A Proposal for Finite But Unbounded Human Lifetimes

Close analysis of an extensive data set combined with independent evidence prompts our proposal to view human lifetimes as individually finite but collectively unbounded. We formulate a model incorporating this idea whose predictions agree very well with the observed data. In the model, human lifetimes are theoretically unbounded, but the probability of an individual living to an extreme age is negligible, so lifetimes are effectively limited. Our model incorporates a mortality hazard rate plateau and a late-life mortality deceleration effect in conjunction with a newly observed advanced age mortality acceleration. This reconciles many previously observed effects. The model is temporally stable: consistent with observation, parameters do not change over time. As an application, assuming no major medical advances, we predict the emergence of many individuals living past 120, but due to accelerating mortality find it unlikely that any will subsequently survive to an age of 125.

Neonatal and Postneonatal Death Clustering Among Siblings in Bangladesh: Evidence from Bangladesh Demographic and Health Survey 2017–2018

Despite knowledge of neonatal and postneonatal mortality determinants in Bangladesh, some families continue to lose a larger share of children, a phenomenon known as early-life mortality clustering. This study uses the random intercept Weibull survival regression model to explore the correlation of mortality risk among siblings at the family (or, mother) and community levels. Utilizing the Bangladesh Demographic and Health Survey 2017–2018, we found evidence of death scarring, where children whose previous sibling was not alive at the time of conception had significantly higher odds of neonatal mortality. Moreover, the neonatal (and postneonatal) mortality hazard was highest for children with a birth interval of fewer than 19 months, corresponding to the preceding sibling. The intraclass correlation coefficient's statistically significant values show that neonatal and postneonatal mortality risk is correlated among children of the same family and community. The findings suggest focusing on high-risk families and communities to reduce the mortality level effectively.

Excess Mortality by Multimorbidity, Socioeconomic, and Healthcare Factors, amongst Patients Diagnosed with Diffuse Large B-Cell or Follicular Lymphoma in England

(1) Background: Socioeconomic inequalities of survival in patients with lymphoma persist, which may be explained by patients’ comorbidities. We aimed to assess the association between comorbidities and the survival of patients diagnosed with diffuse large B-cell (DLBCL) or follicular lymphoma (FL) in England accounting for other socio-demographic characteristics. (2) Methods: Population-based cancer registry data were linked to Hospital Episode Statistics. We used a flexible multilevel excess hazard model to estimate excess mortality and net survival by patient’s comorbidity status, adjusted for sociodemographic, economic, and healthcare factors, and accounting for the patient’s area of residence. We used the latent normal joint modelling multiple imputation approach for missing data. (3) Results: Overall, 15,516 and 29,898 patients were diagnosed with FL and DLBCL in England between 2005 and 2013, respectively. Amongst DLBCL and FL patients, respectively, those in the most deprived areas showed 1.22 (95% confidence interval (CI): 1.18–1.27) and 1.45 (95% CI: 1.30–1.62) times higher excess mortality hazard compared to those in the least deprived areas, adjusted for comorbidity status, age at diagnosis, sex, ethnicity, and route to diagnosis. (4) Conclusions: Deprivation is consistently associated with poorer survival among patients diagnosed with DLBCL or FL, after adjusting for co/multimorbidities. Comorbidities and multimorbidities need to be considered when planning public health interventions targeting haematological malignancies in England.

Thyroid disease and hepatocellular carcinoma survival. A Danish nationwide cohort study

Introduction Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality worldwide. Recent animal studies suggest that thyroid hormone treatment improves HCC prognosis. The aim of this study was to describe the association between thyroid disease and HCC prognosis in humans. Methods We performed a nationwide cohort study including all persons with an HCC diagnosis from 2000-2018. Patients’ age, sex, HCC treatment, and diagnoses of thyrotoxicosis, nontoxic goitre, and myxoedema, were obtained from Danish national healthcare registries. We used regression models to examine the association between thyroid disease and mortality hazard and restricted mean survival time after HCC diagnosis, adjusting for confounding by sex and age. Results We included 4,812 patients with HCC and 107 patients with thyroid disease. Median follow-up time was 5 months (total 5,985 person-years). The adjusted mortality hazard ratio was 0.68 (95% CI 0.47-0.96) for thyrotoxicosis and 0.60 (95% CI 0.41-0.88) for nontoxic goitre. The restricted mean survival time during the five years following HCC diagnosis was 6.8 months (95% CI 1.1–12.6) longer for HCC patients with thyrotoxicosis than for patients without thyroid disease, and it was 6.9 months (95% CI 0.9–12.9) longer for HCC patients with nontoxic goitre than for patients without thyroid disease. Conclusions In this large nationwide cohort study, thyrotoxicosis and nontoxic goitre were associated with prolonged HCC survival.

Effect of Nephrology Care on Mortality in Incident Dialysis Patients: A Population-Based Cohort Study

Long-term and continuous nephrology care effects on post-dialysis mortality remain unclear. This study aims to systematically explore the causal effect of nephrology care on mortality for patients with dialysis initiation. We conducted a retrospective cohort study to include incident patients with dialysis for ≥ 3 months in Taiwan from 2004 through 2011. The continuous nephrology care of incident patients in the three years before their dialysis was measured every six months. Continuous nephrology care was determined by 0–6, 0–12, …, 0–36 months and their counterparts; and none, intermittent, 0–6 months, …, and 0–36 months. Simple and weighted hazards ratio (HR) and 95% confidence interval (CI) for one-year mortality were estimated after propensity score (PS) matching. We included a total of 44,698 patients (mean age 63.3 ± 14.2, male 51.9%). Receiving ≥ 1 year predialysis nephrology care was associated with a 22% lower post-dialysis mortality hazard. No different effects were found (ranges of PS matching HR: 0.77–0.80) when comparing the defined duration of nephrology care with their counterparts. Stepped survival benefits were newly identified in the intermittent care, which had slightly lower HRs (weighted HR: 0.88, 95% CI: 0.79–0.97), followed by reviving care over six months to two years (ranges of weighted HR: 0.60–0.65), and reviving care over two years (ranges of weighted HR: 0.48–0.52). There was no existing critical period of nephrology care effect on post-dialysis, but there were extra survival benefits when extending nephrology care to >2 years, which suggests that continuous and long-term care during pre-dialysis/chronic kidney disease phase is required.

Autoimmune diseases in HIV-negative cryptococcal meningitis

Aim: The purpose of our study was to assess the differences between HIV-negative cryptococcal meningitis (CM) patients with and without autoimmune diseases. Methods: A total of 43 CM patients with autoimmune diseases and 67 without autoimmune diseases were enrolled for analysis. Results: CM patients with autoimmune diseases had higher fever, modified Rankin Scale scores, C-reactive protein and erythrocyte sedimentation rate, but had lower rates of visual and hearing symptoms, ventriculoperitoneal shunts, MRI meningeal enhancement and amphotericin B treatment, as well as lower cerebrospinal fluid pressure and fungal counts. When divided according to gender, each group had lower intracranial pressure and higher inflammation indicators. No differences in outcomes, sequelae and mortality hazard were found. Fluconazole treatment was a prognostic factor for CM without autoimmune diseases. Conclusions: Both antifungal and anti-inflammatory therapy should be considered in CM patients with autoimmune diseases.

Socioeconomic Environment and Survival in Patients with Digestive Cancers: A French Population-Based Study

Social inequalities are an important prognostic factor in cancer survival, but little is known regarding digestive cancers specifically. We aimed to provide in-depth analysis of the contextual social disparities in net survival of patients with digestive cancer in France, using population-based data and relevant modeling. Digestive cancers (n = 54,507) diagnosed between 2006–2009, collected through the French network of cancer registries, were included (end of follow-up 06/30/2013). Social environment was assessed by the European Deprivation Index. Multidimensional penalized splines were used to model excess mortality hazard. We found that net survival was significantly worse for individuals living in a more deprived environment as compared to those living in a less deprived one for esophageal, liver, pancreatic, colon and rectal cancers, and for stomach and bile duct cancers among females. Excess mortality hazard was up to 57% higher among females living in the most deprived areas (vs. least deprived) at 1 year of follow-up for bile duct cancer, and up to 21% higher among males living in the most deprived areas (vs. least deprived) regarding colon cancer. To conclude, we provide a better understanding of how the (contextual) social gradient in survival is constructed, offering new perspectives for tackling social inequalities in digestive cancer survival.

ESTIMATION AND UNIQUENESS OF THE GOMPERTZ FORCE OF MORTALITY IN TERMS OF THE MODAL AGE AT DEATH

The initial level of mortality and the rate at which mortality rises with age are generally expressed in terms of the Gompertz force of mortality (hazard function). In their paper, James W. Vaupel and others define the Gompertz force of mortality as the rate at which mortality rises with age and the modal age at death. In this paper we estimate the Gompertz force of mortality and prove uniqueness theorem.

Incidence of stroke, transient ischaemic attack and determinants of poststroke mortality among immigrants in Denmark, 2004‒2018: a population-based cohort study

ObjectiveUsing recent registry data, we aimed to quantify the incidence of stroke and transient ischaemic attack (TIA) and to examine factors influencing the risk of poststroke mortality among immigrants compared with Danish-born individuals.DesignPopulation-based cohort study between 2004 and 2018. We estimated age-standardised incidence rate ratios (IRR) of stroke, stroke types and TIA for each ethnic group using Danish-born individuals as the reference by direct method of standardisation. We calculated the risk of poststroke mortality using Cox proportional hazard regression.SettingThe study was conducted using Danish nationwide registers.ParticipantsAll cases of first-ever stroke and TIA by country of origin (n=132 936) were included.ResultsOverall, Western immigrants (IRR=2.25; 95% CI 2.20 to 2.31) and non-Western immigrants (IRR=1.37; 95% CI 1.30 to 1.44) had a higher risk of stroke than Danish-born individuals. The risk of TIA was higher in Western immigrants (IRR=2.08; 95% CI 1.93 to 2.23) followed by non-Western immigrants (IRR=1.45; 95% CI 1.27 to 1.63) than in Danish-born individuals. All-cause 1-year mortality hazard was higher but not significantly different in non-Western men (adjusted HR=1.38; 95% CI 0.92 to 2.08) compared with Danish-born men and additional adjustment for comorbidities reduced the HR to 0.85 (0.51 to 1.40) among ischaemic stroke cases. Among intracerebral haemorrhage cases, the adjusted mortality hazard was decreased in Western men (from HR of 1.76; 95% CI 1.09 to 2.85 to HR of 1.30; 95% CI 0.80 to 2.11) compared with Danish-born men after adjustment for stroke severity. Immigrants with ≤15 years of residence had a lower poststroke mortality hazard than Danish-born individuals after additional adjustment for sociodemographic factors (HR=0.36; 95% CI 0.14 to 0.91).ConclusionsThe age-standardised risk of stroke and TIA was significantly higher among the majority of immigrants than Danish-born individuals. Interventions that reduce the burden of comorbidities, improve acute stroke care and target sociodemographic factors may address the higher risk of poststroke mortality among immigrants.

Determinants of hospital outcomes for COVID-19 infections in a large Pennsylvania Health System

There is growing evidence that racial and ethnic minorities bear a disproportionate burden from COVID-19. Temporal changes in the pandemic epidemiology and diversity in the clinical course require careful study to identify determinants of poor outcomes. We analyzed 6255 individuals admitted with PCR-confirmed COVID-19 to one of 5 hospitals in the University of Pennsylvania Health System between March 2020 and March 2021, using electronic health records to assess risk factors and outcomes through 8 weeks post-admission. Discharge, readmission and mortality outcomes were analyzed in a multi-state model with multivariable Cox models for each transition. Mortality varied markedly over time, with cumulative incidence (95% CI) 30 days post-admission of 19.1% (16.9, 21.3) in March-April 2020, 5.7% (4.2, 7.5) in July-October 2020 and 10.5% (9.1,12.0) in January-March 2021; 26% of deaths occurred after discharge. Average age (SD) at admission varied from 62.7 (17.6) to 54.8 (19.9) to 60.5 (18.1); mechanical ventilation use declined from 21.3% to 9-11%. Compared to Caucasian, Black race was associated with more severe disease at admission, higher rates of co-morbidities and low-income resident zip code. Between-race risk differences in mortality risk diminished in multivariable models; while admitting hospital, increasing age, admission early in the pandemic, and severe disease and low blood pressure at admission were associated with increased mortality hazard. Hispanic ethnicity was associated with fewer baseline co-morbidities and lower mortality hazard (0.57, 95% CI: 0.37, .087). Multi-state modeling allows for a unified framework to analyze multiple outcomes throughout the disease course. Morbidity and mortality for hospitalized COVID-19 patients varied over time but post-discharge mortality remained non-trivial. Black race was associated with more risk factors for morbidity and with treatment at hospitals with lower mortality. Multivariable models suggest there are not between-race differences in outcomes. Future work is needed to better understand the identified between-hospital differences in mortality.