88 research outputs found
Proenkephalin and the risk of new-onset heart failure:data from prevention of renal and vascular end-stage disease
BACKGROUND: Enkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and newâonset HF in the general population remains to be established. HYPOTHESIS: We hypothesized that plasma PENK concentrations are associated with newâonset HF in the general population. METHODS: We included 6677 participants from the prevention of renal and vascular endâstage disease study and investigated determinants of PENK concentrations and their association with newâonset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]). RESULTS: Median PENK concentrations were 52.7 (45.1â61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NTâproBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all pâ<â.001). After a median 8.3 (7.8â8.8) years followâup, 221 participants developed HF; 127 HFrEF and 94 HFpEF. PENK concentrations were higher in subjects who developed HF compared with those who did not, 56.2 (45.2â67.6) versus 52.7 (45.1â61.6) pmol/L, respectively (p = .003). In competingârisk analyses, higher PENK concentrations were associated with higher risk of newâonset HF (hazard ratio [HR] = 2.09[1.47â2.97], pâ<â.001), including both HFrEF (HR = 2.31[1.48â3.61], pâ<â.001) and HFpEF (HR = 1.74[1.02â2.96], p = .042). These associations were, however, lost after adjustment for eGFR. CONCLUSIONS: In the general population, higher PENK concentrations were associated with lower eGFR and higher NTâproBNP concentrations. Higher PENK concentrations were not independently associated with newâonset HFrEF and HFpEF and mainly confounded by eGFR
Effect of a multidisciplinary stress treatment programme on the return to work rate for persons with work-related stress. A non-randomized controlled study from a stress clinic
<p>Abstract</p> <p>Background</p> <p>In recent years an increasing number of patients have been referred to the medical sector with stress symptoms. Moreover, these conditions imply increased sickness absence. This indicates a need for treatment programmes in general medical practice. The aim of this study was to test the effect of a multidisciplinary stress treatment programme on the return to work (RTW) rate in persons with work-related stress and establish predictive factors for this outcome.</p> <p>Methods</p> <p>During a two-year period 63 out of 73 referrals to the Stress Clinic (a section of a Clinic of Occupational Medicine) completed a stress treatment programme consisted of the following:</p> <p>1) Identification of relevant stressors. 2. Changing the coping strategies of the participants. 3. Evaluating/changes in participant workload and tasks. 4. Relaxation techniques. 5. Physical exercise. 6. Psychiatric evaluation when indicated by depression test score.</p> <p>On average each patient attended six one-hour sessions over the course of four months.</p> <p>A group of 34 employees referred to the Clinic of Occupational Medicine by their general practitioners served as a control group. Each participant had a one-hour consultation at baseline and after four months. A specialist in occupational medicine carried out all sessions.</p> <p>Return To Work (RTW), defined as having a job and not being on sick leave at the census, was used as outcome measure four months after baseline, and after one and two years.</p> <p>Results</p> <p>The level of sick leave in the stress treatment group dropped from 52% to 16% during the first four months of follow-up and remained stable. In the control group, the reduction in sick leave was significantly smaller, ranging from 48% at baseline to 27% after four months and 24% after one year. No statistically significant difference between the two groups was observed after one and two years. Age below 50 years and being a manager increased the odds ratio for RTW after one and two years, while gender and depression had no predictive value.</p> <p>Conclusions</p> <p>The stress treatment programme showed a significant effect on the return to work rate. The stress treatment programme seems feasible for general practitioners.</p> <p>Trial Registration</p> <p>ISRCTN04354658</p
Fibroblast Growth Factor 23 and Risk of New Onset Heart Failure With Preserved or Reduced Ejection Fraction:The PREVEND Study
Background The role of fibroblast growth factor 23 (FGF23) in the development of new-onset heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF) in the general population is unknown. Therefore, we set out to investigate associations of C-terminal FGF23 with development of new-onset HF and, more specifically, with HFrEF or HFpEF in a large, prospective, population-based cohort. Methods and Results We studied 6830 participants (aged 53.8 +/- 12.1 years; 49.7% men; estimated glomerular filtration rate, 93.1 +/- 15.7 mL/min per 1.73 m(2)) in the community-based PREVEND (Prevention of Renal and Vascular End-Stage Disease) study who were free of HF at baseline. Cross-sectional multivariable linear regression analysis showed that ferritin (standardized beta, -0.24; P= 50%). After median follow-up of 7.4 [IQR 6.9-7.9] years, 227 individuals (3.3%) developed new-onset HF, of whom 132 had HFrEF and 88 had HFpEF. A higher FGF23 level was associated with an increased risk of incident HF (fully adjusted hazard ratio, 1.29 [95% CI, 1.06-1.57]) and with an increased risk of incident HFrEF (fully adjusted hazard ratio, 1.31 [95% CI, 1.01-1.69]). The association between FGF23 and incident HFpEF lost statistical significance after multivariable adjustment (hazard ratio, 1.22 [95% CI, 0.87-1.71]). Conclusions Higher FGF23 is independently associated with new-onset HFrEF in analyses fully adjusted for cardiovascular risk factors and other potential confounders. The association between FGF23 and incident HFpEF lost statistical significance upon multivariable adjustment
Heart failure and inflammation-related biomarkers as predictors of new-onset diabetes in the general population
Background: There is a strong reciprocal relationship between heart failure (HF) and diabetes mellitus (DM). Shared pathophysiological mechanisms might be a possible explanation. Therefore, we hypothesised that biomarkers linked to HF would also predict new-onset type 2 DM in the general population. Methods and results: We utilized the Prevention of Vascular and Renal End-stage Disease (PREVEND) cohort (mean age 48.9 years, 51% female) to study the relationship between HF and DM in 7953 participants free of baseline HF and DM. Multiple HF-related, inflammation-related and renal function-related biomarkers were evaluated regarding their predictive utility in new-onset DM. Incidence of DM in participants who developed HF was 11.8%, versus 5.4% in those who had not developed HF (p <0.001). Incidence of HF in participants who developed DM was 8.5%, versus 3.8% in those who had not developed DM (p <0.001). Classical HF biomarkers, NT-proBNP and hs-TnT were not associated with an increased risk for new-onset DM. However, inflammatory biomarkers hs-CRP [hazard ratio (HR) 1.16, (95% CI 1.05 to 1.29), p = 0.005], procalcitonin [HR 1.34, (95% CI 1.07 to 1.69), p = 0.012] and PAI-1 [HR 1.55, (95% CI 1.37 to 1.75), p <0.001] remained significantly associated with new-onset DM, even after multivariable adjustment for established predictors of DM. Conclusions: Although HF and DM have a strong correlation with each other, systemic biomarkers that predict HF do not have a predictive value in new-onset DM. This suggests that other, indirect, pathophysiological mechanisms related to inflammation may explain their strong relation. (C) 2017 Elsevier B.V. All rights reserved
Heart failure and inflammation-related biomarkers as predictors of new-onset diabetes in the general population
APOE and Alzheimer disease: a major gene with semi-dominant inheritance
Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10â132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease
Effectiveness and cost-effectiveness of an exposure-based return-to-work programme for patients on sick leave due to common mental disorders: design of a cluster-randomized controlled trial
<p>Abstract</p> <p>Background</p> <p>To reduce the duration of sick leave and loss of productivity due to common mental disorders (CMDs), we developed a return-to-work programme to be provided by occupational physicians (OPs) based on the principles of exposure in vivo (RTW-E programme). This study evaluates this programme's effectiveness and cost-effectiveness by comparing it with care as usual (CAU). The three research questions we have are: 1) Is an RTW-E programme more effective in reducing the sick leave of employees with common mental disorders, compared with care as usual? 2) Is an RTW-E programme more effective in reducing sick leave for employees with anxiety disorders compared with employees with other common mental disorders? 3) From a societal perspective, is an RTW-E programme cost-effective compared with care as usual?</p> <p>Methods/design</p> <p>This study was designed as a pragmatic cluster-randomized controlled trial with a one-year follow-up and randomization on the level of OPs. We aimed for 60 OPs in order to include 200 patients. Patients in the intervention group received the RTW-E programme. Patients in the control group received care as usual. Eligible patients had been on sick leave due to common mental disorders for at least two weeks and no longer than eight weeks. As primary outcome measures, we calculated the time until full return to work and the duration of sick leave. Secondary outcome measures were time until partial return to work, prevalence rate of sick leave at 3, 6, 9, and 12 months' follow-up, and scores of symptoms of distress, anxiety, depression, somatization, and fatigue; work capacity; perceived working conditions; self-efficacy for return to work; coping behaviour; avoidance behaviour; patient satisfaction; and work adaptations. As process measures, we used indices of compliance with the intervention in the intervention group and employee-supervisor communication in both groups. Economic costs were calculated from a societal perspective. The total costs consisted of the costs of consuming health care, costs of production loss due to sick leave and reduced productivity, and out-of-pocket costs of patients for travelling to their OP.</p> <p>Discussion</p> <p>The results will be published in 2009. The strengths and weaknesses of the study protocol are discussed.</p> <p>Trial registration</p> <p>ISRCTN72643128</p
Relating the Chondrocyte Gene Network to Growth Plate Morphology: From Genes to Phenotype
During endochondral ossification, chondrocyte growth and differentiation is controlled by many local signalling pathways. Due to crosstalks and feedback mechanisms, these interwoven pathways display a network like structure. In this study, a large-scale literature based logical model of the growth plate network was developed. The network is able to capture the different states (resting, proliferating and hypertrophic) that chondrocytes go through as they progress within the growth plate. In a first corroboration step, the effect of mutations in various signalling pathways of the growth plate network was investigated
Connecting Planetary Composition with Formation
The rapid advances in observations of the different populations of
exoplanets, the characterization of their host stars and the links to the
properties of their planetary systems, the detailed studies of protoplanetary
disks, and the experimental study of the interiors and composition of the
massive planets in our solar system provide a firm basis for the next big
question in planet formation theory. How do the elemental and chemical
compositions of planets connect with their formation? The answer to this
requires that the various pieces of planet formation theory be linked together
in an end-to-end picture that is capable of addressing these large data sets.
In this review, we discuss the critical elements of such a picture and how they
affect the chemical and elemental make up of forming planets. Important issues
here include the initial state of forming and evolving disks, chemical and dust
processes within them, the migration of planets and the importance of planet
traps, the nature of angular momentum transport processes involving turbulence
and/or MHD disk winds, planet formation theory, and advanced treatments of disk
astrochemistry. All of these issues affect, and are affected by the chemistry
of disks which is driven by X-ray ionization of the host stars. We discuss how
these processes lead to a coherent end-to-end model and how this may address
the basic question.Comment: Invited review, accepted for publication in the 'Handbook of
Exoplanets', eds. H.J. Deeg and J.A. Belmonte, Springer (2018). 46 pages, 10
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Prediction of diabetic retinopathy: role of oxidative stress and relevance of apoptotic biomarkers
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