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Anne Clausen,1,2 Sören Möller,1,2 Michael Kriegbaum Skjødt,1,3,4 Rasmus Bank Lynggaard,5 Pernille Just Vinholt,5,6 Martin Lindberg-Larsen,7 Jens Søndergaard,8 Bo Abrahamsen,1,4 Katrine Hass Rubin1,2 1Research Unit OPEN, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 2OPEN - Open Patient Data Explorative Network, Odense University Hospital, Odense, Denmark; 3Department of Medicine, Herlev Hospital, Copenhagen, Denmark; 4Department of Medicine, Holbæk Hospital, Holbæk, Denmark; 5Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark; 6Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 7Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Odense, Denmark; 8The Research Unit of General Practice, Department of Public Health, University of Southern Denmark, Odense, DenmarkCorrespondence: Katrine Hass Rubin, Tel +45 21261966, Email Katrine.Rubin@rsyd.dkObjective: 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.Keywords: major osteoporotic fractures, validity, positive predictive value, the Danish National Patient Register, algorithmic search function, epidemiology

Camilla Rye,1,2 Katrine Hass Rubin,2 Frederik Trier Moller,3,4 Mette Julsgaard,5 Tine Jess,6 Vibeke Andersen1,2,7 1Research Unit for Molecular Diagnostics and Clinical Research, Institute for Regional Health Research-Center of Southern Jutland, University Hospital of Southern Denmark, Aabenraa, Denmark; 2OPEN - Open Patient Data Explorative Network, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark; 3Department of Epidemiological Research, Statens Serum Institute, Copenhagen, Denmark; 4Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institute, Copenhagen, Denmark; 5Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 6Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; 7Institute of Molecular Medicine, University of Southern Denmark, Odense, DenmarkCorrespondence: Vibeke AndersenResearch Unit for Molecular Diagnostics and Clinical Research, University Hospital of Southern Denmark, Kresten Philipsens Vej 15, Aabenraa, DK-6200, DenmarkTel +45-21157790Email va@rsyd.dkPurpose: Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic diseases. The aim was to validate diagnoses of IBD among patients aged 50+ years in the Danish National Patient Registry (NPR) by comparison with patient medical records.Patients and Methods: Men and women in the Diet, Cancer and Health (DCH) cohort were linked to NPR, and cases with a diagnosis of IBD and their respective hospital records were identified. Validation was performed by comparing patient medical records with information on discharge diagnoses of IBD from the NPR.Results: Of 57,053 individuals in the DCH-cohort, 339 were registered with an IBD diagnosis in NPR, with 277 (82%) records available for review. Among 277 patients, the positive predictive values (PPVs) of one CD or UC registration in NPR were 78% for IBD overall, 51% for CD and 54% for UC. One hundred fifty-seven patients had at least two CD and/or UC registrations with PPVs of 90% for IBD overall, 65% for CD and 73% for UC. One hundred and two patients had at least three registrations with PPVs of 97% for IBD overall, 75% for CD and 88% for UC. 96% were diagnosed at a specialized department. Other diagnoses coded as IBD mostly included microscopic colitis, irritable bowel syndrome and cancer.Conclusion: Validity of IBD diagnoses in the registry of individuals aged 50+ years increased with the number of registrations. It is recommended that these results are taken into consideration in future studies, especially in epidemiology research using NPR as a data source for patients diagnosed with IBD.Keywords: inflammatory bowel disease, Danish National Patient Registry, register study, diagnostic accuracy, diagnosis

Objective: In this retrospective population-based register study, we wanted to determine the positive predictive values (PPVs) of immunoglobulin M rheumatoid factor (IgM RF) and anti-citrullinated protein antibodies (ACPAs) at 3 × upper normal limit (UNL), since they are weighted equally in the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis (RA).Methods: Test results, ordering unit, test date, and patient social security number were collected from the Department of Clinical Immunology at Odense University Hospital from 2007 to 2016 and merged with patient diagnosis from the Danish National Patient Registry.Results: The PPV of IgM RF at 3 × UNL was 14%, compared to a PPV of 43% for ACPAs at 3 × UNL.Conclusion: The PPV of ACPAs is higher than the PPV of IgM RF at 3 × UNL. These findings are not reflected in the ACR/EULAR 2010 classification criteria for RA. [ABSTRACT FROM AUTHOR]

The correlates between public and private self-consciousness and internalizing difficulties were examined during early adolescence. Friendship quality was assessed as a possible moderator of the relation between self-consciousness and maladjustment. One hundred and thirty-seven young adolescents (N=87 girls; M age=13.98 years) reported on their self-consciousness, internalizing problems, and the quality of their best friendship. Results indicated stronger associations between private self-consciousness and internalizing correlates than between public self-consciousness and internalizing problems, suggesting that private self-consciousness may be a stronger risk factor during adolescence. Contrary to expectations, evidence revealed that positive friendship quality may exacerbate some difficulties associated with self-consciousness. Results pertaining to friendship quality add to the growing literature on the ways in which friendships can contribute to adjustment difficulties. [ABSTRACT FROM AUTHOR]

Objective. The purpose of this study was to examine the socialization beliefs (goals, attributions, strategies) of European American and Mainland Chinese mothers regarding preschoolers' social skills (sharing, controlling negative emotions, and helping others) within a cultural framework. Design. Participants were 103 European American mothers from Washington, DC, and 100 Mainland Chinese mothers from Beijing and Baoding cities, China. Mothers' cognitions regarding the socialization of competent skills were assessed. The reasons that mothers provided for the importance of each skill, their causal attributions for the acquisition of those skills, and the socialization strategies that would be most effective were targeted. Results. Findings for the European American mothers were generally consistent with previous research on U.S. mothers' socialization beliefs, whereas the Mainland Chinese mothers' beliefs were related to traditional Chinese ideologies and values in meaningful ways. The Chinese mothers provided more social conventional reasons for the importance of children's skills, made more external causal attributions, and endorsed higher proportions of training and education strategies than the European American mothers. Conclusions. The study highlights the significance of cultural ideologies regarding children and the family in the study of maternal beliefs regarding child socialization. [ABSTRACT FROM AUTHOR]

Background: Concerns about falling (CaF) are common in older people and can lead to avoidance of activities, social isolation and reduced physical function. However, there is limited knowledge about CaF in people with osteoarthritis (OA); yet, symptoms may increase CaF. We aimed to evaluate the prevalence of CaF and associated factors in people with knee or hip OA., Methods: This cross-sectional study used data from the Good Life with osteoArthritis in Denmark registry including patients with OA treated in primary care. CaF was assessed with the Short Falls Efficacy Scale International (Short FES-I, range 7-28, low to high). Associations between CaF and pain, function and psychological factors were evaluated using multivariable linear Tobit regression., Results: In total, 7442 patients were included [mean age 67 years (SD: 9.6), 67% females]. Mean Short FES-I was 9.8 [95% confidence interval (CI): 9.7; 9.8]. Moderate CaF was observed in 48.1% (95% CI: 46.7; 48.9) of participants, whilst 11.3% (95% CI: 10.7; 12.1) had a high level of CaF. CaF was more prevalent in the oldest participants and in females. Pain intensity [β-value (95% CI): 0.52 (0.48; 0.55)], chair stand test [-0.21 (-0.22; -0.19)] and fear of movement [1.38 (1.19; 1.56)] were significantly associated with increased CaF across age groups and sex., Conclusions: CaF is common in people with OA, especially in the oldest participants and in females. Higher pain, lower function and psychological distress are associated with CaF; yet, the causality of the associations remain to be determined. Integrating CaF assessments and interventions into OA management in primary care seems highly relevant., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Preschoolers who display extremely inhibited behavior are at risk for the development of anxiety disorders. However, behavioral inhibition (BI) is a multifaceted characteristic. Some children with BI are fearful when confronted by unfamiliar adults, peers, and objects; others are fearful when separated from their parents. In the present study, we examined specific features of BI that predicted observed friendship formation among preschoolers who are behaviorally inhibited. We also examined whether teacher ratings of classroom behaviors predicted friendship formation. Sixty highly inhibited children (35 female, M age = 52.57 months) were observed during eight weekly free-play sessions with initially unfamiliar inhibited peers. Free-play periods occurred before weekly intervention sessions for children with BI and their parents. An observational protocol was developed to identify children who made a friend during the eight weekly sessions. Before the first session, different subtypes of BI were assessed by parents; preschool teachers assessed the children's classroom behaviors with familiar peers. Twenty-six children met the criteria for having made and kept a friend. Probit regression analyses revealed that parent ratings of BI among unfamiliar peers and teacher ratings of children's social anxiety before the intervention were associated with a decreased probability of making a friend. No evidence was found linking children's responses to the intervention and friendship formation. Results suggest that extremelyinhibited preschoolers are capable of making friends. Implications for future research and intervention efforts that focus on individual differences of children with BI are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Osteoporotic fractures pose a growing public health concern. Osteoporosis is underdiagnosed and undertreated, highlighting the necessity of systematic screening programs. We aimed to evaluate the effectiveness of a two-step population-based osteoporotic screening program., Methods: This ten-year follow-up of the Risk-stratified Osteoporosis Strategy Evaluation (ROSE) randomized trial tested the effectiveness of a screening program utilizing the Fracture Risk Assessment Tool (FRAX) for major osteoporotic fractures (MOF) to select women for dual-energy x-ray absorptiometry (DXA) scan following standard osteoporosis treatment. Women residing in the Region of Southern Denmark, aged 65-80, were randomised (single masked) into a screening or a control group by a computer program prior to inclusion and subsequently approached with a mailed questionnaire. Based on the questionnaire data, women in the screening group with a FRAX value ≥15% were invited for DXA scanning. The primary outcome was MOF derived from nationwide registers. ClinicalTrials.gov: NCT01388244, status: Completed., Findings: All randomised women were included February 4, 2010-January 8, 2011, the same day as approached to participate. During follow-up, 7355 MOFs were observed. No differences in incidences of MOF were identified, comparing the 17,072 women in the screening group with the 17,157 controls in the intention-to-treat analysis (IRR 1.01, 0.95; 1.06). However, per-protocol, women DXA-scanned exhibited a 14% lower incidence of MOF (IRR 0.86, 0.78; 0.94) than controls with a FRAX value ≥15%. Similar trends were observed for hip fractures, all fractures, and mortality., Interpretation: While the ROSE program had no overall effect on osteoporotic fracture incidence or mortality it showed a preventive effect for women at moderate to high risk who underwent DXA scans. Hence the overall effect might have been diluted by those who were not at an intervention level threshold risk or those who did not show up for DXA. Using self-administered questionnaires as screening tools may be inefficient for systematic screening due to the low and differential screening uptake., Funding: INTERREG and the Region of Southern Denmark., Competing Interests: BA has received institutional research grants from UCB, Kyowa-Kirin and Pharmacosmos, personal consulting fees from UCB and Kyowa-Kirin, and speakers fees from Gedeon-Richter. APH has received Lecture honoraria from UCB, AMGEN, and Gideon Richter, Travel Grants from UCB, and grant to participate on a Data Safety Monitoring Board/Advisory Board from UCB and Gideon Richter. KEÅ has received lectures without fees from Amgen, UCB, and honoraria from Astellas Pharma. MKJ has received personal honoraria from Amgen, UCB, Abbvie, Besin Healthcare, and Sanofi and personal support for attending meetings/travel from UCB., (© 2024 The Author(s).)

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., Competing Interests: Acknowledgements The authors gratefully acknowledge the contribution of Anders Green, MD, DrMedSci, Institute of Applied Economics and Health Research and Odense University Hospital, Odense, Denmark, in providing scientific support and advice on access to, and management of data from the Danish registries. Writing support was provided by Parexel, funded by Takeda Pharmaceutical Company Ltd., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The goals of this study were to examine maternal beliefs about the primary benefits and costs of their children's time spent with friends, and to explore child age and gender differences in these beliefs. Participants were N = 512 mothers (M childage  = 10.18 years; 11% ethnic minority). Open-ended responses to questions about the benefits and costs were coded and analysed, with results indicating that mothers consider opportunities for social skills and social-cognitive development a primary benefit of spending time with friends. Negative friend influence was the most commonly cited cost of friendship. Child age was associated with a number of maternal beliefs (e.g., mothers of adolescents were more likely than mothers of young children to report intimacy as a benefit), but child gender was not. Findings highlight the importance of considering child age in studies of maternal beliefs about friendship and set the stage for future research in this area., (© 2023 The British Psychological Society.)

Objective: The association between gestational diabetes mellitus (GDM) and incident kidney disease, the mediating effects of diabetes and hypertension, and the impact of severity of metabolic dysfunction during pregnancy on the risk of incident kidney disease were investigated in this study., Research Design and Methods: This Danish, nationwide, register-based cohort study included all women giving birth between 1997 and 2018. Outcomes included chronic kidney disease (CKD) and acute kidney disease, based on diagnosis codes. Cox regression analyses explored the association between GDM and kidney disease. A proxy for severity of metabolic dysfunction during pregnancy was based on GDM diagnosis and insulin treatment during GDM in pregnancy and was included in the models as an interaction term. The mediating effects of subsequent diabetes and hypertension prior to kidney disease were quantified using mediation analyses., Results: Data from 697,622 women were used. Median follow-up was 11.9 years. GDM was associated with higher risk of CKD (adjusted hazard ratio [aHR] 1.92; 95% CI 1.67-2.21), whereas acute kidney disease was unrelated to GDM. The proportions of indirect effects of diabetes and hypertension on the association between GDM and CKD were 75.7% (95% CI 61.8-89.6) and 30.3% (95% CI 25.2-35.4), respectively, as assessed by mediation analyses. The CKD risk was significantly increased in women with insulin-treated GDM and no subsequent diabetes compared with women without GDM (aHR 2.35; 95% CI 1.39-3.97)., Conclusions: The risk of CKD was significantly elevated after GDM irrespective of subsequent development of diabetes and hypertension. Furthermore, women with severe metabolic dysfunction during pregnancy had the highest CKD risk., (© 2024 by the American Diabetes Association.)

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.

Parent-child interaction is crucial for children's cognitive and affective development. While bio-synchrony models propose that parenting influences interbrain synchrony during interpersonal interaction, the brain-to-brain mechanisms underlying real-time parent-child interactions remain largely understudied. Using functional near-infrared spectroscopy, we investigated interbrain synchrony in 88 parent-child dyads (Mage children = 8.07, 42.0% girls) during a collaborative task (the Etch-a-Sketch, a joint drawing task). Our findings revealed increased interbrain synchrony in the dorsolateral prefrontal cortex and temporo-parietal areas during interactive, collaborative sessions compared to non-interactive, resting sessions. Linear regression analysis demonstrated that interbrain synchrony in the left temporoparietal junction was associated with enhanced dyadic collaboration, shared positive affect, parental autonomy support, and parental emotional warmth. These associations remained significant after controlling for demographic variables including child age, child gender, and parent gender. Additionally, differences between fathers and mothers were observed. These results highlight the significant association between brain-to-brain synchrony in parent-child dyads, the quality of the parent-child relationship, and supportive parenting behaviors. Interbrain synchrony may serve as a neurobiological marker of real-time parent-child interaction, potentially underscoring the pivotal role of supportive parenting in shaping these interbrain synchrony mechanisms., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Digital health solutions hold the potential for supporting general practitioners in decision-making, and include telemedicine systems, decision support systems, patient apps, wearables, fitness trackers, etc. AIM: This review aimed to identify digital solutions developed for, tested, or implemented in general practice to support the decisions of GPs in disease detection and management, using Denmark as an example country of a universal healthcare setting., Methods: This study was conducted as a rapid review. The primary search included a database search conducted in Embase and MEDLINE. The supplementary search was conducted in Infomedia and additionally included a snowball search in reference lists and citations of key articles identified in the database search. Titles were screened by two reviewers., Results: The review included 15 studies as key articles describing a total of 13 digital solutions for decision support in general practice in Denmark. 1.123 titles were identified through the database search and 240 titles were identified through the supplementary and snowball search., Conclusions: The review identified 13 digital solutions for decision support in general practice in a Danish healthcare setting aimed at detection and/or management of cancer, COPD, type 2 diabetes, depression, liver disease or multiple lifestyle-related diseases. Implementation aspects should be reported more transparently in future publications to enable applicability of digital solutions as decision support to aid general practitioners in disease detection and management., (© 2023. The Author(s).)

Background: Given the robust evidence base for the efficacy of evidence-based treatments targeting youth anxiety, researchers have advanced beyond efficacy outcome analysis to identify mechanisms of change and treatment directionality. Grounded in developmental transactional models, interventions for young children at risk for anxiety by virtue of behaviorally inhibited temperament often target parenting and child factors implicated in the early emergence and maintenance of anxiety. In particular, overcontrolling parenting moderates risk for anxiety among highly inhibited children, just as child inhibition has been shown to elicit overcontrolling parenting. Although longitudinal research has elucidated the temporal unfolding of factors that interact to place inhibited children at risk for anxiety, reciprocal transactions between these child and parent factors in the context of early interventions remain unknown., Method: This study addresses these gaps by examining mechanisms of change and treatment directionality (i.e., parent-to-child vs. child-to-parent influences) within a randomized controlled trial comparing two interventions for inhibited preschoolers (N = 151): the multicomponent Turtle Program ('Turtle') and the parent-only Cool Little Kids program ('CLK'). Reciprocal relations between parent-reported child anxiety, observed parenting, and parent-reported accommodation of child anxiety were examined across four timepoints: pre-, mid-, and post-treatment, and one-year follow-up (NCT02308826)., Results: Hypotheses were tested via latent curve models with structured residuals (LCM-SR) and latent change score (LCS) models. LCM-SR results were consistent with the child-to-parent influences found in previous research on cognitive behavioral therapy (CBT) for older anxious youth, but only emerged in Turtle. LCS analyses revealed bidirectional effects of changes in parent accommodation and child anxiety during and after intervention, but only in Turtle., Conclusion: Our findings coincide with developmental transactional models, suggesting that the development of child anxiety may result from child-to-parent influences rather than the reverse, and highlight the importance of targeting parent and child factors simultaneously in early interventions for young, inhibited children., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Objectives: This study aimed to examine the risk of mortality following incident and subsequent osteoporotic fractures, the effect of different fracture type combinations, and the mediating role of postfracture morbidity in a Danish population., Methods: We used the National Patient Registry to identify patients ≥60 years with incident major osteoporotic fracture of the hip, vertebrae, wrist or humerus between 2013 and 2018, and controls matched 1:10 on age and sex. Possible mediators were identified using International Classification of Diseases, 10th Revision codes registered in the 6 months following index fracture. HRs were estimated using Cox regression analyses with 95% CIs. The effect of possible mediators was estimated using mediation analyses., Results: The study included 106 303 patients and 1 062 988 controls. Mortality following index fracture was highest in the month following hip fractures (HR 10.98 (95% CI 10.23 to 11.79) in women and HR 16.40 (95% CI 15.00 to 17.93) in men). Subsequent hip fractures resulted in the highest HRs for all fracture type combinations. In women, the highest HR was observed in patients with index wrist/subsequent hip fractures (HR 2.43 (95% CI 2.12 to 2.78)). In men, the highest HR was observed in patients with index humerus/subsequent hip fractures (HR 2.69 (95% CI 2.04 to 3.54)). Pneumonia mediated the largest proportion of mortality, but dehydration, urinary tract infection and sepsis were also important factors., Conclusions: The highest mortality risk was found in the month immediately following both index and subsequent fracture. The combination of index and subsequent fractures at different skeletal sites had a substantial impact on the risk of mortality. Postfracture morbidities were found mediate the association., Competing Interests: Competing interests: ERC, AC, TGP, SM and KHR declare no competing interests. BA reports institutional research grants and personal fees from UCB, institutional research grants and personal fees from Kyowa-Kirin, institutional research grants and personal fees from Pharmacosmos, speakers fees from Amgen and speakers fees from Gedeon-Richter. MKS reports an educational grant from UCB, institutional research grants from UCB/Amgen and Region Zealand Health Scientific Research Foundation and a personal speakers fee from UCB Nordic., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Several psychiatric disorders are linked with an increased risk of developing type 2 diabetes (T2D), but the mediating mechanisms are unclear. We aimed to investigate health behaviors, obesity, psychotropic medication use, and comorbidity as potential mediating mechanisms explaining these associations., Methods: We combined data from a large population-based survey with register-based data and followed a sample of 250,013 Danes (≥16 years) for up to 8.9 years. We conducted mediation analyses investigating 10 potential mediators of the associations between psychiatric disorders and incident T2D., Results: Individuals with a substance use disorder, schizophrenia, mood disorder, neurotic disorder, eating disorder, or a personality disorder had a significantly higher risk of developing T2D. Organic disorders, intellectual disabilities, developmental and behavioral disorders were not associated with T2D-risk. For all psychiatric disorders significantly associated with T2D, the use of antidepressant medication had the largest proportional mediating effect on the association (13-32 %)., Conclusions: Use of antidepressant medication had the largest contribution to the associations between psychiatric disorders and incident T2D. Future epidemiological studies and prevention studies should focus on optimizing the use of antidepressant medication with minimal side effects, and the promotion of health behaviors in individuals with a psychiatric disorder to prevent T2D., Competing Interests: Declaration of competing interest GSA own shares in Novo Nordisk A/S. All other authors declare that they have no conflict of interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The Danish Registry of Diabetic Retinopathy includes information from >200 000 patients who attends diabetic retinopathy (DR) screening in Denmark. Screening of patients with uncomplicated type 2 diabetes is often performed by practicing ophthalmologists, while patients with type 1 and complicated type 2 diabetes attends screening at hospitals. We performed a clinical reliability study of retinal images from Danish screening facilities to explore the inter-grader agreement between the primary screening ophthalmologist and a blinded, certified grader., Methods: Invitations to participate were sent to screening facilities across Denmark. The primary grader uploaded fundus photographs with information on estimated level of DR (International Clinical Diabetic Retinopathy scale as 0 [no DR], 1-3 [mild, moderate or severe nonproliferative DR {NPDR}], or 4 [proliferative DR {PDR}]), region of screening, image style, and screening facility. Images were then regraded by a blinded, certified, secondary grader. Weighted kappa analysis was performed to evaluate agreement., Results: Fundus photographs from 230 patients (458 eyes) were received from practicing ophthalmologists (52.6%) and hospital-based grading centres (47.4%) from all Danish regions. Reported levels of DR by the primary graders were 66.8%, 12.2%, 13.1%, 1.3% and 5.5% for DR levels 0-4. The overall agreement between primary and secondary graders was 93% (κ = 0.83). Based on screening facility agreement was 96% (κ = 0.89) and 90% (κ = 0.76) for practicing ophthalmologists and hospital-based graders., Conclusion: In this nationwide study, we observed a high overall inter-grader agreement and based on this, it is reasonable to assume that reported DR gradings in the screening programme in Denmark, accurately reflect the truth., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Osteoporosis poses a growing healthcare challenge owing to its rising prevalence and a significant treatment gap, as patients are widely underdiagnosed and consequently undertreated, leaving them at high risk of osteoporotic fracture. Several tools aim to improve case-finding in osteoporosis. One such tool is the Fracture Risk Evaluation Model (FREM), which in contrast to other tools focuses on imminent fracture risk and holds potential for automation as it relies solely on data that is routinely collected via the Danish healthcare registers. The present article is an analysis protocol for a prediction model that is to be used as a modified version of FREM, with the intention of improving the identification of subjects at high imminent risk of fracture by including pharmacological exposures and using more advanced statistical methods compared to the original FREM. Its main purposes are to document and motivate various aspects and choices of data management and statistical analyses., Methods: The model will be developed by employing logistic regression with grouped LASSO regularization as the primary statistical approach and gradient-boosted classification trees as a secondary statistical modality. Hyperparameter choices as well as computational considerations on these two approaches are investigated by an unsupervised data review (i.e., blinded to the outcome), which also investigates and handles multicollinarity among the included exposures. Further, we present an unsupervised review of the data and testing of analysis code with respect to speed and robustness on a remote analysis environment. The data review and code tests are used to adjust the analysis plans in a blinded manner, so as not to increase the risk of overfitting in the proposed methods., Discussion: This protocol specifies the planned tool development to ensure transparency in the modeling approach, hence improving the validity of the enhanced tool to be developed. Through an unsupervised data review, it is further documented that the planned statistical approaches are feasible and compatible with the data employed., (© 2023. BioMed Central Ltd., part of Springer Nature.)

A decline in intellectual functioning (intelligence quotient [IQ]) is often observed following more severe forms of traumatic brain injury (TBI) and is a useful index for long-term outcome. Identifying brain correlates of IQ can serve to inform developmental trajectories of behavior in this population. Using magnetic resonance imaging (MRI), we examined the relationship between intellectual abilities and patterns of cortical thickness in children with a history of TBI or with orthopedic injury (OI) in the chronic phase of injury recovery. Participants were 47 children with OI and 58 children with TBI, with TBI severity ranging from complicated-mild to severe. Ages ranged from 8 to 14 years old, with an average age of 10.47 years, and an injury-to-test range of ∼1-5 years. The groups did not differ in age or sex. The intellectual ability estimate (full-scale [FS]IQ-2) was derived from a two-form (Vocabulary and Matrix Reasoning subtests) Wechsler Abbreviated Scale of Intelligence (WASI). MRI data were processed using the FreeSurfer toolkit and harmonized across data collection sites using neuroComBat procedures, while holding demographic features (i.e., sex, socioeconomic status [SES]), TBI status, and FSIQ-2 constant. Separate general linear models per group (TBI and OI) and a single interaction model with all participants were conducted with all significant results withstanding correction for multiple comparisons via permutation testing. Intellectual ability was higher ( p  < 0.001) in the OI group (FSIQ-2 = 110.81) than in the TBI group (FSIQ-2 = 99.81). In children with OI, bi-hemispheric regions, including the right pre-central gyrus and precuneus and bilateral inferior temporal and left occipital areas were related to IQ, such that higher IQ was associated with thicker cortex in these regions. In contrast, only cortical thickness in the right pre-central gyrus and bilateral cuneus positively related to IQ in children with TBI. Significant interaction effects were found in the bilateral temporal, parietal, and occipital lobes and left frontal regions, indicating that the relationship between IQ and cortical thickness differed between groups in these regions. Changes in cortical associations with IQ after TBI may reflect direct injury effects and/or adaptation in cortical structure and intellectual functioning, particularly in the bilateral posterior parietal and inferior temporal regions. This suggests that the substrates of intellectual ability are particularly susceptible to acquired injury in the integrative association cortex. Longitudinal work is needed to account for normal developmental changes and to investigate how cortical thickness and intellectual functioning and their association change over time following TBI. Improved understanding of how TBI-related cortical thickness alterations relate to cognitive outcome could lead to improved predictions of outcome following brain injury.

Anxious-withdrawal is a well-established individual risk factor for psychosocial difficulties during adolescence. It is unknown, however, whether it also places youth at increased risk for physical health problems, such as sleep difficulties. This study examines the concurrent and prospective associations between anxious-withdrawal and six types of sleep difficulties (i.e., sleeping too much, sleeping too little, talking/walking in sleep, being overtired, nightmares, and general trouble sleeping). We further evaluate whether these associations differ for adolescents who are high versus low in exclusion and victimization. The participants were 395 adolescents ( M age = 13.61 years; 35% ethnic minority) who completed peer nominations of anxious-withdrawal, exclusion, and victimization at Time 1 (T1). Their mothers completed reports of sleep difficulties at T1 and at Time 2 (T2). Path analyses revealed unique associations between anxious-withdrawal and several types of sleep difficulties (e.g., sleeping too much) at T1. Analyses also revealed a significant interaction effect between T1 anxious-withdrawal and exclusion/victimization such that anxious-withdrawal was prospectively associated with trouble sleeping only for those young adolescents who are highly excluded/victimized. Our findings are the first to link anxious-withdrawal to a physical health outcome in adolescence and point to the need for future research to not only examine anxious-withdrawal and physical health but also to include assessments of peer difficulties.

Importance: Gender affirming treatment aims to improve mental health., Objective: To investigate longitudinal mental health outcomes in Danish transgender persons., Design: National register-based cohort study in Danish transgender persons with diagnosis code of "gender identity disorder" during the period 2000-2021., Participants: Five age-matched controls of the same sex at birth and five age-matched controls of the other sex at birth were included for each transgender person., Main Outcomes: Diagnosis codes of mental and behavioral disorders and/or prescription of psychopharmacological agents until June 2022., Results: The cohort included 3812 transgender persons with median age (interquartile range) 19 (15; 24) years for persons assigned female at birth (AFAB, N = 1993) and 23 (19; 33) years for persons assigned male at birth (AMAB, N = 1819) and 38 120 controls. Follow up duration was up to 10 years with mean (standard deviation) 4.5 (4.3) years. In transgender persons AFAB compared to control women, the odds ratio (OR) (95% confidence interval) for mental and behavioral disorders was 6.7 (5.5; 8.1) before the index date, 9.9 (8.4; 11.7) at 1 year, 5.8 (4.4; 7.7) at 5 years, and 3.4 (2.1; 7.5) at 8 years follow up. In transgender persons AMAB compared to control men, corresponding ORs were 5.0 (4.0; 6.4), 11.3 (9.3; 13.7), 4.8 (3.5; 6.5), and 6.6 (4.2; 10.3) at 8 years follow up (all P < .001)., Conclusion: The OR for mental health disorders was higher in transgender persons compared to controls and remained elevated throughout follow up, especially in transgender persons AMAB., Competing Interests: Conflicts of interest: The authors declare that they have no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Peer reputation (PR) refers to how peer groups collectively view an individual in terms of socio-behavioral characteristics, such as aggression, social withdrawal, leadership, and prosociality. Despite considerable research on PR, few studies have considered PRs in relation to indices of friendship, particularly with a person-centered approach. The goal of the current study was to adopt such an approach and identify peer reputation configurations and their defining characteristics, and to examine how such configurations are linked to friendship prevalence and quality. Four hundred and twenty-six Italian seventh-grade students (57.3% male, M age = 12.07) completed peer nomination measures of PR and reported on their friendships. Their mutual best friends were subsequently determined, and a friendship quality measure was completed. Teachers rated participants' problem behaviors and competencies. Cluster analytic methods produced four PR configurations that were defined by the following characteristics: (1) Shy/Excluded/Victimized, (2) Normative, (3) Aggressive/Arrogant, and (4) Prosocial/Popular. Teacher ratings supported these configurations such that Prosocial/Popular students were rated the lowest in problem behaviors and Shy/Excluded/Victimized and Aggressive/Arrogant were the highest in learning problems. Additional analyses showed numerous linkages between the configurations and friendship. For instance, Prosocial/Popular students were more likely to have mutual and satisfying friendships relative to students in the other groups. These findings provide new insights into the complex linkages between group- and dyadic-level peer experiences during early adolescence and may inform prevention and intervention efforts aimed at Shy/Excluded/Victimized youth struggling with peers.

Early behavioral inhibition (BI) is a known risk factor for later anxiety disorder. Variability in children's parasympathetic nervous system (PNS) functioning may provide insight into the substantial heterogeneity in anxiety outcomes for children high in BI. However, gaps persist due to an over-reliance on static measures of functioning, which limits our ability to leverage PNS functioning to identify risk for anxiety. We address these gaps using baseline data from an early intervention study of inhibited preschoolers by characterizing vagal flexibility (VF), an index of non-linear change in PNS functioning, across social stressor tasks and by examining the associations between VF and anxiety. One hundred and fifty-one parents and their 3.5- to 5-year-old children were selected on the basis of BI to participate in an early intervention program (ClinicalTrials.gov registration: NCT02308826). A structural equation modeling framework was used to model children's VF across tasks designed to mimic exposure to novel social interactions and to test the predictive links between VF and anxiety. Children who showed less VF, characterized by less suppression and flatter recovery, were rated by both parents and clinicians as more anxious. Moreover, a multiple group model showed that children meeting diagnostic criteria for social anxiety disorder demonstrated significantly less VF across social stressor tasks. Among inhibited youth, reduced VF is a risk factor for anxiety and may reflect an individual's reduced capacity to actively cope with external demands. Study results contribute to our understanding of the regulatory processes underlying risk for anxiety in early childhood., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The emergence of the COVID-19 pandemic and the derived changes in maternity care have created stress and anxiety among pregnant women in different parts of the world. In times of stress and crisis, spirituality, including spiritual and religious practices, may increase., Objective: To describe if the COVID-19 pandemic influenced pregnant women's considerations and practises of existential meaning-making and to investigate such considerations and practices during the early pandemic in a large nationwide sample., Methods: We used survey data from a nationwide cross-sectional study sent to all registered pregnant women in Denmark during April and May 2020. We used questions from four core items on prayer and meditation practices., Results: A total of 30,995 women were invited, of whom 16,380 participated (53%). Among respondents, we found that 44% considered themselves believers, 29% confirmed a specific form of prayer, and 18% confirmed a specific form of meditation. In addition, most respondents (88%) reported that the COVID-19 pandemic had not influenced their responses., Conclusion: In a nationwide Danish cohort of pregnant women, existential meaning-making considerations and practices were not changed due to the COVID-19 pandemic. Nearly one in two study participants described themselves as believers, and many practised prayer and/or meditation., Competing Interests: Declaration of Competing Interest None of the authors have financial or other conflicts of interests related to the subject of this study., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Behavioral inhibition (BI) is a temperamental trait characterized by a bias to respond with patterns of fearful or anxious behavior when faced with unfamiliar situations, objects, or people. It has been suggested that children who are inhibited may experience early peer difficulties. However, researchers have yet to systematically compare BI versus typically developing children's observed asocial and social behavior in familiar, naturalistic settings., Method: We compared the in-school behaviors of 130 ( M  = 54 months, 52% female) highly inhibited preschoolers (identified using the parent-reported Behavioral Inhibition Questionnaire) to 145 ( M  = 53 months, 52% female) typically developing preschoolers. Both samples were observed on at least two different days for approximately 60 min. Observers used the Play Observation Scale to code children's behavior in 10-s blocks during free play. Teachers completed two measures of children's behavior in the classroom., Results: Regression models with robust standard errors controlling for child sex, age, and weekly hours in school revealed that preschoolers identified as BI engaged in significantly more observed reticent and solitary behavior, and less social play and teacher interaction than the typically developing sample. Children with BI also initiated social interaction with their peers and teachers less often than their counterparts who were not inhibited. Teachers reported that children identified as BI were more asocial and less prosocial than their non-BI counterparts., Discussion: Significantly, the findings indicated that inhibited children displayed more solitude in the context of familiar peers. Previous observational studies have indicated behavioral differences between BI and unfamiliar typical age-mates in novel laboratory settings. Children identified as BI did not receive fewer bids for social interaction than their typically developing peers, thereby suggesting that children who are inhibited have difficulty capitalizing on opportunities to engage in social interaction with familiar peers. These findings highlight the need for early intervention for children with BI to promote social engagement, given that the frequent expression of solitude in preschool has predicted such negative outcomes as peer rejection, negative self-regard, and anxiety during the elementary and middle school years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Druskin, Novick, Smith, Chronis-Tuscano, Wagner, Pham, Fleece, Danko and Rubin.)

Purpose: We aimed to investigate if diabetic retinopathy (DR), glaucoma and/or ocular hypertension (OHT) are prospectively linked, as previous studies have proposed cross-sectional associations, but longitudinal data from larger cohorts are lacking., Methods: We performed a bidirectional 5 years prospective, registry-based cohort study. We extracted data from national registers, including the Danish Registry of Diabetic Retinopathy, the Danish Civil Registration System, the Danish National Patient Register and the Danish National Prescription Registry. DR level was defined by the highest level of the two eyes. Glaucoma and/or OHT was defined by diagnostic codes (H40*) or at least three redeemed prescriptions of glaucoma medication (S01E*) within 1 year. We included 205 970 persons with diabetes and 1 003 170 age- and gender-matched non-diabetes controls. Exposures were level-specific DR (i) and glaucoma and/or OHT (ii), and outcomes were hazard ratios (HRs) for 5 years incident glaucoma and/or OHT (i) and DR (ii)., Results: Persons with diabetes were more likely to develop glaucoma and/or OHT (multivariable adjusted HR 1.11, 95% CI 1.06-1.15), but this did not depend on the level of DR. In persons with diabetes, those with glaucoma and/or OHT were more likely to develop DR (multivariable adjusted HR 1.12, 95% CI 1.03-1.23) within 5 years., Conclusion: In a national cohort, diabetes associated with a little higher risk of upcoming glaucoma and/or OHT, and, inversely, the presence of the latter predicted a higher risk of incident DR. Nevertheless, our data do not seem to justify including glaucoma evaluation in the national Danish DR-screening programme., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Introduction: Behavioral inhibition during early childhood is one of the strongest risk factors for the development of later anxiety disorders. Recently developed in-person interventions that target both young children who are highly inhibited and their parents (e.g., the Turtle Program ), have decreased children's anxiety and have increased social participation in the peer group. However, researchers have yet to examine the effects of intervention mode of delivery. In the present study, we compared the pre-to post-intervention changes in child and parenting functioning of families participating in the Turtle Program, delivered in-person and online with those changes made in families allocated to a waiting-list condition; compared session attendance, homework completion and satisfaction with the intervention outcomes of families involved in the Turtle Program, delivered in-person and online; and explored the predictive role of parenting and child factors in session attendance, homework completion and satisfaction with the outcomes of families involved in the Turtle Program, depending on the mode of delivery (in-person vs. online)., Method: Fifty-seven parents of highly inhibited preschoolers (3-5 years), with no diagnosis of selective mutism or developmental disorders, who were randomly allocated to waiting-list ( n = 20), Turtle Program delivered in-person ( n = 17) and online ( n = 20) conditions completed the Portuguese versions of the Behavioral Inhibition Questionnaire , the Preschool Anxiety Scale , the Social Behavior and Competence Scale , the Modified Child-Rearing Practices Questionnaire at pre- and post-intervention assessment. Parents also completed the Preschool Shyness Study Satisfaction Survey at post-intervention assessment., Results: Independent of intervention mode of delivery, generalized equation estimates revealed a reduction in children's total anxiety symptoms and an improvement in parental nurturing behaviors. Child anxiety and social competence at pre-assessment were the most prominent predictors of session attendance and satisfaction with post-intervention child and parenting outcomes., Discussion: Overall, this study showed that parents in both intervention conditions perceived comparable positive changes in child functioning from pre- to post-intervention assessment and similar levels of session attendance, homework completion, and satisfaction. Significantly, however, perceived satisfaction with post-intervention child and parenting outcomes was higher, when children were reported to display higher SEL skills at baseline, independent of the intervention mode of delivery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guedes, Maia, Matos, Antunes, Rolão, Chronis-Tuscano, Rubin, Veríssimo and Santos.)

Objective: To investigate associations between previous gestational diabetes mellitus (GDM) and incident psychiatric morbidity, and to explore the role of subsequent diabetes development in psychiatric morbidity risk., Research Design and Methods: A nationwide register-based cohort study including all women delivering in Denmark from 1997 to 2018 was conducted. GDM exposure was based on diagnosis code, whereas psychiatric morbidity outcome was based on diagnosis code and psychopharmacological medication use. Multiple Cox regression and mediation analyses were performed., Results: In a study population of 660,017 women, previous GDM was associated with increased risk of depression based on diagnosis code and/or medication use (adjusted hazard ratio [aHR] 1.22 [95% CI 1.18-1.27]), any psychiatric diagnosis (aHR 1.20 [95% CI 1.13-1.27]), and any psychopharmacological medication use (aHR 1.21 [95% CI 1.17-1.25]). Moreover, risk of depressive and anxiety disorders, as well as antidepressant and antipsychotic medication use, was increased, with aHRs ranging from 1.14 (95% CI 1.05-1.25) to 1.32 (95% CI 1.22-1.42). No associations were found regarding substance use disorders, psychotic disorders, bipolar disorders, postpartum psychiatric disease, or anxiolytic medication use. Psychiatric morbidity risk was higher in women with versus without subsequent diabetes development. However, GDM history affected risk estimates only in women without subsequent diabetes. Subsequent diabetes mediated 35-42% of the associations between GDM and psychiatric morbidity., Conclusions: GDM was associated with increased psychiatric morbidity risk. Subsequent diabetes development played a significant role in future psychiatric morbidity risk after GDM, although it only partly explained the association., (© 2023 by the American Diabetes Association.)

Introduction: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark., Material and Methods: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers., Results: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7)., Conclusions: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Lung cancer can be challenging to diagnose in the early stages, where treatment options are optimal. We aimed to develop 1-year prediction models for the individual risk of incident lung cancer for all individuals aged 40 or above living in Denmark on 1 January 2017. The study was conducted using population-based registers on health and sociodemographics from 2007-2016. We applied backward selection on all variables by logistic regression to develop a risk model for lung cancer and applied the models to the validation cohort, calculated receiver-operating characteristic curves, and estimated the corresponding areas under the curve (AUC). In the populations without and with previously confirmed cancer, 4274/2,826,249 (0.15%) and 482/172,513 (0.3%) individuals received a lung cancer diagnosis in 2017, respectively. For both populations, older age was a relevant predictor, and the most complex models, containing variables related to diagnoses, medication, general practitioner, and specialist contacts, as well as baseline sociodemographic characteristics, had the highest AUC. These models achieved a positive predictive value (PPV) of 0.0127 (0.006) and a negative predictive value (NPV) of 0.989 (0.997) with a 1% cut-off in the population without (with) previous cancer. This corresponds to 1.2% of the screened population experiencing a positive prediction, of which 1.3% would be incident with lung cancer. We have developed and tested a prediction model with a reasonable potential to support clinicians and healthcare planners in identifying patients at risk of lung cancer.

Objective: The primary aim of this study was to investigate whether secure parent-adolescent attachment relationships moderate the longitudinal relation between 9th grade (G9) ADHD symptoms and 12th grade (G12) delinquency within a community sample of adolescents., Method: Participants included 335 9th graders, of whom 203 students completed measures again in 12th grade. Mothers reported on their adolescents' ADHD symptoms and aggressive behaviors, and adolescents completed measures of their own delinquency and their perceptions of their parent-child attachment relationships., Results: G9 ADHD symptoms predicted increases in G12 delinquent behaviors. Moderation effects were also found such that G9 ADHD symptoms predicted G12 delinquency for only those youth who had moderate or low levels of secure maternal attachment. Paternal secure attachment did not moderate the effects of G9 ADHD symptoms on G12 delinquency., Conclusion: Findings underscore the importance of secure maternal attachment relationships in the development of delinquency among adolescents with ADHD symptoms.

Aims: A nationwide diabetic retinopathy (DR) screening program has been established in Denmark since 2013. We aimed to perform an evaluation of adherence to DR screenings and to examine whether non-adherence was correlated to DR progression., Methods: The population consisted of a register-based cohort, who participated in the screening program from 2013 to 2018. We analyzed age, gender, marital status, DR level (International Clinical DR severity scale, none, mild-, moderate-, severe non-proliferative DR (NPDR) and proliferative DR (PDR)), comorbidities and socioeconomic factors. The attendance pattern of patients was grouped as either timely (no delays > 33%), delayed (delays > 33%) or one-time attendance (unexplained)., Results: We included 205,970 patients with 591,136 screenings. Rates of timely, delayed and one-time attendance were 53.0%, 35.5% and 11.5%, respectively. DR level at baseline was associated with delays (mild-, moderate-, severe NPDR and PDR) and one-time attendance (moderate-, severe NPDR and PDR) with relative risk ratios (RRR) of 1.68, 2.27, 3.14, 2.44 and 1.18, 2.07, 1.26, respectively (P < 0.05). Delays at previous screenings were associated with progression to severe NPDR or PDR (hazard ratio (HR) 2.27, 6.25 and 12.84 for 1, 2 and 3+ delays, respectively). Any given delay doubled the risk of progression (HR 2.28)., Conclusions: In a national cohort of 205,970 patients, almost half of the patients attended DR screening later than scheduled or dropped out after first screening episode. This was, in particular, true for patients with any levels of DR at baseline. DR progression in patients with delayed attendance, increased with the number of missed appointments., (© 2022. The Author(s).)

Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment., Introduction: In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting., Methods: In this registry-based cohort study of osteoporosis patients (n = 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women., Results: Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (p = 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (p = 0.03), femoral neck (p = 0.04), and lumbar spine (p = 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (p = 0.02) and lumbar spine (p = 0.006)., Conclusion: Measurement of pre-treatment BTM levels predicts osteoporosis patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Aim: To investigate the risk of depression in Danish women with PCOS compared to controls and possible mediators for depression in PCOS. National register-based study in Danish women with PCOS (PCOS Denmark, N = 25,203) and age-matched controls ( N = 112,414). PCOS Odense University Hospital (PCOS OUH, N = 998) was a sub-cohort of women with PCOS with available clinical and biochemical results. The main study outcome was depression occurring after PCOS diagnosis. Depression was defined according to hospital ICD-10 diagnosis codes and/or inferred from filled medicine prescription of antidepressants. Diabetes, medical comorbidity, infertility, hormonal anti-contraception and low family income were entered as mediators in Cox regression analyses for depression. In PCOS OUH, PCOS characteristics (age, BMI, Ferriman-Gallwey score) were entered in Cox regression analyses. The median age at cohort entry was 28 (interquartile range (IQR) 23; 35) years. The median follow-up time to incident depression or censuring was 4.8 (IQR 2.2; 8.8) years in PCOS Denmark and 5.2 (IQR 2.4; 9.2) years in controls. Women with PCOS had a 40% increased risk of depression compared to controls (Hazard Ratio 1.42 (95% CI 1.38; 1.47). In regression analyses, diabetes, medical comorbidity, infertility, hormonal anticonception, and low family income were significant mediators of depression. Mediation analyses showed that the proportion of the association explained by diabetes was 12.5% (95% CI 10.4; 14.5). In PCOS OUH, BMI, waist and Ferriman-Gallwey score predicted development of depression., Conclusion: The risk of depression was increased in PCOS. Diabetes was an important mediator of depression in PCOS.

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., (© 2022. The Author(s).)

Purpose: To develop a predictive model based on Danish administrative registers to facilitate automated identification of individuals at risk of any type of cancer., Methods: A nationwide register-based cohort study covering all individuals in Denmark aged +20 years. The outcome was all-type cancer during 2017 excluding nonmelanoma skin cancer. Diagnoses, medication, and contact with general practitioners in the exposure period (2007-2016) were considered for the predictive model. We applied backward selection to all variables by logistic regression to develop a risk model for cancer. We applied the models to the validation cohort, calculated the receiver operating characteristic curves, and estimated the corresponding areas under the curve (AUC)., Results: The study population consisted of 4.2 million persons; 32,447 (0.76%) were diagnosed with cancer in 2017. We identified 39 predictive risk factors in women and 42 in men, with age above 30 as the strongest predictor for cancer. Testing the model for cancer risk showed modest accuracy, with an AUC of 0.82 (95% CI 0.81-0.82) for men and 0.75 (95% CI 0.74-0.75) for women., Conclusion: We have developed and tested a model for identifying the individual risk of cancer through the use of administrative data. The models need to be further investigated before being applied to clinical practice.

Background: Cardiovascular risk could be increased in transgender persons, but the mechanism is undetermined., Aim: The aim of this study was to assess the risk of cardiovascular outcomes in Danish transgender persons compared to controls., Methods: The study design was a historical register-based cohort study in Danish transgenders and age-matched controls. The main outcome measure was cardiovascular diagnosis (any CVD) including medicine prescriptions for CVD during 2000-2018. The transgender cohort (n = 2671) included persons with International Classification of Diseases-10 diagnosis code of 'gender identity disorder' (n = 1583) and persons with legal sex change (n = 1088), 1270 were assigned female at birth (AFAB) and 1401 were assigned male at birth (AMAB). Controls (n = 26 710) were matched by age (n = 5 controls of same and n = 5 controls of other birth sex) of the respective transgender., Results: The median (interquartile range) age at study inclusion was 22 (18; 29) years for AFAB and 26 (21; 39) years for AMAB. The mean (s.d.) follow-up time was 4.5 (4.2) years for AFAB and 5.7 (4.8) years for AMAB. The hazard ratio (HR) for any CVD was significantly higher in transgenders vs controls of same and other birth sex, with highest adjusted HR in transgenders AFAB vs control men: 2.20 (95% CI: 1.64;2.95), P < 0.001. Gender-affirming hormone treatment (GAHT) explained part of elevated risk of CVD in transgenders AFAB, whereas GAHT did not contribute to the elevated risk of CVD in transgenders AMAB., Conclusions: The risk of cardiovascular diagnosis was increased in transgenders. The mechanism should be further investigated.

Aim: We aimed to describe the aim, data collection and content from a survey completed among pregnant women during the first peak of the COVID-19 pandemic in Denmark., Methods: The declaration of the COVID-19 pandemic in early 2020 challenged pregnant women's mental well-being due to a concern for their unborn child and their need for healthcare services through pregnancy and birth. To explore how the COVID-19 pandemic and the intensified measures such as the lockdown of Denmark impacted pregnant women's well-being and mental health, we conducted a questionnaire survey in the spring of 2020 when the COVID-19 pandemic was at its first peak, and the consequences for pregnant women and the unborn child were very uncertain. All women residing in Denmark and registered with an ongoing pregnancy on 24 April 2020 were invited to participate. The questionnaire included background information, variables on COVID-19 symptoms and validated batteries of questions on loneliness, anxiety, stress, quality of life, meditation and prayers. Additional questions were included to examine concerns related to pregnancy and childbirth during the pandemic., Cohort Characteristics: Almost 18,000 women answered the questionnaire, which represents 60% of all invited women who experienced a national lockdown for the first time. Their median age was 30 years, and they were more likely to be multiparous., Conclusions: Data from the COVIDPregDK Study will enable us to gain valuable knowledge on how the pandemic, the intensified measures from the health authorities and the national lockdown affected pregnant women's mental health and their concerns during the COVID-19 pandemic.

Migraine is a disease characterized by cerebral vasodilation. While diabetes has previously been associated with a lower risk of migraine, it is not known if diabetic retinopathy (DR), a retinal peripheral vascular occlusive disease, is a potential biomarker of protection against migraine. Therefore, we aimed to examine diabetic retinopathy as a marker of prevalent and 5-year incident migraine. In a national cohort, we compared patients with diabetes attending DR screening from The Danish National Registry of Diabetic Retinopathy (cases, n = 205,970) to an age- and gender-matched group of patients without diabetes (controls, n = 1,003,170). In the cross-sectional study, a multivariable model demonstrated a lower prevalence of migraine among cases compared with controls (OR 0.83, 95% CI 0.81-0.85), with a lower risk in cases with DR than in those without (OR 0.69, 95% CI 0.65-0.72). In the prospective study, a lower risk of incident migraine was found in a multivariable model in cases (HR 0.76, 95% CI 0.70-0.82), but this did not depend upon the presence of DR. To conclude, in a national study of more than 1.2 million people, patients screened for DR had a lower risk of present migraine, but DR was not a protective marker of incident migraine., (© 2022. The Author(s).)

Background: Gender affirming hormonal treatment (GAHT) is a cornerstone in transgender care. National data are sparse regarding use of hormonal treatment by transgender persons., Aim: To assess use of GAHT in transgender persons., Design: National register-based cohort study in Danish transgender persons followed from 2000 until 2018. The main outcome measure was prescription and purchase of GAHT. Persons with ICD-10 diagnosis code of "gender identity disorder" (CGI-cohort) and persons with legal sex change but without diagnosis (CPR-cohort) were included. In the CGI-cohort, transgender women were defined by prescription of estrogen and/or cyproterone acetate and/or testosterone-5-alpha reductase inhibitors, and transgender men were defined by prescription of testosterone after study inclusion. Discontinuation of GAHT was defined as no purchase of GAHT ≥13 months or shift from feminizing to masculinizing hormone treatment, or vice versa., Results: The cohort included 2789 transgender persons (n = 1717, CGI-cohort and n = 1072, CPR-cohort). The median age (interquartile range) at study inclusion was 26.1 (17.7) years for persons assigned male at birth (n = 1447) and 22.5 (10.5) years for persons assigned female at birth (n = 1342). In the CGI-cohort, the event rate for GAHT in transgender women increased from 4.0 (95% confidence interval [CI]: [3.1; 5.2]) events per 100 person in year 2000-2005 to 20.6 (17.8; 23.7) between 2014 and 2018. In transgender men, the event rate of GAHT increased from 4.2 (2.8; 6.2) to 18.8 (16.4; 21.6). The rate of discontinuation of GAHT was 0.06 (95% CI 0.049; 0.071) per person year., Conclusions: The event rate of GAHT increased during 2000-2018. Our data suggested high adherence to GAHT., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

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., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)