Increase In Mortality Rate Research Articles

A worldwide perspective of sepsis epidemiology and survival according to age: Observational data from the ICON audit

PurposeTo investigate age-related differences in outcomes of critically ill patients with sepsis around the world. MethodsWe performed a secondary analysis of data from the prospective ICON audit, in which all adult (>16 years) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups – ≤50, 51–60, 61–70, 71–80, >80 years. Sepsis was defined as infection plus at least one organ failure. ResultsA total of 2963 patients had sepsis, with similar proportions across the age groups (≤50 = 25.2%; 51–60 = 30.3%; 61–70 = 32.8%; 71–80 = 30.7%; >80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients ≤50 years (49.3% vs 25.2%, p < .05). The maximum rate of increase in mortality was about 0.75% per year, occurring between the ages of 71 and 77 years. In multilevel analysis, age > 70 years was independently associated with increased risk of dying. ConclusionsThe odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years.

Concentration and value of endocan on outcome in adult patients after severe sepsis

BackgroundEndothelial dysfunction plays a central role in severe sepsis. Endocan is constitutively expressed in human endothelial cells when sepsis occurs. We tested the hypothesis that endocan concentrations are substantially increased in severe sepsis and decrease after antimicrobial therapy, and that endocan concentrations can predict treatment outcomes. MethodsBiomarkers of the endothelium including endocan and cell adhesion molecules were prospectively evaluated in 153 patients with severe sepsis on days 1, 4, and 7 after admission along with biochemical and clinical data. ResultsSepsis non-survivors had significantly higher endocan, ICAM-1, and VCAM-1 concentrations and lower platelet concentrations upon admission than the survivors. Non-survivors had significantly higher endocan and VCAM-1 concentrations than the survivors on serial analysis (days 1, 4, and 7). After stepwise logistic regression model and AUC analysis, endocan was revealed as a good predictor of outcome in severe sepsis, and the cut-off value for predicting fatality was 6.28 ng/ml. An increase in the endocan concentration by one ng/ml indicated an increase in fatality rate by 11.1%. ConclusionsBased on our results, serial endocan concentration meets the major requirements for predicting outcome in patients with severe sepsis. An assay of endocan concentration may be a good prognostic biomarker in the clinic for severe sepsis.

Study of Electrolyte Serum Disturbances and Acid-base Status in Patients with Oral-maxillofacial and Dental Sepsis

Septicaemia is an important public health issue and a clinical challenge with a major impact on healthcare expenditure and resources. The present retrospective study was conducted over 127 patients registered during 2006-2015 for the area of Moldavia, Romania. In our study we are concerned about the serum electrolyte disturbances and acid-base status in patients with oral-maxillofacial and dental septicaemia. We measured serum levels of sodium, potassium, chloride, alkali reserve and pH. The prevalence of electrolyte disturbances was: 15.85% for sodium, 69.15% for potassium and 55.50% for chloride. Early recognition of acid-base status and serum electrolytes disturbances proves to be of great importance for clinical management since it signalizes the gravity of the disease and the increase of fatality rate, and is imperative to save the lives of patients with dental and oral-maxillofacial septicaemia.

Relationship of traffic fatality rates to maximum state speed limits

ABSTRACTObjectives: The objective of this study was to examine the safety effects of increases in U.S. state maximum speed limits during the period 1993–2013.Methods: Poisson regression was used to model state-by-state annual traffic fatality rates per mile of travel as a function of time, the unemployment rate, the percentage of the driving age population that was younger than 25, per capita alcohol consumption, and the maximum posted speed limit on any road in the state. Separate analyses were conducted for all roads, interstates and freeways, and all other roads.Results: A 5 mph increase in the maximum state speed limit was associated with an 8% increase in fatality rates on interstates and freeways and a 4% increase on other roads. In total, there were an estimated 33,000 more traffic fatalities during the years 1995–2013 than would have been expected if maximum speed limits had not increased. In 2013 alone, there were approximately 1,900 additional deaths—500 on interstates/freeways and 1,400 on other roads.Conclusions: There is a definite trend of increased fatality risk when speed limits are raised. As roadway sections with higher speed limits have become more ubiquitous, the increase in fatality risk has extended beyond these roadways. The increase in risk has been so great that it has now largely offset the beneficial effects of some other traffic safety strategies. State policy makers should keep this trade-off in mind when considering proposals to raise speed limits.

A high-fat diet temporarily renders Sod1-deficient mice resistant to an oxidative insult

Patients with nonalcoholic fatty liver disease may subsequently develop nonalcoholic steatohepatitis after suffering from a second insult, such as oxidative stress. Aim of this study was to investigate the pathogenesis of the liver injury caused when lipids accumulate under conditions of intrinsic oxidative stress using mice that are deficient in superoxide dismutase 1 (SOD1) and the leptin receptor (Lepr). We established Sod1−/−::Leprdb/db mice and carried out analyses of four groups of genetically modified mice, namely, wild type, Sod1−/−, Leprdb/db and Sod1−/−::Leprdb/db mice. Mice with defects in the SOD1 or Lepr gene are vulnerable to developing fatty livers, even when fed a normal diet. Feeding a high-fat diet (HFD) caused an increase in the number of lipid droplets in the liver to different extents in each genotypic mouse. an HFD caused the accelerated death of db/db mice, but contradictory to our expectations, the death rates for the Sod1-deficient mice were decreased by feeding HFD. Consistent with the improved probability of survival, liver damage was significantly ameliorated by feeding an HFD compared to a normal diet in the mice with an Sod1-deficient background. Oxidative stress markers, hyperoxidized peroxiredoxin and lipid peroxidation products, were decreased somewhat in Sod1−/− mice by feeding HFD. We conclude that lipids reacted with reactive oxygen species and eliminated them in the livers of the young mice, which resulted in the alleviation of oxidative stress, but in advanced age oxidized products accumulated, leading to the aggravation of the liver injury and an increase in fatality rate.

Evolutionary ecology of aging: time to reconcile field and laboratory research.

Aging is an increase in mortality risk with age due to a decline in vital functions. Research on aging has entered an exciting phase. Advances in biogerontology have demonstrated that proximate mechanisms of aging and interventions to modify lifespan are shared among species. In nature, aging patterns have proven more diverse than previously assumed. The paradigm that extrinsic mortality ultimately determines evolution of aging rates has been questioned and there appears to be a mismatch between intra‐ and inter‐specific patterns. The major challenges emerging in evolutionary ecology of aging are a lack of understanding of the complexity in functional senescence under natural conditions and unavailability of estimates of aging rates for matched populations exposed to natural and laboratory conditions. I argue that we need to reconcile laboratory and field‐based approaches to better understand (1) how aging rates (baseline mortality and the rate of increase in mortality with age) vary across populations within a species, (2) how genetic and environmental variation interact to modulate individual expression of aging rates, and (3) how much intraspecific variation in lifespan is attributable to an intrinsic (i.e., nonenvironmental) component. I suggest integration of laboratory and field assays using multiple matched populations of the same species, along with measures of functional declines.

Epidemiology of traumatic spinal cord injuries in Austria 2002-2012.

The aim of this study was to analyse the epidemiological patterns (mortality, incidence of non-fatal cases and overall incidence), of traumatic spinal cord injuries (TSCI) in 2002-2012 in Austria. TSCI-related deaths and hospital admissions in Austria 2002-2012 were obtained from Statistics Austria and analysed. Mortality rates, as well as non-fatal and overall incidence rates were calculated and compared across the age spectrum and by sex. Additionally, the main causes and demographic characteristics of victims were analysed. The crude overall incidence rate of TSCI was 16.96, CI 95 % 16.95-16.97 and the standardized incidence rate was 13.98, CI 95 % 13.97-13.99 per million (annual average rate). An annual increase in fatality rates was observed occurring mostly in the age group >65 years (Kendall's Tau = 0.1). Falls (mortality rate 19.58, CI 95 % 19.57-19.59) and injuries at home (incidence rate 56.57, CI 95 % 56.56-56.58) were the principal causes of fatal and non-fatal TSCI, respectively. Injuries to the neck region were the most common. All indicators were the highest for the age group >65 years: non-fatal incidence rate 23.55, CI 95 % 23.54-23.56; mortality rate 21.4, CI 95 % 21.39-21.41; and overall incidence rate 47.9, CI 95 % 47.89-47.91. A clear male dominance was observed (incidence rate ratio 1.9, CI 95 % 1.4-2.7). The population >65 years has been at the highest risk of TSCI in Austria for the analysed period and therefore preventive activities should be focused on this group. The increasing overall incidence of TSCI was driven by the increasing mortality rates that were highest in the age group >65 years. We advocate harmonization of epidemiological reporting especially regarding aetiology of TSCI in order to better inform policy makers and prevention.

Time Dependent Relative Risks in Life Insurance Medical Underwriting.

Introduction .- Life insurance medicine focuses on mortality hazards in specified periods. People are free to insure their lives for shorter or longer terms. Because the chosen terms range from 1 year to a life time, life insurers have to take into account the fact that the predictive value of risk indicators can and will change over time. The time a risk indicator keeps its predictive value, will be dependent on its biological effects, volatility, and treatability. For a given applicant this implies that the relative hazard (RH) calculated for his/her medical condition should be dependent on the term of the insurance. The main objective of this study is to determine if some commonly used risk indicators - previously used to study age dependency of relative risks - have a predictive value that increases with the observation period. (1) Methods .- This population-based cohort study uses NHANES-data files from the Third National Health and Nutrition Examination Survey (NHANES III) and the NHANES Linked Mortality Files 2010. Only participants aged 20 to 69 that were examined in mobile examination centers, without a history of some prevalent high risk diseases were included. The observed mortality was compared to the expected mortality in a Generalized Linear Model (GLM) with Poisson error structure with two reference populations, which both can serve as preferred reference for life insurers: The United States Life Tables 2008 (USLT) and the 2008 Valuation Basic Tables (VBT) based on the insured population of 35 US Life insurers. The time dependency of the RHs of the systolic blood pressure (SBP), aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), serum albumin and albuminuria, was assessed, with correction for ethnicity, household income, history of diabetes mellitus, BMI and serum cholesterol. To be able to compare the results with the results of the Age Dependency Study (ADS), the same data, risk indicators, statistical analysis method, and the Generalized Linear Model (GLM) were used. Results .- Contrary to the results in the univariate analyses, the multivariate analyses show no difference between the USLT and VBT models. In both models the RHs of SBP and albuminuria increase over time, while the RH of LDH decreases over time. Only the slopes are different, reflecting the rate of mortality increase between USLT and VBT. The RHs of ASAT and serum albumin are independent of time in both models. Discussion .- Time dependency of RHs can be assumed to exist with many risk indicators. Time dependency may take two forms: decreasing the RH and increasing the RH of a variable as time passes. Medical underwriting guidelines should therefore differentiate between short term and long term life insurances. Medical directors should realize that the presence of time dependency diminishes the value of short term clinical studies for life insurance medical underwriting. Life insurance mortality studies should always contain a discussion of the time dependency of the predictive value of the variables under study.

Effet des chocs de mortalité sur le profil par âge de la mortalité des adultes

Quel sont les effets des modifications soudaines des conditions exterieures sur le niveau et les profils par âge de la mortalite humaine ? Divers travaux ont analyse des evenements brutaux comme la famine ou la deportation, mais on ne dispose pas d’evaluation systematique de l’effet des chocs sur le taux de croissance de la mortalite au fil des âges. A la suite d’un choc, l’evolution de la mortalite peut suivre trois scenarios : elle peut augmenter proportionnellement a tous les âges, davantage aux âges eleves, ou davantage aux jeunes âges. Deux cas d’experience naturelle sont analyses : celui des prisonniers civils australiens dans un camp japonais pendant la seconde guerre mondiale et celui de la famine en Ukraine en 1933. Les taux de mortalite des prisonniers de guerre se sont accrus pendant leur detention mais la pente de la courbe est restee la meme que dans un regime de mortalite normale. En revanche, en Ukraine, les courbes de mortalite se sont elevees pendant les annees de famine, mais la hausse a ete moindre aux âges eleves, la pente des courbes etant ainsi modifiee. En outre, quand la mortalite augmente moins aux âges eleves, la preuve de l’existence d’un effet de selection comme mecanisme sous-jacent apparait faible et peu concluante. Mais d’autres mecanismes pourraient contribuer a des schemas semblables, aussi serait-il necessaire d’analyser davantage d’experiences de mortalite naturelle et de recueillir davantage de donnees sur le sujet.

An examination of black/white differences in the rate of age-related mortality increase.

BACKGROUNDThe rate of mortality increase with age among adults is typically used as a measure of the rate of functional decline associated with aging or senescence. While black and white populations differ in the level of mortality, mortality also rises less rapidly with age for blacks than for whites, leading to the well-known black/white mortality “crossover”.OBJECTIVEThis paper investigates black/white differences in the rate of mortality increase with age for major causes of death in order to examine the factors responsible for the black/white crossover.METHODSThe analysis considers two explanations for the crossover: selective survival and age misreporting. Mortality is modeled using a Gompertz model for 11 causes of death from ages 50–84 among blacks and whites by sex.RESULTSMortality increases more rapidly with age for whites than for blacks for nearly all causes of death considered. The all-cause mortality rate of mortality increase is nearly two percentage points higher for whites. The analysis finds evidence for both selective survival and age misreporting, although age misreporting is a more prominent explanation among women.CONCLUSIONSThe black/white mortality crossover reflects large differences in the rate of age-related mortality increase. Instead of reflecting the impact of specific causes of death, this pattern exists across many disparate disease conditions, indicating the need for a broad explanation.

HUMAN ACTUARIAL AGING INCREASES FASTER WHEN BACKGROUND DEATH RATES ARE LOWER: A CONSEQUENCE OF DIFFERENTIAL HETEROGENEITY?

Many analyses of human populations have found that age-specific mortality rates increase faster across most of adulthood when overall mortality levels decline. This contradicts the relationship often expected from Williams' classic hypothesis about the effects of natural selection on the evolution of senescence. More likely, much of the within-species difference in actuarial aging is not due to variation in senescence, but to the strength of filters on the heterogeneity of frailty in older survivors. A challenge to this differential frailty hypothesis was recently posed by an analysis of life tables from historical European populations and traditional societies that reported variation in actuarial aging consistent with Williams' hypothesis after all. To investigate the challenge, we reconsidered those cases and aging measures. Here we show that the discrepancy depends on Ricklefs' aging rate measure, ω, which decreases as mortality levels drop because it is an index of mortality level itself, not the rate of increase in mortality with age. We also show unappreciated correspondence among the parameters of Gompertz-Makeham and Weibull survival models. Finally, we compare the relationships among mortality parameters of the traditional societies and the historical series, providing further suggestive evidence that differential heterogeneity has strong effects on actuarial aging.

Successful treatment of rhino-orbital mucormycosis by a new combination therapy with liposomal amphotericin B and micafungin

Mucormycosis is a rapidly progressive fungal infection that usually occurs in patients with diabetes mellitus or in immunocompromised patients. Sinus involvement is the most common clinical presentation and the rates of mortality increase with the orbital extension. The treatment of mucormycosis includes aggressive surgical debridement and systemic antifungal therapy. Early diagnosis and prompt initiation of effective antifungal drugs are essential for successful outcome. However, the role of orbital exenteration for the case of orbital involvement remains controversial, and the drugs effective against mucormycosis are limited. We present a successfully treated case with rhino-orbital mucormycosis caused by Rhizopus oryzae in a diabetic and dialysis patient. The early diagnosis, surgical debridement and a new combination therapy with liposomal amphotericin B and micafungin were effective. This new combination antifungal therapy will be useful for the treatment of mucormycosis.

Insights from comparative analyses of aging in birds and mammals

Many laboratory models used in aging research are inappropriate for understanding senescence in mammals, including humans, because of fundamental differences in life history, maintenance in artificial environments, and selection for early aging and high reproductive rate. Comparative studies of senescence in birds and mammals reveal a broad range in rates of aging among a variety of taxa with similar physiology and patterns of development. These comparisons suggest that senescence is a shared property of all vertebrates with determinate growth, that the rate of senescence has been modified by evolution in response to the potential life span allowed by extrinsic mortality factors, and that most variation among species in the rate of senescence is independent of commonly ascribed causes of aging, such as oxidative damage. Individuals of potentially long-lived species, particularly birds, appear to maintain high condition to near the end of life. Because most individuals in natural populations of such species die of aging-related causes, these populations likely harbor little genetic variation for mechanisms that could extend life further, or these mechanisms are very costly. This, and the apparent evolutionary conservatism in the rate of increase in mortality with age, suggests that variation in the rate of senescence reflects fundamental changes in organism structure, likely associated with the rate of development, rather than physiological or biochemical processes influenced by a few genes. Understanding these evolved differences between long-lived and short-lived organisms would seem to be an essential foundation for designing therapeutic interventions with respect to human aging and longevity.

The Effect of the 1997 Texas Motorcycle Helmet Law on Motorcycle Crash Fatalities

This study seeks to determine the effect of the Texas motorcycle helmet law on fatalities since the repeal of the universal helmet law in 1997. Texas monthly motorcycle accident data between 1994 and 2004 were obtained from the National Highway Transportation Safety Administration's Fatality Analysis Reporting System (FARS) and supplemented with motorcycle registration data from the Texas Department of Transportation. An ARIMA model was used to estimate the impact of the law. A sharp increase in fatality rates occurred immediately following the implementation of the law in September 1997. Deaths increased by 30%, fatality rates per motorcycle registrations increased by 15.2%, and fatality rates per vehicle miles traveled increased by 25% after repeal. Helmet use decreased from 77% in 1996 to 63% in 1997 and 36% in 1998 and thereafter. The parameter estimates of the ARIMA model (0,0,0) (0,1,1) show that the change in the law led to statistically significant increases of 2.3 fatalities and 1.18 fatality rate per 100 billion vehicle miles traveled. The repeal of the universal helmet law in Texas in 1997 has had a significant adverse effect on motorcyclist fatalities in Texas.

Mortality shifts in Caenorhabditis elegans: remembrance of conditions past

The analysis of age-specific mortality can yield insights into how anti-aging interventions operate that cannot be matched by simple assessment of longevity. Mortality, as opposed to longevity, can be used to assess the effects of an anti-aging intervention on a daily basis, rather than only after most animals have died. Various gerontogene mutations in Caenorhabditis elegans have been shown to increase longevity as much as tenfold and to decrease mortality at some ages even more. Environmental alterations, such as reduced food intake (dietary restriction) and lower temperature also result in reduced mortality soon after the intervention. Here, we ask how soon anti-aging interventions, applied during adult life, affect age-specific mortality in nematodes. Using maximum likelihood analysis, we estimated the Gompertz parameters after shifts of temperature, and of food concentration and maintenance conditions. In separate experiments, we altered expression of age-1 and daf-16, using RNAi. Using about 44 000 nematodes in total, to examine daily mortality, we find that for both types of environmental shift, mortality responded immediately in the first assessment, while RNAi-induced changes resulted in a slower response, perhaps due to delayed mechanics of RNAi action. However, under all conditions there is a permanent 'memory' of past states, such that the initial mortality component [a] of the Gompertz equation [mu(x) = ae(bx)] bears a permanent 'imprint' of that earlier state. However, 'b' (the rate of mortality increase with age) is always specified by the current conditions.

Multiple mild heat-shocks decrease the Gompertz component of mortality in Caenorhabditis elegans

Exposure to mild heat-stress (heat-shock) can significantly increase the life expectancy of the nematode Caenorhabditis elegans. A single heat-shock early in life extends longevity by 20% or more and affects life-long mortality by decreasing initial mortality only; the rate of increase in subsequent mortality (Gompertz component) is unchanged. Repeated mild heat-shocks throughout life have a larger effect on life span than does a single heat-shock early in life. Here, we ask how multiple heat-shocks affect the mortality trajectory in nematodes and find increases of life expectancy of close to 50% and of maximum longevity as well. We examined mortality using large numbers of animals and found that multiple heat-shocks not only decrease initial mortality, but also slow the Gompertz rate of increase in mortality. Thus, multiple heat-shocks have anti-aging hormetic effects and represent an effective approach for modulating aging.

Commentary: Pedestrians: Truly Vulnerable Road Users

Commentary: Pedestrians: Truly Vulnerable Road Users

The U-Shaped Response of Initial Mortality in Caenorhabditis elegans to Mild Heat Shock: Does It Explain Recent Trends in Human Mortality?

U-shaped dose-response relationships (hormesis) have been documented in numerous biological, toxicological, and pharmacological investigations. For example, in response to a mild 35 degrees C heat shock, the longevity of Caenorhabditis elegans exhibits an inverted U-shaped dose-response. By applying the demographic concept of heterogeneity, we find that this U-shaped curve for longevity response is driven by a U-shaped dose-response of initial mortality. When worms are subjected to mild heat shock, the initial mortality decreases compared to the control. This initial mortality benefit increases with moderate increases in the length of heat shock, peaking at a point that coincides with the induction of damage to the worms. The dose of heat shock that coincided with this benefit in initial mortality did not affect the rate of increase in mortality.

The Genetic Architecture of Life Span and Mortality Rates: Gender and Species Differences in Inbreeding Load of Two Seed-Feeding Beetles

We examine the inbreeding load for adult life span and mortality rates of two seed beetle species, Callosobruchus maculatus and Stator limbatus. Inbreeding load differs substantially between males and females in both study populations of C. maculatus--life span of inbred females was 9-13% shorter than the life span of outbred females, whereas the life span of inbred males did not differ from the life span of outbred males. The effect of inbreeding on female life span was largely due to an increase in the slope of the mortality curve. In contrast, inbreeding had only a small effect on the life span of S. limbatus--life spans of inbred beetles were approximately 5% shorter than those of outbred beetles, and there was no difference in inbreeding load between the sexes. The inbreeding load for mean life span was approximately 0.4-0.6 lethal equivalents per haploid gamete for female C. maculatus and approximately 0.2-0.3 for both males and females of S. limbatus, all within the range of estimates commonly obtained for Drosophila. However, contrary to the predictions of mutation-accumulation models, inbreeding load for loci affecting mortality rates did not increase with age in either species, despite an effect of inbreeding on the initial rate of increase in mortality. This was because mortality rates decelerated with age and converged to a mortality plateau for both outbred and inbred beetles.

Evolutionary genetics of lifespan and mortality rates in two populations of the seed beetle, Callosobruchus maculatus.

The age at which individuals die varies substantially within and between species, but we still have little understanding of why there is such variation in life expectancy. We examined sex-specific and genetic variation in adult lifespan and the shape of mortality curves both within and between two populations of the seed beetle, Callosobruchus maculatus, that differ in a suite of life history characters associated with adaptation to different host species. Mean adult lifespan and the shape of the logistic mortality curves differed substantially between males and females (males had lower initial mortality rates, but a faster increase in the rate of mortality with increasing age) and between populations (they differed in the rate of increase in mortality with age). Larger individuals lived longer than smaller individuals, both because they had lower initial mortality rates and a slower increase in the rate of mortality with increasing age. However, differences in body size were not adequate to explain the differences in mortality between the sexes or populations. Both lifespan and mortality rates were genetically variable within populations and genetic variance/covariance matrices for lifespan differed between the populations and sexes. This study thus demonstrated substantial genetic variation in lifespan and mortality rates within and between populations of C. maculatus.