Search

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Abstract Background Identifying spontaneous circulation during cardiopulmonary resuscitation (CPR) is challenging. Current methods, which involve intermittent and time-consuming pulse checks, necessitate pauses in chest compressions. This issue is problematic in both in-hospital cardiac arrest and out-of-hospital cardiac arrest situations, where resources for identifying circulation during CPR may be limited. The fraction of chest compression plays a pivotal role in improving survival rates. To address this challenge, we evaluated a newly developed hands-free, continuous carotid Doppler system (RescueDoppler), designed to identify spontaneous circulation during chest compressions. In our study, we utilized a porcine model of cardiac arrest to investigate sequences of ventricular fibrillation, followed by defibrillation, and monitoring for the return of spontaneous circulation during chest compressions with the carotid Doppler system. We explored both manual compressions at 100 and 50 compressions per minute and mechanical compressions. To estimate the detection rate (i.e., sensitivity), we employed a logistic mixed model with animal identity as random effect. Results Offline analysis of Doppler color M-mode and spectral display successfully identified spontaneous circulation during chest compressions in all compression models. Spontaneous circulation was detected in 51 of 59 sequences, yielding an expected sensitivity of 98% with a 95% confidence interval of 59% to 99%. Conclusion The RescueDoppler, a continuous hands-free carotid Doppler system, demonstrates an expected sensitivity of 98% for identifying spontaneous circulation during both manual and mechanical chest compressions. Clinical studies are needed to further validate these findings.

Background: Little is known about long-term outcomes beyond survival following acute aortic dissection. The aim of this research was to evaluate rates of home care initiation and nursing home admission during the first year after discharge and to assess factors associated with these needs. Methods: All patients in Denmark with a first-time diagnosis of acute aortic dissection type A or B between 2006 and 2015 were identified using national registries. Patients discharged alive without nursing home or home care use before aortic dissection were included, along with age-matched and sex-matched population controls without aortic dissection (at a ratio of 1:5). Cause-specific multivariable Cox regression was used to derive adjusted hazard ratios. Results: The study population comprised 1093 patients and 5465 control individuals with a median (IQR) age of 64 (55-71) years; 70.6% were men. During their hospital stay, 2.7% of patients were registered with a first-time diagnosis of stroke, 7.1% with heart failure, and 2.2% with acute kidney failure; 5.9% of patients needed first-time dialysis. During the first year after discharge, 0.8% of patients who had had aortic dissection were admitted to a nursing home, 7.8% started home care, and 5.9% died. Among controls, these rates were 0.2%, 1.2%, and 1.2%, respectively. Patients who had had aortic dissection had significantly increased risk of initiating home care (hazard ratio, 7.47 [95% CI, 5.38-18.37]; P < .001) and of being admitted to a nursing home (hazard ratio, 4.28 [95% CI, 1.73-10.59]; P = .001). Initiation of home care and nursing home admission were related to advanced age, female sex, preexisting comorbidities, in-hospital complications, and conservative management of type A aortic dissection. Conclusion: Only a small proportion of patients who survived an aortic dissection needed home care or nursing home admission after hospital discharge.

Introduction: According to the WHO, a health-promoting health service should be linked to a holistic approach to improve public health. Based on this, it is interesting to explore if the Healthy Life Centers can be described as a health-promoting health service. This article seeks a deeper understanding of the Healthy Life Centers health promoting function by exploring the relationship between theory and practice, and to assess possible development areas and a new framework for understanding the service. Main part: Through an analysis of the Healthy Life Center’s services, we point out both potentials, obstacles and focus areas. The health authorities' description of the service and its purpose can be regarded as potentials, the power relation between purpose and practice, discipline and policy, and individual needs and autonomy as obstacles, and the adaptation of international standards for health-promoting health services (HPH-standards) as focus areas. Conclusion: The Healthy Life Center has a potential to become a health-promoting health service, although several factors should be addressed to facilitate change in that direction. The HPH-standards can contribute to a more uniform and expanded understanding of the service's mandate, purpose, values and activities, which are summarized in a "new" framework of the service.

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age2, along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the steppe population and later in Europe, probably driven by pathogenic challenges coinciding with changes in diet, lifestyle and population density. This study highlights the critical importance of the Neolithic period and Bronze Age as determinants of modern immune responses and their subsequent effect on the risk of developing MS in a changing environment.

Abstract Aims Chronic kidney disease (CKD) is a well‐established risk factor for heart failure (HF); however, patients with an estimated glomerular filtration rate (eGFR) eGFR ≥ 30 and eGFR eGFR ≥ 30 and 72.2% for patients with eGFR eGFR ≥ 30 and eGFR 30 (4 year incidence of kidney outcome as the first event was 5.0% for eGFR ≥ 60, 4.8% for 60 > eGFR ≥ 30 and 20.1% for eGFR

Abstract Background Foodborne pathogens such as Campylobacter jejuni are responsible for a large proportion of the gastrointestinal infections worldwide associated with poultry meat. Campylobacter spp. can be found in the chicken fecal microbiome and can contaminate poultry meat during the slaughter process. Commonly used sampling methods to detect Campylobacter spp. at poultry farms use fecal droppings or boot swabs in combination with conventional culture techniques or PCR. In this pilot study, we have used air filtering and filters spiked with mock communities in combination with shotgun metagenomics to detect Campylobacter and test the applicability of this approach for the detection and characterization of foodborne pathogens. To the best of our knowledge is this the first study that combines air filtering with shotgun metagenomic sequencing for detection and characterization of Campylobacter. Results Analysis of air filters spiked with different levels of Campylobacter, into a background of mock or poultry house communities, indicated that we could detect as little as 200 colony forming units (CFU) Campylobacter per sample using our protocols. The results indicate that even with limited sequencing effort we could detect Campylobacter in the samples analysed in this study. We observed significant amounts of Campylobacter in real-life samples from poultry houses using both real-time PCR as well as shotgun metagenomics, suggesting that the flocks in both houses were infected with Campylobacter spp. Interestingly, in both houses we find diverse microbial communities present in the indoor air which reflect the fecal microbiome of poultry. Some of the identified genera such as Staphylococcus, Escherichia and Pseudomonas are known to contain opportunistic pathogenic species. Conclusions These results show that air sampling of poultry houses in combination with shotgun metagenomics can detect and identify Campylobacter spp. present at low levels. This is important since early detection of Campylobacter enables measures to be put in place to ensure the safety of broiler products, animal health and public health. This approach has the potential to detect any pathogen present in poultry house air.

Abstract Background Chest pain is a frequent cause of health care contacts. We examined the prehospital management, in-hospital discharge diagnoses, and mortality of patients calling a non-emergency and emergency medical service with chest pain. Methods The Copenhagen Emergency Medical Services (EMS) consists of a non-emergency medical helpline (calls to 1813) and emergency medical service (1-1-2 calls). We included all calls to the Copenhagen EMS with a primary complaint of chest pain from 2014 to 2018 in Copenhagen, Denmark. The outcomes were: emergency response (ambulance dispatch, other transports/self-transport/home visits, self-care, and unknown/cancelled response), in-hospital diagnosis within 7 days after the call (cardiovascular, pulmonary, or other non-cardiovascular/pulmonary) and 30-day mortality. Results Among 4,834,071 calls, 91,671 were registered with chest pain at the Copenhagen EMS. The first call for each patient was kept for analysis (n = 66,762). In total, 91.4% were referred to the hospital, 75.8% (n = 50,627) received an ambulance and 15.6% (n = 10,383) received other transport/self-transport/home visits. Overall, 26.9% (n = 17,937) were diagnosed with a cardiovascular disease, 5.2% (n = 3,490) a pulmonary disease, 52.8% (n = 35.242) other non-cardiovascular/pulmonary disease, and 15.1% (n = 10,093) received no diagnosis. Among ambulance-transported patients, the prevalence of cardiovascular discharge diagnoses was higher (32.1%) and fewer received no diagnosis (11.0%). Cardiovascular disease was less prevalent among patients not transported by ambulance and patients not referred to hospital at all (2-13.4%) and in patients ≤ 40 years of age (

Abstract Prematurity has physical consequences, such as lower birth weight, decreased muscle mass and increased risk of adult‐onset metabolic disease. Insulin‐like growth factor 1 (IGF‐1) has therapeutic potential to improve the growth and quality of muscle and tendon in premature births, and thus attenuate some of these sequalae. We investigated the effect of IGF‐1 on extensor carpi radialis muscle and biceps brachii tendon of preterm piglets. The preterm group consisted of 19‐day‐old preterm (10 days early) piglets, treated with either IGF‐1 or vehicle. Term controls consisted of groups of 9‐day‐old piglets (D9) and 19‐day‐old piglets (D19). Muscle samples were analysed by immunofluorescence to determine the cross‐sectional area (CSA) of muscle fibres, fibre type composition, satellite cell content and central nuclei‐containing fibres in the muscle. Tendon samples were analysed for CSA, collagen content and maturation, and vascularization. Gene expression of the tendon was measured by RT‐qPCR. Across all endpoints, we found no significant effect of IGF‐1 treatment on preterm piglets. Preterm piglets had smaller muscle fibre CSA compared to D9 and D19 control group. Satellite cell content was similar across all groups. For tendon, we found an effect of age on tendon CSA, and mRNA levels of COL1A1, tenomodulin and scleraxis. Immunoreactivity for elastin and CD31, and several markers of tendon maturation, were increased in D9 compared to the preterm piglets. Collagen content was similar across groups. IGF‐1 treatment of preterm‐born piglets does not influence the growth and maturation of skeletal muscle and tendon.

Christian Madelaire,1,2 Thomas Gerds,3,4 Lars Køber,5 Finn Gustafsson,5 Charlotte Andersson,1,6 Søren Lund Kristensen,5 Jawad Haider Butt,1 Deewa Zahir Anjum,1 Ann Banke,2 Emil Loldrup Fosbøl,5 Gunnar Gislason,1,4 Christian Torp-Pedersen,7 Morten Schou1 1Department of Cardiology, Herlev and Gentofte Hospital, Hellerup, Denmark; 2Department of Cardiology, Odense University Hospital, Odense, Denmark; 3Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 4The Danish Heart Foundation, Copenhagen, Denmark; 5Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 6Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, Boston University, Boston, MA, USA; 7Department of Clinical Research and Cardiology, Nordsjællands Hospital, Hillerød, DenmarkCorrespondence: Christian Madelaire, Email Christian.madelaire@rsyd.dkBackground: Heart failure (HF) is associated with increased risk of death and a hospitalization, but for patients initiating guideline directed medical therapy, it is unknown how high these risks are compared to the general population – and how this may vary depending on age and comorbidity.Methods: In this retrospective cohort study, we identified patients diagnosed with HF in the period 2011– 2017, surviving the initial 120 days after diagnosis. Patients who were on angiotensin converting enzyme inhibitor (ACEi)/ angiotensin receptor blocker (ARB) and beta-blocker were included and matched to 5 non-HF individuals from the background population each based on age and sex. We assessed the 5-year risk of all-cause death, HF and non-HF hospitalization according to sex and age and baseline comorbidity.Results: We included 35,367 patients with HF and 176,835 matched non-HF individuals. Patients with HF had a five-year excess risk (absolute risk difference) of death of 13% (31% [for HF] – 18% [for non-HF]), of HF hospitalization of 17% and of non-HF hospitalization of 24%. Excess risk of death increased with increasing age, whereas the relative risk decreased - for women in their twenties, the excess risk was 7%, risk ratio 7.2, while the excess risk was 18%, risk ratio 1.5 for women in their eighties. Having HF as a 60-year old man was associated with a five-year risk of death similar to a 75-year old man without HF. Further, HF was associated with an excess risk of non-HF hospitalization, ranging from 8% for patients > 85 years to 30% for patients < 30 years.Conclusion: Regardless of age, sex and comorbidity, HF was associated with excess risk of mortality and non-HF hospitalizations, but the relative risk ratio diminishes sharply with advancing age, which may influence allocation of resources for medical care across populations.Keywords: heart failure, excess risk, mortality, hospitalization

Background & Aims: Quantifying alcohol intake is crucial for subclassifying participants with steatotic liver disease (SLD) and interpreting clinical trials of alcohol-related liver disease (ALD) and metabolic and alcohol-related liver disease (MetALD). However, the accuracy of self-reported alcohol intake is considered imprecise. We compared the diagnostic and prognostic utility of self-reported alcohol intake with blood-based biomarkers of alcohol intake: phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT). Methods: We studied 192 participants from two randomized controlled trials on MetALD and ALD, all with current or former excessive alcohol intake (≥24/36 [♀/♂] grams daily for at least 1 year) and biopsy-proven liver disease. We assessed self-reported alcohol intake, PEth, and CDT at four time points. We collected follow-up data on hepatic decompensation and death manually through electronic medical records. Results: Most participants were male (n = 161, 84%) with a mean age of 59 (SD 9) years and 73 participants reported 1-week abstinence before inclusion; the remaining reported a median alcohol intake of 43 g/day. Median PEth was 0.5 μmol/L (IQR: 0.0–1.3) and %CDT = 1.9 (IQR: 1.6–2.3). Of 32 patients reporting at least 6 months of abstinence; 27 (84%) was confirmed by PEth

In 1862, the French civil engineer Charles-Joseph Minard published his Figurative and Approximate Map Representing the Emigrants of the Globe in the Year 1858, the Countries from Which They Leave and Those Where They Arrive. The world map showcases broad lines connecting the continents, dividing the categories of people travelling by nationality or city of departure and sorts them by colour, such as blue or green. However, the last three categories, the country of China, the continent of Africa,and the region of South Asia, are depicted in yellow, light brown, and dark brown. It is one of the earliest flow-maps of migration, and it contains no borders.

Aim The latest guidelines from ACC/AHA define hypertension at systolic blood pressure (SBP) 130-139 mmHg or diastolic blood pressure (DBP) 80-89 mmHg in contrast to guidelines from ESC/ESH defining hypertension at SBP ≥ 140 mmHg or DBP ≥ 90 mmHg. The aim was to determine whether the ACC/AHA definition of hypertension identifies persons at elevated risk for future cardiovascular outcome.Methods In a Danish prospective cardiovascular study, 19,721 white men and women aged 20-98 years were examined up to five occasions between 1976 and 2015. The population was followed until December 2018. The ACC/AHA definition of the BP levels were applied: Normal: SBP

Abstract Background Severe epidermolysis bullosa (EB) is caused by premature termination codons (PTCs) in a significant minority of the patients. Topical gentamicin has been shown to increase wound healing and can restore protein translation in patients with EB through PTC suppression. However, only intensive treatment of limited wound areas have been reported previously. Objectives The objectives of this study is to investigate whether nonintensive topical gentamicin therapy is an effective wound‐healing treatment in patients with severe EB caused by PTCs. Methods A randomized, open‐controlled, single‐centre, single‐arm clinical trial designed to determine effectiveness at an individual level was performed. Each patient served as their own control and received topical 0.1% gentamicin ointment once daily for 6 weeks on all wounds on one body half. Wound areas were measured at Weeks 0 and 6. Change in wound areas at Week 6 compared with baseline was calculated and the changes in treated areas were compared with control areas. Immunohistochemistry was performed at Weeks 0 and 6. Results Four patients were included. One patient withdrew before completion. No significant effect on wound healing was seen. Immunohistochemistry analysis supported successful PTC suppression in two patients. Conclusions Our data suggest that nonintensive topical treatment with 0.1% gentamicin ointment for 6 weeks does not improve wound healing.

Abstract 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

Abstract Background Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. Methods To identify DMRs, we employed the bump hunter method in samples from young (9–16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28–33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. Results One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring’s own adiposity. Conclusions Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.

Background: Ongoing opioid treatment can potentially modify symptoms of myocardial infarction (MI) and cause a lack of recognition and treatment delay. Objectives: The purpose of this study was to examine MI symptoms and the time to hospitalization for patients in ongoing opioid treatment compared to patients without ongoing opioid treatment. Methods: We evaluated calls to the Copenhagen Emergency Medical Services in Denmark from 2014 to 2018. Calls were included when followed by hospitalization and a diagnosis of MI. Symptoms of MI and the time from call to hospitalization in patients in ongoing opioid treatment initiated prior to the onset of MI were compared to a control group of MI patients without opioid treatment. Results: In total, 6,633 calls were included; 552 calls from patients in opioid treatment and 6,081 calls from controls. Patients in opioid treatment were older and had more comorbidities than controls. Chest pain was less prevalent in MI patients in opioid treatment compared to controls (adjOR: 0.70; 95% CI: 0.57-0.85). The median time from the call to hospitalization was longer in patients in opioid treatment than in controls (50 vs 47 minutes; P = 0.006). Conclusions: In calls to the Emergency Medical Services, opioid treatment initiated prior to the onset of MI was associated with less frequent chest pain in MI. Therefore, awareness of ongoing opioid treatment may improve telephone triage of patients with MI, as symptom presentation in opioid-treated patients may differ and potentially challenge and delay the emergency response.

Abstract Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) are increasingly being prescribed in drug‐naive patients. We aimed to contrast add‐on therapy, adherence, and changes in biomarkers, 1 year after treatment initiation with GLP‐1 RA or metformin. Methods Using Danish nationwide registers, we included incident GLP‐1 RA or metformin users from 2018 to 2021 with glycated hemoglobin (HbA1c) ≥ 42 mmol/mol. GLP‐1 RA initiators were matched to metformin initiators in a ratio of 1:1 to assess outcomes in prediabetes and diabetes. Main outcomes analyzed were 1‐year risk of add‐on glucose‐lowering medication and 1‐year risk of nonadherence. One‐year risks were estimated with multiple logistic regression and standardized. Multiple linear regression was used to estimate the average differences in biomarker changes. Results In total, 1778 individuals initiating GLP‐1 RA and metformin were included. After standardizing for various factors, GLP‐1 RA compared with metformin was associated with reduced 1‐year risk of add‐on glucose‐lowering treatment in patients with prediabetes (1‐year risk ratio [RR]: 0.27, 95% confidence interval [CI]: 0.10–0.44) and diabetes (RR: 0.67, 95% CI: 0.37–0.98). GLP‐1 RA was associated with higher 1‐year risk of nonadherence among patients with prediabetes (RR: 1.60, 95% CI: 1.45–1.75), but no difference in patients with diabetes (RR: 0.88, 95% CI: 0.70–1.06). Compared to metformin, GLP‐1 RA was associated with greater HbA1c reduction (prediabetes: −2.59 mmol/mol 95% CI: −3.10 to −2.09, diabetes: −3.79 mmol/mol, 95% CI: −5.28 to −2.30). Conclusions GLP‐1 RA was associated with a reduced risk of additional glucose‐lowering medication, achieving better glycated hemoglobin control overall. However, among patients with prediabetes, metformin was associated with better adherence.