-time amputations from nationwide Danish databases.

BACKGROUND AND PURPOSE: Mortality after major lower extremity amputations is high and may depend on amputation level. We aimed to examine the mortality risk in the first year after major lower extremity amputation divided into transtibial and transfemoral amputations. METHODS: This observational cohort study used data from the Danish Nationwide Health registers. 11,205 first-time major lower extremity amputations were included from January 1, 2010, to December 31, 2021, comprising 3,921 transtibial amputations and 7,284 transfemoral amputations. RESULTS: The 30-day mortality after transtibial amputation was overall 11%, 95% confidence interval (CI) 10-12 (440/3,921) during the study period, but declined from 10%, CI 7-13 (37/381) in 2010 to 7%, CI 4-11 (15/220) in 2021. The 1-year mortality was 29% overall, CI 28-30 (1,140 /3,921), with a decline from 31%, CI 21-36 (117/381) to 20%, CI 15-26 (45/220) during the study period. For initial transfemoral amputation, the 30-day mortality was overall 23%, CI 22-23 (1,673/7,284) and declined from 27%, CI 23-31 (138/509) to 22%, CI 19-25 (148/683) during the study period. The 1-year mortality was 48% overall, CI 46-49 (3,466/7,284) and declined from 55%, CI 50-59 (279/509) to 46%, CI 42-50 (315/638). CONCLUSION: The mortality after major lower extremity amputation declined in the 12-year study period; however, the 1-year mortality remained high after both transtibial and transfemoral amputations (20% and 46% in 2021). Hence, major lower extremity amputation patients constitute one of the most fragile orthopedic patient groups, emphasizing an increased need for attention in the pre-, peri-, and postoperative setting.

Major lower extremity amputations - risk of re-amputation, time to re-amputation, and risk factors: a nationwide cohort study from Denmark.

BACKGROUND AND PURPOSE: Re-amputation after lower extremity amputation is frequent. The primary aim of our study was to investigate cumulative re-amputation risk after transtibial amputation (TTA), knee disarticulation (KD), and transfemoral amputation (TFA) and secondarily to investigate time to re-amputation, and risk factors. METHODS: This observational cohort study was based on data from the Danish Nationwide Health registers. The population included first-time major lower extremity amputations (MLEA) performed in patients ≥ 50 years between 2010 and 2021. Both left and right sided MLEA from the same patient were included as index procedures. RESULTS: 11,743 index MLEAs on 10,052 patients were included. The overall cumulative risks for re-amputation were 29% (95% confidence interval [CI] 27-30), 30% (CI 26-35), and 11% (CI 10-12) for TTA, KD, and TFA, respectively. 58% of re-amputations were performed within 30 days after index MLEA. Risk factors for re-amputation within 30 days were dyslipidemia (hazard ratio [HR] 1.2, CI 1.0-1.3), renal insufficiency (HR 1.2, CI 1.1-1.4), and prior vascular surgery (HR 1.3, CI 1.2-1.5). CONCLUSION: The risk of re-amputation was more than twice as high after TTA (29%) and KD (30%) compared with TFA (11%). Most re-amputations were conducted within 30 days of the index MLEA. Dyslipidemia, renal insufficiency, and prior vascular surgery were associated with higher risk of re-amputation.

Cardiovascular and metabolic morbidity in women with previous gestational diabetes mellitus: a nationwide register-based cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes and has maternal health implications reaching beyond the perinatal period. We aimed to investigate the incidence and severity of cardiovascular and metabolic morbidity in women with previous GDM in a Danish population and to study whether proxies of impaired beta cell function-insulin treatment during GDM pregnancy and development of subsequent manifest diabetes mellitus-influence incident risk of cardiovascular and metabolic morbidity. METHODS: A nationwide register-based cohort study was conducted on the complete cohort of 700,648 women delivering in Denmark during 1997-2018. The exposure variable was GDM and primary outcome was overall cardiovascular and metabolic morbidity. Secondary outcomes were major cardiovascular disease (ischemic heart disease, heart failure, and/or stroke/transient cerebral ischemia), hypertension, dyslipidemia, and venous thrombosis. Severity of morbidity was assessed using number of hospital contacts with diagnosis codes related to cardiovascular and metabolic morbidity and number of redemptions of prescribed medication related to cardiovascular and metabolic morbidity in women who developed cardiovascular and metabolic morbidity after pregnancy. RESULTS: The median follow-up period was 10.2-11.9 years with a total range of 0-21.9 years. GDM was associated with increased risk of any cardiovascular and metabolic morbidity (adjusted HR 2.13 [95% CI 2.07-2.20]), major cardiovascular disease (adjusted HR 1.69 [95% CI 1.55-1.84]), hypertension (adjusted HR 1.89 [95% CI 1.82-1.96], dyslipidemia (adjusted HR 4.48 [95% CI 4.28-4.69]), and venous thrombosis (adjusted HR 1.32 [95% CI 1.16-1.50]). Insulin treatment during pregnancy and subsequent development of manifest diabetes exacerbated the risk estimates. Previous GDM was associated with more hospital contacts and more redeemed prescriptions in women developing cardiovascular and metabolic morbidity (p < 0.001). CONCLUSIONS: Previous GDM was associated with significantly higher risk of cardiovascular and metabolic morbidity, especially incident dyslipidemia. Risks were exacerbated by proxies of beta cell impairment. Severity of morbidity was significantly worse if GDM preceded cardiovascular and metabolic morbidity.

FREM predicts 10-year incident fracture risk independent of FRAX® probability: a registry-based cohort study.

The Danish Fracture Risk Evaluation Model (FREM) was found to predict fracture risk independent of 10-year fracture probability derived with the FRAX® tool including bone mineral density from DXA. INTRODUCTION: FREM was developed from Danish public health registers without DXA information to identify high imminent risk of major osteoporotic fracture (MOF) and hip fracture (HF), while FRAX® estimates 10-year fracture probability from clinical risk factors and femoral neck bone mineral density (BMD) from DXA. The FREM algorithm showed significant 1- and 2-year fracture risk stratification when applied to a clinical population from Manitoba, Canada. We examined whether FREM predicts 10-year fracture risk independent of 10-year FRAX probability computed with BMD. METHODS: Using the Manitoba BMD Program registry, we identified women and men aged ≥ 45 years undergoing baseline BMD assessment. We calculated FREM and FRAX scores, and identified incident fractures over 10 years. Hazard ratios (HRs) for incident fracture were estimated according to FREM quintile, adjusted for FRAX probability. We compared predicted with observed 10-year cumulative fracture probability estimated with competing mortality. RESULTS: The study population comprised 74,446 women, mean age 65.2 years; 7945 men, mean age 67.5 years. There were 7957 and 646 incident MOF and 2554 and 294 incident HF in women and men, respectively. Higher FREM scores were associated with increased risk for MOF (highest vs middle quintile HRs 1.49 women, 2.06 men) and HF (highest vs middle quintile HRs 2.15 women, 2.20 men) even when adjusted for FRAX. Greater mortality with higher FREM scores attenuated its effect on 10-year fracture probability. In the highest FREM quintile, observed slightly exceeded predicted 10-year probability for MOF (ratios 1.05 in women, 1.49 in men) and HF (ratios 1.29 in women, 1.34 in men). CONCLUSIONS: Higher FREM scores identified women and men at increased fracture risk even when adjusted for FRAX probability that included BMD; hence, FREM provides additional predictive information to FRAX. FRAX slightly underestimated 10-year fracture probability in those falling within the highest FREM quintile.

Prediction of imminent fracture risk in Canadian women and men aged 45 years or older: external validation of the Fracture Risk Evaluation Model (FREM).

The Fracture Risk Evaluation Model (FREM) identifies individuals at high imminent risk of major osteoporotic fractures. We validated FREM on 74,828 individuals from Manitoba, Canada, and found significant fracture risk stratification for all FREM scores. FREM performed better than age alone but not as well as FRAX® with BMD. INTRODUCTION: The FREM is a tool developed from Danish public health registers (hospital diagnoses) to identify individuals over age 45 years at high imminent risk of major osteoporotic fractures (MOF) and hip fracture (HF). In this study, our aim was to examine the ability of FREM to identify individuals at high imminent fracture risk in women and men from Manitoba, Canada. METHODS: We used the population-based Manitoba Bone Mineral Density (BMD) Program registry, and identified women and men aged 45 years or older undergoing baseline BMD assessment with 2 years of follow-up data. From linked population-based data sources, we constructed FREM scores using up to 10 years of prior healthcare information. RESULTS: The study population comprised 74,828 subjects, and during the 2 years of observation, 1612 incident MOF and 299 incident HF occurred. We found significant fracture risk stratification for all FREM scores, with AUC estimates of 0.63-0.66 for MOF for both sexes and 0.84 for women and 0.65-0.67 for men for HF. FREM performed better than age alone but not as well as FRAX® with BMD. The inclusion of physician claims data gave slightly better performance than hospitalization data alone. Overall calibration for 1-year MOF prediction was reasonable, but HF prediction was overestimated. CONCLUSION: In conclusion, the FREM algorithm shows significant fracture risk stratification when applied to an independent clinical population from Manitoba, Canada. Overall calibration for MOF prediction was good, but hip fracture risk was systematically overestimated indicating the need for recalibration.

Methodical considerations on adjusting for Charlson Comorbidity Index in epidemiological studies.

Confounding by comorbidities is of concern in many epidemiological studies. To take this into account a common strategy is to calculate each participant's Charlson Comorbidity Index (CCI) and use this for adjustment in regression analyses. Various CCI adjustment strategies are possible, and it is unclear, which is preferable. In this simulation study, we compared common adjustment strategies in Cox regression analyses to determine to which degree they mitigate confounding and conservative bias caused by missing adjustment for independent predictors. We found that adjustment for each comorbidity as separate dichotomous covariate is the preferable adjustment strategy in samples of sufficient size as this mitigates both bias sources to the largest degree. If this is impractical in smaller studies adjustment for CCI split into multiple categories is preferable. In conclusion, the choice of CCI adjustment strategy impacts mitigation of bias in this simulation study, and suboptimal adjustment strategies can cause an observable bias, although of quite limited magnitude of only a few percent in this simulation example. Researcher should be careful when deciding on the adjustment strategies applied to ensure that the desired mitigation of bias sources is achieved.

Trends of anti-reflux surgery in Denmark 2000-2017: a nationwide registry-based cohort study.

BACKGROUND: The utilisation of laparoscopic fundoplication peaked internationally around 2000. Perioperative morbidity, mortality, and length of stay initially declined as the use of laparoscopic technique increased. Studies indicate that complication rates have increased over time, probably as a consequence of rising age and level of comorbidity. None of these previous studies is nationwide. Therefore, this study aimed to investigate trends in the utilisation of anti-reflux surgery in the entire Danish population from 2000 to 2017. METHODS: Nationwide Danish health registries were utilised to include all Danish patients undergoing anti-reflux surgery 2000-2017. The utilisation of anti-reflux surgery in procedures per 100.000 inhabitants was compared to the utilisation of proton-pump inhibitors for each year. Postoperative complications, mortality, and length of stay per year, including yearly changes, were also calculated. RESULTS: The use of anti-reflux surgery peaked in 2001 with 5.9 procedures per 100,000 inhabitants and reached its lowest point in 2008 with 2.8 procedures per 100,000 inhabitants. The use of proton-pump inhibitors increased from 3,370 users per 100,000 inhabitants in 2000 to 10,284 users per 100,000 inhabitants in 2017. The 30-day and 90-day mortality ranged from 0 to 1.2%. The 30-day hospital-registered complications were 1.3-6.1%, and the 90-day hospital-registered complications were 2.4-8.3%. Length of stay was consistently low, with a median of 2 days in 2000 reduced to a median of 1 day by 2017. CONCLUSION: The utilisation of anti-reflux surgery in Denmark from 2000 to 2017 declined, and the use of PPI increased dramatically. Age, comorbidity, and postoperative complications increased, while the use of laparoscopic technique remained high, and mortality was consistently low.

Concerns about transmission, changed services and place of birth in the early COVID-19 pandemic: a national survey among Danish pregnant women. The COVIDPregDK study.

BACKGROUND: The outbreak of the COVID-19 pandemic caused great uncertainty about causes, treatment and mortality of the new virus. Constant updates of recommendations and restrictions from national authorities may have caused great concern for pregnant women. Reports suggested an increased number of pregnant women choosing to give birth at home, some even unassisted ('freebirth') due to concerns of transmission in hospital or reduction in birthplace options. During April and May 2020, we aimed to investigate i) the level of concern about coronavirus transmission in Danish pregnant women, ii) the level of concern related to changes in maternity services due to the pandemic, and iii) implications for choice of place of birth. METHODS: We conducted a nationwide cross-sectional online survey study, inviting all registered pregnant women in Denmark (n = 30,009) in April and May 2020. RESULTS: The response rate was 60% (n = 17,995). Concerns of transmission during pregnancy and birth were considerable; 63% worried about getting severely ill whilst pregnant, and 55% worried that virus would be transmitted to their child. Thirtyeight percent worried about contracting the virus at the hospital. The most predominant concern related to changes in maternity services during the pandemic was restrictions on partners' attendance at birth (81%). Especially nulliparous women were concerned about whether cancelled antenatal classes or fewer physical midwifery consultations would affect their ability to give birth or care for their child postpartum.. The proportion of women who considered a home birth was equivalent to pre-pandemic home birth rates in Denmark (3%). During the temporary discontinue of public home birth services, 18% of this group considered a home birth assisted by a private midwife (n = 125), and 6% considered a home birth with no midwifery assistance at all (n = 41). CONCLUSION: Danish pregnant womens' concerns about virus transmission to the unborn child and worries about contracting the virus during hospital appointments were considerable during the early pandemic. Home birth rates may not be affected by the pandemic, but restrictions in home birth services may impose decisions to freebirth for a small proportion of the population.

Associations between participation in, intensity of, and time spent on leisure time physical activity and risk of inflammatory bowel disease among older adults (PA-IBD): a prospective cohort study.

BACKGROUND: Inflammatory bowel diseases (IBDs) are diseases of the immune system that share some genetic and lifestyle-related predisposing factors. Increasing incidences have been reported in all age groups. Based on experimental studies suggesting a role of physical activity on intestinal inflammation, this study aimed to investigate the association between leisure time physical activity and the risk of IBD in older adults. METHODS: The study is a prospective cohort study using Danish registry data and questionnaire data from the Danish "Diet, Cancer and Health" cohort. The outcome IBD was defined as having at least two main diagnoses of Crohn's disease or ulcerative colitis registered in the National Patient Registry from the period between December 1993 and May 1997 with an average follow-up of 25 years. Cox proportional hazard models were used to estimate hazard-ratios for IBD onset associated with being physically active and with levels of the metabolic equivalent of task (MET) hours/week of physical activity and hours/week spent on six types of physical activity. All analyses were adjusted for potential confounders. Furthermore, the analyses were stratified according to age-group, occupational physical activity, smoking, BMI and work status to test for effect modification. RESULTS: In total, 54,645 men and women aged between 50 and 64 years were included, and of which there were 529 cases. When comparing physically active with inactive participants measured by MET hours/week there was no statistically significant difference in risk of IBD (0.89 [0.13; 6.27]), regardless of how participation was measured. Results did not indicate any dose-response effect when comparing quartile groups of MET hours/week (HR = 0.97 [0.76; 1.22], HR = 0.82 [0.64; 1.05] and HR = 0.83 [0.65; 1.07] or whether five of the six types of activities were compared with the lowest quartile as reference. For do-it-yourself-work, the third quartile of hours/week was associated with a higher risk of IBD compared to the second quartile of hours/week (HR = 1.44 [1.10; 1.90]. No effect modification was found. CONCLUSIONS: There was no association between physical activity and risk of IBD when comparing physically active with inactive participants. Neither did the results indicate any dose-response effect when comparing quartile groups of MET hours/week with the lowest quartile as reference. Do-it-yourself work, however, appeared to be associated with a higher risk of IBD when comparing the third quartile with the second quartile of hours/week. The study has clinical relevance by its contribution to the explanatory field of the causes of IBD. However, the study has some limitations, and further research is needed to clarify associations between physical activity and risk of IBD.

Intake of dietary fibre, red and processed meat and risk of late-onset Chronic Inflammatory Diseases: A prospective Danish study on the "diet, cancer and health" cohort.

Background: Human and animal studies support the involvement of diet in the development of CID -chronic inflammatory diseases such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, psoriatic arthritis, and multiple sclerosis. Objective: This cohort study aimed to investigate the association between intake of fibre, red and processed meat, and occurrence of late-onset CID (50+ years of age) in the DCH: Danish Diet, Cancer and Health cohort. We hypothesised that risk of late-onset CID would be lower among those with high intake of fibre and/or low intake of meat compared to individuals with low fibre and/or high meat intake. Methods: The DCH recruited 56,468 individuals, aged 50-64 years, between 1993 and 1997. At recruitment, diet intake was registered using food frequency questionnaires as well as lifestyle factors in 56,075 persons. Exposure variables were generated as sex-adjusted tertiles of fibre and meat (g/day). Development of CIDs was identified in national registries. Hazard ratios (HR) of late-onset CIDs (adjusted for age, sex, energy intake, alcohol, smoking, education, comorbidity, and civil status) were estimated for all three exposure variables. Results: During follow-up of 1,123,754 years (median (Interquartile range) = 22.2 (20.1-23.1)), 1,758 (3.1%) participants developed at least one CID. The adjusted HRs for developing CID (low fibre 1.04 [0.89-1.22] and medium fibre 1.04 [0.91-1.18] (high fibre as reference), and medium meat 0.96 [0.86-1.09] and high meat 0.94 [0.82-1.07] (low meat as reference)) or the individual diseases were not statistically significant. Conclusion: This large study did not support that a high intake of fibre and/or a low intake of meat had a high impact on the risk of late-onset CID.

Treatment of newly-diagnosed gastroesophageal reflux disease: a nationwide register-based cohort study.

Objective: The aim of this study was to describe short-term treatment of gastroesophageal reflux disease (GERD) in patients registered with a GERD-diagnosis as part of evaluation with endoscopy using national Danish registers. Methods: The study population included all adults undergoing upper gastrointestinal endoscopy in Denmark from 1 January 2000 to 31 December 2015, who within 90 days received a diagnosis of GERD. We obtained nationwide data from The National Patient Registry on procedures (endoscopy and anti-reflux surgery) and diagnosis (GERD diagnosis and comorbidity), The Danish National Prescription Registry on the use of anti-reflux medication and ulcerogenic drugs, and The National Civil Registry on death and civil status. The primary outcome was a type of treatment of GERD within two years of primary endoscopy defined as either no treatment, medical treatment alone, surgical treatment alone or both medical and surgical treatment. Results: A total of 36,292 patients were included in the study. Endoscopies were performed without biopsies in 67.5% (n = 24,479) of cases. The majority (66.3%, n = 24,077) was registered as GERD with esophagitis. After initial endoscopy, 10.6% (n = 3862) received no pharmacological or surgical treatment for GERD within two years of follow-up, 87.5% (n = 31,761) received only pharmacological treatment, 0.1% (n = 50) received only surgical treatment and 1.7% (n = 619) received a combination of pharmacological and surgical treatment. Conclusion: Patients referred to investigation with endoscopy and diagnosed with GERD in Denmark are primarily treated with pharmacological anti-reflux treatment within the first two years with PPI being the primary agent. Only a small fraction of patients is treated surgically.

Rate and predictors for non-attendance of patients undergoing hospital outpatient treatment for chronic diseases: a register-based cohort study.

BACKGROUND: Failure to keep medical appointments results in inefficiencies and, potentially, in poor outcomes for patients. The aim of this study is to describe non-attendance rate and to investigate predictors of non-attendance among patients receiving hospital outpatient treatment for chronic diseases. METHODS: We conducted a historic, register-based cohort study using data from a regional hospital and included patients aged 18 years or over who were registered in ongoing outpatient treatment courses for seven selected chronic diseases on July 1, 2013. A total of 5895 patients were included and information about their appointments was extracted from the period between July 1, 2013 and June 30, 2015. The outcome measure was occurrence of non-attendance. The associations between non-attendance and covariates (age, gender, marital status, education level, occupational status, specific chronic disease and number of outpatient treatment courses) were investigated using multivariate logistic regression models, including mixed effect. RESULTS: During the two-year period, 35% of all patients (2057 of 5895 patients) had one or more occurrences of non-attendance and 5% of all appointments (4393 of 82,989 appointments) resulted in non-attendance. Significant predictors for non-attendance were younger age (OR 4.17 for 18 ≤ 29 years as opposed to 80+ years), male gender (OR 1.35), unmarried status (OR 1.39), low educational level (OR 1.18) and receipt of long-term welfare payments (OR 1.48). Neither specific diseases nor number of treatment courses were associated with a higher non-attendance rate. CONCLUSIONS: Patients undergoing hospital outpatient treatments for chronic diseases had a non-attendance rate of 5%. We found several predictors for non-attendance but undergoing treatment for several chronic diseases simultaneously was not a predictor. To reduce non-attendance, initiatives could target the groups at risk. TRIAL REGISTRATION: This study was approved by the Danish Data Protection Agency (Project ID 18/35695 ).

Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with obesity and low grade inflammation and the risk for cardiovascular disease (CVD) could be increased in PCOS. METHODS: National register-based study including women with PCOS and no previous diagnosis of CVD, hypertension, or dyslipidemia. PCOS Denmark (N = 18,112) included women with PCOS in the Danish National Patient Register. PCOS Odense University Hospital (OUH, N = 1165) was an embedded cohort including premenopausal women with PCOS and clinical and biochemical examination. Three age-matched controls were included per patient in PCOS Denmark (N = 52,769). The main study outcome was CVD events including hypertension and dyslipidemia defined according to nationwide in- and outpatient hospital contact diagnosis codes and/or inferred from filled medicine prescriptions. RESULTS: The age at inclusion was median (quartiles) 29 (23-35) years and follow up was 11.1 (6.9-16.0) years. The Hazard ratio (95% CI) for development of CVD in PCOS Denmark was 1.7 (1.7; 1.8) (P < 0.001) and the total event rate of CVD was 22.6 per 1000 patient years in PCOS Denmark vs. 13.2 per 1000 patient years in controls (P < 0.001). The median age at diagnosis of CVD was 35 (28-42) years in PCOS Denmark vs. 36 (30-43) years in controls (P < 0.001). Obesity, diabetes, and infertility, and previous use of oral contraceptives were associated with increased risk of development of CVD in PCOS Denmark (P < 0.001). Women in PCOS OUH resembled women in PCOS Denmark regarding risk of CVD. Age, BMI, blood pressure, lipid status, and glycemic status predicted development of CVD in PCOS OUH. CONCLUSION: The event rate of CVD including hypertension and dyslipidemia was higher in PCOS compared to controls. The risk of developing CVD must be considered even in young women with PCOS.

Point-of-Care Phalangeal Bone Mineral Density Measurement Can Reduce the Need of Dual-Energy X-Ray Absorptiometry Scanning in Danish Women at Risk of Fracture.

Identifying persons with a high risk of osteoporotic fractures remains a challenge. DXA uptake in women with elevated risk of osteoporosis seems to be depending on distance to scanning facilities. This study aimed to investigate the ability of a small portable scanner in identifying women with reduced bone mineral density (BMD), and to define triage thresholds for pre-selection. Total hip and lumbar spine BMD was measured by dual-energy X-ray absorptiometry and phalangeal BMD by radiographic absorptiometry in 121 Danish women with intermediate or high 10-year fracture probability (aged 61-81 years). Correlation between the two methods was estimated using correlation coefficient (r) and Bland-Altman plots. A moderate correlation between phalangeal BMD versus total hip (r = 0.47) and lumbar spine (r = 0.51), and an AUC on 0.80 was found. The mean difference between phalangeal T score and total hip T score/lumbar spine T score was low, and ranged from -0.26 SD to -0.31 SD depending on site and reference database used for calculation of T scores, but, large variation was seen at an individual level. When applying a triage approach approx. one-third of all DXA scan could be avoided and only 6 % of women in the low-risk group would be false negatives.

The risk-stratified osteoporosis strategy evaluation study (ROSE): a randomized prospective population-based study. Design and baseline characteristics.

The risk-stratified osteoporosis strategy evaluation study (ROSE) is a randomized prospective population-based study investigating the effectiveness of a two-step screening program for osteoporosis in women. This paper reports the study design and baseline characteristics of the study population. 35,000 women aged 65-80 years were selected at random from the population in the Region of Southern Denmark and-before inclusion-randomized to either a screening group or a control group. As first step, a self-administered questionnaire regarding risk factors for osteoporosis based on FRAX(®) was issued to both groups. As second step, subjects in the screening group with a 10-year probability of major osteoporotic fractures ≥15% were offered a DXA scan. Patients diagnosed with osteoporosis from the DXA scan were advised to see their GP and discuss pharmaceutical treatment according to Danish National guidelines. The primary outcome is incident clinical fractures as evaluated through annual follow-up using the Danish National Patient Registry. The secondary outcomes are cost-effectiveness, participation rate, and patient preferences. 20,904 (60%) women participated and included in the baseline analyses (10,411 in screening and 10,949 in control group). The mean age was 71 years. As expected by randomization, the screening and control groups had similar baseline characteristics. Screening for osteoporosis is at present not evidence based according to the WHO screening criteria. The ROSE study is expected to provide knowledge of the effectiveness of a screening strategy that may be implemented in health care systems to prevent fractures.

Fracture risk prediction using phalangeal bone mineral density or FRAX(®)?-A Danish cohort study on men and women.

In this prospective study, we investigated the ability of Fracture Risk Assessment Tool (FRAX), phalangeal bone mineral density (BMD), and age alone to predict fractures using data from a Danish cohort study, Danish Health Examination Survey 2007-2008, including men (n = 5206) and women (n = 7552) aged 40-90 yr. Data were collected using a self-administered questionnaire and by phalangeal BMD measurement. Information on incident and prevalent fractures, rheumatoid arthritis, and secondary osteoporosis was retrieved from the Danish National Patient Registry. Survival analyses were used to examine the association between low, intermediate, and high risk by phalangeal T-score or FRAX and incident fractures, and receiver operating characteristic curves were obtained. Mean follow-up time was 4.3 yr, and a total of 395 persons (3.1%) experienced a fracture during follow-up. The highest rate of major osteoporotic fractures was observed in persons with a high combined risk (FRAX ≥20% and T-score ≤-2.5; women: 32.7 and men: 27.6 per 1000 person-yr). This group also had the highest risk of hip fractures (women: 8.1 and men: 7.2 per 1000 person-yr). FRAX and T-score in combination analyzed as continuous variables performed overall best in the prediction of major osteoporotic fractures. In predicting hip fractures, there was a tendency of T-score performing worse than the other methods.

Validity of Major Osteoporotic Fracture Diagnoses in the Danish National Patient Registry.

Objective: To evaluate the validity of diagnosis codes for Major Osteoporotic Fracture (MOF) in the Danish National Patient Registry (NPR) and secondly to evaluate whether the fracture was incident/acute using register-based definitions including date criteria and procedural codes. Methods: We identified a random sample of 2400 records with a diagnosis code for a MOF in the NPR with dates in the year of 2018. Diagnoses were coded with the 10th revision of the International Classification of Diseases (ICD-10). The sample included 2375 unique fracture patients from the Region of Southern Denmark. Medical records were retrieved for the study population and reviewed by an algorithmic search function and medical doctors to verify the MOF diagnoses. Register-based definitions of incident/acute MOF was evaluated in NPR data by applying date criteria and procedural codes. Results: The PPV for MOF diagnoses overall was 0.99 (95% CI: 0.98;0.99) and PPV=0.99 for the four individual fracture sites, respectively. Further, analyses of incident/acute fractures applying date criteria, procedural codes and using patients' first contact in the NPR resulted in PPV=0.88 (95% CI: 0.84;0.91) for hip fractures, PPV=0.78 (95% CI: 0.74;0.83) for humerus fractures, PPV=0.78 (95% CI: 0.73;0.83) for clinical vertebral fractures and PPV=0.87 (95% CI: 0.83;0.90) for wrist fractures. Conclusion: ICD-10 coded MOF diagnoses are valid in the NPR. Furthermore, a set of register-based criteria can be applied to qualify if the MOF fracture was incident/acute. Thus, the NPR is a valuable and reliable data source for epidemiological research on osteoporotic fractures.

Real-world treatment patterns and outcomes for patients with multiple myeloma in Denmark, Finland and Sweden: An analysis using linked Nordic registries.

AIM: The Health outcomes and Understanding of MyelomA multi-National Study (HUMANS) was a large-scale, retrospective study conducted across Denmark, Finland and Sweden using linked data from national registries. We describe the characteristics, treatment patterns and clinical outcomes for patients with newly diagnosed multiple myeloma (NDMM) over 2010-2018. METHODS: Patients with NDMM who received MM-specific, first-line treatments, were categorised by treatment (autologous stem cell transplantation [ASCT] or a combination chemotherapy regimen based on bortezomib, lenalidomide or melphalan-prednisolone-thalidomide). RESULTS: 11,023 patients received treatment over 2010-2018. Time between diagnosis and treatment was shortest in Denmark (0.9 months), then Sweden (2.9 months) and Finland (4.6 months). Around one third of patients underwent ASCT. Lenalidomide-based regimens were prescribed to 23-28% of patients in Denmark and Finland, versus 12% in Sweden. Patients receiving lenalidomide had the longest wait for treatment, from 3.2 months (Denmark) to 12.1 months (Sweden). Treatment persistence was highest among patients receiving melphalan-prednisolone-thalidomide (7-8 months) in Finland and Sweden and lowest among those receiving bortezomib (3.5 months) in Finland. Overall survival (OS) was longest among patients with ASCT (7-10 years). Among patients receiving chemotherapy, OS (from diagnosis/treatment initiation), varied between cohorts. In a sensitivity analysis excluding patients with smouldering MM, OS decreased for all; for patients receiving bortezomib or lenalidomide, OS from diagnosis was 40-49 and 27-54 months, respectively. CONCLUSIONS: This population-based study of patients with NDMM receiving first-line MM-specific treatment, provides real-world data on treatment patterns and outcomes to complement data from randomised clinical trials.

Gender affirming treatment and employment rate in 3,812 Danish transgender persons and 38,120 controls.

OBJECTIVE: Gender affirming care could be associated with higher employment rate. We assessed employment rates in transgender persons compared to controls and demographic, health and treatment-related factors associated with employment in transgender persons. METHODS: National register-based cohort study in Danish persons with diagnosis code of gender dysphoria during year 2000-2021. Five age-matched controls of the same sex at birth and five age-matched controls of the other sex at birth were included. The date of study inclusion was the first date of transgender diagnosis. Employment was the primary study outcome. RESULTS: The cohort included 3,812 transgender persons and 38,120 cisgender controls. The median age (interquartile range) was 19 (15; 24) years for transgender men, n = 1,993 and 23 (19; 33) years for transgender women, n = 1,819. In transgender men compared to control cisgender women, the odds ratio (95% confidence interval) for employment was 0.33 (0.29; 0.38) before study inclusion and 0.24 (0.20; 0.29) in the fifth calendar year after index; in transgender women compared to control cisgender men, corresponding ORs were 0.30 (0.70; 0.34) and 0.21 (0.18; 0.25). Similar findings were found between transgender persons and cisgender controls of other sex. Use of gender affirming hormone in transgender men increased probability of employment at all time points with odds ratio after 5 years: 1.61 (1.08; 2.42), p = 0.02 (95% confidence interval). In transgender women, use of hormone treatment was not associated with changed employment rates, 5 years odds ratio 1.31 (0.94; 1.82), p = 0.11. CONCLUSION: Masculinizing hormone treatment was associated with higher probability of employment.