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Objective To develop a prognostic model of 1-year mortality for individuals aged 65+ presenting at the emergency department (ED) with a fall based on health care spending patterns to guide clinical decision-making. Design Population-based cohort study (n = 35,997) included with a fall in 2013 and followed 1 year. Methods Health care spending indicators (dynamical indicators of resilience, DIORs) 2 years before admission were evaluated as potential predictors, along with age, sex and other clinical and sociodemographic covariates. Multivariable logistic regression models were developed and internally validated (10-fold cross-validation). Performance was assessed via discrimination (area under the receiver operating characteristic curve, AUC), Brier scores, calibration and decision curve analysis. Results The AUC of age and sex for mortality was 72.5% [95% confidence interval 71.8 to 73.2]. The best model included age, sex, number of medications and health care spending DIORs. It exhibited high discrimination (AUC: 81.1 [80.5 to 81.6]), good calibration and potential clinical benefit for various threshold probabilities. Overall, health care spending patterns improved predictive accuracy the most while also exhibiting superior performance and clinical benefit. Conclusions Patterns of health care spending have the potential to significantly improve assessments on who is at high risk of dying following admission to the ED with a fall. The proposed methodology can assist in predicting the prognosis of fallers, emphasising the added predictive value of longitudinal health-related information next to clinical and sociodemographic predictors.

Background The ability to accurately predict survival in older adults is crucial as it guides clinical decision making. The added value of using health care usage for predicting mortality remains unexplored. The aim of this study was to investigate if temporal patterns of healthcare expenditures, can improve the predictive performance for mortality, in spousal bereaved older adults, next to other widely used sociodemographic variables. Methods This is a population-based cohort study of 48,944 Danish citizens 65 years of age and older suffering bereavement within 2013–2016. Individuals were followed from date of spousal loss until death from all causes or 31st of December 2016, whichever came first. Healthcare expenditures were available on weekly basis for each person during the follow-up and used as predictors for mortality risk in Extreme Gradient Boosting models. The extent to which medical spending trajectories improved mortality predictions compared to models with sociodemographics, was assessed with respect to discrimination (AUC), overall prediction error (Brier score), calibration, and clinical benefit (decision curve analysis). Results The AUC of age and sex for mortality the year after spousal loss was 70.8% [95% CI 68.8, 72.8]. The addition of sociodemographic variables led to an increase of AUC ranging from 0.9% to 3.1% but did not significantly reduce the overall prediction error. The AUC of the model combining the variables above plus medical spending usage was 80.8% [79.3, 82.4] also exhibiting smaller Brier score and better calibration. Overall, patterns of healthcare expenditures improved mortality predictions the most, also exhibiting the highest clinical benefit among the rest of the models. Conclusion Temporal patterns of medical spending have the potential to significantly improve our assessment on who is at high risk of dying after suffering spousal loss. The proposed methodology can assist in a more e

PURPOSE: The Danish Pathology Life Course (PATHOLIFE) cohort was established to facilitate epidemiological research relating histological and cytological features extracted from patient tissue specimens to the rich life course histories, including both prior and future register data, of the entire Danish population. Research results may increase quality of diagnosis, prognosis and stratification of patient subtypes, possibly identifying novel routes of treatment.PARTICIPANTS: All Danish residents from 1 January 1986 to 31 December 2019, totalling 8 593 421 individuals.FINDINGS TO DATE: We provide an overview of the subpopulation of Danish residents who have had a tissue specimen investigated within the Danish healthcare system, including both the primary sector and hospitals. We demonstrate heterogeneity in sociodemographic and prognostic factors between the general Danish population and the above mentioned subpopulation, and also between the general Danish population and subpopulations of patients with tissue specimens from selected anatomical sites. Results demonstrate the potential of the PATHOLIFE cohort for integrating many different factors into identification and selection of the most valuable tissue blocks for studies of specific diseases and their progression. Broadly, we find that living with a partner, having higher education and income associates with having a biopsy overall. However, this association varies across different tissue and patient types, which also display differences in time-to-death and causes of death.FUTURE PLANS: The PATHOLIFE cohort may be used to study specified patient groups and link health related events from several national health registries, and to sample patient groups, for which stored tissue specimens are available for further research investigations. The PATHOLIFE cohort thereby provides a unique opportunity to prospectively follow people that were characterised and sampled in the past.

Alcohol consumption increases circulating high-density lipoprotein cholesterol (HDL-C), but HDL protein cargo may better reflect HDL function. This study examined the associations between alcohol intake and HDL subspecies containing or lacking apoC3, apoE, and apoJ in a well-phenotyped cohort. We performed a cross-sectional analysis of 2092 Cardiovascular Health Study participants aged 70 or older with HDL subspecies measured in stored specimens from 1998 to 1999. Associations between alcohol intake and apoA1 defined HDL subspecies lacking or containing apoC3, apoE, and apoJ, and circulating levels of total apoA1, apoC3, apoE, and apoJ were examined. HDL subspecies lacking and containing apoC3, apoE, and apoJ were all positively associated with alcohol intake, with ∼1% per additional drink per week or ∼7% per additional drink per day (subspecies without the apolipoproteins, P ≤ 2 × 10−9, subspecies with the apolipoproteins, P ≤ 3 × 10−5). Total apoA1 was also directly associated with alcohol consumption, with a 1% increase per additional drink per week (P = 1 × 10−14). Total apoC3 blood levels were 0.5% higher per additional drink per week (P = 0.01), but the association was driven by a few heavily drinking men. Alcohol intake was positively associated with HDL subspecies lacking and containing apoC3, apoE, or apoJ, and with total plasma apoA1. ApoC3 was directly, albeit not as robustly associated with alcohol intake. HDL protein cargo is crucial for its anti-atherosclerotic functions, but it remains to be determined whether HDL subspecies play a role in the putative association between limited alcohol intake and lower risk of coronary heart disease.

PURPOSE: The MUNICH Preterm and Term Clinical (MUNICH-PreTCl) birth cohort was established to uncover pathological processes contributing to infant/childhood morbidity and mortality. We collected comprehensive medical information of healthy and sick newborns and their families, together with infant blood samples for proteomic analysis. MUNICH-PreTCl aims to identify mechanism-based biomarkers in infant health and disease to deliver more precise diagnostic and predictive information for disease prevention. We particularly focused on risk factors for pregnancy complications, family history of genetically influenced health conditions such as diabetes and paediatric long-term health-all to be further monitored and correlated with proteomics data in the future.PARTICIPANTS: Newborns and their parents were recruited from the Perinatal Center at the LMU University Hospital, Munich, between February 2017 and June 2019. Infants without congenital anomalies, delivered at 23-41 weeks of gestation, were eligible.FINDINGS: Findings to date concern the clinical data and extensive personal patient information. A total of 662 infants were recruited, 44% were female (36% in preterm, 46% in term). 90% of approached families agreed to participate. Neonates were grouped according to gestational age: extremely preterm (<28 weeks, N=28), very preterm (28 to <32 weeks, N=36), late preterm (32 to <37 weeks, N=97) and term infants (>37+0 weeks, N=501). We collected over 450 data points per child-parent set, (family history, demographics, pregnancy, birth and daily follow-ups throughout hospitalisation) and 841 blood samples longitudinally. The completion rates for medical examinations and blood samples were 100% and 95% for the questionnaire.FUTURE PLANS: The correlation of large clinical datasets with proteomic phenotypes, together with the use of medical registries, will enable future investigations aiming to decipher mechanisms of disorders in a system

The incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing. This study evaluates the referral pattern of patients with NAFLD. A cohort study evaluating all patients with NAFLD referred to a single Gastroenterology Department from January 2017 to June 2020. Electronic patient referral letters were reviewed, and patients with NAFLD were diagnosed using standardized tests as part of a prospective cohort study. Predictors of nonalcoholic steatohepatitis (NASH) with significant (>= F2) fibrosis were evaluated in logistic regression analyses. In total, 323 (18.6%) of 1735 patients referred to the Gastro Unit during the study period were diagnosed with NAFLD. Patients were referred from general practitioners (62.5%) or other hospital departments (37.5%). Most referral letters included information suggesting a possible diagnosis of NAFLD (patient history, blood tests, or diagnostic imaging) or used the nonspecific general diagnosis suspected disease (Z.038). Out of 110 patients referred for a liver biopsy, 71 (22%) had NASH with significant fibrosis (F2 n = 39, F3 n = 19, F4 n = 13). Thirty-nine of these patients were referred from the primary sector. A logistic regression analysis (adjusted for age and gender) including all 323 patients showed that type 2 diabetes was the only significant independent predictor of NASH with fibrosis.

High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.

Background-Network-based approaches may leverage genome-wide association (GWA) analysis by testing for the aggregate association across several pathway members. We aimed to examine if networks of genes that represent experimentally determined protein-protein interactions (PPIs) are enriched in genes associated with risk of coronary heart disease (CHD). Methods and Results-Genome-wide association analyses of approximately approximate to 700 000 single-nucleotide polymorphisms in 899 incident CHD cases and 1823 age-and sex-matched controls within the Nurses' Health and the Health Professionals Follow-up Studies were used to assign genewise P values. A large database of PPIs was used to assemble 8351 unbiased protein complexes and corresponding gene sets. Superimposed genewise P values were used to rank gene sets based on their enrichment in genes associated with CHD. After correcting for the number of complexes tested, 1 gene set was overrepresented in CHD-associated genes (P = 0.002). Centered on the beta 1-adrenergic receptor gene (ADRB1), this complex included 18 protein interaction partners that have not been identified as candidate loci for CHD. Of the 19 genes in the top complex, 5 are involved in abnormal cardiovascular system physiological features based on knockout mice (4-fold enrichment; Fisher exact test, P = 0.006). Ingenuity pathway analysis revealed that canonical pathways, especially related to blood pressure regulation, were significantly enriched in the genes from the top complex. Conclusions-The integration of a GWA study with PPI data successfully identifies a set of candidate susceptibility genes for incident CHD that would have been missed in single-marker GWA analysis. (Circ Cardiovasc Genet. 2011; 4:549-556.)

The European Clinical Trials Directive (CTD) came into force on May 1st 2004. The CTD provides the legal basis for monitoring the safety of clinical trials and covers the requirements for notification of SUSAR. Implementation of the CTD into national legislation in each Member State has resulted in various interpretations of CTD requirements. The objective of this paper is to investigate how the European Member States administer the safety reporting requirements of the CTD and to clarify the requirements for SUSAR notification in the different Member States. Data was collected through publicly available sources and questionnaires sent to the Competent Authorities and Ethics Committees in 30 European countries. The results document that Competent Authorities and Ethics Committees in the different Member States administer the legislation very differently. This has resulted in different requirements for notification of SUSARs in the Member States, as well as different requirements between the Competent Authorities and Ethics Committees in the same Member State. These requirements have not previously been described and the present overview of the legislation and the requirements of SUSAR reporting is of immediate practical use to especially non-commercial sponsors when conducting clinical trials in Europe.

AIM OF THE STUDY: Several studies using a variety of assessment approaches have demonstrated that young doctors possess insufficient resuscitation competence. The aims of this study were to assess newly graduated doctors' resuscitation competence against an internationally recognised standard and to study whether teaching site affects their resuscitation competence. MATERIALS AND METHODS: The entire cohort of medical students from Copenhagen University expected to graduate in June 2006 was invited to participate in the study. Participants' ALS-competence was assessed using the Advanced Life Support Provider (ALS) examination standards as issued by the European Resuscitation Council (ERC). The emergency medicine course is conducted at three different university hospital teaching sites and teaching and assessment might vary across sites, despite the common end objectives regarding resuscitation teaching issued by the university. RESULTS: Participation was accepted by 154/240 (64%) graduates. Only 23% of the participants met the ALS pass criteria. They primarily lacked skills in managing cardiopulmonary arrest. There were significant differences in ALS-competence between teaching sites. CONCLUSION: Newly graduated doctors do not have sufficient competence in managing cardiopulmonary arrests according to the current guidelines published by ERC. There were significant differences in ALS-competence between sites. Change in teaching and assessment practice in undergraduate emergency medicine courses is needed in order to increase the level of ALS-competence of newly graduated doctors Udgivelsesdato: 2008/4

Alcohol; HDL-C; Generalized Additive Models; Nonlinear