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Patients with psychotic disorders exhibit elevated mortality and morbidity rates compared to the general population primarily due to comorbid somatic diseases. This study aims to describe the prevalence of selected risk factors and somatic disorders among psychiatric patients with a diagnosis of psychotic disorder. Material and methods: Data were retrieved from Greenland's nationwide electronic medical record. The study population consists of 104 patients diagnosed with a psychotic disorder, encompassing schizophrenia or schizotypal and delusional disorders, residing in Nuuk. The study population comprised 104 patients (68 males and 36 females) with a mean age of 40 years. More than 80% were daily smokers, and 68% had harmful use of cannabis. More than half had dyslipidemia (any imbalance in lipids), while over a quarter were classified as obese with body mass index of 30 kg/m2 or higher. Eighteen percent had hypertension, and six percent suffered from diabetes. This study revealed a notable prevalence of risk factors for somatic diseases, particularly smoking and cannabis use among patients with schizophrenia in Nuuk, indicating that a high prevalence of somatic diseases might be expected as the population gets older and the risk of developing somatic diseases becomes greater. Increased focus on monitoring and preventing those as part of the health care is recommended.

This cross-sectional study sought to assess the prevalence of atrial fibrillation (AF) diagnosis in Greenland among various age groups and examine the corresponding quality of care. We collected data from Greenland's electronic medical records and evaluated the quality of care using six internationally recommended indicators, which are: percentage of AF patients with an assessment of smoking status within the previous year, an assessment of body mass index within the previous year, assessment of blood pressure within the previous year, measurement of thyroid stimulating hormone (TSH), treatment with an anticoagulant and percentage of patients with a measurement of serum-creatinine. We found the prevalence of AF among patients aged 20 years or older in Greenland to be 1.75% (95% CI 1.62-1.88). We found an increasing prevalence of AF with age and a greater proportion of men than women until the age of 74 years. Our study suggests that the associated quality of care could be higher as the requirement of only one of the six quality indicators was met. A lack of registration may partly explain this, and initiatives to improve the quality of care are recommended.

Background: Population-based incidence data on young-adult-onset type 1 diabetes and type 2 diabetes are limited. We aimed to examine secular trends in the incidence of diagnosed type 1 diabetes and type 2 diabetes with an age of onset between 15 and 39 years., Methods: In this multicountry aggregate data analysis, we assembled eight administrative datasets from high-income jurisdictions and countries (Australia, Denmark, Finland, Hungary, Japan, Scotland, South Korea, and Spain [Catalonia]) that had appropriate data available from an international diabetes consortium (GLOBODIAB) describing incidence by diabetes type among people aged 15-39 years from 2000 to 2020. We modelled type 1 diabetes and type 2 diabetes incidence rates using Poisson regression including age and calendar time by sex., Findings: During the years 2000-20, there were 349 591 incident diabetes (both types) cases from 346 million person-years of follow-up among people aged 15-39 years. Over time, there was no statistically significant change in the incidence of type 1 diabetes in Hungary and Japan. The incidence of type 1 diabetes significantly increased in Australia, Denmark, Finland, Scotland, South Korea, and Spain, with annual changes ranging from 0·5% to 6·0%. The incidence of type 2 diabetes significantly increased in four of eight jurisdictions (Denmark, Finland, Japan, and South Korea), with annual increases from 2·0% to 8·5%. The magnitude of increase in incidence of type 2 diabetes was greater in Asian than non-Asian jurisdictions. There was no statistically significant change in type 2 diabetes incidence in Australia and Hungary. The incidence of type 2 diabetes significantly decreased in Scotland and Spain, with annual changes of -0·7% and -1·5%, respectively., Interpretation: There is variability in the trajectory of the incidence of young-adult-onset type 2 diabetes among high-income countries or jurisdictions, with a greater evidence of increase in Asian than non-Asian countries. Evolving trends in the incidence of type 1 and type 2 diabetes in young adults call for the ongoing surveillance of diabetes incidence and a greater research focus on this population., Funding: US Centers for Disease Control and Prevention, Diabetes Australia Research Programme, and Victoria State Government Operational Infrastructure Support Programme., Competing Interests: Declaration of interests BC has received stock or stock options from Novo Nordisk. HMC has received payments or honoraria for speakers bureaus from Novo Nordisk; has been supported for participation on an Advisory Board from Novo Nordisk and Bayer AG; and has received stock or stock options from Roche Pharmaceuticals and Bayer AG. ZK is employed by MSD Pharma Hungary, outside the current work. YN received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Sanofi, Daiichi Sankyo, and DeSC Healthcare. DM has received consulting fees from AB Biotics, Amarna, Ferrer, Eli Lilly, MSD, Novo Nordisk, and Sanofi; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbott, Amgen, AstraZeneca, Gilead, Eli Lilly, Menarini, Novo Nordisk, and Sanofi. JES has received consulting fees from AstraZeneca, Sanofi, Novo Nordisk, MSD, Eli Lilly, Pfizer, and GSK; and has also received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Mylan, Sanofi, Boehringer Ingelheim, Zuellig, and Abbott., (Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The global prevalence of chronic kidney disease (CKD) is approximately 9%. CKD is predicted to become the fifth largest global cause of death by 2040. Moreover, CKD causes disability, diminished quality of life and poses a high cost to healthcare systems. Delaying the development and progression of CKD is therefore of the utmost importance. Several kidney-specific outcome trials on sodium-glucose co-transporter-2 inhibitors (SGLT-2s) have recently provided a paradigm shift in the treatment of people with CKD, with or without diabetes, as these agents have been shown to reduce the progression of CKD on top of maximally tolerated renin-angiotensin-aldosterone system (RAAS) blockade. The relative benefit and safety of SGLT-2is seems to be consistent across ethnicities, ages and frailty categories; however, this needs to be tested in dedicated clinical trials. Guidelines make clear recommendations for the prescription of SGLT-2is and RAAS inhibitors as standard of care for people with CKD. Their combination with other newer antidiabetic agents may provide further benefits by targeting different components of CKD mechanisms. Dedicated randomized controlled trials are needed to test whether combination with other agents could extend the use of SGLT2is and identify people in whom a combination of drugs may be most effective. Increased efforts to implement the guidelines on treatment with SGLT-2is for people with CKD are needed, particularly in those at the highest risk of adverse outcomes and without type 2 diabetes. Moreover, strategies to target the equitable use of SGLT-2is are needed., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Nine cyclists (age: 26 ± 5 years, height: 168 ± 5 cm and mass 58.5 ± 4.5 kg) were observed using continuous glucose monitoring devices throughout a training camp. Interstitial glucose [iG] data were captured via the Abbott libre sense biosensor (Abbott Laboratories) and paired with the Supersapiens software (TT1 Products Inc.). [iG] data were split into time ranges, that is, overall (24-hourly), day-time (06:00-23:59), night-time (00:00-05:59) and exercise. [iG] data were stratified into percentage of time, below range ([TBR] < 70 mg/dl), in range ([TIR] 70-140 mg/dl) and above range ([TAR] ≥ 141 mg/dl). Differences in diurnal and nocturnal data were analysed via repeated measures analysis of variance and paired t-tests where appropriate. p-value of ≤0.05 was accepted as significant. Riders spent an average of 3 ± 1% TAR, 93 ± 2% TIR and 8 ± 3% TBR. Mean 24 h [iG] was 93 ± 2 mg/dl with a coefficient of variation (CV) of 18 ± 1%. Mean (day: 95 ± 3 vs. night: 86 ± 3 mg/dl and p < 0.001) and CV (day: 18 ± 1 vs. night: 9 ± 1% and p < 0.001) in [iG] were higher during the day-time hours. TAR was greater during the day (day: 3 ± 1 vs. night: 0 ± 0% and p < 0.001) but TBR and TIR were similar. Glucose levels below the clinical range may have implications for those without diabetes and warrants further investigation., (© 2024 The Author(s). European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)

Aim: To analyse patterns of glucose-lowering therapies among people with type 2 diabetes (T2D) in Denmark from 2016 to 2023., Materials and Methods: We examined time trends in the clinical profiles of people with T2D who initiated different glucose-lowering therapy classes for the first time. We furthermore investigated individual-level treatment trajectories following first-ever glucose-lowering therapy in people with or without cardiorenal disease. The study utilized data from the nationwide Danish health registries and included all individuals who filled a first-ever prescription for metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 inhibitors (SGLT-2is) or insulin, excluding those without HbA1c-confirmed T2D or probable type 1 diabetes., Results: We included 260 393 individuals initiating a new glucose-lowering therapy class from 2016 to 2023, during which there were 6- and 3-fold increases in initiators of GLP-1RAs and SGLT-2is, respectively. The median HbA1c level at treatment initiation with GLP-1RAs or SGLT-2is decreased, from 67-68 mmol/mol in 2016-2017 to 57-58 mmol/mol in 2022-2023. Among individuals who initiated metformin as first-line therapy, the proportion who started additional glucose-lowering therapy within 2 years increased from 25% in 2016 to 40% in 2021. Among the 38% of individuals who had established cardiorenal disease when they initiated first-ever glucose-lowering therapy in 2020, 22% used SGLT-2is and 18% GLP-1RAs after 2.5 years, compared with 17% and 21% among initiators without cardiorenal disease, respectively., Conclusions: Our study documents a trend towards earlier T2D treatment intensification and an increase in the use of GLP-1RAs and SGLT-2is in Denmark. However, optimal T2D treatment is still not received by most individuals with early T2D and established cardiorenal disease., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To assess the level of adherence to glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment using real-world data and to investigate the sociodemographic and clinical factors associated with discontinuation of GLP-1RAs., Methods: First-time users of GLP-1RAs with type 2 diabetes mellitus (T2DM), aged ≥18 years, in the period 2007 to 2020, were identified using Danish registries, allowing all participants a minimum of 18 months' follow-up. Adherence to GLP-1RA therapy (medication possession ratio >0.80) and discontinuation of GLP-1RA therapy was estimated at 6- and 12-month follow-ups. Multivariable cause-specific Cox regression was used to identify sociodemographic and clinical factors associated with risk of discontinuation., Results: In total, 44 343 first-time users of GLP-1RAs with T2DM were identified (mean age 58.6 years, 42.7% female, median duration of T2DM 6.8 years, median glycated haemoglobin level 65 mmol/mol). The absolute risk of discontinuing GLP-1RA treatment within 6 months was 14.2% (95% confidence interval [CI] 13.9-14.6) and 21.2% (95% CI 20.8-21.5) within 12 months. At 6 months, 50.4% were adherent to GLP-1RA therapy and at 12 months, 48.6% remained adherent. In the multivariable model, younger (<40 years) and older age (>75 years), higher Charlson Comorbidity Index score, lower household income, high school and longer university degree as educational attainment level, and longer diabetes duration were associated with a higher risk of discontinuing GLP-1RA treatment., Conclusion: Approximately one in five patients discontinued GLP-1RA therapy within the first 12 months and only half were adherent. Overall, lower socioeconomic status and higher comorbidity burden were associated with higher risk of discontinuing GLP-1RA treatment., (© 2024 John Wiley & Sons Ltd.)

Aim: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Objectives: Exercise is a recommended component of type 1 diabetes (T1D) treatment because high physical activity levels improve health outcomes. However, many people with T1D do not meet physical activity recommendations. Our aim in this study was to identify factors influencing physical activity levels in people with T1D., Methods: This questionnaire-based study included adults with T1D from 1 outpatient clinic in the United Kingdom and 2 clinics in Denmark. Exercise characteristics, motivators, and barriers were assessed. Physical activity level was measured using the Saltin-Grimby Physical Activity Level Scale. Respondents were categorized into 3 activity groups: inactive, light active, and moderate-to-vigorous active., Results: Of the 332 respondents, 8.4% rated themselves as inactive, 48% as light active, and 43% as moderate-to-vigorous active. Seventy-eight percent of inactive and light active repondents expressed a desire to become more physically active. Fifty-three percent of respondents had received guidance concerning exercise/physical activity from their diabetes team. Being male and having received guidance were associated with a higher physical activity level. The major motivators for exercising/being physically active were improved mental and physical health and glycemic management, whereas the most frequent barriers were busyness with work/private life and lack of motivation. Worries about glucose excursions, costs, lack of knowledge, and health-related reasons were more prevalent barriers in the least active groups., Conclusions: This study demonstrated that 78% of inactive and light active respondents reported wishing to become more physically active. Receiving guidance about exercise/physical activity was associated with a higher physical activity level, but only 53% of respondents had received support from their diabetes team., (Copyright © 2024 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Ensuring adequate iodine nutrition during pregnancy is crucial for fetal brain development. Thus, the WHO recommend monitoring iodine nutrition in pregnant women. With changing dietary habits and declining iodine intake in coastal populations, iodine nutrition in pregnant Faroese women was a focus in newly established pregnancy cohorts. This study aimed to monitor the iodine status of pregnant women in the Faroe Islands by assessing urinary iodine concentration (UIC) and maternal iodine intake. For 2 years, all pregnant women were invited to participate in a nationwide study. Participants completed questionnaires addressing personal and lifestyle factors, supplement intake and dietary habits, Additionally, they provided spot urine samples for UIC measurements. Iodine was measured spectrophotometrically using the ceri/arsen method after alkaline-ashing. Among the 1030 invited, 654 participated and 647 provided a spot-urine sample. The average age was 30·4 years (18–47 years). The overall median UIC was 110 µg/l, declined from 117 to 101 µg/l over 2 years ( P = 0·004). UIC was significantly impacted by diet. Women consuming fish and eggs had a higher median UIC compared with those whose primary iodine source was dairy: fish-dinner, 151 µg/l; dairy products, 112 µg/l ( P < 0·001). Furthermore, there was a positive association between maternal age, reported intake of iodine-containing supplements and the UIC. This nationwide study of pregnant Faroese women found UIC below the WHO-recommended cut-off for pregnant women and decreasing with time. This decline highlights the importance of continuous monitoring to prompty identify shifts in iodine status, enabling timely intervention to address emerging deficiencies.

The 2021 European Society of Cardiology guideline on diagnosis and treatment of acute and chronic heart failure (HF) and the 2023 Focused Update include recommendations on the pharmacotherapy for patients with New York Heart Association (NYHA) class II-IV HF with reduced ejection fraction. However, multinational data from the EVOLUTION HF study found substantial prescribing inertia of guideline-directed medical therapy (GDMT) in clinical practice. The cause was multifactorial and included limitations in organizational resources. Digital solutions like digital consultation, digital remote monitoring, digital interrogation of cardiac implantable electronic devices, clinical decision support systems, and multifaceted interventions are increasingly available worldwide. The objectives of this Clinical Consensus Statement are to provide (i) examples of digital solutions that can aid the optimization of prescription of GDMT, (ii) evidence-based insights on the optimization of prescription of GDMT using digital solutions, (iii) current evidence gaps and implementation barriers that limit the adoption of digital solutions in clinical practice, and (iv) critically discuss strategies to achieve equality of access, with reference to patient subgroups. Embracing digital solutions through the use of digital consults and digital remote monitoring will future-proof, for example alerts to clinicians, informing them of patients on suboptimal GDMT. Researchers should consider employing multifaceted digital solutions to optimize effectiveness and use study designs that fit the unique sociotechnical aspects of digital solutions. Artificial intelligence solutions can handle larger data sets and relieve medical professionals' workloads, but as the data on the use of artificial intelligence in HF are limited, further investigation is warranted., Competing Interests: Conflict of interest: M.J.S. received an independent research grant from AstraZeneca to the research institute. A.R.L. has received speaker, advisory board, or consultancy fees and/or research grants from Pfizer, Novartis, Servier, AstraZeneca, Bristol Myers Squibb, GSK, Amgen, Takeda, Roche, Janssens-Cilag Ltd, Clinigen Group, Eli Lily, Eisai Ltd, Ferring Pharmaceuticals, Boehringer Ingelheim, Akcea Therapeutics, Myocardial Solutions, iOWNA Health, and Heartfelt Technologies Ltd. All other authors declare no relevant competing interests., (© 2024 the European Society of Cardiology.)

Background and Purpose: Cardiovascular outcome trials demonstrate that glucagonlike peptide-1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes (T2D), whereas dipeptidyl peptidase-4 inhibitors (DPP-4is) have not shown cardiovascular benefits. We compared acute ischemic stroke (AIS) with T2D treated with either a GLP-1RA or DPP-4i prior to the index stroke., Methods: This national cohort study included AIS patients with T2D from 2017 to 2020 in Denmark who were users of a GLP-1RA or DPP-4i. To be categorized as a user, we required at least 12 months of exposure and no concurrent treatment with another newer glucose-lowering medication during the last 3 months prior to the index stroke. GLP-1RA users were compared to users of DPP-4i while adjusting for the calendar year of index stroke, age, sex, comorbidity, and socioeconomic factors., Results: The study included 1567 AIS events with T2D; 593 were users of GLP-1RA and 974 of DPP-4i. The absolute risk of a very severe stroke was 2.4% (95% confidence interval [CI] = 1.2-3.7) in GLP-1RA users and 6.1% (95% CI = 4.6-7.7) in DPP-4i users. The corresponding adjusted risk ratio (aRR) of GLP-1RA versus DPP-4i was 0.49 (95% CI = 0.24-1.00). The aRRs of 30-day and 365-day mortality were 0.55 (95% CI = 0.32-0.94) and 0.72 (95% CI = 0.53-0.98), respectively., Conclusions: The risk of a very severe stroke as well as the 30-day and 365-day poststroke mortality rates were lower among the AIS patients with comorbid T2D receiving GLP-1RA prior to the index stroke compared to those receiving DPP-4i. Hence, GLP-1RA may improve stroke outcomes in comparison with DPP-4i., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: This study validates the application of Systematized Nomenclature of Medicine second edition (SNOMED II) codes used to describe medical kidney biopsies in Denmark in encoded form, aiming to support robust epidemiological research on the causes, treatments and prognosis of kidney diseases., Methods: Kidney biopsy reports from 1 January 1998 to 31 December 2018 were randomly extracted from the Danish National Patobank, using SNOMED codes. A 5% sample was selected, and nephrologists assessed the corresponding medical records, assigning each case the applied clinical diagnoses. Sensitivity, specificity, positive predictive values (PPV), negative predictive values and Cohen's kappa coefficient for the retrieved SNOMED codes were calculated., Results: A total of 613 kidney biopsies were included. The primary clinical disease groups were glomerular disease ( n  = 368), tubulointerstitial disease ( n  = 67), renal vascular disease ( n  = 51), diabetic nephropathy ( n  = 51) and various renal disorders ( n  = 40). Several SNOMED codes were used to describe each clinical disease group and PPV for the combined SNOMED codes were high for glomerular disease (94%), diabetic nephropathy (85%) and systemic diseases affecting the kidney (96%). Conversely, tubulointerstitial disease (62%), renal vascular disease (60%) and other renal disorders (17%) showed lower PPV., Conclusions: SNOMED codes have a high PPV for glomerular diseases, diabetic nephropathy and systemic diseases affecting the kidney, in which they could be applied for future epidemiological research., Competing Interests: No potential conflicts of interest were reported by M.M., I.B., H.D., J.W.G., H.H., K.H., P.I., K.H.R., M.B.J., D.K., F.H.M., P.R., K.E.O., F.P. and K.D.S. T.K. reports honoraria for education and consultancy from AstraZeneca. R.B. reports honoraria for education and consultancy from AstraZeneca, Bayer, Mundipharma, Vifor and Boehringer Ingelheim. M.H. reports honoraria for advisory boards for AstraZeneca, Bayer, Boeringer Ingelheim, Vifor, GSK and Novo Nordisk A/S, and education for AstraZeneca, Boeringer Ingelheim and Novo Nordisk A/S outside the scope of this manuscript. D.H. reports research grant from Vifor Pharma and Gedeon Richter, and consultancy fees and lecture fees from UCB Nordic, GSK and AstraZeneca., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background and Hypothesis: This post-hoc analysis explored the semaglutide effects on eGFR slope by baseline glycemic control, blood pressure (BP), body mass index (BMI), and albuminuria status in people with type 2 diabetes and high cardiovascular risk., Methods: Pooled SUSTAIN 6 and PIONEER 6 data were analyzed for change in estimated glomerular filtration (eGFR) slope by baseline HbA1c (<8%/≥8%; <64 mmol/mol/≥64 mmol/mol), systolic BP (<140/90 mmHg/≥140/90 mmHg), and BMI (<30 kg/m2/≥30 kg/m2). SUSTAIN 6 data were analyzed by baseline urinary albumin: creatinine ratio (UACR; <30/30 - 300/>300 mg/g)., Results: The estimated absolute treatment differences (ETD) overall in eGFR slope [95% confidence intervals] favored semaglutide versus placebo in the pooled analysis (0.59 [0.29;0.89] mL/min/1.73m2/year) and in SUSTAIN 6 (0.60 [0.24;0.96] mL/min/1.73m2/year); the absolute benefit was consistent across all HbA1c, BP, BMI, and UACR subgroups (all p-interaction > 0.5)., Conclusion: A clinically meaningful reduction in risk of chronic kidney disease progression was observed with semaglutide versus placebo regardless of HbA1c, BP, BMI, and UACR levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Physicians manage multiple obligations, providing best-practice treatment and patient- centred care in the standard treatment pathway while contributing to clinical trials simultaneously. These multifaceted responsibilities may introduce barriers and dilemmas to clinical trial execution, potentially impacting the clinical trial decision- making process. This study explores physicians' barriers and dilemmas in executing clinical trials and the impact on clinical trial decision-making., Method: Qualitative semi-structured interviews were conducted with experienced oncologists. Moreover, participant observations were performed during clinical encounters involving discussions about clinical trials. The analysis followed a structured approach: (1) transcription of data, (2) inductive text coding, (3) exploration of patterns, and (4) interpretation, leading to the results. The results were discussed and validated by the study participants., Results: The results comprise (1) a description of the clinical practice, which presents the setting of clinical trial execution; (2) results regarding physicians' barriers and dilemmas in executing clinical trials, leading to (3) the impact on clinical trial decision- making. The results involve barriers to time constraints for clinical trial tasks, dilemmas emerging from trial requirements or deviations from standard guidelines, and challenges with providing sufficient trial communication and adequate decision-making support, balancing between a paternalistic approach and respecting patient autonomy., Conclusion: The demanding obligations of clinical practice constitute a complex setting for executing clinical trials, resulting in numerous barriers and dilemmas that impact the decision-making process in clinical trials. The study emphasises the need for tailored clinical trial decision-making interventions to facilitate supportive, informed, and non-directive clinical trial decision-making., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: The prevalence of diabetes and coexisting multimorbidity rises worldwide. Treatment of this patient group can be complex. Providing an evidence-based, coherent, and patient-centred treatment of patients with multimorbidity poses a challenge in healthcare systems, which are typically designed to deliver disease-specific care. We propose an intervention comprising multidisciplinary team conferences (MDTs) to address this issue. The MDT consists of medical specialists in five different specialities meeting to discuss multimorbid diabetes patients. This protocol describes a feasibility test of MDTs designed to coordinate care and improve quality of life for people with diabetes and multimorbidity., Methods: A mixed-methods one-arm feasibility test of the MDT. Feasibility will be assessed through prospectively collected data. We will explore patient perspectives through patient-reported outcomes (PROs) and assess the feasibility of electronic questionnaires. Feasibility outcomes are recruitment, PRO completion, technical difficulties, impact of MDT, and doctor preparation time. During 17 months, up to 112 participants will be recruited. We will report results narratively and by the use of descriptive statistics. The collected data will form the basis for a future large-scale randomised trial., Discussion: A multidisciplinary approach focusing on better management of diabetic patients suffering from multimorbidity may improve functional status, quality of life, and health outcomes. Multimorbidity and diabetes are highly prevalent in our healthcare system, but we lack a solid evidence-based approach to patient-centred care for these patients. This study represents the initial steps towards building such evidence. The concept can be efficiency tested in a randomised setting, if found feasible to intervention providers and receivers. If not, we will have gained experience on how to manage diabetes and multimorbidity as well as organisational aspects, which together may generate hypotheses for research on how to handle multimorbidity in the future., Administrative Information: Protocol version: 01 TRIAL REGISTRATION: NCT05913726 - registration date: 21 June 2023., (© 2024. The Author(s).)

Glioblastoma is a highly heterogeneous tumor whose pathophysiological complexities dictate both the diagnosis of disease severity as well as response to therapy. Conventional diagnostic tools and standard treatment regimens have only managed to achieve limited success in the management of patients suspected of glioblastoma. Extracellular vesicles are an emerging liquid biopsy tool that has shown great promise in resolving the limitations presented by the heterogeneous nature of glioblastoma. Here we discuss the contrasting yet interdependent dual role of extracellular vesicles as communication agents that contribute to the progression of glioblastoma by creating a heterogeneous microenvironment and as a liquid biopsy tool providing an opportunity to accurately identify the disease severity and progression., (© 2024. The Author(s).)

Introduction: The purpose of this study was to investigate the risk of metabolic sequelae and all-cause mortality in a population-based cohort of chronic pancreatitis (CP) patients with and without prior acute pancreatitis (AP)., Methods: We used nationwide health registries to identify all Danish residents (18 years and older) with incident CP from 2000 to 2018. Information on AP/CP diagnoses, metabolic sequelae (post-pancreatitis diabetes mellitus [PPDM], exocrine pancreatic dysfunction, and osteoporosis), and all-cause mortality were obtained from Danish national health registries. CP cases were stratified based on the presence of AP before CP diagnosis. The risk of metabolic sequelae and all-cause mortality was expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), calculated using multivariate Cox proportional hazards models., Results: A total of 9,655 patients with CP were included. Among patients with CP, 3,913 (40.5%) had a prior AP diagnosis. Compared with patients without a history of AP, patients with prior AP had a decreased risk of death (HR 0.79, 95% CI 0.74-0.84), which was largely confined to the initial period after CP diagnosis. Patients with prior AP had an increased risk of PPDM (HR 1.53, 95% CI 1.38-1.69), which persisted for up to a decade after CP diagnosis. No overall differences in risk were observed for exocrine pancreatic dysfunction (HR 0.97, 95% CI 0.87-1.07) and osteoporosis (HR 0.87, 95% CI 0.74-1.02)., Discussion: This nationwide study revealed that most of the patients with CP have no prior episode(s) of AP, indicating that an attack of AP sensitizing the pancreas is not essential for CP development. CP patients with and without prior AP have different risk profiles of PPDM and all-cause mortality., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Previous studies have indicated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) may enhance bone formation and have neutral or beneficial effects on fracture risk. We evaluated the effect of the GLP-1RA semaglutide on the bone formation marker Procollagen type I N-terminal propeptide (PINP) in adults with increased fracture risk., Methods: This randomised, placebo-controlled, double-blinded, phase 2 clinical trial was conducted at two public hospitals in Denmark. We enrolled 64 men and women with increased fracture risk based on a T-score < -1.0 at the total hip or lumbar spine and/or low-energy fracture within three years of recruitment. Participants were randomised (1:1) to receive once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary outcome was changes in plasma (P)-PINP from baseline to week 52. Primary and safety outcomes were assessed and evaluated for all participants. This trial is complete and registered with ClinicalTrials.gov, NCT04702516., Findings: Between March 24 and December 8, 2021, 55 (86%) postmenopausal women and nine men with a mean age of 63 years (SD 5.5) and BMI of 27.5 kg/m 2 (SD 4.5) were enrolled. There was no effect on changes in P-PINP from baseline to week 52 between the two groups (estimated treatment difference (ETD) semaglutide versus placebo 3.8 μg/L [95% CI -5.6 to 13.3]; p = 0.418), and no difference in P-PINP levels between groups at week 52 (semaglutide 64.3 μg/L versus placebo 62.3 μg/L [95% CI -10.8 to 15.0]; p = 0.749). The secondary outcomes showed higher plasma levels of bone resorption marker Collagen type I cross-linked C-terminal telopeptide (P-CTX) in the semaglutide group than in the placebo group (ETD 166.4 ng/L [95% CI 25.5-307.3]; p = 0.021). Compared to placebo, lumbar spine and total hip areal bone mineral densities (aBMD) were lower in the semaglutide group after 52 weeks ((ETD lumbar spine -0.018 g/cm 3 [95% CI -0.031 to -0.005]; p = 0.007); ETD total hip -0.020 g/cm 2 ([95% CI -0.032 to -0.008]; p = 0.001). Treatment differences in femoral neck aBMD were not observed ([95% CI [-0.017 to 0.006]; p = 0.328). Further, body weight was lower in the semaglutide group than in the placebo group after 52 weeks (ETD -6.8 kg [95% CI -8.8 to -4.7]; p < 0.001). Thirty-one [97%] in the semaglutide group and 18 [56%] in the placebo group experienced at least one adverse event, including four serious events (two in each group). No episodes of hypoglycaemia or deaths were reported., Interpretation: In adults with increased fracture risk, semaglutide once weekly did not increase bone formation based on the bone formation marker P-PINP. The observed increase in bone resorption in the semaglutide group may be explained by the accompanying weight loss., Funding: Region of Southern Denmark, Novo Nordisk Foundation, and Gangsted Foundation. Novo Nordisk provided the investigational drug and placebo., Competing Interests: EMW, SJ, SGH, JJM, and CE declare no conflicts of interest. MSH and MF have received funding from the Novo Nordisk Foundation. RE receives consultancy funding from Immunodiagnostic Systems, Sandoz, Samsung, CL Bio, Biocon, Takeda, UCB, meeting presentations for Pharmacosmos, Alexion, UCB and Amgen, and grant funding from Alexion. NRJ has received assays and reagents from IDS and Roche for clinical studies. MF has received consultancy funding from Novo Nordisk and is shareholder at Novo Nordisk and Eli Lily. Novo Nordisk, Denmark, provided the investigational drug and placebo., (© 2024 The Author(s).)

Focus on patient and public involvement and engagement (PPIE) is increasing in health policy and research governance. PPIE is considered by some to be a democratic right, and by others to be a way to improve health care and research outcomes and implementation. Most recently, policy makers, funders and (clinical) research institutions are making PPIE a strategic requirement for health research urging researchers to invite patients and relatives into their research activities. Our study is based in a Danish university hospital where PPIE has been introduced as one of five strategic research goals. We investigated how researchers experienced this new practice and how their research practices connect to the wider context of the Danish health care system. Ten cases were studied during a year using observations, interviews, and document analysis. As our method of inquiry, we used institutional ethnography to look at researchers' work from their perspective and to understand how PPIE practices are part of a larger institutional research culture reaching far beyond the individual. We found that current research culture has implications for the selection of patients and relatives and for what they are asked to do. Researchers who experienced that PPIE outcomes aided their existing research practices felt motivated. Researchers who engaged patients and relatives before it was a strategy, were ideologically driven and their approaches resulted in an increased diversity of inclusion and researcher assimilation. These findings add to the current knowledge on PPIE practices and help us understand that further development towards collaborative research practices require a change in key performance indicators and training and perhaps call for attention to our shared acceptance of knowledge generation in research., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Physical activity is associated with improved health in people with type 1 diabetes. However, physical activity level may be associated with socioeconomic status. The primary aim of this study was to investigate the association between education level and physical activity level among people with type 1 diabetes., Methods: In this cross-sectional study, data on physical activity level (high or low) was measured using the Saltin-Grimby Physical Activity Level Scale, and education level (low, medium, or high) was self-reported., Results: Respondents were recruited from outpatient clinics (Steno Diabetes Centre Aarhus, Denmark; Nordsjællands Hospital, Denmark; or Sheffield Diabetes and Endocrine Centre, United Kingdom), by health-care personnel from September 2019 to July 2021. A total of 324 people with type 1 diabetes were included (54% male, median age 50 years [interquartile range 30-60 years]). Education level was low in 10%, medium in 33%, and high in 57%. A logistic regression analysis, adjusted for age, sex, cohabitation status and nationality, found that a medium vs. high education level was associated with lower odds of a high physical activity level (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.32-0.94, p=0.029), while no association was found for low vs. high education level with high physical activity level (OR 0.56, 95% CI 0.25-1.29, p=0.173)., Conclusions: Medium education level compared with a high education level was associated with a lower level of physical activity in people with type 1 diabetes. Health-care professionals are advised to be attentive of physical activity levels among people with type 1 diabetes., Competing Interests: Author Disclosures S.H. has acted as consultant and served on advisory panels for Zucara Therapeutics, Zealand, Novo Nordisk, Eli Lilly, and Vertex A/S, for which his institution has received remuneration. He has served on speaker panels for Novo Nordisk and Medtronic, for which he has received renumeration. He has received research support from Dexcom. He is chair of the International Hypoglycaemia Study Group and is a panelist for the NIHR PGfAR funding stream, both unpaid positions, and serves as national specialty lead in Diabetes for the NIHR Clinical Research Network, for which he receives a salary. P.L.K. has received speaker’s fees from Sanofi A/S, Novo Nordisk A/S, Boehringer Ingelheim A/S, and AstraZeneca A/S. No other authors have any conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Legalized use of cannabis for medical or recreational use is becoming more and more common. With respect to potential side-effects on bone health only few clinical trials have been conducted - and with opposing results. Therefore, it seems that there is a need for more knowledge on the potential effects of cannabinoids on human bone cells. We studied the effect of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) (dose range from 0.3 to 30 μM) on human osteoclasts in mono- as well as in co-cultures with human osteoblast lineage cells. We have used CD14 + monocytes from anonymous blood donors to differentiate into osteoclasts, and human osteoblast lineage cells from outgrowths of human trabecular bone. Our results show that THC and CBD have dose-dependent effects on both human osteoclast fusion and bone resorption. In the lower dose ranges of THC and CBD, osteoclast fusion was unaffected while bone resorption was increased. At higher doses, both osteoclast fusion and bone resorption were inhibited. In co-cultures, both osteoclastic bone resorption and alkaline phosphatase activity of the osteoblast lineage cells were inhibited. Finally, we observed that the cannabinoid receptor CNR2 is more highly expressed than CNR1 in CD14 + monocytes and pre-osteoclasts, but also that differentiation to osteoclasts was coupled to a reduced expression of CNR2, in particular. Interestingly, under co-culture conditions, we only detected the expression of CNR2 but not CNR1 for both osteoclast as well as osteoblast lineage nuclei. In line with the existing literature on the effect of cannabinoids on bone cells, our current study shows both stimulatory and inhibitory effects. This highlights that potential unfavorable effects of cannabinoids on bone cells and bone health is a complex matter. The contradictory and lacking documentation for such potential unfavorable effects on bone health as well as other potential effects, should be taken into consideration when considering the use of cannabinoids for both medical and recreational use., Competing Interests: Declaration of competing interest Authors declare to have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Sodium-glucose cotransporter 2 inhibitors decrease blood pressure in patients with type 2 diabetes, but the consistency and magnitude of blood pressure lowering with dapagliflozin in patients with chronic kidney disease (CKD) is unknown. We conducted a prespecified analysis of the DAPA-CKD trial to investigate the effect of dapagliflozin on systolic blood pressure (SBP) in patients with CKD, with and without type 2 diabetes., Methods: A total of 4304 adults with baseline estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m 2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g were randomized to either dapagliflozin 10 mg or placebo once daily; median follow-up was 2.4 years. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or death from a kidney or cardiovascular cause. Change in SBP was a prespecified outcome., Results: Baseline mean (SD) SBP was 137.1 mmHg (17.4). By Week 2, dapagliflozin compared to placebo reduced SBP by 3.6 mmHg (95% CI 2.8-4.4 mmHg), an effect maintained over the duration of the trial (2.9 mmHg, 2.3-3.6 mmHg). Time-averaged reductions in SBP were 3.2 mmHg (2.5-4.0 mmHg) in patients with diabetes and 2.3 mmHg (1.2-3.4 mmHg) in patients without diabetes. The time-averaged effect of dapagliflozin on diastolic blood pressure (DBP) was 1.0 mmHg (0.6-1.4 mmHg); 0.8 mmHg (0.4-1.3 mmHg) in patients with diabetes and 1.4 mmHg (0.7-2.1 mmHg) in patients without diabetes. Benefits of dapagliflozin on the primary composite and secondary endpoints were evident across the spectrum of baseline SBP and DBP., Conclusion: In patients with CKD and albuminuria, randomization to dapagliflozin was associated with modest reductions in systolic and diastolic BP., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Living with type 1 diabetes is challenging, and to support self-management, repeated consultations in specialist outpatient care are often required. The emergence of new digital solutions has revolutionized how health care services can be patient centered, providing unprecedented opportunities for flexible, high-quality care. However, there is a lack of studies exploring how the use of digital patient-reported outcome measures (PROMs) for flexible specialist care affects diabetes self-management. To provide new knowledge on the relevance of using PROMs in standard care, we have designed a multimethod prospective study., Objective: The overall aim of this protocol is to describe our prospective multimethod observational study designed to investigate digital PROMs in a routine specialist outpatient setting for flexible patient-centered diabetes care (DigiDiaS)., Methods: This protocol outlines the design of a multimethod prospective observational cohort study that includes data from electronic health records, self-reported questionnaires, clinical consultation field observations, and individual in-depth interviews with patients and diabetes health care personnel. All patients with type 1 diabetes at a designated outpatient clinic were invited to participate and use the digital PROM implemented in clinical care. Both users and nonusers of the digital PROM were eligible for the prospective study, allowing for a comparison of the two groups. Data were collected at baseline and after 12 months, including self-management as the primary outcome assessed using the Patient Activation Measure, along with the secondary outcomes of digital health literacy, quality of life, health economy, and clinical variables such as glycated hemoglobin., Results: The digital solution was implemented for routine clinical care in the department in November 2021, and data collection for the prospective study started in October 2022. As of September 6, 2023, 84.6% (186/220) of patients among those in the digital PROM and 15.5% (34/220) of patients among the nonusers have consented to participate. We expect the study to have enough participants by the autumn of 2023. With 1 year of follow-up, the results are expected by spring 2025., Conclusions: In conclusion, a multimethod prospective observational cohort study can offer valuable insights into the relevance, effectiveness, and acceptability of digital tools using PROMs in diabetes specialist care. Such knowledge is crucial for achieving broad and successful implementation and use of these tools in a large diabetes outpatient clinic., International Registered Report Identifier (irrid): DERR1-10.2196/52766., (©Astrid Torbjørnsen, Ingeborg Spildo, Maria Aadland Mollestad, Annesofie Lunde Jensen, Tone Singstad, Nina Mickelson Weldingh, Pål Joranger, Lis Ribu, Heidi Holmen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.03.2024.)

Background: In response to the increasing prevalence of people with chronic conditions, healthcare systems restructure to integrate care across providers. However, many systems fail to achieve the desired outcomes. One likely explanation is lack of financial incentives for integrating care., Objectives: We aim to identify financial incentives used to promote integrated care across different types of providers for patients with common chronic conditions and assess the evidence on (cost-)effectiveness and the facilitators/barriers to their implementation., Methods: This scoping review identifies studies published before December 2021, and includes 33 studies from the United States and the Netherlands., Results: We identify four types of financial incentives: shared savings, bundled payments, pay for performance, and pay for coordination. Substantial heterogeneity in the (cost-)effectiveness of these incentives exists. Key implementation barriers are a lack of infrastructure (e.g., electronic medical records, communication channels, and clinical guidelines). To facilitate integration, financial incentives should be easy to communicate and implement, and require additional financial support, IT support, training, and guidelines., Conclusions: All four types of financial incentives may promote integrated care but not in all contexts. Shared savings appears to be the most promising incentive type for promoting (cost-)effective care integration with the largest number of favourable studies allowing causal interpretations. The limited evidence pool makes it hard to draw firm conclusions that are transferable across contexts., Competing Interests: Declaration of competing interest The authors were supported by Steno Diabetes Center Aarhus. Steno Diabetes Center Aarhus, Aarhus University Hospital is partially funded by an unrestricted donation from the Novo Nordisk Foundation. This funding source had no role in the design, execution, or data analysis and interpretation., (Copyright © 2024. Published by Elsevier B.V.)

Background: Cereals foods with a high content of dietary fibres or amylose have potential to lower postprandial glucose levels. Optimisation of cereal foods may improve management of type 2 diabetes (T2D)., Methods: We investigated the impact on 4 h postprandial glucose responses given as incremental area under curve (iAUC) of bread made of either 50% RNAi-based (genetically modified) amylose-only barley flour (AmOn) (and 50% wheat flour), 50% hulless barley flour (and 50% wheat flour) or 75% hulless barley (and 25% wheat flour) in subjects with T2D compared with 100% wheat flour bread., Design: Twenty adults with T2D were randomly allocated to one of four breads at four separate visits. We measured fasting and 4 h postprandial responses of glucose, insulin, glucagon, triacylglycerol (TG), free fatty acids (FFA), glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). Mixed model ANOVA was used to examine the differences., Results: Bread made from 50% AmOn lowered the 4 h postprandial glucose by 34%, 27%, 23% (P < 0.05) compared with 100% wheat, 50% or 75% hulless barley, respectively. Bread made from 75% hulless barley reduced the postprandial glucose response (iAUC) by 11% (P < 0.05) compared to 100% wheat bread. Postprandial insulin responses (iAUC) were reduced for 50% AmOn compared with 100% wheat and 50% hulless barley and for 75% hulless compared to 50% hulless barley bread (P < 0.05). 4 h postprandial glucagon (tAUC) did not differ between the four bread types (P > 0.05). Lower postprandial GIP (iAUC) was observed after all barley breads compared to 100% wheat (P < 0.05), whereas no difference was seen in postprandial GLP-1. Postprandial TG and FFA (tAUC) were difficult to judge due to differences in fasting values., Conclusions: Bread made by replacing wheat flour with either 50% high-amylose or 75% hulless barley flour lowered postprandial glucose responses compared to 100% wheat bread indicating a beneficial impact on glucose regulation in T2D subjects. This trial was registered at clinicaltrials.gov as NCT04646746., (© 2023. The Author(s).)

Background: The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial enrolled patients with estimated glomerular filtration rate 25-75 mL/min/1.73 m 2 and urine albumin-to-creatinine ratio >200 mg/g. The Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial enrolled patients with type 2 diabetes, a higher range of kidney function and no albuminuria criterion. The study objective was to estimate the cost-effectiveness of dapagliflozin in a broad chronic kidney disease population based on these two trials in the UK, Spain, Italy and Japan., Methods: We adapted a published Markov model based on the DAPA-CKD trial but to a broader population, irrespective of urine albumin-to-creatinine ratio, using patient-level data from the DAPA-CKD and DECLARE-TIMI 58 trials. We sourced cost and utility inputs from literature and the DAPA-CKD trial. The analysis considered healthcare system perspectives over a lifetime horizon., Results: Treatment with dapagliflozin was predicted to attenuate disease progression and extend projected life expectancy by 0.64 years (12.5 versus 11.9 years, undiscounted) in the UK, with similar estimates in other settings. Clinical benefits translated to mean quality-adjusted life year (QALY; discounted) gains between 0.45 and 0.68 years across countries. Incremental cost-effectiveness ratios in the UK, Spain, Italy and Japan ($10 676/QALY, $14 479/QALY, $7771/QALY and $13 723/QALY, respectively) were cost-effective at country-specific willingness-to-pay thresholds. Subgroup analyses suggest dapagliflozin is cost-effective irrespective of urinary albumin-to-creatine ratio and type 2 diabetes status., Conclusion: Treatment with dapagliflozin may be cost-effective for patients across a wider spectrum of estimated glomerular filtration rates and albuminuria than previously demonstrated, with or without type 2 diabetes, in the UK, Spanish, Italian and Japanese healthcare systems., Competing Interests: P.M., J.A.D. and P.D.G. are employees of Health Economics and Outcomes Research Ltd, Cardiff, UK. Health Economics and Outcomes Research Ltd received fees from AstraZeneca in relation to this study. D.C.W. provided ongoing consultancy services to AstraZeneca in the last 2 years and has received honoraria and/or consultancy fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Eledon, Galderma, Gilead, GlaxoSmithKline, George Clinical, Janssen, Merck Sharp and Dohme, ProKidney, Takeda, Vifor and Zydus. He also reports speaking fees from Astellas, AstraZeneca and Vifor, and support for travel/meeting attendance from Astellas, AstraZeneca and Pro. He has served on DSMBs for Eledon, Galderma, Merck, ProKidney and Pathalys. He is a member of the International Society of Nephrology and National Institute of Health Research, UK. P.R. has received honoraria to Steno Diabetes Center Copenhagen for consultancy from AstraZeneca, Astellas, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi and Vifor, and research support from AstraZeneca, Bayer and Novo Nordisk. G.M.C. received fees from AstraZeneca for service on the DAPA-CKD trial steering committee. He serves on the Board of Directors for Satellite Healthcare, a non-profit dialysis provider. He has received research grants to his institution from NIDDK, NIAID and CSL Behring. He has served on trial-steering committees with Akebia, AstraZeneca, Gilead, Sanifit and Vertex. He has served as an advisor to Applaud, Ardelyx, CloudCath, Durect, Eliaz Therapeutics, Miromatrix, Outset, Renibus, Unicycive and Vertex. He has served on DSMBs for NIDDK, Bayer, Mineralys and ReCor. He also declares stock or stock options for Applaud, Ardelyx, CloudCath, Durect, Eliaz Therapeutics, Miromatrix, Outset and Renibus. R.C.-R. has received honoraria as consultant from AstraZeneca, Boehringer Ingelheim, Bayer, Chinook, AbbVie and Novo Nordisk, and research support from AstraZeneca, Boehringer Ingelheim, Roche and Novo Nordisk. He has received speaking fees from AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Amgen. K.T. has honoraria as lecture fee from Novartis, AstraZeneca, Ono, Daiichi-Sankyo, Takeda, Otsuka, Bayer and Kyowa-Kirin. He has received research support from AstraZeneca, Ono, Bayer, Kyowa-Kirin, Otsuka, Takeda and Daiichi-Sankyo. S.B. and J.J.G.S. are employees of AstraZeneca., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Excess aldosterone accelerates chronic kidney disease progression. This phase 2 clinical trial assessed BI 690517, an aldosterone synthase inhibitor, for efficacy, safety, and dose selection., Methods: This was a multinational, randomised, controlled, phase 2 trial. People aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 30 to less than 90 mL/min/1·73 m 2 , a urine albumin to creatinine ratio (UACR) of 200 to less than 5000 mg/g, and serum potassium of 4·8 mmol/L or less, taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, were enrolled. Participants were randomly assigned (1:1) to 8 weeks of empagliflozin or placebo run-in, followed by a second randomisation (1:1:1:1) to 14 weeks of treatment with once per day BI 690517 at doses of 3 mg, 10 mg, or 20 mg, or placebo. Study participants, research coordinators, investigators, and the data coordinating centre were masked to treatment assignment. The primary endpoint was the change in UACR measured in first morning void urine from baseline (second randomisation) to the end of treatment. This study is registered with ClinicalTrials.gov (NCT05182840) and is completed., Findings: Between Feb 18 and Dec 30, 2022, of the 714 run-in participants, 586 were randomly assigned to receive BI 690517 or placebo. At baseline, 33% (n=196) were women, 67% (n=390) were men, 42% (n=244) had a racial identity other than White, and mean participant age was 63·8 years (SD 11·3). Mean baseline eGFR was 51·9 mL/min/1·73 m 2 (17·7) and median UACR was 426 mg/g (IQR 205 to 889). Percentage change in first morning void UACR from baseline to the end of treatment at week 14 was -3% (95% CI -19 to 17) with placebo, -22% (-36 to -7) with BI 690517 3 mg, -39% (-50 to -26) with BI 690517 10 mg, and -37% (-49 to -22) with BI 690517 20 mg monotherapy. BI 690517 produced similar UACR reductions when added to empagliflozin. Investigator-reported hyperkalaemia occurred in 10% (14/146) of those in the BI 690517 3 mg group, 15% (22/144) in the BI 690517 10 mg group, and 18% (26/146) in the BI 690517 20 mg group, and in 6% (nine of 147) of those receiving placebo, with or without empagliflozin. Most participants with hyperkalaemia did not require intervention (86% [72/84]). Adrenal insufficiency was an adverse event of special interest reported in seven of 436 study participants (2%) receiving BI 690517 and one of 147 participants (1%) receiving matched placebo. No treatment-related deaths occurred during the study., Interpretation: BI 690517 dose-dependently reduced albuminuria with concurrent renin-angiotensin system inhibition and empagliflozin, suggesting an additive efficacy for chronic kidney disease treatment without unexpected safety signals., Funding: Boehringer Ingelheim., Competing Interests: Declaration of interests KRT reports grants for investigator-initiated research from NIDDK, NHLBI, NCATS, NIMHD, NIH Data Science office, Travere, Bayer, and Goldfinch Bio; contracts from CDC; consulting fees from Boehringer Ingelheim, Janssen, Novo Nordisk, AstraZeneca, Bayer, Eli Lilly, Gilead, and Merck Sharp & Dohme; payment for manuscript writing for Boehringer Ingelheim, Novo Nordisk, Bayer, Eli Lilly, and Gilead; payment of honoraria for Novo Nordisk, AstraZeneca, Bayer, Eli Lilly, and Gilead; payment for travel for Novo Nordisk; travel to meetings from Novo Nordisk; chair and member of a data safety monitoring committee for NIDDK and George Clinical; and leadership role for the American Society of Nephrology. MEC reports grants for investigator-initiated research and research funding from Baxter and Fresenius; and payment of honoraria for lectures, presentations, and education events from AstraZeneca, Fresenius, Bayer, Pfizer, and Bracepharma. MLC reports research grant support from NIH and NIDDK (all to the University of Minnesota and Cleveland Clinic) and research grant support sponsored by Bayer Pharmaceuticals (all to the University of Minnesota); consulting fees from Bayer Pharmaceuticals, Novo Nordisk, and AstraZeneca; payment for speaker bureaus and educational events from Bayer Pharmaceuticals; payment of honoraria for lectures and educational events from Cardiorenal Connections, Heart in Diabetes, Translational Medicine Academy, and the American College of Cardiology; support to attend investigator meetings for Kidney Precision Medicine Project from the NIH and NIDDK, American Diabetes Association meetings from NIH and NIDDK, and University of Minnesota and American Society of Nephrology meetings from NIH and NIDDK and Cleveland Clinic Foundation (all to the University of Minnesota); participation on and site principle investigator for the Data Safety Monitoring Board for Preventing Early Renal Loss in Diabetes Study for NIH and NIDDK (all to the University of Minnesota); and attendee of Kidney Disease Improving Global Outcomes writing group meetings. DC reports research grants from Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL Behring, and Novo Nordisk; consulting fees from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi Tanabe, AbbVie, Janssen, Bayer, Prometic, Bristol Myers Squibb, Maze, Gilead, CSL Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK, and Novo Nordisk; payment of honoraria for lectures and advisory boards from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi Tanabe, Janssen, Bayer, and Novo Nordisk; support for traveling to and attending meetings from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Janssen, Bayer, and Novo Nordisk; and receipt of a drug for research from AstraZeneca. HJLH reports funding to conduct clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and Novo Nordisk (all to the University of Groningen); consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Behring, DImerix, Eli Lilly, Fresenius, Gilead, Janssen, Novo Nordisk, Novartis, and Travere Therapeutics; payment of honoraria for lectures from AstraZeneca, Novo Nordisk, and Bayer; support for traveling to and attending the American Diabetes Association meeting and American Society of Nephrology meeting from AstraZeneca and Eli Lilly (to HJLH and the University of Groningen); and receipt of the study drug from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and Novo Nordisk. MN reports donations for research through Shogaku Kifu practice from KyowaKiirin, Mitsubishi Tanabe, Chugai, Boehringer Ingelheim, Torii, Takeda, Daiichi Sankyo, and JT; consulting fees from KyowaKiirin and Mitsubishi Tanabe; and payment of honoraria for lectures from KyowaKiirin, Mitsubishi Tanabe, Bayer, Astellas, JT, and AstraZeneca. RCR reports participation as a trial investigator for Novo Nordisk and AstraZeneca; consulting fees from Boehringer Ingelheim, Bayer, AstraZeneca, Chinook, and Novo Nordisk; payment of honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Amgen, and Bayer; and voluntary membership of the steering committee for World Kidney Day and of the Diabetes Committee. AS reports research contracts from Boehringer Ingelheim, Mineralysis, ProKidney, Reata, and Novartis; consulting fees from Boehringer Ingelheim, Ardelyx, and Pro Kidney; payment of honoraria for presentations from ProKidney, Boehringer Ingelheim, AstraZeneca, and Bayer; and participation on an Advisory Board for Travere, Boehringer Ingelheim, and Reata. DdZ reports consulting fees from Bayer, Fresenius, and Travere. PR reports grants and payment of honoraria for lectures, educational events, and steering group participation from AstraZeneca, Bayer, and Novo Nordisk (all to the Steno Diabetes Center Copenhagen); payment of honoraria for lectures and participation in advisory boards from Boehringer Ingelheim, Sanofi, Abbott, and Astellas (all to the Steno Diabetes Center Copenhagen). SJH, LC, SVS, and ZS are employees of Boehringer Ingelheim. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection., Methods: Healthy 5-7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.govNCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks.Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR)., Findings: 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4-5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3-1.9) after routine MMR.Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9-1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8-4.0); none deemed vaccine related., Interpretation: Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5-7 months was safe and not associated with higher rates of reactogenicity than placebo., Funding: Innovation Fund Denmark., Competing Interests: The majority of authors have no conflicts of interest to declare (AJ, ACZ, JKS, NKS, LGS, MR, and SC). DMV has received payment for teaching activities supported by MSD. MM received grants from Helsefonden, The Beckett Fund, and the Rosalie Petersen’s Fund. EAFS has received grants or contracts from AstraZeneca, Johnson and Johnson, Merck, Pfizer, and Roche; consulting fees from Adiago Therapeutics, Cidara Therapeutics, Merck, Nuance Pharmaceuticals, Pfizer, Sobi Inc., Icosavax, Johnson and Johnson, and Sanofi; payment or honoraria from AstraZeneca and Pfizer; support for meeting attendance and/or travel from AstraZeneca; and has participated in data safety monitoring boards or advisory boards for AbbVie, the Bill and Melinda Gates Foundation, and GSK. SB received a grant from the Innovation Fund Denmark. JS owns stocks in Novo Nordisk., (© 2024 The Authors.)

Objective: Post-pancreatitis diabetes mellitus (PPDM) is a frequent complication of pancreatitis and is associated with an increased risk of adverse outcomes. Metformin is recommended for the treatment of PPDM, but evidence of its risk-benefit profile is limited. In a pharmaco-epidemiologic study, we investigated the association between metformin treatment and adverse outcomes in patients with PPDM., Design and Methods: In a Danish nationwide population-based cohort study, we included adults (≥18 years) with incident PPDM or type 2 diabetes between 2009 and 2018. Post-pancreatitis diabetes mellitus was categorised into acute and chronic subtypes (PPDM-A and PPDM-C). Associations between metformin treatment and severe hypoglycaemia, major adverse cardiovascular events (MACE), and all-cause mortality were examined across the diabetes subgroups using Cox regression analysis. Treatments with metformin, insulin, and other glucose-lowering therapies were handled as time-varying exposures., Results: We included 222 337 individuals with new-onset type 2 diabetes and 3781 with PPDM, of whom 2305 (61%) were classified as PPDM-A and 1476 (39%) as PPDM-C. Treatment with metformin was associated with a lower risk of severe hypoglycaemia (adjusted hazard ratio [HR] 0.41, 95% CI 0.27-0.62, P < .0001), MACE (HR 0.74, 95% CI 0.60-0.92, P = .0071), and all-cause mortality (HR 0.56, 95% CI 0.49-0.64, P < .0001) in patients with PPDM. In sensitivity analyses and among individuals with type 2 diabetes, metformin treatment exhibited comparable trends of risk reduction., Conclusions: Metformin is associated with a lower risk of adverse outcomes, including all-cause mortality in patients with PPDM, supporting the use of metformin as a glucose-lowering therapy for these patients., Competing Interests: Conflict of interest: M.H.J. is an employee at Novo Nordisk and holds shares in Novo Nordisk. Co-author F.K.K. is on the editorial board of EJE. He was not involved in the review or editorial process for this paper, on which he is listed as author. No other potential conflicts of interest relevant to this article were reported., (© 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.)

Introduction: Obesity is associated with compromised glucose metabolism. Hence, it is of interest to investigate if the lifestyle interventions used in the LIBRA-cohort, which aimed at not only weight loss, but also patient well-being, could also help obese patients improve glucose metabolism by evidence of reduced HbA 1c . The aim of the study was to retrospectively investigate if patients who were referred to a lifestyle intervention for obesity, were able to alter HbA 1c ., Research Design and Methods: Patients with a BMI≥30 undergoing a 6-month lifestyle intervention, who also completed physical and mental health surveys and whose baseline and 6-month blood samples were available, were included in the analysis. For changes in HbA 1c and body weight a clinically relevant change of 5≥mmom/mol and 5%≥, respectively, was chosen. Participants were divided into groups according to their baseline HbA 1c level: "Diabetes": HbA 1c of ≥6.5% (≥48 mmol/mol), "Prediabetes": HbA 1c of 5.7% to 6.4% (39-47.99 mmol/mol) or "Normal" HbA 1c <5.7% (<39 mmol/mol)., Results: 180 patients met the stated inclusion criteria and these patients were divided into groups (median age (25 th ;75 th quartile): Diabetes: n=47, age 54 (43;60), 51% women, Prediabetes: n=68, age 60 (50;66), 71% women and Normal: n=65, median age 61 (50;66), 85% women. Significant reductions were found in all three groups and specifically in the diabetes group HbA 1c was reduced (mean [95%CI]) -5[-8;-2] mmol/mol from baseline to the end of the intervention. Furthermore, 35% of patients with prediabetes normalized their HbA 1c (<39) and 30% patients with diabetes reduced their HbA 1c <48. All groups had clinically relevant (≥5%) reductions in body weight (p<0.01). There was an association between body weight reduction and HbA 1c reduction in the diabetes group (p<0.01). All groups reported improvements in physical health (p<0.01)., Conclusion: In this retrospective cohort study, all patients achieved clinically relevant weight loss after participation in the lifestyle intervention and obese patients with diabetes achieved clinically relevant reductions in HbA 1c after 6-months. More than 1/3 of patients with prediabetes normalized their HbA 1c ., 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 Høgsholt, Kierkegaard-Brøchner, Sørensen, Lange, Mortensen and Bruun.)

Summary: In patients with diabetes mellitus, the toxic milieu caused by abnormal glucose and free fatty acid handling can lead to heart failure (HF). Referred to as diabetic cardiomyopathy (DMCM), this syndrome often exists in the absence of conventional risk factors for HF such as history of myocardial infarction or hypertension. Low-carbohydrate diets (LCDs) have recently been endorsed as an efficacious therapeutic dietary approach to prevent and reverse cardiometabolic disease including type 2 diabetes mellitus (T2DM). LCDs improve systemic insulin resistance (IR), reverses cardiac remodelling in a rodent model and downregulates the expression of sodium-glucose co-transporter 2 (SGLT2) receptors in the kidney. It is therefore conceivable that a lifestyle approach such as adopting an LCD can be offered to patients with DMCM. The reported case is that of a 45-year-old man with a 15-year history of non-ischaemic cardiomyopathy, T2DM and obesity. The patient volunteered to engage in a 16-week low-carbohydrate dietary intervention trial and then self-selected to remain on this diet for 1 year. The whole-food LCD was based on simple 'traffic light' style food lists and not designed to restrict calories, protein, fat or salt. After 1 year, the patient had lost 39 kg and his cardiometabolic markers had significantly improved. LCDs present a potentially beneficial approach for patients with DMCM and could be considered as a lifestyle intervention before SGLT2i therapy is commenced., Learning Points: Diabetic cardiomyopathy (DMCM) is a syndrome precipitated mainly by the detrimental effects of glucose metabolism disorders such as insulin resistance and diabetes. Low-carbohydrate diets (LCD) mimic many effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i). LCDs are a dietary pattern which can have significant and beneficial effects on metabolic and anthropometric markers in patients with DMCM. LCDs and SGLT2i therapy could be combined and may achieve better clinical outcomes for patients with DMCM. Combination therapy may be carried out under close supervision as the real risk for diabetic ketoacidosis remains.

Introduction: Clinical trials lead the progress in healthcare. To ensure reliable research conclusions, it is essential to enroll diverse patient groups. Identifying and understanding patient-reported barriers to clinical trials may help enhance recruitment among diverse patient groups.The clinical potential of proton therapy (PT) to reduce late effects is being investigated in clinical trials worldwide. Thus, for some patients, PT is only accessible by participating in clinical trials.Individuals with smoking-related head and neck cancer (HNC) are sometimes socioeconomically deprived, leading to barriers to trial participation. This study aims to identify barriers to their participation in a randomised controlled trial (RCT) involving PT., Method: Interviews were conducted with 14 HNC patients declining participation in an RCT involving PT. The interviews were transcribed and systematically analysed using an inductive approach identifying categories and themes., Results: The identified barriers to RCT-participation are: (1) existential distress, which influenced participants' mental and cognitive capacities, (2) insufficient RCT-related knowledge arising from information overload during clinical consultations, (3) the wish for safety and familiarity during the treatment trajectory, particularly for participants needing accommodation during  radiotherapy, and (4) the motivation for study participation was impacted by uncertainty due to randomisation and clinical equipoise. Existential distress is identified as an overarching theme because it influences and amplifies the other three themes., Conclusion: Existential distress is a central theme that influences and amplifies other participation barriers in PT RCTs. It affects participants' comprehension of trial information, their preference for familiar environments, and their motivation to participate in clinical trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background and Aims: Heart failure, insulin resistance and/or type 2 diabetes mellitus coexist in the syndrome that is diabetic cardiomyopathy. Patients with diabetic cardiomyopathy experience high symptom burden and poor quality of life. We tested the hypothesis that a low carbohydrate diet improves heart failure symptoms and quality of life in patients with diabetic cardiomyopathy., Methods and Results: We conducted a 16-week randomised controlled pilot trial comparing the effects of a low carbohydrate diet (LC) to usual care (UC) in 17 adult patients with diabetic cardiomyopathy. New York Heart Association classification, weight, thirst distress and quality of life scores as well as blood pressure and biochemical data were assessed at baseline and at 16 weeks. Thirteen (n = 8 LC; n = 5 UC) patients completed the trial. The low carbohydrate diet induced significant weight loss in completers (p = 0.004). There was a large between-group difference in systolic blood pressure at the end of the study (Hedges's g 0.99[-014,2.08]). There were no significant differences in thirst or quality of life between groups., Conclusion: This is the first clinical trial utilising the low carbohydrate dietary approach in patients with diabetic cardiomyopathy in an outpatient setting. A low carbohydrate diet can lead to significant weight loss in patients with diabetic cardiomyopathy. Future clinical trials with larger samples and that focus on fluid and sodium requirements of patients with diabetic cardiomyopathy who engage in a low carbohydrate diet are warranted., Clinical Trial Registration Number: Australian New Zealand Clinical Trial Registry (ANZCTR): ACTRN12620001278921., Date of Registration: 26th November 2020., Competing Interests: Declaration of competing interest The authors did not use any form of generative artificial intelligence (AI) and/or AI-assisted technologies during the writing process or the preparation of this manuscript., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: This systematic review aims to identify current methods used for the assessment of insulin adherence in adults with insulin-treated type 2 diabetes. The primary goal is to offer recommendations for clinical practice to improve quantification of adherence., Methods: The review was conducted in accordance with PRISMA 2020 and registered at PROSPERO (CRD42022334134). PubMed, Embase, CINAHL, and PsycINFO were searched on 15 November 2022 and included three blocks: Type 2 diabetes, insulin, and adherence. We considered primary full-text studies describing an assessment method and a threshold for assessment of insulin adherence in adults with insulin-treated type 2 diabetes., Results: A final sample of 50 studies were included. Identified methods fell into four categories: self-report, pharmacy claims, inulin count, and data from an insulin pen device. Commonly reported methods included: The Morisky Medication Adherence Scale, the (adjusted) Medication Possession Ratio, and the Proportions of Days Covered. A threshold of <80% was used to define non-adherence in nearly half of the studies. Yet, several thresholds were reported., Conclusions: Most available methods for assessing insulin adherence in adults with insulin-treated type 2 diabetes are severely limited in providing in-depth insights into timing, dosing size, injection patterns, and adherence behavior. However, recognizing diverse types of non-adherence is crucial, as they denote unique behavioral entities requiring targeted intervention. Employing insulin injection data (e.g., from a smart insulin pen cap) to underlie an assessment method is a potential new approach to objectively assess insulin timing and dosing adherence in adults with insulin-treated type 2 diabetes., Competing Interests: Declaration of competing interest M.H.J. is an employee of, and holds stock in, Novo Nordisk A/S. Apart from that, we declare that no conflicts of interest are associated with this publication and that Novo Nordisk A/S did not influence the research or its presentation., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patient-reported outcome (PRO) measures are increasingly used in clinical diabetes care to increase patient involvement and improve healthcare services. The objectives were to identify instruments used to measure PROs in outpatient diabetes clinics and to investigate the use of these PRO measures alongside the experiences of patients and healthcare personnel in a clinical setting., Research Design and Methods: A scoping review was conducted according to the framework of Arksey and O'Malley with scoping searches of Cinahl, EMBASE, Medline and Health and Psychosocial Instruments. Studies reporting on adults with diabetes in a clinical setting where the PRO measure response directly affected patient care were eligible for inclusion., Results: In total, 35 197 citations were identified, of which 7 reports presenting 4 different PRO measures were included in the review. All four of the included items measured psychosocial aspects of diabetes, and three included elements of the Problem Areas in Diabetes scale. All the patients were satisfied with the use of PRO measures in clinical care, whereas the level of satisfaction among healthcare personnel with PRO measures varied within and among studies., Conclusions: The limited number of eligible studies in this review suggests that research on PRO measures for diabetes outpatient care is scarce. Patients welcome the opportunity to express their concerns through the systematic collection of PRO measures, and some healthcare personnel value the broader insight that PRO measures provide into the impact of diabetes on patients' lives. However, the heterogeneity among services and among patients challenges the implementation of PRO measures. Research is needed to explore how PRO measures in clinical outpatient care affect healthcare personnel workflow., Review Registration: https://doi.org/10.17605/OSF.IO/46AHC., Competing Interests: Competing interests: ALJ was part of the Danish DiabetesFlex study, and thus there may be potential bias. The remaining authors declare that they have no competing interests., (© 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.)

Clinical studies indicate that microvascular disease (MVD) affects bone microstructure and decreases bone strength in type 2 diabetes mellitus (T2D). Osteocytes are housed in small voids within the bone matrix and lacunae and act as sensors of mechanical forces in bone. These cells regulate osteoclastic bone resorption and osteoblastic bone formation as well as osteocytic perilacunar remodeling. We hypothesized that MVD changes morphometric osteocyte lacunar parameters in individuals with T2D. We collected iliac crest bone biopsies from 35 individuals (10 female, 25 male) with T2D with MVD (15%) or without MVD (21%) with a median age of 67 years (interquartile range [IQR] 62-72 years). The participants were included based on c-peptide levels >700 pmol L -1 , absence of anti-GAD65 antibodies, and glycated hemoglobin (HbA1c) levels between 40 and 82 mmol mol -1 or 5.8% and 9.7%, respectively. We assessed osteocyte lacunar morphometric parameters in trabecular and cortical bone regions using micro-computed tomography (micro-CT) at a nominal resolution of 1.2 μm voxel size. The cortical osteocyte lacunar volume (Lc.V) was 7.7% larger ( p  = 0.05) and more spherical (Lc.Sr, p  < 0.01) in the T2D + MVD group. Using linear regression, we found that lacunar density (Lc.N/BV) in trabecular but not cortical bone was associated with HbA1c ( p  < 0.05, R 2  = 0.067) independently of MVD. Furthermore, Lc.V was larger and Lc.Sr higher in the center than in the periphery of the trabecular and cortical bone regions ( p  < 0.05). In conclusion, these data imply that MVD may impair skeletal integrity, possibly contributing to increased skeletal fragility in T2D complicated by MVD. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: The authors do not have any conflicts of interest to declare., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Objective: To evaluate the value of the thyrotropin-releasing hormone (TRH) test in the diagnosis of central hypothyroidism (CH) in patients with pituitary disease., Methods: Systematic evaluation of 359 TRH tests in patients with pituitary disease including measurements of thyroxine (T4), TBG-corrected T4 (T4 corr ), baseline TSH (TSH 0 ) and relative or absolute TSH increase (TSH fold , TSH absolute )., Results: Patients diagnosed with CH (n=39) show comparable TSH 0 (p-value 0.824) but lower T4 corr (p-value <0.001) and lower TSH increase (p-value <0.001) compared to patients without CH. In 54% (42 of 78 cases) of patients with low T4 corr , the CH diagnosis was rejected based on a high TSH fold . In these cases, a spontaneous increase and mean normalization in T4 corr (from 62 to 73 nmol/L, p-value <0.001) was observed during the follow-up period (7.6 ± 5.0 years). Three of the 42 patients (7%) were started on replacement therapy due to spontaneous deterioration of thyroid function after 2.8 years. Patients diagnosed with CH reported significantly more symptoms of hypothyroidism (p-value 0.005), although, symptoms were reported in most patients with pituitary disease. The TRH test did not provide clinical relevant information in patients with normal T4 or patients awaiting pituitary surgery (78%, 281 of 359). There were only mild and reversible adverse effects related to the TRH test except for possibly one case (0.3%) experiencing a pituitary apoplexy., Conclusion: The TRH test could be reserved to patients with pituitary disease, low T4 levels without convincing signs of CH. Approximately 50% of patients with a slightly decreased T4 were considered to have normal pituitary thyroid function based on the TRH test results., 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 Christensen, Smith, Rosendal, Gulisano, Ettrup, Vestergaard, Nielsen, Karmisholt and Dal.)

It is well established that overweight and obesity are often accompanied by stigmatization. However, the influence of stigmatization on interventions for overweight and obesity remains unknown. Stigma may be particularly harmful to children. This study aimed to examine how stigmatization affects efforts to reduce childhood overweight and obesity through family interventions. This research was conducted in a socially disadvantaged area in Denmark. Twenty-seven families and forty professionals participated in in-depth interviews or workshops. The data were analyzed using CMO configurations from a realist evaluation and the theory of stigmatization developed by Link and Phelan. Thus, an abductive approach was employed in the analysis, with its foundation rooted in the empirical data. The study found that the mechanisms of stigmatization could 1. restrain professionals and parents from approaching the problem-thereby challenging family recruitment; 2. prevent parents from working with their children to avoid eating unhealthy food for fear of labeling the child as overweight or obese; and 3. cause children with obesity to experience a separation from other slimmer family members, leading at times to status loss, discrimination, and self-stigmatization. The study showed how the mechanisms of stigmatization may obstruct prevention and treatment of childhood obesity through family interventions. It is suggested that the concept of stigma should be incorporated into the program theories of interventions meant to reduce childhood overweight and obesity.

Introduction: Contrast-enhanced CT (CECT) is widely used for diagnostic purposes. The use of contrast medium carries a risk for postcontrast acute kidney injury (PC-AKI), especially in patients with AKI or chronic kidney disease (CKD). Current guidelines recommend prophylactic intravenous hydration to prevent PC-AKI in high-risk patients. Oral hydration is non-inferior to intravenous hydration in patients with moderate CKD, but it has not been evaluated in high-risk patients., Methods and Analysis: The ENRICH trial will enrol 254 patients with estimated glomerular filtration rate ≤30 mL/min/1.73 m 2 undergoing intravenous CECT, who are block randomised (2-4-2) with stratification for CKD stage, diabetes status, and indication for referral to prophylactic treatment with oral or intravenous hydration. PC-AKI is defined as an absolute increase in SCr of >0.3 mg/dL or >1.5 from baseline at 2-5 days. Renal function will also be evaluated <90 days, <7 days and 1-3 days before intravenous CECT, and 25-40 days after intravenous CECT. Secondary outcomes include dialysis, renal adverse events, hospitalisation due to hydration-related or contrast-related sequelae, and all-cause mortality ≤30 days postcontrast. Pre- and postcontrast plasma and urinary biomarkers will be evaluated for diagnostic and prognostic accuracy of the primary and secondary outcomes., Ethics and Dissemination: Oral hydration is patient-friendly and less costly compared with intravenous hydration. If oral hydration is non-inferior to intravenous hydration in high-risk patients, it could be implemented as new hydration strategy, which will facilitate the clinical diagnosing of elective patients with severe CKD without unnecessary resource utilisation. The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20210126), and the Data Protection Agency (21/66779). The study is conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported in international peer-reviewed journals., Trial Registration Number: NCT05283512., Competing Interests: Competing interests: None declared., (© 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.)

Background: Successful diabetes management requires collaboration between patients and healthcare professionals and should be aligned with an individual's condition and resources. We developed a flexible, individualised, patient-reported outcome (PRO)-based telehealth intervention called "DiabetesFlex Care" in which patients completed an annual self-reported questionnaire from home, one required face-to-face appointment, and two optional outpatient consultations. In this study, we investigated patients' experiences using DiabetesFlex Care., Methods: We conducted a qualitative, interpretive descriptive (ID) study based on semi-structured interviews with a purposeful sample of 36 patients with type 1 diabetes (T1D) who had used DiabetesFlex Care. Recorded audio data were transcribed and analysed inductively using the constant comparative method., Results: DiabetesFlex Care changed participants' perspectives on living with diabetes. Patients became more involved in their own care and found that DiabetesFlex Care helped to make their conversations with healthcare professionals more relevant. Furthermore, participants appreciated the ability to both choose the format of their appointments (face-to-face vs. phone call) and cancel unnecessary appointments., Conclusion: DiabetesFlex Care was a flexible and inclusive health service that enabled patients to take more responsibility for their own diabetes management. The questionnaire-based approach in DiabetesFlex Care can help healthcare professionals systematically account for patients' perspectives and support user involvement and self-management. By extension, this approach can also help minimise healthcare-related disruptions in patients' lives. Further studies are needed to determine whether flexible PRO-based telehealth is an acceptable solution for all patients., (© 2023 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Background: Active acromegaly is characterized by increased lean body mass, but the mechanisms underlying the protein anabolic effect are unclear., Aim: To study if active acromegaly induces reversible changes in whole-body and skeletal muscle protein kinetics., Patients and Methods: Eighteen patients with acromegaly were investigated before and 47 ± 10 weeks after disease control by surgery (n = 8) and/or medical treatment (n = 10). Labeled phenylalanine and tyrosine tracers were employed to assess whole-body and regional forearm muscle protein kinetics. Intramyocellular protein signaling was assessed in skeletal muscle biopsies, and whole-body dual-energy X-ray absorptiometry scan and indirect calorimetry assessed lean body mass (LBM) and resting energy expenditure, respectively., Results: Disease control induced a 7% decrease in lean body mass (P < .000) and a 14% decrease in LBM-adjusted energy expenditure. Whole-body phenylalanine breakdown decreased after disease control (P = .005) accompanied by a decrease in the degradation of phenylalanine to tyrosine (P = .005) and a decrease in whole-body phenylalanine synthesis (P = .030). Skeletal muscle protein synthesis tended to decrease after disease control (P = .122), whereas the muscle protein breakdown (P = .437) and muscle protein loss were unaltered (P = .371). Unc-51 like autophagy activating kinase 1 phosphorylation, an activator of protein breakdown, increased after disease control (P = .042)., Conclusions: Active acromegaly represents a reversible high flux state in which both whole-body protein breakdown and synthesis are increased, whereas forearm muscle protein kinetics are unaltered. Future studies are needed to decipher the link between protein kinetics and the structure and function of the associated growth hormone-induced increase in lean body mass., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Patients from Greenland are transferred overseas for highly specialised treatment, mainly to the National University Hospital, Rigshospitalet, Denmark. We aimed to investigate the pattern of transfers from Greenland to Denmark, focusing on cardiology., Methods: This descriptive quality assurance study included all Greenlandic citizens receiving healthcare services at Rigshospitalet from 2017-2021. Unique patients and disease courses were accounted for and patients were stratified across specialties., Results: A total of 3,201 unique patients (56% males, mean age 51.0 years, 325 were 18 years or younger) from Greenland received healthcare services at Rigshospitalet. As some patients were seen two or more times, this corresponds to almost 900 patients (approximately 1,500 disease courses) or 1.2% of the entire Greenlandic population being referred annually. The referrals increased by 52% during the period. The Centre of Head and Orthopaedics received most referrals, followed by the Heart Centre. A modest increase in referrals due to heart diseases was observed with ischaemic heart disease being the more prevalent diagnosis. Coronary artery revascularisation rates in Greenlandic citizens aged 55-74 years were at least as high as in the same age-group for all Danes., Conclusion: During the past five years, a 52% increase has been observed in the referral rate from Greenland to Rigshospitalet for diagnostics and treatment. In cardiology, ischaemic heart disease represented the largest share with a high revascularisation rate being observed in older Greenlandic citizens., Funding: None., Trial Registration: Not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Objective: Breast cancer is the most common cancer diagnosis among women. The acute crisis and uncertainty that often follow diagnosis put the family at risk of exhaustion and dysfunction. Adolescents have been identified as a particularly vulnerable group of relatives. To investigate how to prevent distress in this group, we systematically reviewed research on adolescents' (11-21 years) needs for information and psycho-social support during their mothers' breast cancer trajectory., Method: Systematic searches were conducted in five bibliometric databases. Peer-reviewed, original research of adolescents aged 11-21 with a mother diagnosed with breast cancer was included. Two researchers conducted screening, quality assessment, and data extraction independently. Thematic synthesis was applied to the included studies., Results: A total of 8066 studies were screened, and five quantitative and six qualitative studies were included. The results indicated that adolescents' information and psycho-social support needs were poorly met. Many were reluctant to share feelings with family and peers and experienced abandonment during the crisis. Adolescents who were not well informed experienced distress. Poor family functioning increased the level of adolescents' distress., Conclusions: Despite limitations regarding heterogeneity among the studies, eligibility criteria, and quality assessment, this review provides clear clinical implications. Encounter groups may support adolescents during their mother's breast cancer trajectory. Furthermore, healthcare professionals could provide more indirect support to adolescents by providing support and clearer guidelines to parents. Finally, adolescents from poor-functioning families need extra attention., (© 2023 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)