Mortality Plateaus Research Articles

Trends in sudden cardiac death mortality in Italy, 2013-2019.

We sought to analyse the incidence of sudden cardiac deaths (SCDs) amongst subjects aged less than 39years in Italy and its time trend between 2013 and 2019. Data regarding cause-specific mortality and population size by sex in 5-year age groups were extracted from the World Health Organization (WHO) mortality database. Decedents reporting the codes I46.1, I45.6, I47.2, I41.9, R09.2 and R96.0 of the International Classification of Disease-10 (ICD-10) coding system, were extracted. The age-adjusted mortality rates (AAMRs), with relative 95% confidence intervals (CIs) stratified by sex, were determined using the direct method. Joinpoint regression analyses were used to identify periods with statistically distinct log linear trends in SCD-related death rates. To calculate nationwide annual trends in SCD-related mortality, we assessed the annual and average annual per cent change (AAPC) and relative 95% CIs. Over the study period, 314 deaths [220 males (70.0%) and 94 females] were due to SCD corresponding to a 0.06 per 100,000 per year (0.10 per 100,000 in males and 0.04 per 100,000 in females, respectively). Proportional mortality slightly increased, without reaching the statistical significance (p = 0.82) from 3.06 to 3.56 per 100 deaths, with a similar trend in both sexes. Joinpoint regression analysis revealed a plateau in age-standardised SCD-related mortality over the period [AAPC: -4.2 (95% CI: -24.0 to 20.8, p = 0.71], which was consistent between males and females. In Italy, SCD remains a public health issue of concern in the last decade after adjusting for age.

Introduction to the Compendium on Early Cardiovascular Disease.

Introduction to the Compendium on Early Cardiovascular Disease.

The question of the human mortality plateau: Contrasting insights by longevity pioneers

The debate about limits to the human life span is often based on outcomes from mortality at the oldest ages among longevity pioneers. To this day, scholars disagree on the existence of a late-life plateau in human mortality. Amid various statistical analys

Has the United States Reached a Plateau in Overdoses Caused by Synthetic Opioids After the Onset of the COVID-19 Pandemic? Examination of Centers for Disease Control and Prevention Data to November 2021.

BackgroundOverdoses caused by synthetic mu-opioid receptor (MOR) agonists such as fentanyl are causing increasing mortality in the United States. The COVID-19 pandemic continues to have complex effects on public health, including opioid use disorders (OUD). It is unclear whether recent increases in mortality caused by synthetic opioids have reached a plateau (i.e., a stable period), after the onset of the COVID-19 pandemic.MethodThis study examined provisional overdose mortality data from the Centers for Disease Control and Prevention, for synthetic opioids excluding methadone (code T40.4; monthly data available from 39 States, plus New York City and Washington DC), for June 2019–November 2021. Data were first examined as crude mortality rates. The presence of a maximum plateau was analyzed for the last 4 months of available data. For authorities in which a plateau in mortality was detected, sigmoidal Boltzmann equations were used to model parameters of this phenomenon (e.g., level of the plateau).ResultsAt the end of the study period, all but one authority (New Hampshire) reported increases in mortality rates for synthetic opioids, compared to the baseline month of June 2019 (range: 111–745% of baseline). A plateau was observed over the last 4 months of the study period (Aug 2021–Nov 2021) in 29 of the authorities. Ten other authorities had not reached a stable plateau at the end of the study period. For the authorities where a plateau was detected, a sigmoidal Boltzmann model revealed a fitted maximum of 262% rise in mortality over the study period, from the baseline month. The midpoint in the rise in mortality was fitted in September 2020. After separation of data into census regions, the highest plateau was observed in the West region, followed by South, Midwest, and Northeast (fitted plateau values were 409, 262, 204, and 149% of baseline, respectively).DiscussionThere were increases in overdose mortality due to synthetic opioids across most states, ranging considerably in magnitude. A plateau in overdose mortality was detected at the end of the study period in most of these authorities. The reasons for these plateaus should be explored, in order to develop optimized public health interventions.

Gompertz law revisited: Forecasting mortality with a multi-factor exponential model

This paper provides a flexible way to address some ongoing challenges in mortality modeling, with a special focus on the mortality curvature and possible mortality plateau for extremely old ages. In particular, we extend the Gompertz law by proposing a multi-factor exponential model, a framework that is able to capture flexible mortality patterns, and allows for a convenient estimation and prediction algorithm. An extensive empirical analysis is conducted using the proposed framework with a merged mortality database containing a large number of countries and regions with credible old-age mortality data. We find that the proposed exponential model leads to superior goodness-of-fit to historical data, and better out-of-sample forecasting performance. Moreover, the exponential model predicts more balanced mortality improvements across ages, and thus leads to higher projected remaining life expectancy for the old ages than existing Gompertz-based mortality models. Finally, the modeling capacity of the proposed exponential model is further demonstrated by a multi-population extension, and an illustrative example of estimation and forecast is provided.

Social and economic determinants of the age structure of mortality from suicide in Russia

The purpose of the study is to analyze mortality from suicide in the post-Soviet Russia in terms of its age-related changes and determinants. Material and methods. The authors used data of the Federal State Statistics Service (Rosstat) calculated in the FAISS-Potential system (Factographic analytical information and statistical system) for the period 1989-2018 as well as age and standardized (European standard population) indices by death causes according to ICD-10. Results. During crises, the age structure of mortality from suicide is highly gender-specific. In males, there is a plateau of super mortality in working ages with a local (and sometimes absolute) maximum in persons aged 50-59 years; the difference from the non-crisis periods is mainly determined by young working ages. In females, the “crisis” age structure of suicide mortality is characterized by a stable upward trend without any pronounced maxima. Discussion. Comparing regions by mortality from officially registered suicide, on the one hand, and latent suicide (hanging, fall/jump from a height, and drug poisoning), on the other hand, substantiates objectivity of this problem - namely, a significant underestimation of mortality from suicide. The study shows the opposite groups of these regions to mirror each other, i.e. regions with low mortality from suicide are characterized by a significant latent suicide component. Conclusions. Dynamics in suicide mortality in the post-Soviet Russia was determined by its social and economic changes. A social determinant of mortality from suicide is reflected by its age structure: there is a significant increase in the risk of suicide in working-age groups during the crisis and super mortality among the working-age population in the disadvantaged territories even during non-crisis periods, while there is an opposite trend in the structure of suicide mortality in older ages. The general determinant patterns of the age structure of suicide mortality are distorted by its under-registration.

Analysis of Adverse Events Related to Impella Usage (from the Manufacturer and User Facility Device Experience and National Inpatient Sample Databases)

Impella devices are increasingly utilized for hemodynamic support in high-risk percutaneous coronary intervention or cardiogenic shock despite a lack of randomized clinical trial data showing clinical benefit and newer observational data suggesting harm. In this retrospective analysis, our aim was to determine the most common adverse events associated with Impella usage reported annually to the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database and to estimate via the National Inpatient Sample (NIS) database the number of percutaneous ventricular assist devices utilized and associated with inpatient mortality since introduction of the Impella. Among the 885 complete reports submitted to the MAUDE database from 2008 to 2019 related to Impella usage, there were 1,206 complications coded; 88.2% of reports occurred from 2016 to 2019. Among patients with adverse events reported, bleeding (32.8%), device deployment or retrieval issues (18.2%), vascular complications (15.8%), and death (12.4%) were the most common, and 7.9% of all complications were attributable to operator decision-making or technique. From 2007 to 2017 there was a >100-fold increase in percutaneous ventricular assist devices use with an increase and plateau in in-hospital mortality to 31% from 2012 to 2016 based on NIS data. In conclusion, Impella use has increased substantially over the last decade but remains associated with high inpatient mortality and serious complications based on data from the NIS and MAUDE databases. These findings emphasize the need for high quality randomized controlled trials to determine the clinical utility of Impella in high-risk percutaneous coronary intervention and cardiogenic shock.

Assessing outcomes in a lupus nephritis cohort over a 40-year period.

To characterize a LN cohort over 40 years, assessing its evolution, analysing two major outcomes: the development of end-stage renal disease and mortality rates in the first 5 years after LN diagnosis. An observational retrospective study of patients with LN, followed up from 1975 at University College Hospital. Patients were divided into four groups, depending on the decade of LN diagnosis: 1975-1985 (D1), 1986-1995 (D2), 1996-2005 (D3) and 2006-2015 (D4). Comparison between groups was performed with respect to demographic, clinical, serological and histological characteristics and outcome. Two hundred and nineteen patients with LN were studied. There was a change in ethnic distribution, with a decreasing proportion of Caucasians (58.6% in D1 to 31.3% in D4, P = 0.018) and increase in African-ancestry (17.2% in D1 to 39.6% in D4, P = 0.040). Serological and histological patterns changed throughout time, with a reduction in class IV nephritis (51.7% in D1 to 27.1% in D4, P = 0.035), and increase in class II nephritis (10% in D2 to 18.8% in D4, P = 0.01) and anti-extractable nuclear antigen antibody positivity (17.2% in D1 to 83.3% in D4, P = 0.0001). The 5-year mortality rates decreased from D1 (24.1%) to D2 (4%), stabilizing for the next 30 years. The 5-year progression to end-stage renal disease remained stable over the decades. Despite the changes in treatment of LN in the past 20 years, we have reached a plateau in 5-year mortality and progression to end-stage renal disease rates, suggesting that new therapeutic and management approaches, and strategies to enhance adherence, are needed to improve outcomes further in LN patients.

Terminal life history: late-life fecundity and survival in experimental populations of Drosophila melanogaster.

There are two life history landmarks that can be used to define the terminal period in individual Drosophila melanogaster females: the cessation of daily oviposition, which defines the start of the retired stage, and final oviposition, which defines the start of post-ovipository survival. The terminal period is a substantial component of D. melanogaster life history. Analysis of published data on the daily fecundity and survival of 3971 individually maintained, mated female flies reveals that the terminal period is far more variable within populations than other life history components, including total adult life span. It has been reported that there is a negative correlation between fecundity and duration of the terminal state in recently collected wild stocks. Here I show that the negative correlation occurs in multiple inbred and outbred lab-adapted populations as well. In terms of proportion of adult life, lower fecundity flies spend on average twice as much time in the terminal stage as higher fecundity flies from the same population. Both high and low fecundity flies experience end-of-life plateaus in mortality, with the former exhibiting higher plateau levels. The negative correlation between fecundity and terminal survival is of sufficient magnitude to create heterogeneity among the oldest old: the final 10% of survivors are predominately flies with a history of high fecundity, but about one in five is a low fecundity fly with long terminal stage.

Transcriptome Profiling of Pacu (Piaractus mesopotamicus) Challenged With Pathogenic Aeromonas hydrophila: Inference on Immune Gene Response.

Pacu (Piaractus mesopotamicus) is a Neotropical fish of major importance for South American aquaculture. Septicemia caused by Aeromonas hydrophila bacteria is currently considered a substantial threat for pacu aquaculture that have provoked infectious disease outbreaks with high economic losses. The understanding of molecular aspects on progress of A. hydrophila infection and pacu immune response is scarce, which have limited the development of genomic selection for resistance to this infection. The present study aimed to generate information on transcriptome of pacu in face of A. hydrophila infection, and compare the transcriptomic responses between two groups of time-series belonging to a disease resistance challenge, peak mortality (HM) and mortality plateau (PM) groups of individuals. Nine RNA sequencing (RNA-Seq) libraries were prepared from liver tissue of challenged individuals, generating ∼160 million 150 bp pair-end reads. After quality trimming/cleanup, these reads were assembled de novo generating 211,259 contigs. When the expression of genes from individuals of HM group were compared to individuals from control group, a total of 4,413 differentially expressed transcripts were found (2,000 upregulated and 2,413 downregulated candidate genes). Additionally, 433 transcripts were differentially expressed when individuals from MP group were compared with those in the control group (155 upregulated and 278 downregulated candidate genes). The resulting differentially expressed transcripts were clustered into the following functional categories: cytokines and signaling, epithelial protection, antigen processing and presentation, apoptosis, phagocytosis, complement system cascades and pattern recognition receptors. The proposed results revealing relevant differential gene expression on HM and PM groups which will contribute to a better understanding of the molecular defense mechanisms during A. hydrophila infection.

Are We Approaching a Biological Limit to Human Longevity?

Until recently human longevity records continued to grow in history, with no indication of approaching a hypothetical longevity limit. Also, earlier studies found that age-specific death rates cease to increase at advanced ages (mortality plateau) suggesting the absence of fixed limit to longevity too. In this study, we reexamine both claims with more recent and reliable data on supercentenarians (persons aged 110 years and older). We found that despite a dramatic historical increase in the number of supercentenarians, further growth of human longevity records in subsequent birth cohorts slowed down significantly and almost stopped for those born after 1879. We also found an exponential acceleration of age-specific death rates for persons older than 113 years in more recent data. Slowing down the historical progress in maximum reported age at death and accelerated growth of age-specific death rates after age 113 years in recent birth cohorts may indicate the need for more conservative estimates for future longevity records unless a scientific breakthrough in delaying aging would happen. The hypothesis of approaching a biological limit to human longevity has received some empirical support and it deserves further study and testing.

One or more rates of ageing? The extended gamma-Gompertz model (EGG)

Hidden heterogeneity poses serious challenges to survival analysis because the observed (aggregate) and the unobservable (individual) hazard functions may differ markedly from each other. However, the recent discovery of the so-called “mortality plateau” (i.e., the approximately constant value when mortality levels off, at very old ages) has brought new insights and pushed researchers towards the use of the gamma-Gompertz mortality model. Among the assumptions of this model, two are particularly relevant here: the shape, not the level, of the individual hazard function is a constant and so is the rate of ageing, i.e., the relative increase in mortality risks as people get older. The latter, however, does not pass empirical tests: the rate of ageing seems to vary (albeit only slightly) by age, gender, birth cohort and country. In this paper, we propose a new model (EGG, or extended gamma-Gompertz) which overcomes this limitation by allowing the rate of ageing to increase gradually with age before converging to a constant value, as in Gompertz. While preserving all the fine theoretical and empirical properties of its simpler predecessor, the EGG model adapts better to empirical reality, i.e., in this paper, the mortality profile of the cohorts born between 1820 and 1899 in five countries with high-quality data. The advantages of this more refined mortality model are discussed.

Climate, rather than human disturbance, is the main driver of age-specific mortality trajectories in a tropical tree

Environmental and anthropogenic stressors can interact (e.g., drought, harvest or herbivory) to shape plant demography and evolutionary strategies with implications for sustainable resource management plans. Harvest or recurrent biomass removal can act as a selective force. However, our understanding of how harvest and changes in climate can synergistically shape plant evolutionary strategies is limited. We used age-from-stage matrix modeling to investigate how chronic anthropogenic disturbance (severe foliage and bark harvest) affects age-specific mortality trajectories of a tropical tree, Khaya senegalensis in two contrasting climatic regions (dry versus moist) in West Africa. We then developed a stochastic model to test if changes in disturbance regime and the environmental conditions in which a cohort is born may alter stochastic age-specific mortality rates. The effect of harvest on age-specific mortality trajectories was modest and only noticeable in the moist region. Age-specific mortality trajectories differed significantly between regions. In the moist region, mortality rates decreased with age for the first 30 years of life to a minimum rate and then increased gradually after to reach an old age mortality plateau. In the dry region, mortality rates decreased with age to reach a plateau asymptotically. This difference in age-specific mortality trajectory is due to a greater delay in reaching reproductive size/age in the dry region. Our findings underscore intraspecific variation in age-specific mortality schedules and indicate that climatic effect may override the impact of anthropogenic activities on plant demography. Harvest, by favoring fast life stage transition to reproductive stages, can buffer the effect of drought.

Two stochastic processes shape diverse senescence patterns in a single-cell organism.

Despite advances in aging research, a multitude of aging models, and empirical evidence for diverse senescence patterns, understanding of the biological processes that shape senescence is lacking. We show that senescence of an isogenic Escherichia coli bacterial population results from two stochastic processes. The first process is a random deterioration process within the cell, such as generated by random accumulation of damage. This primary process leads to an exponential increase in mortality early in life followed by a late age mortality plateau. The second process relates to the stochastic asymmetric transmission at cell fission of an unknown factor that influences mortality. This secondary process explains the difference between the classical mortality plateaus detected for young mothers' offspring and the near nonsenescence of old mothers' offspring as well as the lack of a mother-offspring correlation in age at death. We observed that lifespan is predominantly determined by underlying stochastic stage dynamics. Surprisingly, our findings support models developed for metazoans that base their arguments on stage-specific actions of alleles to understand the evolution of senescence. We call for exploration of similar stochastic influences that shape aging patterns beyond simple organisms.

Late-life mortality is underestimated because of data errors.

Knowledge of true mortality trajectory at extreme old ages is important for biologists who test their theories of aging with demographic data. Studies using both simulation and direct age validation found that longevity records for ages 105 years and older are often incorrect and may lead to spurious mortality deceleration and mortality plateau. After age 105 years, longevity claims should be considered as extraordinary claims that require extraordinary evidence. Traditional methods of data cleaning and data quality control are just not sufficient. New, more strict methodologies of data quality control need to be developed and tested. Before this happens, all mortality estimates for ages above 105 years should be treated with caution.

Gompertz Law Revisited: Forecasting Mortality with a Multi-factor Exponential Model

This paper provides a flexible multi-factor framework to address some ongoing challenges in mortality modeling, with a special focus on the mortality curvature and possible mortality plateau for extremely old ages. We extend the Gompertz law Gompertz (1825) by proposing a multi-factor exponential model. The proposed framework is based on the Laguerre approximating functions, and is able to capture flexible mortality patterns, and allows for a convenient estimation and prediction algorithm. An extensive empirical analysis is conducted using the proposed framework with a merged mortality database containing a large number of countries and regions with credible old-age mortality data. We find that the proposed exponential model leads to superior goodness-of-fit to historical data, and better out-of-sample forecast performance. Moreover, the exponential model predicts more balanced mortality improvements across ages, and thus leads to higher projected remaining life expectancy for the old ages than existing Gompertz-based mortality models. Finally, the modeling capacity of the proposed exponential model is further demonstrated by a multi-population extension, and an illustrative example of estimation and forecast is provided.

Plane inclinations: A critique of hypothesis and model choice in Barbi et al.

This study highlights how the mortality plateau in Barbi and colleagues can be generated by low-frequency, randomly distributed age-misreporting errors. Furthermore, sensitivity of the late-life mortality plateau in Barbi and colleagues to the particular age range selected for regression is illustrated. Collectively, the simulation of age-misreporting errors in late-life human mortality data and a less-specific model choice than that of Barbi and colleagues highlight a clear alternative hypothesis to explanations based on evolution, the cessation of ageing, and population heterogeneity.

Response to Comment on "The plateau of human mortality: Demography of longevity pioneers".

Beltrán-Sánchez et al based their comment on misleading calculations of the maximum survival age. With realistic numbers of people attaining age 105 and the estimated plateau, the Jeanne Calment record is indeed plausible.

Comment on "The plateau of human mortality: Demography of longevity pioneers".

Barbi et al (Reports, 29 June 2018, p. 1459) reported that human mortality rate reached a "plateau" after the age of 105, suggesting there may be no limit to human longevity. We show, using their data, that potential lifespans cannot increase much beyond the current 122 years unless future biomedical advances alter the intrinsic rate of human aging.

The burden of disease in Russia from 1980 to 2016: a systematic analysis for the Global Burden of Disease Study 2016

SummaryBackgroundOver the past few decades, social and economic changes have had substantial effects on health and wellbeing in Russia. We aimed to use data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to evaluate trends in mortality, causes of death, years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and associated risk factors in Russia from 1980 to 2016.MethodsWe estimated all-cause mortality by use of a multistage modelling process that synthesised data from vital registration systems, surveys, and censuses. A composite measure of health loss due to both fatal and non-fatal disease burden (DALYs) was calculated as the sum of YLLs and YLDs for each age, sex, year, and location. Health progress was evaluated in comparison with patterns of change in similar countries by use of the Socio-demographic Index that was developed for GBD 2016.FindingsFollowing rapid decreases in life expectancy after the collapse of the Soviet Union, life expectancy at birth in Russia improved between 2006 and 2016. The all-cause mortality rate decreased by 16·6% (95% uncertainty interval 9·4–33·8) between 1980 and 2016. This overall decrease encompasses the cycles of sharp increases and plateaus in mortality that occurred before 2005. Child mortality decreased by 57·5% (53·5–61·1) between 2000 and 2016. However, compared with countries at similar Socio-demographic Index levels, rates of mortality and disability in Russia remain high and life expectancy is low. Russian men have a disproportionate burden of disease relative to women. In 2016, 59·2% (55·3–62·6) of mortality in men aged 15–49 years and 46·8% (44·5–49·5) of mortality in women were attributable to behavioural risk factors, including alcohol use, drug use, and smoking.InterpretationTrends in mortality in Russia from 1980 to 2016 might be related to complicated patterns of behavioural risk factors associated with economic and social change, to shifts in disease burden, and to changes in the capacity of and access to health care. Ongoing mortality and disability from causes and risks amenable to health-care interventions and behaviour modifications present opportunities to continue to improve the wellbeing of Russian citizens.FundingBill & Melinda Gates Foundation.