High cardiovascular mortality risk among older merkel cell carcinoma patients.

OBJECTIVE: Previous research has primarily focused on the incidence and mortality rates of Merkel cell carcinoma (MCC), neglecting the examination of cardiovascular mortality (CVM) risk among survivors, particularly older patients. This study aims to assess the risk of CVM in older individuals diagnosed with MCC. METHODS: Data pertaining to older MCC patients were obtained from the Surveillance, Epidemiology, and End Results database (SEER). CVM risk was measured using standardized mortality ratio (SMR) and cumulative mortality. Multivariate Fine-Gray's competing risk model was utilized to evaluate the risk factors contributing to CVM. RESULTS: Among the study population of 2,899 MCC patients, 465 (16.0%) experienced CVM during the follow-up period. With the prolongation of the follow-up duration, the cumulative mortality rate for CVM reached 27.36%, indicating that cardiovascular disease (CVD) became the second most common cause of death. MCC patients exhibited a higher CVM risk compared to the general population (SMR: 1.69; 95% CI: 1.54-1.86, p < 0.05). Notably, the SMR for other diseases of arteries, arterioles, and capillaries displayed the most significant elevation (SMR: 2.69; 95% CI: 1.16-5.29, p < 0.05). Furthermore, age at diagnosis and disease stage were identified as primary risk factors for CVM, whereas undergoing chemotherapy or radiation demonstrated a protective effect. CONCLUSION: This study emphasizes the significance of CVM as a competing cause of death in older individuals with MCC. MCC patients face a heightened risk of CVM compared to the general population. It is crucial to prioritize cardiovascular health starting from the time of diagnosis and implement personalized CVD monitoring and supportive interventions for MCC patients at high risk. These measures are essential for enhancing survival outcomes.

Cancer Mortality in People Receiving Dialysis for Kidney Failure: An Australian and New Zealand Cohort Study, 1980-2013.

RATIONALE & OBJECTIVE: Cancer is a significant cause of morbidity in the population with kidney failure; however, cancer mortality in people undergoing dialysis has not been well described. We sought to compare cancer mortality in people on dialysis for kidney failure with cancer mortality in the general population. STUDY DESIGN: A retrospective cohort study using linked health-administrative and dialysis registry data. SETTING & PARTICIPANTS: All people receiving dialysis represented in the Australian and New Zealand Dialysis and Transplantation Registry, 1980-2013. EXPOSURE: Dialysis; hemodialysis (HD) and peritoneal dialysis (PD). OUTCOME: Death and underlying cause of death ascertained using health administrative data and classified using International Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes. ANALYTICAL APPROACH: Indirect standardization on age at death, sex, year, and country to estimate standardized mortality ratios (SMR). RESULTS: Over 269,598 person years of observation, 34,100 deaths occurred among 59,648 people on dialysis, including 3,677 cancer deaths. The relative risk of all-site cancer death in dialysis was twice (SMR, 2.4 [95% CI, 2.33-2.49]) that of the general population and highest for oral and pharynx cancers (SMR, 24.3 [95% CI, 18.0-31.5]) and multiple myeloma (SMR, 22.5 [95% CI, 20.3-23.9]). Women on dialysis had a significantly higher risk of all-site cancer mortality (SMR, 2.7 [95% CI, 2.59-2.89]) compared with men (SMR, 2.3 [95% CI, 2.17-2.36]) (P < 0.001). People on HD (SMR, 2.2 [95% CI, 2.11-2.30]) experienced greater excess deaths from all-site cancer compared with people on PD (SMR, 1.3 [95% CI, 1.23-1.44]). Excess deaths have gradually decreased over time for all-site, multiple myeloma, and kidney cancers (P < 0.001) but have not kept up with improvements in the general population. By contrast, among people receiving dialysis, excess deaths increased for colorectal and lung cancers (P < 0.001). LIMITATIONS: Confirmation of cancer diagnoses and population incidence data were not available; inability to exclude pre-existing cancers. CONCLUSIONS: People on dialysis experience excess all-site and site-specific cancer mortality compared with the general population. Mortality differs by modality type, age, and sex. Understanding the role of kidney failure and other morbidities in the treatment of cancer is important for shared decision-making regarding cancer treatments and identifying potential approaches to improve outcomes.

Mortality in neuropsychiatric systemic lupus erythematosus (NPSLE).

The standardized mortality ratio (SMR) for systemic lupus erythematosus (SLE) is three; SMR increases to six in case of renal involvement. Up to now data on survival in case of neuropsychiatric involvement in SLE (NPSLE) have been scarce, therefore we calculated an SMR for NPSLE. Furthermore, we identified characteristics that influenced survival by Cox regression analyses. All patients suspected of NPSLE in our center since 1989 were evaluated and included in this study when a diagnosis of primary NPSLE could be established. Patient's life/death status was tracked using the civic registries. Thirty-two (19%) of the 169 included NPSLE patients died within a median follow-up period of six years (range 0.5-24 years). This resulted in a significantly increased mortality rate compared to the general population: SMR 9.5 (95% CI 6.7-13.5). Hazard ratios (HRs) were highest in patients with acute confusional state (HR 3.4) and older age at diagnosis of NPSLE (HR 1.1). A decreased mortality risk was seen with the prescription of antiplatelet therapy (HR 0.22). The time period in which NPSLE was diagnosed did not significantly influence survival. Most frequent causes of death were infection and NPSLE itself.

Machine learning and XAI approaches highlight the strong connection between O 3 and N O 2 pollutants and Alzheimer's disease.

Alzheimer's disease (AD) is the most common type of dementia with millions of affected patients worldwide. Currently, there is still no cure and AD is often diagnosed long time after onset because there is no clear diagnosis. Thus, it is essential to study the physiology and pathogenesis of AD, investigating the risk factors that could be strongly connected to the disease onset. Despite AD, like other complex diseases, is the result of the combination of several factors, there is emerging agreement that environmental pollution should play a pivotal role in the causes of disease. In this work, we implemented an Artificial Intelligence model to predict AD mortality, expressed as Standardized Mortality Ratio, at Italian provincial level over 5 years. We employed a set of publicly available variables concerning pollution, health, society and economy to feed a Random Forest algorithm. Using methods based on eXplainable Artificial Intelligence (XAI) we found that air pollution (mainly O 3 and N O 2 ) contribute the most to AD mortality prediction. These results could help to shed light on the etiology of Alzheimer's disease and to confirm the urgent need to further investigate the relationship between the environment and the disease.

Characteristics, incidence, and risk factors for death from fatal pneumonia among patients with primary malignant bone tumors: a SEER-based observational study.

BACKGROUND: (I) To determine whether patients with malignant bone tumors had a higher risk of dying from pneumonia compared with the general US population; (II) to identify the independent risk factor associated with fatal pneumonia among these patients. METHODS: We identified 18,583 patients diagnosed with primary malignant bone tumors between 1973 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios (SMRs) were calculated based on the mortality data of the general population gathered by the National Center for Health Statistics, which provided the risk of death from pneumonia among cancer patients relative to that of the general population. Given that other causes of death were considered as competing events, we also designed the Fine-Gray model to identify demographic and tumor-related characteristics associated with a higher risk of dying from pneumonia among these patients. RESULTS: Patients with primary malignant bone tumors had a higher risk of dying from pneumonia than the general population after adjusting the distribution difference of age, sex, and race among them (SMR =2.79; 95% CI: 2.17-3.59). The older age, Black and earlier period of diagnosis were found to be the independent prognostic factor for a higher risk of death from pneumonia for these patients. Additionally, amputation due to malignant bone tumors significantly increased the risk of death from pneumonia compared with non-surgery. The highest mortality rate of pneumonia was observed among patients with chordoma. Interaction tests demonstrated that amputation only increased the relative risk of fatal pneumonia among patients with osteosarcoma. Throughout the follow-up period, the mortality rate of fatal pneumonia was the highest within the first year after diagnosis, and the highest relative suicide risks persisted over time in patients with osteosarcoma. CONCLUSIONS: To mitigate the risk of fatal pneumonia among patients with bone tumors, we call for long-term clinical monitoring of the lung condition among these patients, especially for those after amputation for bone tumors.

A cohort study of banana plantation workers in the French West Indies: first mortality analysis (2000-2015).

Chlordecone, an organochlorine insecticide, was widely used in the French West Indies banana plantations. We set up a cohort of banana plantation workers who worked between 1973 and 1993, the period of authorized use of chlordecone. Vital status and causes of death were collected from French national registries. Workers were followed up from 1 January 2000 to 31 December 2015. Cause-specific mortality in the cohort was compared to that of the general population of the French West Indies by computing standardized mortality ratios (SMRs). A total of 11,112 workers (149,526 person-years, 77% men) were included in the mortality analysis, and 3647 deaths occurred over the study period. There was a slight deficit in all-cause mortality, which was statistically significant in men (SMR = 0.93, 95% CI 0.89-0.96), but not in women (SMR = 0.96, 95% CI 0.89-1.04). All-cancer mortality did not differ significantly from that of the general population (men: SMR = 0.96, 95% CI 0.90-1.03; women: SMR = 1.04, 95% CI 0.89-1.21). Significant excesses of deaths were observed for stomach cancer in women (SMR = 1.94, 95% CI 1.24-2.89) and pancreatic cancer in women farm owners (SMR = 2.31, 95% CI 1.06-4.39). Mortality from prostate cancer was similar to that of the general population in the whole cohort (SMR = 1.00; 95% CI 0.89-1.13) and non-significantly elevated among farm workers (SMR = 1.10, 95% CI 0.87-1.36). Non-significant increases in mortality were also observed for lung cancer in women, leukemia in men, and non-Hodgkin lymphoma in both genders.

Changing temporal trends in non-AIDS cancer mortality among people diagnosed with AIDS: San Francisco, California, 1996-2013.

BACKGROUND: Antiretroviral therapy (ART) has reduced AIDS-defining cancer (ADC) mortality, but its effect on non-AIDS-defining cancer (NADC) mortality is unclear. To help inform cancer prevention and screening, we evaluated trends in NADC mortality among people with AIDS (PWA) in the ART era. METHODS: This retrospective cohort study analyzed AIDS surveillance data, including causes of death from death certificates, for PWA in San Francisco who died in 1996-2013. Proportional mortality ratios (PMRs), and year, age, race, sex-adjusted standardized mortality ratios (SMRs) were calculated for 1996-1999, 2000-2005, and 2006-2013, corresponding to advances in ART. RESULTS: The study included 5822 deceased PWA of whom 90% were male and 68% were aged 35-54 at time of death. Over time, the PMRs significantly decreased for ADCs (2.6%, 1.4%, 1.2%) and increased for NADCs (4.3%, 7.0%, 12.3%). For all years combined (1996-2013) and compared to the California population, significantly elevated SMRs were observed for these cancers: all NADCs combined (2.1), anal (58.4), Hodgkin lymphoma (10.5), liver (5.2), lung/larynx (3.0), rectal (5.2), and tongue (4.7). Over time, the SMRs for liver cancer (SMR 19.8, 11.2, 5.0) significantly decreased while the SMRs remained significantly elevated over population levels for anal (SMR 123, 48.2, 45.5), liver (SMR 19.8, 11.2, 5.0), and lung/larynx cancer (SMR 5.3, 4.7, 3.6). CONCLUSION: A decline in ADC PMRs and increase in NADC PMRs represent a shift in the cancer burden, likely due to ART use. Moreover, given their elevated SMRs, anal, liver, and lung/larynx cancer remain targets for improved cancer prevention, screening, and treatment.

Demographic and clinical factors associated with suicide in gastric cancer in the United States.

While increased suicidal tendencies among cancer patients have been well documented, there has been no specific examination of suicide and gastric cancer. The purpose of this study is to characterize suicide incidence among patients diagnosed with gastric cancer from 1973 to 2013 and identify variables associated with higher suicide rates. Patients with gastric cancer were identified in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The study included clinical and demographic data from 1973 to 2013. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated. Comparisons with the general US population were based on mortality data collected by the Centers for Disease Control and Prevention's National Center for Injury Prevention and Control using the Web-based Injury Statistics Query and Reporting System. Multivariable logistic regression models generated odds ratios (ORs) to assess factors associated with increased suicide in gastric malignancy. There were 210 suicides for patients with gastric cancer (SMR, 3.21; 95% CI: 2.80-3.67). Female gender (SMR 8.54), White race (SMR 4.08), age ≤39 years (SMR 3.06), and age 70-79 years (SMR 2.90), were found to be significant for an increased incidence of suicide compared with the general population. There was not a statistically significant relationship between suicide and marital status, income, mode of radiation therapy, and the role of surgical intervention. Approximately 77% of deaths by suicide occurred within the first year following diagnosis. Female gender, White race, age ≤39 years, and age 70-79 years are factors associated with increased risk of suicide in patients with gastric cancer. These results, coupled with further studies and analyses, will be used to formulate a comprehensive suicide risk factor scoring system for screening all cancer patients.

Detecting Familial Aggregation.

In addition to characterizing the distribution of genetic features of populations (mutation and allele frequencies; measures of Hardy-Weinberg equilibrium), genetic epidemiology and statistical genetics aim to explore and define the role of genomic variation in risk of disease or variation in traits of interest. To facilitate this kind of exploration, genetic epidemiology and statistical genetics address a series of questions: 1. Does the disease tend to cluster in families more than expected by chance alone? 2. Does the disease appear to follow a particular genetic model of transmission in families? 3. Does variation at a particular genomic position tend to cosegregate with disease in families? 4. Do specific genetic variants tend to be carried more frequently by those with disease than by those without these variants in a given population (or across families)? The first question can be examined using studies of familial aggregation or correlation. An ancillary question: "how much of the susceptibility to disease (or variation in disease-related traits) might be accounted for by genetic factors?" is typically answered by estimating heritability, the proportion of variance in a trait or in risk to a disease attributable to genetics. The second question can be formally tested using pedigrees for which disease affection status or trait values are available through a modeling approach known as segregation analysis. The third question can be answered with data on genomic markers in pedigrees with affected members informative for linkage, where meiotic cross-over events are estimated or assessed. The fourth question is answerable using genotype data on genomic markers on unrelated affected and unaffected individuals and/or families with affected members and unaffected members. All of these questions can also be explored for quantitative (or continuously distributed) traits by examining variation in trait values between family members or between unrelated individuals. While each of these questions and the analytical approaches for answering them is explored extensively in subsequent chapters (heritability in Chapters 8 and 9 ; segregation in Chapter 12 ; linkage in Chapters 13 - 17 ; and association in Chapters 18 - 20 ), this chapter focuses on statistical methods to address questions of familial aggregation of qualitative phenotypes (e.g., disease status) or quantitative phenotypes.While studies exploring genotype-phenotype correlations are arguably the most important and common type of statistical genetic study performed, these studies are performed under the assumption that genetic contributors at least partially explain risk of a disease or a trait of interest. This may not always be the case, especially with diseases or traits known to be strongly influenced by environmental factors. For this reason, before any of the last three questions described above can be answered, it is important to ask first whether the disease clusters among family members more than unrelated persons, as this constitutes evidence of a possible heritable contribution to disease, justifying the pursuit of studies answering the other questions. In this chapter, the underlying principles of familial aggregation studies are addressed to provide an understanding and set of analytical tools to help answer the question if diseases or traits of interest are likely to be heritable and therefore justify subsequent statistical genetic studies to identify specific genetic causes.

Changes in the prognosis of Japanese patients who developed type 1 diabetes before the age of 30 years.

AIMS: We investigated changes in vital prognosis according to the year at diagnosis of type 1 diabetes mellitus (T1DM) in a hospital-based survey. METHODS: Of 1054 Japanese subjects diagnosed as T1DM between 1952 and 1999 before the age of 30 and consulted the diabetes center between 1962 and 1999, the survival status up to 2010 or 20 years of follow-up was investigated. Subjects were divided by the year at diagnosis of T1DM: before 1979 (Group A: n = 359), 1980 to 1989 (Group B: n = 400), and 1990 to 1999 (Group C: n = 295). The mortality (/100,000 person years) and standardized mortality ratio (SMR) were calculated, and the effect of year at diagnosis of T1DM was explored by the Cox proportional hazard model. RESULTS: The survival status was confirmed in 90.0%. The mortality rate (95%CI) and age and sex adjusted SMR (95%CI) were 457 (288-627) and 3.0 (1.9-4.2) in Group A, 265 (143-387) and 2.2 (1.2-3.2) in Group B, and 144 (29-259) and 1.6 (0.3-2.9) in Group C, respectively. The cumulative survival rate was significantly different according to the year at diagnosis of T1DM (p = 0.0239). Cox's proportional hazard model revealed that Groups B and C had significantly lower risks of death than Group A after adjustment for gender and age at diagnosis of T1DM (HR 0.48 [95%CI 0.26-0.87] for Group B and HR 0.25 [95%CI 0.09-0.60] for Group C). CONCLUSION: This study indicated that vital prognosis is improving according to the year at diagnosis of T1DM and suggested the need of a nationwide survey.

Fifteen Years After the Gozan-Dong Glass Fiber Outbreak, Incheon in 1995 / 예방의학회지

OBJECTIVES: In 1995, an outbreak survey in Gozan-dong concluded that an association between fiberglass exposure in drinking water and cancer outbreak cannot be established. This study follows the subjects from a study in 1995 using a data linkage method to examine whether an association existed. The authors will address the potential benefits and methodological issues following outbreak surveys using data linkage, particularly when informed consent is absent. METHODS: This is a follow-up study of 697 (30 exposed) individuals out of the original 888 (31 exposed) participants (78.5%) from 1995 to 2007 assessing the cancer outcomes and deaths of these individuals. The National Cancer Registry (KNCR) and death certificate data were linked using the ID numbers of the participants. The standardized incidence ratio (SIR) and standardized mortality ratio (SMR) from cancers were calculated by the KNCR. RESULTS: The SIR values for all cancer or gastrointestinal cancer (GI) occurrences were the lowest in the exposed group (SIR, 0.73; 95% CI, 0.10 to 5.21; 0.00 for GI), while the two control groups (control 1: external, control 2: internal) showed slight increases in their SIR values (SIR, 1.18 and 1.27 for all cancers; 1.62 and 1.46 for GI). All lacked statistical significance. All-cause mortality levels for the three groups showed the same pattern (SMR 0.37, 1.29, and 1.11). CONCLUSIONS: This study did not refute a finding of non-association with a 13-year follow-up. Considering that many outbreak surveys are associated with a small sample size and a cross-sectional design, follow-up studies that utilize data linkage should become standard procedure.