Health-related quality of life in elderly cardiac patients undergoing cardiac rehabilitation and the association with exercise capacity: The EU-CaRE study.

AIMS: The ability to be physically active is pivotal to the quality of life in elderly patients. This study aims to describe the association between exercise capacity and health-related quality of life (HRQoL), anxiety, and depression following an exercise-based cardiac rehabilitation (CR) program in elderly cardiac patients. METHODS: Patients aged ≥65 years with acute and chronic coronary syndrome or heart valve surgery were consecutively included from 8 CR centers in 7 European countries. Exercise capacity (VO2peak(ml/kg/min)) was assessed with a cardiopulmonary exercise test (97%) or a six-minute walk test. Outcome variables included HRQoL (SF-36 physical and mental component scores (PCS and MCS)), anxiety (GAD-7), and depression (PHQ-9). Mixed models were used to address the association between baseline and the development in VO2peak, and outcome variables stratified on sex, and adjusted for baseline values, age, and CR center. RESULTS: A total of 1,633 patients were included (T0), 1,523 (93%) completed end-of-CR assessment (T1), and 1,457 (89%) 1-year follow-up (T2). Women had higher % of predicted VO2peak, but poorer scores in HRQoL, anxiety and depression at all time-points. All scores improved in both sexes at follow-up. We found significant associations between VO2peak at baseline as well as development in VO2peak and all outcome variables at T1 and T2 in men (all p < 0.001). In women, VO2peak was only associated with PCS scores (p < 0.001). CONCLUSIONS: Improvements in exercise capacity was strongly associated with improvements in HRQoL and mental health, however with stronger associations in men. The results highlight the importance of physical fitness for HRQol and mental health. The findings from this study might be useful to better target individual CR programs.

This study explores the association between exercise capacity and the well-being of elderly cardiac patients participating in a cardiac rehabilitation program, focusing on health-related quality of life (HRQoL), anxiety, and depression. Key Findings:Women, despite having higher percentages of predicted exercise capacity, consistently reported poorer HRQoL, anxiety, and depression scores compared to men at all assessed time points.Improvements in exercise capacity were strongly associated with positive changes in HRQoL and mental health, with these associations being more pronounced in men.

Identifying people living with cystic fibrosis in the Danish National Patient Registry: A validation study.

BACKGROUND: The Danish National Patient Registry (DNPR) serves as a valuable resource for scientific research. However, to ensure accurate results in cystic fibrosis (CF) studies that rely on DNPR data, a robust case-identification algorithm is essential. This study aimed to develop and validate algorithms for the reliable identification of CF patients in the DNPR. METHODS: Using the Danish Cystic Fibrosis Registry (DCFR) as a reference, accuracy measures including sensitivity and positive predictive value (PPV) for case-finding algorithms deployed in the DNPR were calculated. Algorithms were based on minimum number of hospital contacts with CF as the main diagnosis and minimum number of days between first and last contact. RESULTS: An algorithm requiring a minimum of one hospital contact with CF as the main diagnosis yielded a sensitivity of 96.1 % (95 % CI: 94.2 %; 97.4 %) and a PPV of 84.9 % (82.0 %; 87.4 %). The highest-performing algorithm required minimum 2 hospital visits and a minimum of 182 days between the first and the last contact and yielded a sensitivity of 95.9 % (95 % CI: 94.1 %; 97.2 %), PPV of 91.0 % (95 % CI: 88.6 %; 93.0 %) and a cohort entry delay of 3.2 months at the 75th percentile (95th percentile: 38.7 months). CONCLUSIONS: The DNPR captures individuals with CF with high sensitivity and is a valuable resource for CF-research. PPV was improved at a minimal cost of sensitivity by increasing requirements of minimum number of hospital contacts and days between first and last contact. Cohort entry delay increased with number of required hospital contacts.

Adverse Pregnancy Outcomes and Subsequent First-Time Use of Psychiatric Treatment Among Fathers in Denmark.

Importance: Becoming a first-time parent is a major life-changing event and can be challenging regardless of the pregnancy outcome. However, little is known how different adverse pregnancy outcomes affect the father's risk of psychiatric treatment post partum. Objective: To examine the associations of adverse pregnancy outcomes with first-time psychiatric treatment in first-time fathers. Design, Setting, and Participants: This nationwide cohort study covered January 1, 2008, to December 31, 2017, with a 1-year follow-up completed December 31, 2018. Data were gathered from Danish, nationwide registers. Participants included first-time fathers with no history of psychiatric treatment. Data were analyzed from August 1, 2022, to February 20, 2024. Exposures: Adverse pregnancy outcomes including induced abortion, spontaneous abortion, stillbirth, small for gestational age (SGA) and not preterm, preterm with or without SGA, minor congenital malformation, major congenital malformation, and congenital malformation combined with SGA or preterm compared with a full-term healthy offspring. Main Outcomes and Measures: Prescription of psychotropic drugs, nonpharmacological psychiatric treatment, or having a psychiatric hospital contact up to 1 year after the end of the pregnancy. Results: Of the 192 455 fathers included (median age, 30.0 [IQR, 27.0-34.0] years), 31.1% experienced an adverse pregnancy outcome. Most of the fathers in the study had a vocational educational level (37.1%). Fathers experiencing a stillbirth had a significantly increased risk of initiating nonpharmacological psychiatric treatment (adjusted hazard ratio [AHR], 23.10 [95% CI, 18.30-29.20]) and treatment with hypnotics (AHR, 9.08 [95% CI, 5.52-14.90]). Moreover, fathers experiencing an early induced abortion (≤12 wk) had an increased risk of initiating treatment with hypnotics (AHR, 1.74 [95% CI, 1.33-2.29]) and anxiolytics (AHR, 1.79 [95% CI, 1.18-2.73]). Additionally, late induced abortion (>12 wk) (AHR, 4.46 [95% CI, 3.13-6.38]) and major congenital malformation (AHR, 1.36 [95% CI, 1.05-1.74]) were associated with increased risk of nonpharmacological treatment. In contrast, fathers having an offspring being born preterm, SGA, or with a minor congenital malformation did not have a significantly increased risk of any of the outcomes. Conclusions and Relevance: The findings of this Danish cohort study suggest that first-time fathers who experience stillbirths or induced abortions or having an offspring with major congenital malformation had an increased risk of initiating pharmacological or nonpharmacological psychiatric treatment. These findings further suggest a need for increased awareness around the psychological state of fathers following the experience of adverse pregnancy outcomes.

The LIVER CARE trial - screening for liver disease in individuals attending treatment for alcohol use disorder: a randomized controlled feasibility trial.

BACKGROUND: Alcohol-related liver disease is a preventable disease with high mortality. If individuals with alcohol-related liver disease were to be diagnosed earlier by screening and they reduced their alcohol consumption, lives lost to alcohol-related liver disease might be saved. A liver stiffness measurement (FibroScan©) is a key tool to screen for alcohol-related liver disease in asymptomatic individuals. No randomized controlled trials have been conducted to test if screening for liver disease reduces alcohol consumption in individuals with alcohol use disorders, in addition to what can be obtained by motivational interventions. We aimed to assess the feasibility of a randomized controlled trial of a screening for liver disease on the prevalence of alcohol abstinence or light consumption after 6 months in individuals attending outpatient treatment for alcohol use disorder. METHODS: We used an interdisciplinary approach to develop the format of the randomized controlled trial. Individuals were recruited from one outpatient treatment facility for alcohol use disorders. Study participants were randomized 1:1 to receive a) a liver stiffness measurement in addition to usual care (intervention) or b) usual care (control). Follow-up on alcohol consumption was assessed by telephone interview after 6 months and corroborated by data from records from public hospitals and the alcohol treatment facility. Feasibility was assessed by probabilities of recruitment, retention, and completion and estimated by the exact binominal test, with success defined as > 50% participation for each endpoint. The study design was evaluated at interdisciplinary meetings with staff and researchers from the outpatient alcohol treatment facility and the hospital clinic. RESULTS: Forty of 57 invited individuals agreed to participate in the study (recruitment = 70% (95% CI: 57-82)); 19 of 20 participants randomized to the intervention showed up for the screening (retention = 95% (95% CI: 75-100)). Follow-up telephone interviews succeeded for 33 of 39 reachable participants (completion = 85% (95% CI: 69-94)). Treatment records indicated that the 6 participants who were lost to follow-up for the telephone interview had not achieved alcohol abstinence or light consumption. There was no evidence that the intervention increased abstinence or light alcohol consumption at follow-up: 45% (95% CI: 23-68) in the intervention group and 65% (95% CI: 41-85) in the control group had a alcohol consumption below 10 standard drinks/week at 6 months. The main obstacle regarding study feasibility was to avoid disappointment in individuals randomized as controls. CONCLUSIONS: This feasibility study developed a study design to test the influence of screening for liver disease on abstinence or light alcohol consumption in individuals attending treatment for alcohol use disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05244720; registered on February 17, 2022.

Effectiveness of a multidisciplinary and transitional nutritional intervention compared with standard care on health-related quality of life among acutely admitted medical patients aged ≥65 years with malnutrition or risk of malnutrition: A randomized controlled trial.

BACKGROUND & AIM: Malnutrition, risk of malnutrition, and risk factors for malnutrition are prevalent among acutely admitted medical patients aged ≥65 years and have significant health-related consequences. Consequently, we aimed to investigate the effectiveness of a multidisciplinary and transitional nutritional intervention on health-related quality of life compared with standard care. METHODS: The study was a block randomized, observer-blinded clinical trial with two parallel arms. The Intervention Group was offered a multidisciplinary transitional nutritional intervention consisting of dietary counselling and six sub-interventions targeting individually assessed risk factors for malnutrition, while the Control Group received standard care. The inclusion criteria were a Mini Nutritional Assessment Short-Form score ≤11, age ≥65 years, and an acute admittance to the Emergency Department. Outcomes were assessed on admission and 8 and 16 weeks after hospital discharge. The primary outcome was the difference between groups in change in health-related quality of life (assessed by the EuroQol-5D-5L) from baseline to 16 weeks after discharge. The secondary outcomes were difference in intake of energy and protein, well-being, muscle strength, and body weight at all timepoints. RESULTS: From October 2018 to April 2021, 130 participants were included. Sixteen weeks after discharge, 29% in the Intervention Group and 19% in the Control Group were lost to follow-up. Compliance varied between the sub-interventions targeting nutritional risk factors and was generally low after discharge, ranging from 0 to 61%. No difference was found between groups on change in health-related quality of life or on well-being, muscle strength, and body weight at any timepoint, neither using the intention-to-treat analysis nor the per-protocol analysis. The protein intake was higher in the Intervention Group during hospitalization (1.1 (Standard Deviation (SD) 0.4) vs 0.8 (SD 0.5) g/kg/day, p = 0.0092) and 8 weeks after discharge (1.2 (SD 0.5) vs 0.9 (0.4) g/kg/day, p = 0.0025). The percentual intake of calculated protein requirements (82% (SD 24) vs 61% (SD 32), p = 0.0021), but not of calculated energy requirements (89% (SD 23) vs 80% (SD 37), p = 0.2), was higher in the Intervention Group than in the Control Group during hospitalization. Additionally, the Intervention Group had a significantly higher percentual intake of calculated protein requirements (94% (SD 41) vs 74% (SD 30), p = 0.015) and calculated energy requirements (115% (SD 37) vs 94% (SD 31), p = 0.0070) 8 weeks after discharge. The intake of energy and protein was comparable between the groups 16 weeks after discharge. CONCLUSION: We found no effect of a multidisciplinary and transitional nutritional intervention for acutely admitted medical patients aged ≥65 years with malnutrition or risk of malnutrition on our primary outcome, health-related quality of life 16 weeks after discharge. Nor did the intervention affect the secondary outcomes, well-being, muscle strength, and body weight from admission to 8 or 16 weeks after discharge. However, the intervention improved energy and protein intake during hospitalization and 8 weeks after discharge. Low compliance with the intervention after discharge may have compromised the effect of the intervention. The study is registered at ClinicalTrials.gov (identifier: NCT03741283).

Acute patients discharged without an established diagnosis: risk of mortality and readmission of nonspecific diagnoses compared to disease-specific diagnoses.

BACKGROUND: Nonspecific discharge diagnoses after acute hospital courses represent patients discharged without an established cause of their complaints. These patients should have a low risk of adverse outcomes as serious conditions should have been ruled out. We aimed to investigate the mortality and readmissions following nonspecific discharge diagnoses compared to disease-specific diagnoses and assessed different nonspecific subgroups. METHODS: Register-based cohort study including hospital courses beginning in emergency departments across 3 regions of Denmark during March 2019-February 2020. We identified nonspecific diagnoses from the R- and Z03-chapter in the ICD-10 classification and excluded injuries, among others-remaining diagnoses were considered disease-specific. Outcomes were 30-day mortality and readmission, the groups were compared by Cox regression hazard ratios (HR), unadjusted and adjusted for socioeconomics, comorbidity, administrative information and laboratory results. We stratified into short (3-<12 h) or lengthier (12-168 h) hospital courses. RESULTS: We included 192,185 hospital courses where nonspecific discharge diagnoses accounted for 50.7% of short and 25.9% of lengthier discharges. The cumulative risk of mortality for nonspecific vs. disease-specific discharge diagnoses was 0.6% (0.6-0.7%) vs. 0.8% (0.7-0.9%) after short and 1.6% (1.5-1.7%) vs. 2.6% (2.5-2.7%) after lengthier courses with adjusted HRs of 0.97 (0.83-1.13) and 0.94 (0.85-1.05), respectively. The cumulative risk of readmission for nonspecific vs. disease-specific discharge diagnoses was 7.3% (7.1-7.5%) vs. 8.4% (8.2-8.6%) after short and 11.1% (10.8-11.5%) vs. 13.7% (13.4-13.9%) after lengthier courses with adjusted HRs of 0.94 (0.90-0.98) and 0.95 (0.91-0.99), respectively. We identified 50 clinical subgroups of nonspecific diagnoses, of which Abdominal pain (n = 12,462; 17.1%) and Chest pain (n = 9,599; 13.1%) were the most frequent. The subgroups described differences in characteristics with mean age 41.9 to 80.8 years and mean length of stay 7.1 to 59.5 h, and outcomes with < 0.2-8.1% risk of 30-day mortality and 3.5-22.6% risk of 30-day readmission. CONCLUSIONS: In unadjusted analyses, nonspecific diagnoses had a lower risk of mortality and readmission than disease-specific diagnoses but had a similar risk after adjustments. We identified 509 clinical subgroups of nonspecific diagnoses with vastly different characteristics and prognosis.

Association Between First-time Neurologic Events and Metronidazole Treatment: A Case-time Control Study.

PURPOSE: Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events. METHODS: We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use. FINDINGS: Out of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59-1.64, P = 0.95) with no statistically significant association across different subgroups and time windows. IMPLICATIONS: Our findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use.

Education, employment, and income among people living with cystic fibrosis across three decades - A matched cohort study using Danish health registries.

BACKGROUND: Past and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population. METHODS: This nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality. RESULTS: The Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts. CONCLUSIONS: The disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life.

Monitoring and treatment of hypercholesterolemia after an atherosclerotic cardiovascular disease event in Denmark from 2015 to 2020.

BACKGROUND AND AIMS: Lowering the blood concentration of low-density lipoprotein cholesterol (LDL-C), is a cornerstone in preventing atherosclerotic cardiovascular disease (ASCVD). Current European guidelines recommends LDL-C < 1.4 mmol/L for secondary prevention in high-risk patients. The aim of this study is to investigate monitoring and treatment of hypercholesterolemia one year after a ASCVD event. METHODS: Danish patients with hypercholesterolemia and an incident ASCVD event from 2015 to 2020 were included in this nationwide cohort study. Patients' LDL-C measurements and lipid-lowering treatment were followed for one year after ASCVD event, or until death or migration. Imputation was used to estimate absolute LDL-values when patients were unmeasured. RESULTS: A total of 139,043 patients were included in the study with a mean follow-up time of 10.4 months. During the one-year period, 120,020 (86%) patients had their LDL-C measured at least once, 83,723 (60%) patients were measured at least twice. During the period one to six months after ASCVD event 25,999 (19%) achieved an LDL-C < 1.4 mmol/L, 93,349 (67%) failed to achieve an LDL-C < 1.4 mmol/L, and 196,950 (14%) had died or migrated. Missing LDL-C values were estimated via imputation. At the end of month twelve, 60,583 (44%) patients were in statin monotherapy, 2926 (2%) were treated with other lipid-lowering treatment, 42,869 (31%) were in no treatment, and 32,665 (23%) had died or migrated. CONCLUSIONS: Many Danish patients are not appropriately followed-up with LDL-C measurements, and a substantial number of patients are not in lipid-lowering treatment one year after an ASCVD event.

Incidence and Characteristics of the Hyperosmolar Hyperglycemic State: A Danish Cohort Study.

OBJECTIVE: The hyperosmolar hyperglycemic state (HHS) is a rare and life-threatening complication of diabetes. We aimed to estimate the incidence of HHS and describe the clinical and biomarker profiles of patients with HHS, including subgroups with acidosis and acute kidney injury. RESEARCH DESIGN AND METHODS: This nationwide, descriptive cohort study used Danish registry data during years 2016-2018 to identify acutely admitted patients fulfilling the hyperglycemia and hyperosmolarity criteria of HHS (glucose ≥33 mmol/L and osmolarity [2 × sodium + glucose] ≥320 mmol/L). RESULTS: We identified 634 patients (median age, 69 years (first quartile; third quartile: 58; 79) who met the criteria of HHS among 4.80 million inhabitants aged ≥18 years. The incidence rates were 16.5 and 3.9 per 10,000 person-years among people with known type 1 (n = 24,196) and type 2 (n = 251,357) diabetes, respectively. Thirty-two percent of patients with HHS were not previously diagnosed with diabetes. Patients were categorized as pure HHS (n = 394) and combined HHS and diabetic ketoacidosis (HHS-DKA; n = 240). The in-hospital mortality rate for pure HHS was 17% and 9% for HHS-DKA. CONCLUSIONS: The incidence of HHS was higher among patients with type 1 diabetes compared with type 2 diabetes. HHS is a spectrum of hyperglycemic crises and can be divided in pure HHS and HHS-DKA. In one-third of patients, HHS was the debut of their diabetes diagnosis.

Fetal Overgrowth and Preterm Delivery in Women With Type 1 Diabetes Using Insulin Pumps or Multiple Daily Injections: A Post Hoc Analysis of the EVOLVE Study Cohort.

OBJECTIVE: To compare the risk of fetal overgrowth and preterm delivery in pregnant women with type 1 diabetes (T1D) treated with insulin pumps versus multiple daily injections (MDI) and examine whether possible differences were mediated through improved glycemic control or gestational weight gain during pregnancy. RESEARCH DESIGN AND METHODS: The risk of pregnancy and perinatal outcomes were evaluated in a cohort of 2,003 pregnant women with T1D enrolled from 17 countries in a real-world setting during 2013-2018. RESULTS: In total, 723 women were treated with pumps and 1,280 with MDI. At inclusion (median gestational weeks 8.6 [interquartile range 7-10]), pump users had lower mean HbA1c (mean ± SD 50.6 ± 9.8 mmol/mol [6.8 ± 0.9%] vs. 53.6 ± 13.8 mmol/mol [7.1 ± 1.3%], P < 0.001), longer diabetes duration (18.4 ± 7.8 vs. 14.4 ± 8.2 years, P < 0.001), and higher prevalence of retinopathy (35.3% vs. 24.4%, P < 0.001). Proportions of large for gestational age (LGA) offspring and preterm delivery were 59.0% vs. 52.2% (adjusted odds ratio [OR] 1.36 [95% CI 1.09; 1.70], P = 0.007) and 39.6% vs. 32.1% (adjusted OR 1.46 (95% CI 1.17; 1.82), P < 0.001), respectively. The results did not change after adjustment for HbA1c or gestational weight gain. CONCLUSIONS: Insulin pump treatment in pregnant women with T1D, prior to the widespread use of continuous glucose monitoring or automated insulin delivery, was associated with a higher risk of LGA offspring and preterm delivery compared with MDI in crude and adjusted analyses. This association did not appear to be mediated by differences in glycemic control as represented by HbA1c or by gestational weight gain.

Predicting Short-Term Mortality in Older Patients Discharged from Acute Hospitalizations Lasting Less Than 24 Hours.

Purpose: Over coming decades, a rise in the number of short, acute hospitalizations of older people is to be expected. To help physicians identify high-risk patients prior to discharge, we aimed to develop a model capable of predicting the risk of 30-day mortality for older patients discharged from short, acute hospitalizations and to examine how model performance changed with an increasing amount of information. Methods: This registry-based study included acute hospitalizations in Denmark for 2016-2018 lasting ≤24 hours where patients were permanent residents, ≥65 years old, and discharged alive. Utilizing many different predictor variables, we developed random forest models with an increasing amount of information, compared their performance, and examined important variables. Results: We included 107,132 patients with a median age of 75 years. Of these, 3.3% (n=3575) died within 30 days of discharge. Model performance improved especially with the addition of laboratory results and information on prior acute admissions (AUROC 0.835), and again with comorbidities and number of prescription drugs (AUROC 0.860). Model performance did not improve with the addition of sociodemographic variables (AUROC 0.861), apart from age and sex. Important variables included age, dementia, number of prescription drugs, C-reactive protein, and eGFR. Conclusion: The best model accurately estimated the risk of short-term mortality for older patients following short, acute hospitalizations. Trained on a large and heterogeneous dataset, the model is applicable to most acute clinical settings and could be a useful tool for physicians prior to discharge.

Study protocol of the InterVitaminK trial: a Danish population-based randomised double-blinded placebo-controlled trial of the effects of vitamin K (menaquinone-7) supplementation on cardiovascular, metabolic and bone health.

INTRODUCTION: Vitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few well-powered randomised controlled trials have examined whether vitamin K prevents progression of vascular calcification in individuals from the general population. The aim of the InterVitaminK trial is to investigate the effects of vitamin K supplementation (menaquinone-7, MK-7) on cardiovascular, metabolic, respiratory and bone health in a general ageing population with detectable vascular calcification. METHODS AND ANALYSIS: The InterVitaminK trial is a randomised, double-blinded, placebo-controlled, trial. A total of 450 men and women aged 52-82 years with detectable coronary artery calcification (CAC), but without manifest CVD, will be randomised (1:1) to receive daily MK-7 (333 µg/day) or placebo tablets for 3 years. Health examinations are scheduled at baseline, and after 1, 2 and 3 years of intervention. Health examinations include cardiac CT scans, measurements of arterial stiffness, blood pressure, lung function, physical function, muscle strength, anthropometric measures, questionnaires on general health and dietary intake, and blood and urine sampling. The primary outcome is progression of CAC from baseline to 3-year follow-up. The trial has 89% power to detect a between-group difference of at least 15%. Secondary outcomes are bone mineral density, pulmonary function and biomarkers of insulin resistance. ETHICS AND DISSEMINATION: Oral MK-7 supplementation is considered safe and has not been found to cause severe adverse events. The Ethical Committee of the Capital Region (H-21033114) approved the protocol. Written informed consent is obtained from all participants and the trial is conducted in accordance with the Declaration of Helsinki II. Both negative and positive findings will be reported. TRIAL REGISTRATION NUMBER: NCT05259046.

PaCO2 trajectories in mechanically ventilated patients with COVID-19: A population-based cohort study.

OBJECTIVE: To identify PaCO2 trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) during the first and second waves of the pandemic in Denmark. DESIGN: A population-based cohort study with retrospective data collection. PATIENTS: All COVID-19 patients were treated in eight intensive care units (ICUs) in the Capital Region of Copenhagen, Denmark, between March 1, 2020 and March 31, 2021. MEASUREMENTS: Data from the electronic health records were extracted, and latent class analyses were computed based on up to the first 3 weeks of mechanical ventilation to depict trajectories of PaCO2 levels. Multivariable Cox regression analyses were used to calculate adjusted hazard ratios (aHRs) for Simplified Acute Physiology Score 3, sex and age with 95% confidence intervals (CIs) for death according to PaCO2 trajectories. MAIN RESULTS: In latent class trajectory models, including 25,318 PaCO2 measurements from 244 patients, three PaCO2 latent class trajectories were identified: a low isocapnic (Class I; n = 130), a high isocapnic (Class II; n = 80), as well as a progressively hypercapnic (Class III; n = 34) trajectory. Mortality was higher in Class II [aHR: 2.16 {1.26-3.68}] and Class III [aHR: 2.97 {1.63-5.40}]) compared to Class I (reference). CONCLUSION: Latent class analysis of arterial blood gases in mechanically ventilated COVID-19 patients identified distinct PaCO2 trajectories, which were independently associated with mortality.

Shared and distinct factors underlying in-hospital mobility of older adults in Israel and Denmark (97/100).

BACKGROUND: Low in-hospital mobility is widely acknowledged as a major risk factor in acquiring hospital-associated disabilities. Various predictors of in-hospital low mobility have been suggested, among them older age, disabling admission diagnosis, poor cognitive and physical functioning, and pre-hospitalization mobility. However, the universalism of the phenomena is not well studied, as similar risk factors to low in-hospital mobility have not been tested. METHODS: The study was a secondary analysis of data on in-hospital mobility that investigated the relationship between in-hospital mobility and a set of similar risk factors in independently mobile prior to hospitalization older adults, hospitalized in acute care settings in Israel (N = 206) and Denmark (N = 113). In Israel, mobility was measured via ActiGraph GT9X and in Denmark by ActivPal3 for up to seven hospital days. RESULTS: Parallel multivariate analyses revealed that a higher level of community mobility prior to hospitalization and higher mobility ability status on admission were common predictors of a higher number of in-hospital steps, whereas the longer length of hospital stay was significantly correlated with a lower number of steps in both samples. The risk of malnutrition on admission was associated with a lower number of steps, but only in the Israeli sample. CONCLUSIONS: Despite different assessment methods, older adults' low in-hospital mobility has similar risk factors in Israel and Denmark. Pre-hospitalization and admission mobility ability are robust and constant risk factors across the two studies. This information can encourage the development of both international standard risk evaluations and tailored country-based approaches.

Healthcare resource utilization prior to suicide death or suicide attempt in patients with major depressive disorder-A Danish registry-based cohort study.

INTRODUCTION: Major depressive disorder (MDD) is associated with suicide events and with increased healthcare resource utilization (HRU). The aim was to analyze the pattern of HRU prior to death by suicide or suicide attempt in patients with MDD using national registries. METHODS: Danish adults with MDD, who died by suicide or had a first-time suicide attempt, were matched with MDD controls on age, sex, and MDD severity and analyzed for psychiatric and non-psychiatric hospital and private practitioner contacts, and prescriptions 1 year prior to the event. For individuals having a second suicide attempt, HRU prior to first and second suicide attempt was analyzed. RESULTS: Among 1061 individuals dying by suicide and 3759 individuals with suicide attempt, compared with their controls, the proportion with psychiatric hospitalization was more than 50% increased, mainly accounted for by acute contacts. The difference to the matched controls decreased with increasing MDD severity. Non-psychiatric HRU was increased as well. The proportion with psychiatric hospitalizations or ED visits was reduced prior to the second attempt compared with first attempt. CONCLUSION: Among individuals with MDD, psychiatric and non-psychiatric HRU was increased 1 year prior to suicide event. The proportion of individuals who had psychiatric HRU decreased from first to second suicide attempt.

Drug utilization of biologic therapy in Crohn's disease and ulcerative colitis: a population-based Danish cohort study 2015-2020.

OBJECTIVE: The aim of the study was to characterize the drug utilization and switch patterns of biological treatment of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Using Danish national registries, this nationwide study included individuals diagnosed with UC or CD, bio-naïve at the initiation of treatment with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab in 2015-2020. Hazard ratios of discontinuing the first treatment or switching to another biological treatment were explored using Cox regression. RESULTS: Among 2995 UC patients and 3028 CD patients, infliximab was used as a first-line biologic treatment in 89% of UC patients and 85% of CD patients, followed by adalimumab with 6%, vedolizumab with 3%, and golimumab with 1% for UC, and adalimumab with 12%, vedolizumab with 2%, and ustekinumab with 0.4% for CD.When comparing adalimumab as the first treatment series to infliximab, there was a higher risk of treatment discontinuation (excluding switch) among UC patients (hazard ratio: 2.02 [95% confidence interval: 1.57; 2.60]) and CD patients (1.85 [1.52; 2.24]). When comparing vedolizumab to infliximab, there was a lower risk of discontinuation for UC patients (0.51 [0.29-0.89]), and for CD patients, although not significantly (0.58 [0.32-1.03]). We observed no significant difference in the risk of switching to another biologic treatment for any of the biologics. CONCLUSION: More than 85% of UC and CD patients initiating biologic therapy had infliximab as their first-line biologic treatment, in accordance with official treatment guidelines. Future studies should explore the higher incidence of treatment discontinuation of adalimumab as the first treatment series.Key summarySeveral biologic therapies are available in the treatment of ulcerative colitis and Crohn's disease.Clinical guidelines stipulate that infliximab should be the first-line biologic therapy.Drug utilization studies comparing biologic therapies head-to-head are sparse.In Denmark, during 2015-2020 infliximab remained the most widely used biologic treatment, with adalimumab being second.One in four patients experienced more than one biologic during the study period.The risk of discontinuation of biologic treatment (and not starting a new biologic) was higher for initiators of adalimumab.Clinical and social background factors available from the registers could not account for the observed risk difference in discontinuation.

Congenital malformations among offspring of women with type 1 diabetes who use insulin pumps: a prospective cohort study.

AIMS/HYPOTHESIS: Continuous subcutaneous insulin infusion by insulin pump is often superior in improving glycaemic control compared with conventional multiple daily insulin injection (MDI). However, whether pump treatment leads to improved pregnancy outcomes in terms of congenital malformations and perinatal death remains unknown. The present aim was to evaluate the risk of malformations and perinatal and neonatal death in pregnant women with type 1 diabetes treated with pump or MDI. METHODS: We performed a secondary analysis of a prospective multinational cohort of 2088 pregnant women with type 1 diabetes in a real-world setting who were treated by pump (n=750) or MDI (n=1338). ORs for offspring with congenital malformations or perinatal or neonatal death were calculated using crude data and by logistic regression on propensity score-matched data. RESULTS: At enrolment (gestational week 8; 95% CI 4, 14), pump users had a higher educational level (university degree: 37.3% vs 25.1%; p<0.001) and better glycaemic control (mean HbA1c: 51±10 mmol/mol [6.8±0.9%] vs 54±14 mmol/mol [7.1±1.3%], p<0.001) compared with MDI users. Moreover, a greater proportion of pump users had an HbA1c level below 75 mmol/mol (9%) (97.6% vs 91.9%, p<0.001), and more often reported taking folic acid supplementation (86.3% vs 74.8%; p<0.001) compared with MDI users. All clinically important potential confounders were balanced after propensity score matching, and HbA1c remained lower in pump users. The proportion of fetuses with at least one malformation was 13.5% in pump users vs 11.2% in MDI users (crude OR 1.23; 95% CI 0.94, 1.61; p=0.13; propensity score-matched (adjusted) OR 1.11; 95% CI 0.81, 1.52; p=0.52). The proportion of fetuses with at least one major malformation was 2.8% in pump users vs 3.1% in MDI users (crude OR 0.89; 95% CI 0.52, 1.51; p=0.66; adjusted OR 0.78; 95% CI 0.42, 1.45; p=0.43), and the proportions of fetuses carrying one or more minor malformations (but no major malformations) were 10.7% vs 8.1% (crude OR 1.36; 95% CI 1.00, 1.84; p=0.05; adjusted OR 1.23; 95% CI 0.87, 1.75; p=0.25). The proportions of perinatal and neonatal death were 1.6% vs 1.3% (crude OR 1.23; 95% CI 0.57, 2.67; p=0.59; adjusted OR 2.02; 95% CI 0.69, 5.93; p=0.20) and 0.3% vs 0.3% (n=2 vs n=4, p=not applicable), respectively. CONCLUSIONS/INTERPRETATIONS: Insulin pump treatment was not associated with a lower risk of congenital malformations, despite better glycaemic control in early pregnancy compared with MDI. Further studies exploring the efficacy and safety of pump treatment during pregnancy are needed.

From expected to actual barriers and facilitators when implementing a new screening tool: A qualitative study applying the Theoretical Domains Framework.

AIM AND OBJECTIVES: To identify determinants for using a new screening tool to identify older patients eligible for targeted nurse-led intervention, as perceived by healthcare professionals implementing the tool, and to examine how these perceptions changed over time. DESIGN: A cross-sectoral longitudinal qualitative study based on semi-structured interviews with healthcare professionals in a Danish hospital and two collaborating municipalities. METHODS: In three focus groups, seven single interviews and a workshop, we examined the healthcare professionals' perceptions of and attitudes towards the new screening tool before, during and after the implementation. The Theoretical Domains Framework was used to identify the healthcare professionals' perception of barriers and facilitators, followed by content analysis. The results were further discussed using the COM-B system as an analytic framework. This qualitative study is reported according to the Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist. RESULTS: 'Professional role', 'Goals' and 'Environmental context' were the domains most talked about by the healthcare professionals across the three time points. The content analysis identified four determinants for using the new screening tool:Making time for the project, External motivation and management, Expectations and reality, and Professional identity. The healthcare professionals' perception of the determinants changed during the implementation, influencing their behaviour and, consequently, the implementation's sustainability. CONCLUSION: Perception of barriers and facilitators to the interventions were time- and context-sensitive. Beliefs and motivational factors changed during the project, which points out the importance of following implementation processes systematically to understand the outcome of an intervention. RELEVANCE FOR CLINICAL PRACTICE: Perceptions and attitudes towards a new initiative may change over time, emphasising the importance of following barriers and facilitators during the implementation of an intervention and working with an implementation plan that can be adapted along the way.

Duloxetine Exposure During Pregnancy and the Risk of Offspring Being Born Small for Gestational Age or Prematurely: A Nationwide Danish and Swedish Safety Study.

BACKGROUND: Depression or depressive symptoms are common among pregnant women. The use of antidepressants during pregnancy has grown steadily. The risk of offspring being born small for gestational age or prematurely when exposed to duloxetine during pregnancy is not established. OBJECTIVE: We aimed to investigate the association between duloxetine exposure during pregnancy and offspring being born small for gestational age or prematurely. METHODS: We conducted an observational study including live births in Sweden and Denmark (2004-2016). Duloxetine exposure during early (0-140 days) or late (141 to delivery) pregnancy compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, venlafaxine-exposed, and duloxetine discontinuers. RESULTS: In total, 2,083,467 pregnancies were identified, where 1589 and 450 were duloxetine exposed in early and late pregnancy, respectively. For small for gestational age, no increased risk was seen for duloxetine across comparators. In the early and late exposure windows, propensity score-matched odds ratios for small for gestational age ranged between 0.64 (95% confidence interval 0.44-0.95) and 1.48 (95% confidence interval 0.85-2.57). For preterm birth, the findings differed across comparators and exposure-time windows, but trended towards an increased risk for duloxetine-exposed when compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, and duloxetine discontinuers in both early exposure and late exposure. The odds ratios ranged between 1.17 and 2.04, of which some did not reach statistical significance. No clear association was observed when compared with venlafaxine exposed, 0.91 (95% confidence interval 0.73-1.14) for early exposure and 1.26 (95% confidence interval 0.86-1.86) for late exposure. Most preterm births (79.2%) occurred in weeks 33-36 of gestation. CONCLUSIONS: Duloxetine exposure during pregnancy is unlikely to increase the risk of small for gestational age. Although not consequently statistically significant across comparisons, a trend towards an increased risk of preterm birth was observed for duloxetine exposed. Therefore, an increased risk of preterm birth cannot be excluded, especially for women exposed to duloxetine throughout pregnancy.