Impact of organized and opportunistic screening on excess mortality and on social inequalities in breast cancer survival.

In most developed countries, both organized screening (OrgS) and opportunistic screening (OppS) coexist. The literature has extensively covered the impact of organized screening on women's survival after breast cancer. However, the impact of opportunistic screening has been less frequently described due to the challenge of identifying the target population. The aim of this study was to describe the net survival and excess mortality hazard (EMH) in each screening group (OrgS, OppS, or No screening) and to determine whether there is an identical social gradient in each groups. Three data sources (cancer registry, screening coordination centers, and National Health Data System [NHDS]) were used to identify the three screening groups. The European Deprivation Index (EDI) defined the level of deprivation. We modeled excess breast cancer mortality hazard and net survival using penalized flexible models. We observed a higher EMH for "No screening" women compared with the other two groups, regardless of level of deprivation and age at diagnosis. A social gradient appeared for each group at different follow-up times and particularly between 2 and 3 years of follow-up for "OrgS" and "OppS" women. Net survival was higher for "OrgS" women than "OppS" women, especially for the oldest women, and regardless of the deprivation level. This study provides new evidence of the impact of OrgS on net survival and excess mortality hazard after breast cancer, compared with opportunistic screening or no screening, and tends to show that OrgS attenuates the social gradient effect.

Long-term excess mortality and net survival among elderly diffuse large B-cell lymphoma patients after front-line R-CHOP treatment.

In the era of immunochemotherapy, data on the long-term prognosis of elderly patients diagnosed with a diffuse large B-cell lymphoma (DLBCL) are scarce. In this population and on the longer term, other-cause mortality is an important competing risk that needs to be accounted for. Using clinical trial data and relative survival approaches, we estimated the 10-year net survival (NS) and we described the excess mortality hazard (EMH) due (directly or indirectly) to the DLBCL, over time and according to main prognosis factors using flexible regression modelling. The 10-year NS was 65% [59; 71]. Using the flexible modelling, we showed that the EMH decreases steeply after diagnosis. The variables 'performance status', 'number of extra-nodal sites' and the serum 'lactate dehydrogenase' were strongly associated with the EMH, even after adjustment on other important variables. EMH is very close to zero at 10 years for the whole population, so DLBCL patients do not experience an increased mortality compared to the general population in the long term. The number of extra-nodal sites was an important prognostic factor shortly after diagnosis, suggesting that it is correlated with an important but unmeasured prognostic factor that would lead to this selection effect over time.

On models for the estimation of the excess mortality hazard in case of insufficiently stratified life tables.

In cancer epidemiology using population-based data, regression models for the excess mortality hazard is a useful method to estimate cancer survival and to describe the association between prognosis factors and excess mortality. This method requires expected mortality rates from general population life tables: each cancer patient is assigned an expected (background) mortality rate obtained from the life tables, typically at least according to their age and sex, from the population they belong to. However, those life tables may be insufficiently stratified, as some characteristics such as deprivation, ethnicity, and comorbidities, are not available in the life tables for a number of countries. This may affect the background mortality rate allocated to each patient, and it has been shown that not including relevant information for assigning an expected mortality rate to each patient induces a bias in the estimation of the regression parameters of the excess hazard model. We propose two parametric corrections in excess hazard regression models, including a single-parameter or a random effect (frailty), to account for possible mismatches in the life table and thus misspecification of the background mortality rate. In an extensive simulation study, the good statistical performance of the proposed approach is demonstrated, and we illustrate their use on real population-based data of lung cancer patients. We present conditions and limitations of these methods and provide some recommendations for their use in practice.

An investigation of cancer survival inequalities associated with individual-level socio-economic status, area-level deprivation, and contextual effects, in a cancer patient cohort in England and Wales.

BACKGROUND: People living in more deprived areas of high-income countries have lower cancer survival than those in less deprived areas. However, associations between individual-level socio-economic circumstances and cancer survival are relatively poorly understood. Moreover, few studies have addressed contextual effects, where associations between individual-level socio-economic status and cancer survival vary depending on area-based deprivation. METHODS: Using 9276 individual-level observations from a longitudinal study in England and Wales, we examined the association with cancer survival of area-level deprivation and individual-level occupation, education, and income, for colorectal, prostate and breast cancer patients aged 20-99 at diagnosis. With flexible parametric excess hazard models, we estimated excess mortality across individual-level and area-level socio-economic variables and investigated contextual effects. RESULTS: For colorectal cancers, we found evidence of an association between education and cancer survival in men with Excess Hazard Ratio (EHR) = 0.80, 95% Confidence Interval (CI) = 0.60;1.08 comparing "degree-level qualification and higher" to "no qualification" and EHR = 0.74 [0.56;0.97] comparing "apprenticeships and vocational qualification" to "no qualification", adjusted on occupation and income; and between occupation and cancer survival for women with EHR = 0.77 [0.54;1.10] comparing "managerial/professional occupations" to "manual/technical," and EHR = 0.81 [0.63;1.06] comparing "intermediate" to "manual/technical", adjusted on education and income. For breast cancer in women, we found evidence of an association with income (EHR = 0.52 [0.29;0.95] for the highest income quintile compared to the lowest, adjusted on education and occupation), while for prostate cancer, all three individual-level socio-economic variables were associated to some extent with cancer survival. We found contextual effects of area-level deprivation on survival inequalities between occupation types for breast and prostate cancers, suggesting wider individual-level inequalities in more deprived areas compared to least deprived areas. Individual-level income inequalities for breast cancer were more evident than an area-level differential, suggesting that area-level deprivation might not be the most effective measure of inequality for this cancer. For colorectal cancer in both sexes, we found evidence suggesting area- and individual-level inequalities, but no evidence of contextual effects. CONCLUSIONS: Findings highlight that both individual and contextual effects contribute to inequalities in cancer outcomes. These insights provide potential avenues for more effective policy and practice.

A Bayesian joint model for zero-inflated integers and left-truncated event times with a time-varying association: Applications to senior health care.

Population aging in most industrialized societies has led to a dramatic increase in emergency medical demand among the elderly. In the context of private health care, an optimal allocation of the medical resources for seniors is commonly done by forecasting their life spans. Accounting for each subject's particularities is therefore indispensable, so the available data must be processed at an individual level. We use a large and unique dataset of insured parties aged 65 and older to appropriately relate the emergency care usage with mortality risk. Longitudinal and time-to-event processes are jointly modeled, and their underlying relationship can therefore be assessed. Such an application, however, requires some special features to also be considered. First, longitudinal demand for emergency services exhibits a nonnegative integer response with an excess of zeros due to the very nature of the data. These subject-specific responses are handled by a zero-inflated version of the hierarchical negative binomial model. Second, event times must account for the left truncation derived from the fact that policyholders must reach the age of 65 before they may begin to be observed. Consequently, a delayed entry bias arises for those individuals entering the study after this age threshold. Third, and as the main challenge of our analysis, the association parameter between both processes is expected to be age-dependent, with an unspecified association structure. This is well-approximated through a flexible functional specification provided by penalized B-splines. The parameter estimation of the joint model is derived under a Bayesian scheme.

Smokeless tobacco mortality risks: an analysis of two contemporary nationally representative longitudinal mortality studies.

BACKGROUND: Assessments supporting smokeless tobacco (SLT) disease risk are generally decades old. Newer epidemiological data may more accurately represent the health risks associated with contemporary US-based SLT products, many of which contain lower levels of hazardous and potentially hazardous chemicals compared to previously available SLT products. METHODS: Data from two longitudinal datasets (National Longitudinal Mortality Study-NLMS, and the National Health Interview Survey-NHIS) were analyzed to determine potential associations between SLT use and/or cigarette smoking and all-cause and disease-specific mortality. Mortality hazard ratios (HR) were estimated using a Cox proportional hazards regression model applied to various groups, including never users of any tobacco or SLT product, and current and former SLT users and/or cigarette smokers. RESULTS: The two datasets yielded consistent findings with similar patterns evident for the specific causes of death measured. All-cause mortality risk for exclusive SLT users was significantly lower than that observed for exclusive cigarette smokers and dual SLT/cigarette users. Similar trends were found for mortality from diseases of the heart, chronic lower respiratory diseases, and malignant neoplasms. Mortality risk for lung cancer in exclusive cigarette smokers was increased by about 12-fold over never-tobacco users but was rarely present in exclusive SLT users in either survey (NHIS, < 5 cases/1,563 observations; NLMS, 3 cases/1,863 observations). While the data in the surveys are limited, SLT use by former cigarette smokers was not associated with an increase in the lung cancer risk HR compared to that by former cigarette smokers who never used SLT. CONCLUSIONS: Emerging epidemiological data provides a new perspective on the health risks of SLT use compared to risks associated with cigarette smoking. HR estimates derived from two current US datasets, which include data on contemporary tobacco products, demonstrate a clear mortality risk differential between modern SLT products and cigarettes. Cigarette smokers had an increased overall mortality risk and risk for several disease-specific causes of death, while SLT users consistently had lower mortality risks.

Within-host dynamics and random duration of pathogen infection: Implications for between-host transmission.

Taking an ecological perspective, this paper reports theoretical and empirical results concerning fatal bacterial infections of adult insects. Two models, each combining deterministic and stochastic elements, characterize how the pathogen's dynamics might govern an infected host's mortality rate. We analyze the models in detail for exponential pathogen growth, and apply them to observed insect mortality when the pathogen's growth is unregulated. We then allow bacteriophage to generate fluctuations in the within-host pathogen density; we demonstrate that only one of our models matches host mortality rates when pathogen growth is regulated by phage. We generalize our results on mortality hazard of individual hosts to analyze how random duration of the infectious period can combine with probabilistic transmission events to affect between-host transmission.

Deciphering the Timing and Impact of Life-extending Drugs: A Novel Analytic Approach that Differentiates Early, Midlife, and Senescence Phase Efficacies.

Evidence that life-extending interventions are not uniformly effective across the lifespan calls for an analytic tool that can estimate age-specific treatment effects on mortality hazards. Here we report such a tool, applying it to mouse data from 42 agents tested in the NIA Interventions Testing Program. This tool identified agents that either reduced (22) or increased (16) mortality hazards or did both (6), all with marked variation in the duration of efficacy and magnitude of effect size. Only 7 reduced mortality hazards after the 90% mortality, when the burden of senescence is greatest. Sex differences were apparent in all parameters. This new analytic tool complements the commonly used log-rank test. It detects more potential life-extending candidates (22 versus 10) and indicates when during the life course they are effective. It also uncovers adverse effects. Most importantly, it identifies agents that specifically reduce mortality hazards during the senescent phase of life.

Ventriculitis due to multidrug-resistant gram-negative bacilli associated with external ventricular drain: evolution, treatment, and outcomes.

Introduction: Nosocomial infectious ventriculitis caused by multidrug-resistant (MDR) Gram-negative bacilli associated with external ventricular drainage (EVD) placement poses a significant mortality burden and hospital costs. Objectives: This study aims to analyze the characteristics, ventriculitis evolution, treatment, and outcomes of patients with ventriculitis due to MDR Gram-negative bacilli associated with EVD placement. Methods: A retrospective cohort study focusing on patients with nosocomial infection caused by MDR Gram-negative bacilli while on EVD was conducted from 2019 to 2022. Medical, laboratory, and microbiological records were collected. The antibiotic resistance of the Gram-negative bacilli isolated in the cerebrospinal fluid (CSF) of patients was analyzed. The risk factors were identified using univariate risk models and were analyzed using survival curves (Cox regression). An adjusted Cox proportional hazards model was also constructed. Results: Among 530 patients with suspected EVD-associated ventriculitis, 64 patients with isolation of Gram-negative bacilli in CSF were included. The estimated mortality was 78.12%. Hemorrhages (intracranial, subarachnoid, and intraventricular) were observed in 69.8% of patients. Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequently isolated bacilli. In the univariate analysis, significant risk factors for mortality included arterial hypertension, a Glasgow Coma Scale (GCS) score of ≤ 8, invasive mechanical ventilation (IMV) upon hospital admission and during hospitalization, septic shock, and ineffective treatment. The adjusted Cox proportional hazards model revealed that septic shock (HR = 3.3, 95% CI = 1.5-7.2; p = 0.003) and ineffective treatment (HR = 3.2, 1.6-6.5, 0.001) were significant predictors. A high resistance to carbapenems was found for A. baumannii (91.3%) and P. aeruginosa (80.0%). Low resistance to colistin was found for A. baumannii (4.8%) and P. aeruginosa (12.5%). Conclusion: Ineffective treatment was an independent hazard factor for death in patients with ventriculitis caused by MDR Gram-negative bacilli associated with EVD.

Age-Dependent Causes of Death among Patients with Breast Cancer Based on Osaka Cancer Registry and Vital Statistics in Japan.

We aimed to clarify the differences in causes of death among patients with breast cancer according to age at diagnosis and years elapsed since diagnosis. Using data from the Osaka Cancer Registry and Vital Statistics databases, 40,690 female patients diagnosed with primary breast cancer between 1985 and 2006 were included in this study. The statistics on all deaths between 1985 to 2016 were collected, and the observation period was 10 years (2006-2016). Mortality hazards according to age at diagnosis and years elapsed since diagnosis were estimated using a flexible parametric estimation. Of the 40,690 patients, 13,676 (34%) died from all-cause death, and the 10-year survival rate was 65.74% (95% confidence interval: 65.28-66.21). The proportions of deaths were 10,531 (77%) from breast cancer, 1048 (8%) from other cancers, and 2097 (15%) from non-cancer causes. The mortality hazard for deaths from breast cancer was initially high and then declined, whereas that for deaths from other cancers and non-cancer causes was initially low and then increased. The more likely causes of death 5 years after breast cancer diagnosis were other cancers or non-cancer causes among patients aged ≥70 years.

Divergent Survival Outcomes Associated with Elevated Branched-Chain Amino Acid Levels among Older Adults with or without Hypertension and Diabetes: A Validated, Prospective, Longitudinal Follow-Up Study.

Branched-chain amino acids are critical metabolic intermediates that can indicate increased risk of cardiometabolic disease when levels are elevated or, alternatively, suggest sufficient mitochondrial energy metabolism and reserve in old age. The interpretation of BCAA levels can be context-dependent, and it remains unclear whether abnormal levels can inform prognosis. This prospective longitudinal study aimed to determine the interrelationship between mortality hazard and fasting serum BCAA levels among older men and women aged ≥65 years with or without hypertension and diabetes mellitus. At baseline (0Y), fasting serum BCAA concentration in 2997 community-living older men and women were measured. Approximately 14 years later (14Y), 860 study participants returned for repeat measurements. Deaths were analysed and classified into cardiovascular and non-cardiovascular causes using International Classification of Diseases codes. Survival analysis and multivariable Cox regression were performed. During a median follow-up of 17Y, 971 (78.6%) non-cardiovascular and 263 (21.4%) cardiovascular deaths occurred among 1235 (41.2%) deceased (median age, 85.8 years [IQR 81.7-89.7]). From 0Y to 14Y, BCAA levels declined in both sexes, whereas serum creatinine concentration increased (both p < 0.0001). In older adults without hypertension or diabetes mellitus, the relationship between mortality hazard and BCAA level was linear and above-median BCAA levels were associated with improved survival, whereas in the presence of cardiometabolic disease the relationship was U-shaped. Overall, adjusted Cox regression determined that each 10% increment in BCAA concentration was associated with a 7% (p = 0.0002) and 16% (p = 0.0057) reduction in mortality hazard estimated at 0Y and 14Y, respectively. Our findings suggested that abnormally high or low (dyshomeostatic) BCAA levels among older adults with hypertension and/or diabetes mellitus were associated with increased mortality, whereas in those with neither disease, increased BCAA levels was associated with improved survival, particularly in the oldest-old.

Twenty years of melanoma in Victoria, Queensland, and South Australia (1997 - 2016).

BACKGROUND: Given the high incidence of melanoma in Australia alongside high mortality with later stage disease, we investigated the populations and locations most at risk, to optimise public health activities in areas where intervention is most needed. This study examines trends and identifies significant prognostic factors and potential disparities in incidence, mortality and survival between population groups in Victoria, Queensland and South Australia. METHODS: The analysis includes data from the population-based cancer registries of the three states over a twenty-year period (1997-2016). Age-standardized and age-specific incidence rates were calculated, and long-term trends analysed using Joinpoint Regression. Five-year relative survival estimates for the study population were calculated using the cohort method and multivariable flexible parametric survival models were applied for each jurisdiction to calculate adjusted excess mortality hazard ratios for the key characteristics. RESULTS: There were more males with melanoma than females in all the three states. Over 60% of the cases occurred in the 40-74 years age group. Most melanomas had a Breslow thickness less than or equal to 1.0 mm. For males, Victoria and Queensland had a statistically significant increasing trend whereas in South Australia there was a decreasing trend. For females, the incidence rate trend was stable in Victoria but significantly decreasing in South Australia. In Queensland there was an increasing and statistically significant trend from 2006 to 2016. Across all three states there was a reducing incidence rate in the youngest cohort, stabilizing incidence in the 40-59-year-old age group, and increasing in the oldest cohorts. Five-year relative survival decreased with increasing age and with Breslow thickness across all three jurisdictions. Males had between 43%- 46% excess mortality compared to females in all the three states. There was higher risk with increasing age and Breslow thickness, with the largest risk among the 75 + age group and those with a Breslow thickness of > 4 mm. CONCLUSION: It is the first time that data from these three registries has been analysed together in a uniform way, covering more than half of the Australian population. This study compares the epidemiology of melanoma across three states and provides a better understanding of trends and factors affecting outcome for Australians with melanoma. While there has been some improvement in aspects of incidence and mortality, this has not been evenly achieved across Australia.

Female reproduction bears no survival cost in captivity for gray mouse lemurs.

The survival cost of reproduction has been revealed in many free-ranging vertebrates. However, recent studies on captive populations failed to detect this cost. Theoretically, this lack of survival/reproduction trade-off is expected when resources are not limiting, but these studies may have failed to detect the cost, as they may not have fully accounted for potential confounding effects, in particular interindividual heterogeneity. Here, we investigated the effects of current and past reproductive effort on later survival in captive females of a small primate, the gray mouse lemur. Survival analyses showed no cost of reproduction in females; and the pattern was even in the opposite direction: the higher the reproductive effort, the higher the chances of survival until the next reproductive event. These conclusions hold even while accounting for interindividual heterogeneity. In agreement with aforementioned studies on captive vertebrates, these results remind us that reproduction is expected to be traded against body maintenance and the survival prospect only when resources are so limiting that they induce an allocation trade-off. Thus, the cost of reproduction has a major extrinsic component driven by environmental conditions.

Describing the association between socioeconomic inequalities and cancer survival: methodological guidelines and illustration with population-based data.

BACKGROUND: Describing the relationship between socioeconomic inequalities and cancer survival is important but methodologically challenging. We propose guidelines for addressing these challenges and illustrate their implementation on French population-based data. METHODS: We analyzed 17 cancers. Socioeconomic deprivation was measured by an ecological measure, the European Deprivation Index (EDI). The Excess Mortality Hazard (EMH), ie, the mortality hazard among cancer patients after accounting for other causes of death, was modeled using a flexible parametric model, allowing for nonlinear and/or time-dependent association between the EDI and the EMH. The model included a cluster-specific random effect to deal with the hierarchical structure of the data. RESULTS: We reported the conventional age-standardized net survival (ASNS) and described the changes of the EMH over the time since diagnosis at different levels of deprivation. We illustrated nonlinear and/or time-dependent associations between the EDI and the EMH by plotting the excess hazard ratio according to EDI values at different times after diagnosis. The median excess hazard ratio quantified the general contextual effect. Lip-oral cavity-pharynx cancer in men showed the widest deprivation gap, with 5-year ASNS at 41% and 29% for deprivation quintiles 1 and 5, respectively, and we found a nonlinear association between the EDI and the EMH. The EDI accounted for a substantial part of the general contextual effect on the EMH. The association between the EDI and the EMH was time dependent in stomach and pancreas cancers in men and in cervix cancer. CONCLUSION: The methodological guidelines proved efficient in describing the way socioeconomic inequalities influence cancer survival. Their use would allow comparisons between different health care systems.