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Jesper Winkler Andersen,1,2 Annette Høgh,1,3 Jes Sanddal Lindholt,1,3– 6 Rikke Søgaard,5 Henrik Støvring,3,7 Knud Bonnet Yderstræde,5,8 Annelli Sandbæk,9– 11 Marie Dahl1,3– 5 1Vascular Research Unit, Department of Vascular Surgery, Viborg Regional Hospital, Viborg, Denmark; 2Department of Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 4Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark; 5Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 6Elite Centre of Individualized Treatment of Arterial Diseases (CIMA), Odense University Hospital, Odense, Denmark; 7Department of Biomedicine, Aarhus University, Aarhus, Denmark; 8Diabetes Center, Steno, Odense, Denmark; 9Department of Public Health, Aarhus University, Aarhus, Denmark; 10Research unit of General Medical Practice, Aarhus University, Aarhus, Denmark; 11Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, DenmarkCorrespondence: Jesper Winkler Andersen, Vascular Research Unit, Department of Surgery, Viborg Regional Hospital, Toldbodgade 12, Viborg, 8800, Denmark, Tel +45 28118736, Email jesper.andersen@midt.rm.dkPurpose: The present study aims to evaluate the changes in healthcare utilization following population-based screening for diabetes mellitus (DM) using point-of-care HbA1c measurement in the Viborg Screening Program (VISP) cohort, which invites all 67-year-olds in Viborg, Denmark, for cardiovascular disease (CVD) and DM screening.Patients and Methods: We conducted a cohort study using data from VISP and Danish national health registers. The study included 2386 individuals invited to VISP from August 1, 2014, to May 31, 2017. Exclusion criteria were non-attenders, those with prior DM, and those with missing HbA1c measurements. Pre- and post-screening healthcare utilization was analyzed, stratified by HbA1c levels: < 42 mmol/mol (normal), 42– 48 mmol/mol (pre-DM), and ≥ 48 mmol/mol (DM). Statistical analyses were performed using Poisson and logistic regression models to compare ratios of healthcare utilization before and after screening.Results: Of the participants, 16.5% had pre-DM, and 3.4% had DM. Screening resulted in increased general physician contacts across all HbA1c groups, the highest increase was seen in the DM group with a pre- vs post-screening odds ratio [OR] of 3.25 (95% CI: 1.06– 9.95) and a relative odds ratio [ROR] of 2.70 (0.87– 8.39). Also, in this group, the OR for having ≥ 1 HbA1c measurement one year pre- vs post-screening was 5.56 (2.77 − 11.14) and 26.8% (17.6– 37.9) started glucose-lowering treatment within two years post-screening. Despite expectations, healthcare utilization did not decrease among those with normal HbA1c levels.Conclusion: Population-based screening for DM and CVD among 67-year-olds resulted in increased healthcare utilization, particularly among those with screen-detected DM and pre-DM. The anticipated reduction in healthcare utilization among individuals with normal HbA1c levels was not observed. These findings highlight the potential for screening to enhance disease management and underscore the need for strategies to optimize healthcare resource use following screening, especially for individuals without DM.Trial Registration: NCT03395509.Keywords: epidemiology, medication, general practice, Denmark, diabetes

Summary: Background: Despite advances in primary and secondary prevention of cardiovascular disease, excess mortality persists within the diabetes population. This study explores the components of this excess mortality and their interaction with sex. Methods: Using Danish registries (2002–2019), we identified residents aged 18–99 years, their diabetes status, and recorded causes of death. Applying Lexis-based methods, we computed age-standardized mortality rates (asMRs), mortality relative risks (asMRRs), and log-linear trends for cause-specific mortality. Findings: From 2002 to 2019, 958,278 individuals died in Denmark (T2D: 148,620; T1D: 7830) during 84.4 M person-years. During the study period, overall asMRs declined, driven by reducing cardiovascular mortality, notably in men with T2D. Conversely, cancer mortality remained high, making cancer the leading cause of death in individuals with T2D. Individuals with T2D faced an elevated mortality risk from nearly all cancer types, ranging from 9% to 257% compared to their non-diabetic counterparts. Notably, obesity-related cancers exhibited the highest relative risks: liver cancer (Men: asMRR 3.58 (3.28; 3.91); Women: asMRR 2.49 (2.14; 2.89)), pancreatic cancer (Men: asMRR 3.50 (3.25; 3.77); Women: asMRR 3.57 (3.31; 3.85)), and kidney cancer (Men: asMRR 2.10 (1.84; 2.40); Women: asMRR 2.31 (1.92; 2.79)). In men with type 2 diabetes, excess mortality remained stable, except for dementia. In women, diabetes-related excess mortality increased by 6–17% per decade across all causes of death, except cardiovascular disease. Interpretation: In the last decade, cancer has emerged as the leading cause of death among individuals with T2D in Denmark, emphasizing the need for diabetes management strategies incorporating cancer prevention. A sex-specific approach is crucial to address persistently higher relative mortality in women with diabetes. Funding: Supported by Steno Diabetes Center Aarhus, which is partially funded by an unrestricted donation from the Novo Nordisk Foundation, and by The Danish Diabetes Academy.

Abstract Background Primary care providers see patients with obesity in general practice every day but may be challenged regarding communication about obesity. The research question of this study is: how do general practitioners and general practice staff and adult patients with obesity communicate about weight‐related issues? Methods A scoping review approach was used, searching PubMed, Scopus and CINAHL for peer‐reviewed studies – of both quantitative and/or qualitative study designs, and published between 2001 and 2021. Results Twenty articles were included. The weight‐related issues discussed were by far physical issues, and only one study mentioned psychosocial issues. Most of the included studies contained information on who initiates the communication, how the weight‐related issues are addressed and handled, and also obstacles and challenges in relation to the communication. The studies lacked information of when the weight‐related issues are addressed and differences in views and experiences when discussing weight‐related issues in general practice. Conclusion Studies with the main focus communication about obesity and overall health in general practice are needed. Findings also indicate, that non‐stigmatizing communication tools and guidelines are needed on this area to promote these types of conservations.

Background: There is uncertainty about the utility of multiphase computed tomography (CT) compared with single-phase CT in the routine examination of patients with visible haematuria (VH). Objective: To compare the accuracies of single nephrographic phase (NP) CT and four-phase CT in detecting urothelial carcinoma (UC). Design, setting, and participants: This was a single-centre, prospective, paired, noninferiority study of patients with painless VH referred for CT before cystoscopy between September 2019 and June 2021. Patients were followed up for 1 yr to ascertain UC diagnosis. Intervention: All patients underwent four-phase CT (control), from which single NP CT (experimental) was extracted. Both were independently assessed for UC. Outcome measurements and statistical analysis: The primary outcome was the difference in accuracy between the control and experimental CT using a 7.5% noninferiority limit. Histologically verified UC defined a positive reference standard. Secondary outcomes included differences in sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and area under the curve (AUC). All results are reported per patient. Results and limitations: Of the 308 patients included, UC was diagnosed in 45 (14.6%). The difference in accuracy between the control and experimental CT was 1.9% (95% confidence interval −2.8 to 6.7), demonstrating noninferiority. Sensitivity was 93.3% versus 91.1%, specificity was 83.7% versus 81.8%, NPV was 98.7% versus 98.2%, PPV was 49.4% versus 46.1%, and AUC was 0.96 versus 0.94 for the control versus experimental CT. Limitations included a low number of UC cases and no definite criteria for selecting a noninferiority limit. Conclusions: The accuracy of NP CT is not inferior to that of four-phase CT for detecting UC. Patient summary: This study shows that a computed tomography (CT) examination with only one contrast phase is no worse than a more complex CT examination for detecting cancer in the urinary tract among patients presenting with visible blood in the urine.

Abstract Background Sleep duration is associated with BMI and waist circumference. However, less is known about whether sleep duration affects different measurements of obesity differently. Objective To investigate the association between sleep duration and different measures of obesity. Methods In this cross‐sectional analysis 1309, Danish, older adults (55% men) completed at least 3 days of wearing a combined accelerometer and heart rate‐monitor for assessing sleep duration (hours/night) within self‐reported usual bedtime. Participants underwent anthropometry and ultrasonography to assess BMI, waist circumference, visceral fat, subcutaneous fat, and fat percentage. Linear regression analyses examined the associations between sleep duration and obesity‐related outcomes. Results Sleep duration was inversely associated with all obesity‐related outcomes, except visceral‐/subcutaneous‐fat‐ratio. After multivariate adjustment the magnitude of associations became stronger and statistically significant for all outcomes except visceral‐/subcutaneous‐fat‐ratio, and subcutaneous fat in women. The associations with BMI and waist circumference demonstrated the strongest associations, when comparing standardized regression coefficients. Conclusions Shorter sleep duration were associated with higher obesity across all outcomes except visceral‐/subcutaneous‐fat‐ratio. No specifically salient associations with local or central obesity were observed. Results suggest that poor sleep duration and obesity correlate, however, further research is needed to conclude on beneficial effects of sleep duration regarding health and weight loss.

Anders Aasted Isaksen,1,2 Annelli Sandbæk,1,2 Lasse Bjerg1,2 1Department of Public Health, Aarhus University, Aarhus, Denmark; 2Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus N, DenmarkCorrespondence: Anders Aasted Isaksen, Institut for Folkesundhed, Aarhus Universitet, Bartholins Allé 2, Aarhus, 8000, Denmark, Email aai@ph.au.dkPurpose: To validate two register-based algorithms classifying type 1 (T1D) and type 2 diabetes (T2D) in a general population using Danish register data.Patients and Methods: After linking data on prescription drug usage, hospital diagnoses, laboratory results and diabetes-specific healthcare services from nationwide healthcare registers, diabetes type was defined for all individuals in Central Denmark Region age 18– 74 years on 31 December 2018 according to two distinct register-based classifiers: 1) a novel register-based diabetes classifier incorporating diagnostic hemoglobin-A1C measurements, the Open-Source Diabetes Classifier (OSDC), and 2) an existing Danish diabetes classifier, the Register for Selected Chronic Diseases (RSCD). These classifications were validated against self-reported data from the Health in Central Denmark survey – overall and stratified by age at onset of diabetes. The source-code of both classifiers was made available in the open-source R package osdc.Results: A total of 2633 (9.0%) of 29,391 respondents reported having any type of diabetes, divided across 410 (1.4%) self-reported cases of T1D and 2223 (7.6%) cases of T2D. Among all self-reported diabetes cases, 2421 (91.9%) were classified as diabetes cases by both classifiers. In T1D, sensitivity of OSDC-classification was 0.773 [95% CI 0.730– 0.813] (RSCD: 0.700 [0.653– 0.744]) and positive predictive value (PPV) 0.943 [0.913– 0.966] (RSCD: 0.944 [0.912– 0.967]). In T2D, sensitivity of OSDC-classification was 0.944 [0.933– 0.953] (RSCD: 0.905 [0.892– 0.917]) and PPV 0.875 [0.861– 0.888] (RSCD: 0.898 [0.884– 0.910]). In age at onset-stratified analyses of both classifiers, sensitivity and PPV were low in individuals with T1D onset after age 40 and T2D onset before age 40.Conclusion: Both register-based classifiers identified valid populations of T1D and T2D in a general population, but sensitivity was substantially higher in OSDC compared to RSCD. Register-classified diabetes type in cases with atypical age at onset of diabetes should be interpreted with caution. The validated, open-source classifiers provide robust and transparent tools for researchers.Keywords: type 1 diabetes, type 2 diabetes, classification, population-based, open-source

Objective: Physiologically, pregnancy-associated plasma protein-A (PAPP-A) serves to liberate bound IGF1 by enzymatic cleavage of IGF-binding proteins (IGFBPs), IGFBP4 in particular. Clinically, PAPP-A has been linked to cardiovascular disease (CVD). Stanniocalcin-2 (STC2) is a natural inhibitor of PAPP-A enzymatic activity, but its association with CVD is unsettled. Therefore, we examined associations between the STC2–PAPP-A–IGFBP4–IGF1 axis and allcause mortality and CVD in patients with type 2 diabetes (T2D). Design: We followed 1284 participants with T2D from the ADDITION trial for 5 years. Methods: Circulating concentrations of STC2, PAPP-A, total and intact IGFBP4 and IGF1 and -2 were measured at inclusion. End-points were all-cause mortality and a composite CVD event: death from CVD, myocardial infarction, stroke, revascularisation or amputation. Survival analysis was performed by Cox proportional hazards model. Results: During follow-up, 179 subjects presented with an event. After multivariable adjustment, higher levels of STC2, PAPP-A, as well as intact and total IGFBP4, were associated with all-cause mortality; STC2: hazard ratio (HR) = 1.84 (1.09–3.12) (95% CI); P = 0.023, PAPP-A: HR = 2.81 (1.98–3.98); P < 0.001, intact IGFBP4: HR = 1.43 (1.11–1.85); P = 0.006 and total IGFBP4: HR = 3.06 (1.91–4.91); P < 0.001. Higher PAPP-A levels were also associated with CVD events: HR = 1.74 (1.16–2.62); P = 0.008, whereas lower IGF1 levels were associated with all-cause mortality: HR = 0.51 (0.34–0.76); P = 0.001. Conclusions: This study supports that PAPP-A promotes CVD and increases mortality. However, STC2 is also associated with mortality. Given that STC2 inhibits the enzymatic effects of PAPP-A, we speculate that STC2 either serves to counteract harmful PAPP-A actions or possesses effects independently of the PAPP-A–IGF1 axis. Significance statement: PAPP-A has pro-atherosclerotic effects and exerts these most likely through IGF1. IGF1 is regulated by the STC2–PAPP-A–IGFBP4–IGF1 axis, where STC2, an irreversible inhibitor of PAPP-A, has been shown to reduce the development of atherosclerotic lesions in mice. We examined the association of this axis to mortality and CVD in T2D. We demonstrated an association between PAPP-A and CVD. All components of the STC2–PAPP-A– IGFBP4–IGF1 axis were associated with mortality and it is novel that STC2 was associated with mortality in T2D. Our study supports that inhibition of PAPP-A may be a new approach to reducing mortality and CVD. Whether modification of STC2 could serve as potential intervention warrants further investigation.

Abstract Background We aimed to examine the impact of gender and specific type of cardiovascular disease (CVD) diagnosis (ischemic heart disease [IHD], heart failure, peripheral artery disease [PAD] or stroke) on time-to-initiation of either a sodium glucose cotransporter 2 inhibitor or glucagon-like peptide 1 analogue (collectively termed cardioprotective GLD) after a dual diagnosis of type 2 diabetes (T2DM) and CVD. Methods In a nationwide cohort study, we identified patients with a new dual diagnosis of T2DM and CVD (January 1, 2012 and December 31, 2018). Cumulative user proportion (CUP) were assessed. Poisson models were used to estimate the initiation rate of cardioprotective GLDs. The final analyses were adjusted for potential confounders. Results In total, we included 70,538 patients with new-onset T2DM and CVD (38% female, mean age 70 ± 12 years at inclusion). During 183,256 person-years, 6,276 patients redeemed a prescription of a cardioprotective GLD. One-year CUPs of cardioprotective GLDs were lower in women than men. Initiation rates of GLDs were lower in women (female-to-male initiation-rate-ratio crude: 0.76, 95% CI 0.72–0.81); adjusted 0.92, 95% CI 0.87–0.97). In CVD-stratified analysis, the adjusted initiation rate ratio was lower in female patients with IHD and heart failure (IHD: 0.91 [95% CI 0.85–0.98], heart failure: 0.85 [95% CI 0.73–1.00], PAD: 0.92 [95% CI 0.78–1.09], and stroke: 1.06 [95% CI 0.93–1.20]). Conclusions Among patients with a new dual diagnosis of T2DM and CVD, female gender is associated with lower initiation rates of cardioprotective GLDs, especially if the patient has IHD or heart failure.

Abstract Background To support the primary care sector in delivering high-quality type 2 diabetes (T2D), literature reviews emphasize the need for implementing models of collaboration that in a simple and effective way facilitate clinical dialogue between general practitioners (GPs) and endocrinologists. The overall aim of the project is to evaluate if virtual specialist conferences between GPs and endocrinologists about patients living with T2D is clinically effective and improves diabetes competences and organization in general practice in comparison to usual practice. Methods A prospective, pragmatic, and superiority RCT with two parallel arms of general practices in the Municipality of Aarhus, Denmark. All general practices are invited (n = 100). The intervention runs for 12 months and consists of four virtual conferences between endocrinologists and an individual general practice. Before the first conference, an introductory webinar teaches GPs about how to use an IT-platform to identify and manage T2D patients. The main analysis (month 12) concerns the difference between the intervention and control arm. It is expected that the virtual conferences at the patient level will improve adherence to international recommendations on diabetes medication for T2D patients and improve the risk profile with a reduction in glycated haemoglobin, blood pressure, and cholesterol. The study design allows for identifying a significant difference between the intervention (n = 15) and control group (n = 15) regarding the three primary clinical outcomes with a power of 0.8870–0.9941. At the general practice level, it is expected that general practitioners and practice staff in the intervention group will improve self-reported diabetes competence and organization. The control arm will get the intervention when the primary intervention ends (months 12–24), and the intervention arm transitions to a maintenance phase. Discussion The potential of virtual conferences is yet to be fully tapped because of methodological limitations. Studies have also not yet systematically evaluated virtual conferences in the context of chronic care using a high-quality research design. Given the nature of this real-life intervention, general practitioners and endocrinologists cannot be blinded to their allocation to either the intervention or comparison arm. Trial registration ClinicalTrials.gov, United States National Institutes of Health trial ID: NCT05268081. Registered on 4 March 2022.

The prevalence of type 2 diabetes (T2D) is higher in migrants compared to native populations in many countries, but the evidence on disparities in T2D care in migrants is inconsistent. Therefore, this study aimed to examine this in Denmark. In a cross-sectional, register-based study on 254,097 individuals with T2D, 11 indicators of guideline-level care were analysed: a) monitoring: hemoglobin-A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), screening for diabetic nephropathy, retinopathy, and foot disease, b) biomarker control: HbA1c and LDL-C levels, and c) pharmacological treatment: glucose-lowering drugs (GLD), lipid-lowering drugs, angiotensin-converting enzyme-inhibitors/angiotensin receptor blockers, and antiplatelet therapy. Migrants were grouped by countries of origin: Middle East, Europe, Turkey, Former Yugoslavia, Pakistan, Sri Lanka, Somalia, Vietnam. In all migrant groups except the Europe-group, T2D was more prevalent than in native Danes (crude relative risk (RR) from 0.62 [0.61-0.64] (Europe) to 3.98 [3.82-4.14] (Sri Lanka)). In eight indicators, non-fulfillment was common (>25% among native Danes). Apart from monitoring in the Sri Lanka-group, migrants were at similar or higher risk of non-fulfillment than native Danes across all indicators of monitoring and biomarker control (RR from 0.64 [0.51-0.80] (HbA1c monitoring, Sri Lanka) to 1.78 [1.67-1.90] (LDL-C control, Somalia)), while no overall pattern was observed for pharmacological treatment (RR from 0.61 [0.46-0.80] (GLD, Sri Lanka) to 1.67 [1.34-2.09] (GLD, Somalia)). Care was poorest in migrants from Somalia, who had increased risk in all eleven indicators, and the highest risk in nine. Adjusted risks were elevated in some migrant groups, particularly in indicators of biomarker control (fully-adjusted RR from 0.84 [0.75-0.94] (LDL-C levels, Vietnam) to 1.44 [1.35-1.54] (LDL-C levels, Somalia)). In most migrant groups, T2D was more prevalent, and monitoring and biomarker control was inferior compared to native Danes. Migrants from Somalia received the poorest care overall, and had exceedingly high lipid levels.

Aim Methods Results Conclusions The aim of this study is to estimate the causally attributable one‐year healthcare costs for individuals getting a type 2 diabetes diagnosis compared to a matched sample and show the incurred costs of medication and in primary and secondary healthcare.Causal estimation using a difference‐in‐differences design to estimate the one‐year health care costs attributable to type 2 diabetes. Danish registry data consisting of the entire population in years 2016–2019. Newly diagnosed individuals with type 2 diabetes in 2018 were identified using a validated method. Sociodemographic and historical health data were used to identify a matched control group. Individuals were followed for two years before and one year after the date of diagnosis using. Three cost components were analysed: medication and primary and secondary healthcare costs.A total of 18,133 individuals were diagnosed with type 2 diabetes in 2018 and matched successfully 1:1 to a control group. The total attributable one‐year cost of type 2 diabetes was EUR 1316. The main cost component was hospital care (EUR 1004) and primary care (EUR 167). The total attributable cost of incident diabetes in Denmark in 2018 was approx. EUR 24 million.The majority of the first year health care cost of incident diabetes is incurred at the hospital level followed by primary care and medication. Our yearly cost estimate per newly diagnosed is considerably lower than estimates from the US and Australia. [ABSTRACT FROM AUTHOR]

BackgroundDuring the COVID-19 pandemic, video consultations became a common method of delivering care in general practice. To date, research has mostly studied acute or subacute care, thereby leaving a knowledge gap regarding the potential of using video consultations to manage chronic diseases. ObjectiveThis study aimed to examine general practitioners’ technology acceptance of video consultations for the purpose of managing type 2 diabetes in general practice. MethodsA web-based survey based on the technology acceptance model measuring 4 dimensions—perceived usefulness, perceived ease of use, attitude, and behavioral intention to use—was sent to all general practices (N=1678) in Denmark to elicit user perspectives. The data were analyzed using structural equation modeling. ResultsThe survey sample comprised 425 general practitioners who were representative of the population. Structural equation modeling showed that 4 of the 5 hypotheses in the final research model were statistically significant (P

Purpose The Health in Central Denmark (HICD) cohort is a newly established cohort built on extensive questionnaire data linked with laboratory data and Danish national health and administrative registries. The aim is to establish an extensive resource for (1) gaining knowledge on patient-related topics and experiences that are not measured objectively at clinical health examinations and (2) long-term follow-up studies of inequality in diabetes and diabetes-related complications.Participants A total of 1.3 million inhabitants reside in the Central Denmark Region. Using register data and a prespecified diabetes classification algorithm, we identified 45 507 persons aged 18–75 years with prevalent diabetes on 31 December 2018 and a group without diabetes of equal size matched by sex, age and municipality. A 90-item questionnaire was distributed to eligible members of this cohort on 18 November 2020 (estimated time required for completion: 15–20 min).Findings to date We invited 90 854 persons to take part in the survey, of whom 51 854 answered the questionnaire (57.1%). Among these respondents, 2,832 persons had type 1 diabetes (55.9%), 21,140 persons had type 2 diabetes (53.2%), while 27,892 persons were part of the matched group without diabetes (60.4%). In addition to questionnaire data, the cohort is linked to nationwide registries that provide extensive data on hospital diagnoses and procedures, medication use and socioeconomic status decades before enrolment while laboratory registries has provided repeated measures of biochemical markers, for example, lipids, albuminuria and glycated haemoglobin up to 10 years before enrolment.Future plans The HICD will serve as an extensive resource for studies on patient-related information and inequality in type 1 diabetes and type 2 diabetes. Follow-up is planned to continue for at least 10 years and detailed follow-up questionnaires, including new topics, are planned to be distributed during this period, while registry data are planned to be updated every second year.

Introduction Patients with schizophrenia suffer from increased mortality rates equivalent to 15-20 years shorter life expectancy. Up to 60% of this excess mortality can be explained by preventable, somatic conditions like cardiovascular, metabolic, and respiratory comorbidities. As forensic psychiatric (FP) patients often experience the triple stigmatization of mental illness, substance misuse and criminal conviction, the risk of suboptimal diagnosis and treatment may be high. Although benefits from the addition of general practitioner (GP) services to non-FP wards have been shown elsewhere, this cross-sectoral approach has never been attempted in a Danish FP ward. Objectives One purpose of this project is to evaluate the associations between self-reported quality of life and objective measures of somatic health. Methods A clinical intervention in which a GP consults patients in all medium secure wards in the Central Denmark Region (N=72). The consultation includes a physical examination, medication review, and evaluation of blood samples. Data is collected from: electronic patient files and questionnaires regarding quality of life (SF-12), lifestyle, and attitude towards GP services. Results The population will be described in regards to socio-demographic, clinical, and forensic characteristics. Associations will be made between quality of life (SF-12), metabolic syndrome, blood markers, and heart-SCORE risk. Risk profiles for endocrinologic and coronary illness will be examined. Conclusions Results may guide future health interventions and will be used as a basis for adjustments to the current project. Disclosure No significant relationships.

BackgroundThe COVID-19 pandemic has changed various spheres of health care. General practitioners (GPs) have widely replaced face-to-face consultations with telephone or video consultations (VCs) to reduce the risk of COVID-19 transmission. Using VCs for health service delivery is an entirely new way of practicing for many GPs. However, this transition process has largely been conducted with no formal guidelines, which may have caused implementation barriers. This study presents a rapid cycle coproduction approach for developing a guide to assist VC implementation in general practice. ObjectiveThe aim of this paper is to describe the developmental phases of the VC guide to assist general practices in implementing VCs and summarize the evaluation made by general practice users. MethodsThe development of a guide for VC in general practice was structured as a stepped process based on the coproduction and prototyping processes. We used an iterative framework based on rapid qualitative analyses and interdisciplinary collaborations. Thus, the guide was developed in small, repeated cycles of development, implementation, evaluation, and adaptation, with a continuous exchange between research and practice. The data collection process was structured in 3 main phases. First, we conducted a literature review, recorded observations, and held informal and semistructured interviews. Second, we facilitated coproduction with stakeholders through 4 workshops with GPs, a group interview with patient representatives, and individual revisions by GPs. Third, nationwide testing was conducted in 5 general practice clinics and was followed by an evaluation of the guide through interviews with GPs. ResultsA rapid cycle coproduction approach was used to explore the needs of general practice in connection with the implementation of VC and to develop useful, relevant, and easily understandable guiding materials. Our findings suggest that a guide for VCs should include advice and recommendations regarding the organization of VCs, the technical setup, the appropriate target groups, patients’ use of VCs, the performance of VCs, and the arrangements for booking a VC. ConclusionsThe combination of coproduction, prototyping, small iterations, and rapid data analysis is a suitable approach when contextually rich, hands-on guide materials are urgently needed. Moreover, this method could provide an efficient way of developing relevant guide materials for general practice to aid the implementation of new technology beyond the pandemic period.

Conflicting evidence suggests a link between diabetes-related microvascular complications and periodontitis. Reliable estimates have been hindered by small sample sizes and residual confounding. Moreover, the combined effects of microvascular complications and dyslipidemia on periodontitis have not been explored. Therefore, this study aimed to investigate the association between individual and combined diabetic microvascular complications (i.e., neuropathy and retinopathy) and moderate/severe periodontitis in a Danish population-based study. In addition, we assessed whether dyslipidemia modified these associations. This study comprised 15,922 participants with type 2 diabetes from the Health in Central Denmark study. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for individual and joint microvascular diabetes complications. The models adjusted for potential confounders, including sociodemographic factors, lifestyle behaviors, and health conditions. Inverse probability of treatment weighting (IPTW) balanced measured confounders between periodontitis and nonperiodontitis participants. Sensitivity analyses tested the findings' robustness by estimating E-values for unmeasured confounding and varying microvascular complication definitions. After IPTW, adjusted models revealed that diabetic neuropathy (OR 1.36, 95% CI 1.14 to 1.63) and retinopathy (OR 1.21, 95% CI 1.03 to 1.43) were significantly associated with moderate/severe periodontitis. Moreover, the coexistence of microvascular complications increased the odds 1.5-fold for moderate/severe periodontitis (OR 1.51, 95% CI 1.23 to 1.85). An effect modification of dyslipidemia on an additive scale was found, indicated by a positive relative excess risk due to interaction of 0.24 for neuropathy, 0.11 for retinopathy, and 0.44 for both complications. Sensitivity analysis ruled out unmeasured confounders and microvascular complication definitions as explanatory factors. Diabetic neuropathy and retinopathy, individually and combined, were associated with moderate/severe periodontitis. In addition, dyslipidemia had an additive positive effect modification on diabetic microvascular complications, elevating the odds of moderate/severe periodontitis. These findings may aid in identifying at-risk subgroups for diabetes-related microvascular complications and periodontitis, optimizing efforts to mitigate disease burden. [ABSTRACT FROM AUTHOR]

Abstract Background Early detection of lung disease may help reduce disease development. Detection through preventive health checks may be beneficial. Nevertheless, the knowledge is sparse on how to enhance the participation rate in health checks among citizens at risk of developing lung disease. This study investigates if focused information on spirometry can increase the participation rate in a general health check. Methods We conducted an open-label, household cluster-randomised trial with a two-group parallel design including 4407 citizens aged 30–49 years in Denmark and an average cluster size of 1.55 citizens per household. The control group (n = 2213) received a standard invitation describing the content of the general health check and containing practical information. The intervention group (n = 2194) received an extended invitation highlighting the benefits of early detection and prevention of lung disease. The primary outcome was difference in participation rate between the two groups. The secondary outcome was the proportion of participants at risk of lung disease in both groups. Risk profile was defined as current smoking or self-reported lung symptoms. The inclusion period was 25 November 2015–3 February 2017. Results No major difference in participation rate was seen between the intervention group (53.4%) and the control group (52.0%). Participants had statistically significantly higher education level compared to non-participants. A total of 24.2% of the participants were at risk of developing lung disease, but no difference was found between the intervention group and the control group. Conclusion This study revealed no effect on participation rate of including focused spirometry information in the health check invitation. Trial registration ClinicalTrials.gov: NCT02615769. Registered on 25 November 2015. The trial protocol has been published.

Objectives Potentially inappropriate medications (PIMs) pose an increasing challenge in the ageing population. We aimed to assess the extent of PIMs and the prescriber-related variation in PIM prevalence.Design Nationwide register-based cohort study.Setting General practice.Participants The 4.2 million adults listed with general practitioner (GP) clinics in Denmark (n=1906) in 2016.Main outcome measures We estimated the patients’ time with PIMs by using 29 register-operationalised STOPP criteria linking GP clinics and redeemed prescriptions. For each criterion and each GP clinic, we calculated ratios between the observed PIM time and that predicted by multivariate Poisson regressions on the patients. The observed variation was measured as the 90th/10th percentile ratios of these ratios. The extent of expectable random variation was assessed as the 90th/10th percentile ratios in randomly sampled GP populations (ie, the sampled variation). The GP-related excess variation was calculated as the ratio between the observed variation and sampled variation. The linear correlation between the observed/expected ratio for each of the criteria and the observed/expected ratio of total PIM time (for each clinic) was measured by Pearson’s rho.Results Overall, 294 542 individuals were exposed to 1 44 117 years of PIMs. The two most prevalent PIMs were long-term use (>3 months) of non-steroidal anti-inflammatory drugs (51 074 years of PIMs) or benzodiazepines (48 723 years of PIMs). These two criteria showed considerable excess variation of 2.33 and 3.05, respectively; for total PIMs, this figure was 1.65. For more than half of the criteria, we observed a positive correlation between the specific PIM and the sum of remaining PIMs.Conclusions This study documents considerable variations in the prescribing practice of GPs for certain PIMs. These findings highlight a need for exploring the causal explanations for such variations, which could be markers of suboptimal GP-prescribing strategies.

It has been hypothesized that, in aggregate, rare variants in coding regions of genes explain a substantial fraction of the heritability of common diseases. We sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes (including body mass index > 27.5 kg/m(2) and hypertension) and 1,000 healthy controls to an average depth of 56×. Our simulations suggest that our study had the statistical power to detect at least one causal gene (a gene containing causal mutations) if the heritability of these common diseases was explained by rare variants in the coding regions of a limited number of genes. We applied a series of gene-based tests to detect such susceptibility genes. However, no gene showed a significant association with disease risk after we corrected for the number of genes analyzed. Thus, we could reject a model for the genetic architecture of type 2 diabetes where rare nonsynonymous variants clustered in a modest number of genes (fewer than 20) are responsible for the majority of disease risk.

It has been hypothesized that, in aggregate, rare variants in coding regions of genes explain a substantial fraction of the heritability of common diseases. We sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes (including body mass index > 27.5 kg/m2 and hypertension) and 1,000 healthy controls to an average depth of 56×. Our simulations suggest that our study had the statistical power to detect at least one causal gene (a gene containing causal mutations) if the heritability of these common diseases was explained by rare variants in the coding regions of a limited number of genes. We applied a series of gene-based tests to detect such susceptibility genes. However, no gene showed a significant association with disease risk after we corrected for the number of genes analyzed. Thus, we could reject a model for the genetic architecture of type 2 diabetes where rare nonsynonymous variants clustered in a modest number of genes (fewer than 20) are responsible for the majority of disease risk. © 2013 The American Society of Human Genetics.

BackgroundAt time of discharge after a pneumonia admission, care planning for older persons with dementia is essential. However, care planning is limited by lack of knowledge on the short-term prognosis.AimTo investigate 30-day mortality and readmission after hospital discharge for pneumonia in persons with versus without dementia, and to investigate how these associations vary with age, time since discharge, and medication use.MethodsUsing the Danish registries, we investigated 30-day mortality and readmission in persons (+65 years) discharged after pneumonia in 2000-2016 (N = 298,872). Adjusted mortality rate ratios (aMRRs) and incidence rate ratios (aIRRs) were calculated for persons with versus without dementia, and we investigated if these associations varied with use of benzodiazepines, opioids, and antipsychotics, and with age and time since discharge.ResultsAmong 25,948 persons with dementia, 4,524 died and 5,694 were readmitted within 30 days. The risk of 30-day mortality was 129% higher (95% CI 2.21-2.37) in persons with versus without dementia after adjustment for sociodemographic characteristics, admission-related factors, and comorbidities. Further, the highest mortality risk was found in persons with both dementia and use of antipsychotics (aMRR: 3.39, 95% CI 3.19-3.59); 16% of deaths in this group could not be explained by the independent effect of each exposure. In those with dementia, the highest aMRRs were found for the youngest and for the first days after discharge. The risk of 30-day readmission was 7% higher (95% CI 1.04-1.10) in persons with versus without dementia. In those with dementia, the highest aIRRs were found for the first days after discharge.ConclusionsDementia was associated with higher short-term mortality after pneumonia, especially in users of antipsychotics, and with slightly higher readmission, especially in the first days after discharge. This is essential knowledge in the care planning for persons with dementia who are discharged after a pneumonia admission.

A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

Background Stress has been reported to trigger stroke, and the death of a loved one is a potentially extremely stressful experience. Yet, previous studies have yielded conflicting findings of whether bereavement is associated with stroke risk, possibly because of insufficient distinction between ischemic stroke (IS) and intracerebral hemorrhage (ICH). We therefore examined the associations between bereavement and IS and ICH separately in contemporary care settings using nationwide high‐quality register resources. Methods and Results The study cohort included all Danish individuals whose partner died between 2002 and 2016 and a reference group of cohabiting individuals matched 1:2 on sex, age, and calendar time. Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and corresponding 95% CIs during up to 5 years follow‐up. During the study period, 278 758 individuals experienced partner bereavement, of whom 7684 had an IS within the subsequent 5 years (aHR, 1.11; CI, 1.08–1.14 when compared with nonbereaved referents) and 1139 experienced an ICH (aHR, 1.13; CI, 1.04–1.23). For ICH, the estimated association tended to be stronger within the initial 30 days after partner death (aHR, 1.66; CI, 1.06–2.61), especially in women (aHR, 1.99; CI, 1.06–3.75), but the statistical precision was low. In absolute numbers, the cumulative incidence of IS at 30 days was 0.73 per 1000 in bereaved individuals versus 0.63 in their referents, and the corresponding figures for ICH were 0.13 versus 0.08. Conclusions Statistically significant positive associations with partner bereavement were documented for both IS and ICH risk, for ICH particularly in the short term. However, absolute risk differences were small.

Introduction Poor mental health is an important public health concern, but mental health problems are often under-recognised. Providing feedback to general practitioners (GPs) on their patients’ mental health status may improve the identification of cases in need of mental healthcare.Objectives To investigate the extent of initiation of mental healthcare after identification of poor mental health and to identify factors associated with non-initiation.Design Prospective cohort study with 1-year follow-up.Setting In a population-based health preventive programme, Check Your Health, we conducted a combined mental and physical health check in Randers Municipality, Denmark, in 2012–2015 in collaboration with local GPs.Participants Participants were 350 individuals aged 30–49 years old with screen-detected poor mental health who had not received mental healthcare within the past year. The cohort was derived from 14 167 randomly selected individuals of whom 52% (n=7348) participated. Mental health was assessed by the mental component summary score of the 12-item Short-Form Health Survey.Outcome The outcome was initiation of mental healthcare. Mental healthcare included psychometric testing by GP, talk therapy by GP, contact with a psychologist, contact with a psychiatrist and psychotropic medication.Results Within 1 year, 22% (95% CI 18 to 27) of individuals with screen-detected poor mental health initiated mental healthcare. Among individuals who initiated mental healthcare within follow-up, one in six had visited their GP once or less in the preceding year. Male sex (OR: 0.49 (95% CI 0.28 to 0.86)) and less impaired mental health (OR: 0.93 (95% CI 0.89 to 0.98)) were associated with non-initiation of mental healthcare. We found no overall association between socioeconomic factors and initiating mental healthcare.Conclusion Systematic provision of mental health test results to GPs may improve the identification of cases in need of mental healthcare, but does not translate into initiation of mental healthcare. Further research should focus on methods to improve initiation of mental healthcare, especially among men.Trial registration number NCT02028195.

Background: Spirometry is essential to identify cases with obstructive lung diseases (OLDs) in primary care. However, knowledge about the long-term prognostic outcome among younger individuals is sparse. Aim: To describe the predictive value of spirometry among individuals in the age groups 30–49 years and 45–64 years. Design & setting: A population-based cohort study supplied with data from Danish national registries. Method: Spirometry was performed in 905 adults aged 30–49 years in 1991 and in 1277 adults aged 45–64 years in 2006. The participants were categorised into three groups: forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) 75. They were followed throughout 2017 using Danish national registries. Lung disease was defined as fulfilling at least one of the following: two prescriptions for respiratory medicine were redeemed within a year; one lung-related contact to the hospital; or lung-related death. Results: In the 1991 cohort, 21% developed lung diseases and in the 2006 cohort 17% developed lung diseases throughout 2017. The probability of developing lung disease if FEV1/FVC 70–75 was 35% (95% confidence interval [CI] = 25% to 44%) in the 1991 cohort and 23% (95% CI = 17% to 28%) in the 2006 cohort. The positive predicted value (PPV) was higher for both cohorts when focusing on smoking history and self-reported respiratory symptoms. Conclusion: The initial spirometry has a high predictive value to identify cases of future lung diseases. In addition, the group with FEV1/FVC 70–75 had a high risk of developing lung diseases later in life, suggesting this group would be a meaningful target of special interest.

Abstract Background Administrative patient registers are often used to estimate morbidity in epidemiological studies. The validity of register data is thus important. This study aims to assess the positive predictive value of myocardial infarction and stroke registered in the Danish National Patient Register, and to examine the association between cardiovascular risk factors and cardiovascular disease based on register data or validated diagnoses in a well-defined diabetes population. Methods We included 1533 individuals found with screen-detected type 2 diabetes in the ADDITION-Denmark study in 2001–2006. All individuals were followed for cardiovascular outcomes until the end of 2014. Hospital discharge codes for myocardial infarction and stroke were identified in the Danish National Patient Register. Hospital medical records and other clinically relevant information were collected and an independent adjudication committee evaluated all possible events. The positive predictive value for myocardial infarction and stroke were calculated as the proportion of cases recorded in the Danish National Patient Register confirmed by the adjudication committee. Results The positive predictive value was 75% (95% CI: 64;84) for MI and 70% (95% CI: 54;80) for stroke. The association between cardiovascular risk factors and incident cardiovascular disease did not depend on using register-based or verified diagnoses. However, a tendency was seen towards stronger associations when using verified diagnoses. Conclusions Our results show that studies using only register-based diagnoses are likely to misclassify cardiovascular outcomes. Moreover, the results suggest that the magnitude of associations between cardiovascular risk factors and cardiovascular outcomes may be underestimated when using register-based diagnoses.