Increased Risk of Suicide among Cancer Survivors Who Developed a Second Malignant Neoplasm

Background. Cancer diagnosis entails substantial psychological distress and is associated with dramatically increased risks of suicidal behaviors. However, little is known about the suicide risk among cancer survivors who developed a second malignant neoplasm (SMN). Methods. Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study involving 7,824,709 patients with first malignant neoplasm (FMN). We measured the hazard ratios (HRs) of suicide death after receiving a SMN diagnosis using Cox proportional hazard models, as compared with patients with FMN. The comparison with the US population was achieved by calculating standardized mortality ratios (SMRs). Results. Totally 685,727 FMN patients received a diagnosis of SMN during follow-up, and we in total identified 10,930 and 937 suicide deaths among FMN and SMN patients, respectively. The HR of suicide deaths was 1.23 (95% confidence interval (CI), 1.14–1.31) after a SMN diagnosis, compared with FMN patients, after adjusting for sociodemographic factors, tumor characteristics, and cancer treatment. As compared with the general population, while both SMN and FMN patients suffered an increased risk of suicide deaths, the excess risk was higher among SMN patients than FMN patients (age-, sex-, and calendar-year-adjusted SMR 1.65 (95% CI 1.54–1.75) vs. 1.29 (95% CI 1.26–1.31); P difference < 0.0001 ). Notably, across different time periods, we observed the greatest risk elevation during the first 3 months after a cancer diagnosis. Conclusions. Compared with either patients with FMN or the general population, cancer survivors who received a SMN diagnosis were at increased risk of suicide death. The risk elevation was most prominent soon after the cancer diagnosis, highlighting the necessity of providing timely psychological support to cancer survivors with a SMN.

Heterogeneity in Subnational Mortality in The Context of The COVID-19 Pandemic: The Case of Belgian Districts

Background: The COVID-19 pandemic has caused major shocks in mortality trends in many countries. Yet few studies have evaluated the heterogeneity of the mortality shock at the sub-national level, rigorously accounting for the different sources of uncertainty.Methods: Using death registration data from Belgium, we first assess the change in the heterogeneity of subnational standardized mortality ratios in 2020, when compared to previous years. We then measure the shock of the pandemic using district-level values of life expectancy, comparing the observed and projected districts life expectancy, accounting for all sources of uncertainty (related to the life-table construction at district level and to the projection methods at country and district level). The Bayesian modelling approach makes it easy to combine the different sources of uncertainty in the assessment of the shock. This is of particular interest at a finer geographical scale characterized by high stochastic variation in annual death counts.Results: The heterogeneity in the impact of the pandemic on all-cause mortality across districts is substantial, with some districts barely showing any impact whereas the Bruxelles-Capital and Mons districts experienced a decrease in life expectancy at birth of 2.24 (95% CI:1.33-3.05) and 2.10 (95% CI:0.86-3.30) years, respectively. The year 2020 was associated with an increase in mortality levels ' heterogeneity at a subnational level in comparison to past years measured by both the standardized mortality ratios and the life expectancies at birth. Decisions on uncertainty thresholds have a large bearing on the interpretation of the results.Conclusion: Developing sub-national mortality estimates with their uncertainty is key to understanding why certain areas have been hard hit in comparison to others.

Causes of Death during the First COVID-19 Pandemic Wave in Italy: A Comparison with Some European Countries

Studies comparing cause-of-death patterns across countries during the COVID-19 outbreak are still lacking although such studies would contribute to the understanding of the direct and indirect effect of the virus on mortality. In this report, we compare the mortality pattern observed in Italy during the first pandemic wave (March–April 2020) with that of some European countries. We calculated cause-specific, age-standardized mortality ratios (SMR) for Spain, England, and Sweden for the two mentioned months from 2016 to 2020, using already published data. Although Italy presented the highest crude overall mortality rate (267 per 100,000 population), age-adjusted ratios showed that all-cause and COVID-19 mortality in Italy were higher than in Sweden but lower than in the other two countries. Some causes had a similar increase in 2020 compared to previous years in all countries, i.e., endocrine diseases (especially diabetes), dementia and Alzheimer’s (in general mental disorders), and hypertensive heart diseases. Conversely, respiratory diseases, in particular pneumonia and influenza, increased to a greater extent in Italy. This latter result could be, in part, related to the underreporting of COVID-19 on death certificates during the first period of the pandemic, when Italy was the first European country severely hit by the virus.

Chronic Kidney Disease Among Workers Exposed To Perfluorooctanoic Acid (PFOA)

Background: Perfluorooctanoic acid (PFOA), a class of perfluorocarbons, are synthetic environmental contaminants. Their long biological half-lives and their poor ability to metabolize likely add to any chronic health effects they may pose, such as chronic kidney disease (CKD). The causal relationship between PFOA and CKD is still unclear, so it is necessary to look for some evidence regarding this relationship. The search for evidence is also complemented by a seven-step occupational disease assessment to establish occupational diseases. Aim: This study aims to justify chronic kidney disease of workers exposed to perfluorooctanoic acid can be diagnosed as occupational diseases.Methods: Searching literature for the evidence-based has been conducted with a clinical question through “PICO” method. Then continued with literature searching using the electronic database “PubMed”, “JSTOR”, and “Scopus” search engine. The keyword is “PFOA” “perfluoroalkyl substances” “perfluorooctanoic acid” “chronic kidney” “chronic kidney disease” “CKD” and combined with MeSH terms and Boolean operation. The inclusion criteria are research on humans, English language, and the exclusion is retracted articles.Result: From the five literatures obtained, there are differences in results. A study of workers exposed to perfluorooctanoic acid in a DuPont chemical plant with chronic kidney disease was (Standardized Mortality Ratios (SMR) = 3.11, 95% CI: 1.66, 5.32). Study in China found that perfluorooctanoic acid is not associated with renal function and higher risk of CKD (OR = 0.73, 95% CI: 0.57, 0.95; p=0.019).Conclusion: There are insignificant associations between perfluorooctanoic acid and chronic kidney disease.

Incidence and Risk Factors for Cerebrovascular-Specific Mortality in Patients with Colorectal Cancer: A Registry-Based Cohort Study Involving 563298 Patients

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from Surveillance Epidemiology and End Results database with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general US population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during study period. While age and surgery positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, more recent year (2001-2015) of diagnosis as well as multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM, which may be helpful for risk stratification and therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

Cause of Death After Surgical Aortic Valve Replacement: SWEDEHEART Observational Study

Background Prior studies showed that life expectancy in patients who underwent surgical aortic valve replacement (AVR) was lower than in the general population. Explanations for this shorter life expectancy are unknown. The aim of this nationwide, observational cohort study was to investigate the cause‐specific death following surgical AVR. Methods and Results We included 33 018 patients who underwent primary surgical AVR in Sweden between 1997 and 2018, with or without coronary artery bypass grafting. The SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) register and other national health‐data registers were used to obtain and characterize the study cohort and to identify causes of death, categorized as cardiovascular mortality, cancer mortality, or other causes of death. The relative risks for cause‐specific mortality in patients who underwent AVR compared with the general population are presented as standardized mortality ratios. During a mean follow‐up period of 7.3 years (maximum 22.0 years), 14 237 (43%) patients died. The cumulative incidence of death from cardiovascular, cancer‐related, or other causes was 23.5%, 8.3%, and 11.6%, respectively, at 10 years, and 42.8%, 12.8%, and 23.8%, respectively, at 20 years. Standardized mortality ratios for cardiovascular, cancer‐related, and other causes of death were 1.79 (95% CI, 1.75–1.83), 1.00 (95% CI, 0.97–1.04), and 1.08 (95% CI, 1.05–1.12), respectively. Conclusions We found that life expectancy following AVR was lower than in the general population. Lower survival after AVR was explained by an increased relative risk of cardiovascular death. Future studies should focus on the role of earlier surgery in patients with asymptomatic aortic stenosis and on optimizing treatment and follow‐up after AVR. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02276950.

Predictors of Mortality and Outcomes of Liver Transplant in Spur Cell Hemolytic Anemia

BACKGROUND : Spur cell hemolytic anemia (SCHA) is a rare, acquired, non-immune hemolytic anemia of decompensated cirrhosis resulting from abnormal lipid composition of the red cell membrane. Treatment is limited to red cell transfusion. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited; published data on SCHA are limited to single-patient case reports and small single-center case series. The independent prognostic impact of SCHA on patients with cirrhosis remains unclear, and it is not known if hemolytic anemia severity has a significant impact on survival of these patients. As a result, SCHA is not formally considered during liver transplant evaluation, and patients do not receive MELD exception points for this diagnosis. METHODS : We performed a multicenter, 24-year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long-term outcomes of liver transplant. Strict diagnostic criteria for SCHA were applied, requiring all of the following: (1) decompensated cirrhosis; (2) anemia; (3) objective laboratory evidence of hemolysis; (4) no alternate contributing cause of hemolysis or acanthocytosis; and (5) chart documentation of a confirmed diagnosis of SCHA incorporating peripheral blood film examination. The primary outcome was mortality at 3 months after date of SCHA diagnosis. The impact of hemolytic parameters on 3-month mortality was evaluated utilizing multivariable logistic models. Observed mortality vs. expected mortality (per MELD-Na score and Child-Turcotte-Pugh class) was compared using standardized mortality ratios. Given the limited survival of this population, red cell transfusion dependence was defined as 4 or more units of red cells transfused during the 60-day peri-diagnostic period. RESULTS : Patients: 69 patients with SCHA were included (FIGURE 1). The median (interquartile range) age was 53 (42-59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Alcohol contributed to the etiology of cirrhosis in 53 patients (76.8%). The median (IQR) survival from SCHA diagnosis of patients not receiving liver transplant was 58 (23-113) days. 39 patients (56.5%) were red cell transfusion-dependent. Hematologic parameters are described in TABLE 1. Outcomes of Liver Transplant: All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with an improvement in median hematocrit from 22.1% to 34.6% post-transplant (P=0.001) (TABLE 2) and excellent post-transplant outcomes, with 9 patients still alive after 6.1 years median follow-up. Independent Predictors of Mortality in SCHA: In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child-Turcotte-Pugh score, transfusion dependence had an OR for 90-day mortality of 9.14 (95% CI, 2.46-34.00) and reduced pre-transfusion hematocrit had an OR of 4.73 (95% CI, 1.42-15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90-day mortality (FIGURE 2). Performance of MELD-Na and Child-Turcotte-Pugh Scores in Estimating 90-Day Mortality: MELD-Na and Child-Turcotte-Pugh scores consistently significantly underestimated 90-day mortality, with standardized mortality ratios (SMRs) &gt;1 across all scores/classes [MELD-Na 20-29, SMR 2.42 (1.18-4.44); Child-Turcotte-Pugh class B, SMR 4.46 (1.64-9.90)], FIGURE 3. CONCLUSIONS : In this largest study of SCHA to date, SCHA was associated with substantial excess mortality than was predicted by MELD-Na or Child-Turcotte-Pugh scores. Several clinical and laboratory parameters of hemolytic anemia severity, including transfusion burden, hemoglobin, and markers of hemolysis were each independent predictors of 90-day mortality in SCHA. Despite its unique morbidity as a complication of decompensated cirrhosis, outcomes of liver transplant were excellent in all 11 patients undergoing this intervention, with total resolution of SCHA and no evidence of recurrence. These findings should promote greater awareness of SCHA as a clinical entity and broader consideration of MELD exception points for afflicted patients when transplant-eligible. Figure 1 Figure 1. Disclosures Al-Samkari: Novartis: Consultancy; Amgen: Research Funding; Argenx: Consultancy; Rigel: Consultancy; Dova/Sobi: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Moderna: Consultancy.

Population-Based Study on the All-Cause and Cause-Specific Risks of Mortality among Long-Term Opioid Analgesics Users without Cancer in Taiwan

(1) Background: The prevalence of opioid use in Taiwan increased by 41% between 2002 and 2014. However, little is known regarding the risk of mortality among long-term opioid analgesics users who do not have cancer. This study investigated this mortality risk with an emphasis on the calendar year and patients’ age and sex. (2) Methods: This retrospective cohort study included 12,990 adult individuals without cancer who were long-term users of opioid analgesics and were randomly selected from the data set of Taiwan’s National Health Insurance program from 2000 to 2012. They were then followed up through 2013. Information on the underlying causes of death was retrieved from the Taiwan Death Registry. Age, sex, and calendar year-standardized mortality ratios (SMRs) of all-cause and cause-specific mortality were calculated with reference to those of the general population. (3) Results: With up to 14 years of follow-up, 558 individuals had all-cause mortality in 48,020 person-years (cumulative mortality: 4.3%, mortality rate: 11.62 per 1000 person-years). Compared with the general population, the all-cause SMR of 4.30 (95% confidence interval (95% CI): 3.95–4.66) was significantly higher: it was higher in men than in women, declined with calendar year and age, and was significantly higher for both natural (4.15, 95% CI: 3.78–4.53) and unnatural (5.04, 95% CI: 3.88–6.45) causes. (4) Conclusions: Long-term opioid analgesics use among individuals without cancer in Taiwan was associated with a significantly increased risk of mortality. The notably increased mortality in younger adults warrants attention. Strategies to reduce long-term opioid analgesics use, especially their overuse or misuse, are in an urgent need.

Before, During, and After the First Wave of COVID-19: Mortality Analyses Reveal Relevant Trends in Germany and its States until June 2020

ABSTRACT Objective Well-established mortality ratio methodology can contribute to a fuller picture of the SARS-CoV-2/COVID-19 burden of disease by revealing trends and informing mitigation strategies. This work examines respective data from Germany by way of example. Methods Using monthly and weekly all-cause mortality data from January 2016 to June 2020 (published by the German Federal Statistical Institute) for all ages,<65 years and≥65 years, and specified for Germany’s federal states, we explored mortality as sequela of COVID-19. We analysed standardized mortality ratios (SMRs) comparing 2020 with 2016–2019 as reference years with a focus on trend detection. Results In Germany as a whole, elevated mortality in April (most pronounced for Bavaria) declined in May. The states of Hamburg and Bremen had increased SMRs in all months under study. In Mecklenburg-Western Pomerania, decreased SMRs in January turned monotonically to increased SMRs by June. Irrespective of age group, this trend was pronounced and significant. Conclusions Increased SMRs in Hamburg and Bremen must be interpreted with caution because of potential upward distortions due to a “catchment bias”. A pronounced excess mortality in April across Germany was confirmed and a hitherto undetected trend of increasing SMRs for Mecklenburg-Western Pomerania was revealed. To meet the pandemic challenge and to benefit from research based on data collected in standardized ways, national authorities should regularly conduct SMR analyses. For independent analyses, national authorities should also expedite publishing raw mortality and population data, including detailed information on age, sex, and cause of death, in the public domain.