The association between perceived stress and mortality among people with multimorbidity: a prospective population-based cohort study

Multimorbidity is common and is associated with poor mental health and high mortality. Nevertheless, no studies have evaluated whether mental health may affect the survival of people with multimorbidity. We investigated the association between perceived stress and mortality in people with multimorbidity by following a population-based cohort of 118,410 participants from the Danish National Health Survey 2010 for up to 4 years. Information on perceived stress and lifestyle was obtained from the survey. We assessed multimorbidity using nationwide register data on 39 conditions and identified 4,229 deaths for the 453,648 person-years at risk. Mortality rates rose with increasing levels of stress in a dose-response relationship (P-trend < 0.0001), independently of multimorbidity status. Mortality hazard ratios (highest stress quintile vs. lowest) were 1.51 (95% confidence interval (CI): 1.25, 1.84) among persons without multimorbidity, 1.39 (95% CI: 1.18, 1.64) among those with 2 or 3 conditions, and 1.43 (95% CI: 1.18, 1.73) among those with 4 or more conditions, when adjusted for disease severities, lifestyle, and socioeconomic status. The numbers of excess deaths associated with high stress were 69 among persons without multimorbidity, 128 among those with 2 or 3 conditions, and 255 among those with 4 or more conditions. Our findings suggested that perceived stress contributes significantly to higher mortality rates in a dose-response pattern, and more stress-associated deaths occurred in people with multimorbidity

Against the Russellian open future

Todd (2016) proposes an analysis of future-directed sentences, in particular sentences of the form 'will(φ)', that is based on the classic Russellian analysis of definite descriptions. Todd's analysis is supposed to vindicate the claim that the future is metaphysically open while retaining a simple Ockhamist semantics of future contingents and the principles of classical logic, i.e. bivalence and the law of excluded middle. Consequently, an open futurist can straightforwardly retain classical logic without appeal to supervaluations, determinacy operators, or any further controversial semantical or metaphysical complication. In this paper, we will show that this quasi-Russellian analysis of 'will' both lacks linguistic motivation and faces a variety of significant problems. In particular, we show that the standard arguments for Russell's treatment of definite descriptions fail to apply to statements of the form 'will(φ)'

Future Contingents and the Logic of Temporal Omniscience

At least since Aristotle’s famous 'sea-battle' passages in On Interpretation 9, some substantial minority of philosophers has been attracted to the doctrine of the open future--the doctrine that future contingent statements are not true. But, prima facie, such views seem inconsistent with the following intuition: if something has happened, then (looking back) it was the case that it would happen. How can it be that, looking forwards, it isn’t true that there will be a sea battle, while also being true that, looking backwards, it was the case that there would be a sea battle? This tension forms, in large part, what might be called the problem of future contingents. A dominant trend in temporal logic and semantic theorizing about future contingents seeks to validate both intuitions. Theorists in this tradition--including some interpretations of Aristotle, but paradigmatically, Thomason (1970), as well as more recent developments in Belnap, et. al (2001) and MacFarlane (2003, 2014)--have argued that the apparent tension between the intuitions is in fact merely apparent. In short, such theorists seek to maintain both of the following two theses: (i) the open future: Future contingents are not true, and (ii) retro-closure: From the fact that something is true, it follows that it was the case that it would be true. It is well-known that reflection on the problem of future contingents has in many ways been inspired by importantly parallel issues regarding divine foreknowledge and indeterminism. In this paper, we take up this perspective, and ask what accepting both the open future and retro-closure predicts about omniscience. When we theorize about a perfect knower, we are theorizing about what an ideal agent ought to believe. Our contention is that there isn’t an acceptable view of ideally rational belief given the assumptions of the open future and retro-closure, and thus this casts doubt on the conjunction of those assumptions

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Multimorbidity is often defined as two or more long-term conditions, the definition may, however, vary. This review summarises various definitions of multimorbidity. The prevalence of multimorbidity in Denmark is between 7% and 29% depending on data sources and definition and is increasing with age; nonetheless most patients with multimorbidity are of working age. Several multimorbidity indices have been developed for research purposes, but with no clinical consensus. The concept of complex multimorbidity adds psychosocial context and health-care patterns to better describe the group of patients with multimorbidity having the highest needs.</p

The impact of socioeconomic status and multimorbidity on mortality: a population-based cohort study

Objective: Multimorbidity (MM) is more prevalent among people of lower socioeconomic status (SES), and both MM and SES are associated with higher mortality rates. However, little is known about the relationship between SES, MM, and mortality. This study investigates the association between educational level and mortality, and to what extent MM modifies this association. Methods: We followed 239,547 individuals invited to participate in the Danish National Health Survey 2010 (mean follow-up time: 3.8 years). MM was assessed by using information on drug prescriptions and diagnoses for 39 long-term conditions. Data on educational level were provided by Statistics Denmark. Date of death was obtained from the Civil Registration System. Information on lifestyle factors and quality of life was collected from the survey. The main outcomes were overall and premature mortality (death before the age of 75). Results: Of a total of 12,480 deaths, 6,607 (9.5%) were of people with low educational level (LEL) and 1,272 (2.3%) were of people with high educational level (HEL). The mortality rate was higher among people with LEL compared with HEL in groups of people with 0–1 disease (hazard ratio: 2.26, 95% confidence interval: 2.00–2.55) and ≥4 diseases (hazard ratio: 1.14, 95% confidence interval: 1.04–1.24), respectively (adjusted model). The absolute number of deaths was six times higher among people with LEL than those with HEL in those with ≥4 diseases. The 1-year cumulative mortality proportions for overall death in those with ≥4 diseases was 5.59% for people with HEL versus 7.27% for people with LEL, and 1-year cumulative mortality proportions for premature death was 2.93% for people with HEL versus 4.04% for people with LEL. Adjusting for potential mediating factors such as lifestyle and quality of life eliminated the statistical association between educational level and mortality in people with MM. Conclusion: Our study suggests that LEL is associated with higher overall and premature mortality and that the association is affected by MM, lifestyle factors, and quality of life

Variant near ADAMTS9 Known to Associate with Type 2 Diabetes Is Related to Insulin Resistance in Offspring of Type 2 Diabetes Patients—EUGENE2 Study

A meta-analysis combining results from three genome-wide association studies and followed by large-scale replication identified six novel type 2 diabetes loci. Subsequent studies of the effect of these variants on estimates of the beta-cell function and insulin sensitivity have been inconclusive. We examined these variants located in or near the JAZF1 (rs864745), THADA (rs7578597), TSPAN8 (rs7961581), ADAMTS9 (rs4607103), NOTCH2 (rs10923931) and the CDC123/CAMK1D (rs12779790) genes for associations with measures of pancreatic beta-cell function and insulin sensitivity.Oral and intravenous glucose stimulated insulin release (n = 849) and insulin sensitivity (n = 596) estimated from a hyperinsulinemic euglycemic clamp were measured in non-diabetic offspring of type 2 diabetic patients from five European populations. Assuming an additive genetic model the diabetes-associated major C-allele of rs4607103 near ADAMTS9 associated with reduced insulin-stimulated glucose uptake (p = 0.002) during a hyperinsulinemic euglycemic clamp. However, following intravenous and oral administration of glucose serum insulin release was increased in individuals with the C-allele (p = 0.003 and p = 0.01, respectively). A meta-analyse combining clamp and IVGTT data from a total of 905 non-diabetic individuals showed that the C-risk allele associated with decreased insulin sensitivity (p = 0.003) and increased insulin release (p = 0.002). The major T-allele of the intronic JAZF1 rs864745 conferring increased diabetes risk was associated with increased 2(nd) phase serum insulin release during an IVGTT (p = 0.03), and an increased fasting serum insulin level (p = 0.001). The remaining variants did not show any associations with insulin response, insulin sensitivity or any other measured quantitative traits.The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues

Multi-morbid patients with co-existing mental and physical illness

This review investigates the mortality gap that exists between people with or people without mental illness. Poor physical health is the leading cause of excess mortality among people with mental illness. Mental disorders increase the risk of developing a broad range of physical diseases and the risk of death caused by somatic diseases is increased. Also, mental disorder is associated with less optimal treatment in the somatic healthcare system, which is also evident within a broad spectrum of somatic diseases. The role of structural factors such as the design of the healthcare system and stigma are developing.</p

Effects of crystallographic anisotropy on fracture development and acoustic emission in quartz

Transgranular microcracking is fundamental for the initiation and propagation of all fractures in rocks. The geometry of these microcracks is primarily controlled by the interaction of the imposed stress field with the mineral elastic properties. However, the effects of anisotropic elastic properties of minerals on brittle fracture are not well understood. This study examines the effects of elastic anisotropy of quartz on the geometry of brittle fracture and related acoustic emissions (AE) developed during indentation experiments on single crystals at ambient pressure and temperature. A Hertzian cone crack developed during blunt indentation of a single crystal of flawless Brazilian quartz parallel to the c axis shows geometric deviation away from predictions based on the isotropic case, consistent with trigonal symmetry. The visible cone crack penetration depth varies from 3 to 5 mm and apical angle from 53 to 40. Electron backscatter diffraction (EBSD) mapping of the crack tip shows that fracturing initiates along a ~40 μm wide process zone, comprising damage along overlapping en echelon high-index crystallographic planes, shown by discrete bands of reduced electron backscatter pattern (EBSP) quality (band contrast).Coalescence of these surfaces results in a stepped fracture morphology. Monitoring of AE during indentation reveals that the elastic anisotropy of quartz has a significant effect on AE location and focal mechanisms. Ninety-four AE events were recorded during indentation and show an increasing frequency with increasing load. They correspond to the development of subsidiary concentric cracks peripheral to the main cone crack. The strong and complex anisotropy in seismic velocity (~28% Vp, ~43% Vs with trigonal symmetry) resulted in inaccurate and high uncertainty in AE locations using Geiger location routine with an isotropic velocity model. This problem was overcome by using a relative (master event) location algorithm that only requires a priori knowledge of the velocity structure within the source volume. The AE location results correlate reasonably well to the extent of the observed cone crack. Decomposition of AE source mechanisms of the Geiger relocated events shows dominantly end-member behavior between tensile and compressive vector dipole events, with some double-couple-dominated events and no purely tensile or compressive events. The same events located by the master event algorithm yield greater percentage of vector dipole components and no double-couple events, indicating that AE source mechanism solutions can depend on AE location accuracy, and therefore, relocation routine that is utilized. Calculations show that the crystallographic anisotropy of quartz causes apparent deviation of the moment tensors away from double-couple and pure tensile/compressive sources consistent with the observations. Preliminary modeling of calcite anisotropy shows a response distinct from quartz, indicating that the effects of anisotropy on interpreting AE are complex and require detailed further study

Analysis of mortality metrics associated with a comprehensive range of disorders in Denmark, 2000 to 2018: A population-based cohort study

Background: The provision of different types of mortality metrics (e.g., mortality rate ratios [MRRs] and life expectancy) allows the research community to access a more informative set of health metrics. The aim of this study was to provide a panel of mortality metrics associated with a comprehensive range of disorders and to design a web page to visualize all results. Methods and findings: In a population-based cohort of all 7,378,598 persons living in Denmark at some point between 2000 and 2018, we identified individuals diagnosed at hospitals with 1,803 specific categories of disorders through the International Classification of Diseases-10th Revision (ICD-10) in the National Patient Register. Information on date and cause of death was obtained from the Registry of Causes of Death. For each of the disorders, a panel of epidemiological and mortality metrics was estimated, including incidence rates, age-of-onset distributions, MRRs, and differences in life expectancy (estimated as life years lost [LYLs]). Additionally, we examined models that adjusted for measures of air pollution to explore potential associations with MRRs. We focus on 39 general medical conditions to simplify the presentation of results, which cover 10 broad categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, mental, and neurologic conditions and cancer. A total of 3,676,694 males and 3,701,904 females were followed up for 101.7 million person-years. During the 19-year follow-up period, 1,034,273 persons (14.0%) died. For 37 of the 39 selected medical conditions, mortality rates were larger and life expectancy shorter compared to the Danish general population. For these 37 disorders, MRRs ranged from 1.09 (95% confidence interval [CI]: 1.09 to 1.10) for vision problems to 7.85 (7.77 to 7.93) for chronic liver disease, while LYLs ranged from 0.31 (0.14 to 0.47) years (approximately 16 weeks) for allergy to 17.05 (16.95 to 17.15) years for chronic liver disease. Adjustment for air pollution had very little impact on the estimates; however, a limitation of the study is the possibility that the association between the different disorders and mortality could be explained by other underlying factors associated with both the disorder and mortality. Conclusions: In this study, we show estimates of incidence, age of onset, age of death, and mortality metrics (both MRRs and LYLs) for a comprehensive range of disorders. The interactive data visualization site (https://nbepi.com/atlas) allows more fine-grained analysis of the link between a range of disorders and key mortality estimates.publishedVersio