Competing causes of death in patients with neuroendocrine tumor.

e23009 Background: Increasing survival of patients with neuroendocrine tumors (NETs) may be associated with higher risk of mortality due to causes other than the primary NET, namely the competing causes of death (CCD). Therefore, our study focused on comprehensively investigating the magnitude of the CCD on the overall NET mortality and the associated demographic, clinicopathologic and treatment factors using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients with histologically confirmed primary NET diagnosed from 1973 through 2015 were identified using the SEER-9 registries for subsequent data collection and analysis. CCD were stratified and analyzed using standardized mortality ratios (SMRs) as measures of the relative risks of mortality for NET patients in comparison to the general population in the US adjusted by age, sex and race over the same time period. Competing risk regression analysis was performed using Fine and Gray multivariate regression model. Results: A total of 29,981 NET patients were included, 5481 (42.5%) of which deceased due to CCD. Overall SMR attributed to CCD was 2.50 [95% Confidence interval (CI): 2.43–2.56]. The SMR of non-cancer CCD was 2.65 (95% CI:2.58–2.73) and that of SPN was 1.91 (95% CI:1.79–2.04). Heart diseases and other cardiovascular diseases accounted for approximately half of all non-cancer CCD. SPN mortality accounted for 16.1% of CCD, with lung and bronchus cancer being the most prevalent. Stratification by the year of diagnosis revealed a drastic rise in CCD was observed in the last decade between 2005 and 2015, during which the SMR peaked. Advanced age, black race, small intestinal and gastric NETs, and cancer-directed surgery were significantly associated with an increased risk of CCD (p<0.001). Interestingly, female sex, pancreatic NETs, recto-anal NETs, NETs of unknown primary site, race other than white and black, distant and regional spread, chemotherapy and radiotherapy were significantly associated with a decrease in the incidence of CCD. Conclusions: CCD play an increasingly significant role in NET mortality in recent years, especially for those with higher risk of CCD. Further prospective studies are needed to evaluate the association of NETs with these CCD.

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Cohort Differences in the Associations of Selected Candidate Genes With Risk of All-Cause Mortality at Advanced Ages

American Journal of Epidemiology ◽

10.1093/aje/kwaa007 ◽

2020 ◽

Vol 189 (7) ◽

pp. 708-716

Author(s):

Qihua Tan ◽

Rune Jacobsen ◽

Marianne Nygaard ◽

Mette Soerensen ◽

Jonas Mengel-From ◽

...

Keyword(s):

Candidate Genes ◽

Survival Data ◽

Cohort Effect ◽

Human Longevity ◽

Environment Interaction ◽

Relative Risks ◽

Cohort Differences ◽

Risk Of Mortality ◽

Gene Environment ◽

Increased Risk

Abstract Considerable efforts have been made to identify the genetic basis of human longevity, with only limited progress. One important drawback of current genetic studies is the limited knowledge of gene-environment interaction. Using 2 cohorts of long-lived individuals born in 1905 and 1915 in Denmark, we performed survival analysis to estimate risk of mortality for major candidate genes of aging and longevity and their cohort effects. Through statistical modeling that combines individual genetic and survival information with cohort-specific survival data, we estimated the relative risks of mortality from ages 95 to 103 years associated with genetic variants in apolipoprotein E (APOE), forkhead box class O3a, clusterin, and phosphatidylinositol binding clathrin assembly protein. Our analysis estimated a decreased risk of carrying the APOE$\varepsilon $4 allele (change in risk = –0.403, 95% confidence interval (CI): −0.831, 0.021; P = 0.040) in men of the later cohort, although the allele itself was harmful to survival across sexes (relative risk = 1.161, 95% CI: 1.027, 1.345; P = 0.026). We also estimated a cohort effect of increased risk for the minor allele of rs3851179 in phosphatidylinositol binding clathrin assembly protein with borderline significance (change in risk = 0.165, 95% CI: −0.010, 0.331; P = 0.052) in women. Our estimated significant cohort effect on APOE$\varepsilon $4 is indicative of the interplay between the gene and the changing environment that modulates survival at extreme ages.

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Unraveling the Association Between Gait and Mortality—One Step at a Time

The Journals of Gerontology Series A ◽

10.1093/gerona/glz282 ◽

2019 ◽

Vol 75 (6) ◽

pp. 1184-1190 ◽

Cited By ~ 2

Author(s):

Lisanne J Dommershuijsen ◽

Berna M Isik ◽

Sirwan K L Darweesh ◽

Jos N van der Geest ◽

M Kamran Ikram ◽

...

Keyword(s):

Mortality Risk ◽

Gait Speed ◽

Causes Of Death ◽

Health Indicators ◽

Cox Models ◽

Risk Of Mortality ◽

Increased Risk ◽

Specific Mortality ◽

One Step ◽

Base Of Support

Abstract Background Slowness of walking is one of the very first signs of aging and is considered a marker for overall health that is strongly associated with mortality risk. In this study, we sought to disentangle the clinical drivers of the association between gait and mortality. Methods We included 4,490 participants of the Rotterdam Study who underwent a gait assessment between 2009 and 2015 and were followed-up for mortality until 2018. Gait was assessed with an electronic walkway and summarized into the domains Rhythm, Phases, Variability, Pace, Tandem, Turning, and Base of Support. Cox models adjusted for age, sex, and height were built and consecutively adjusted for six categories of health indicators (lifestyle, musculoskeletal, cardiovascular, pulmonary, metabolic, and neurological). Analyses were repeated in comorbidity-free individuals. Results Multiple gait domains were associated with an increased risk of mortality, including Pace (hazard ratio (HR) per SD worse gait, adjusted for other domains: 1.34 [1.19–1.50]), Rhythm (HR: 1.12 [1.02–1.23]) and Phases (HR: 1.12 [1.03–1.21]). Similarly, a 0.1 m/s decrease in gait speed was associated with a 1.21 (1.15–1.27) times higher hazard of mortality (HR fully adjusted: 1.14 [1.08–1.20]). In a comorbidity-free subsample, the HR per 0.1 m/s decrease in gait speed was 1.25 (1.09–1.44). Cause-specific mortality analyses revealed an association between gait speed and multiple causes of death. Conclusions Several gait domains were associated with mortality risk, including Pace which primarily represents gait speed. The association between gait speed and mortality persisted after an extensive adjustment for covariates, suggesting that gait is a marker for overall health.

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Hypertension and the Risk of All-Cause and Cause-Specific Mortality: An Outcome-Wide Association Study of 67 Causes of Death in the National Health Interview Survey

BioMed Research International ◽

10.1155/2021/9376134 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Dagfinn Aune ◽

Wentao Huang ◽

Jing Nie ◽

Yafeng Wang

Keyword(s):

Heart Disease ◽

Causes Of Death ◽

Motor Vehicle ◽

Heart Diseases ◽

Uterine Cancer ◽

Ischemic Heart ◽

Circulatory Disease ◽

Increased Risk ◽

Circulatory System Diseases ◽

All Cause Mortality

Background. Few studies have assessed the association between hypertension and risk of detailed causes of death. We investigated the association between hypertension and all-cause mortality and 67 causes of death in a large cohort. Methods. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for self-reported hypertension vs. no hypertension and mortality. Adults aged ≥18 years ( n = 213798 ) were recruited in 1997-2004 and followed through December 31, 2006. Results. During 5.81 years of follow-up, 11254 deaths occurred. Self-reported hypertension vs. no hypertension was associated with increased risk of all-cause mortality ( HR = 1.25 , 95% CI: 1.19-1.31) and mortality from septicemia (HR =1.66, 1.06-2.59), other infectious parasitic diseases ( HR = 2.67 , 1.09-6.51), diabetes mellitus ( HR = 1.97 , 1.45-2.67), circulatory disease ( HR = 1.49 , 1.37-1.61), hypertensive heart disease ( HR = 3.23 , 2.00-5.20), ischemic heart disease ( HR = 1.35 , 1.23-1.49), acute myocardial infarction ( HR = 1.50 , 1.27-1.77), other chronic ischemic heart diseases ( HR = 1.35 , 1.17-1.56), all other forms of heart disease ( HR = 1.51 , 1.21-1.89), primary hypertension and renal disease ( HR = 3.11 , 1.82-5.30), cerebrovascular disease ( HR = 1.64 , 1.37-1.97), other circulatory system diseases ( HR = 1.71 , 1.09-2.69), other chronic lower respiratory diseases ( HR = 1.39 , 1.12-1.73), other chronic liver disease ( HR = 1.89 , 1.06-3.37), renal failure ( HR = 1.91 , 1.33-2.74), motor vehicle accidents ( HR = 1.60 , 1.07-2.37), and all other diseases (HR =1.30, 1.10-1.54), but with lower risk of uterine cancer ( HR = 0.37 , 95% CI: 0.15-0.90) and Alzheimer’s disease ( HR = 0.65 , 95% CI: 0.47-0.92). Conclusion. Hypertension was associated with increased risk of all-cause mortality and 17 out of 67 causes of death, with most of these being circulatory disease outcomes, however, some of the remaining associations are unlikely to be causal. Further studies are needed to clarify associations with less common causes of death and potential causality across outcomes.

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Birth Defects in Twins: Study in a Spanish Population

Acta geneticae medicae et gemellologiae twin research ◽

10.1017/s0001566000003524 ◽

1991 ◽

Vol 40 (3-4) ◽

pp. 337-344 ◽

Cited By ~ 26

Author(s):

M.A. Ramos-Arroyo

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Birth Defects ◽

Congenital Malformations ◽

Collaborative Study ◽

Congenital Defects ◽

Relative Risks ◽

Increased Risk ◽

The Central Nervous System ◽

Using Data

AbstractThe risk for specific defects among twins compared to singletons was studied using data collected by the Spanish Collaborative Study of Congenital Malformations (ECEMC). A total of 136 twins had a major and/or minor congenital defect. The overall rate of congenital defects in twins (2.37%) did not deviate significantly from the rate in singletons (2.21%). Like-sex (LS) and male-male (MM) twin pairs had a slightly higher rate of birth defects than unlike-sex (US) and female-female (FF) pairs, respectively. Defects of the central nervous system, cardiovascular system and genitourinary system were significantly more frequent in LS twins than in singletons, with relative risks of 2.8, 2.5 and 1.6, respectively. No significantly increased risk was found among US twins. Among defects of the central nervous system, the rates of anencephaly, encephalocele and hydrocephaly were significantly higher in total and LS twins; however, no significantly increased risk for spina bifida was observed when compared to singletons. MM twins were also 1.9 times more likely to have hypospadias, but the risk among males of male-female (FM) pairs was decreased.

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Association of Sex, Age, and Comorbidities with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis

Intervirology ◽

10.1159/000512592 ◽

2020 ◽

pp. 1-12

Author(s):

Mohitosh Biswas ◽

Shawonur Rahaman ◽

Tapash Kumar Biswas ◽

Zahirul Haque ◽

Baharudin Ibrahim

Keyword(s):

Systematic Review ◽

Cardiovascular Disease ◽

Meta Analysis ◽

Statistical Significance ◽

Considerable Proportion ◽

Relative Risks ◽

Risk Of Mortality ◽

Increased Risk ◽

Male Patients ◽

Reduce Risk

Introduction: Although severe acute respiratory syndrome coronavirus-2 infection is causing mortality in considerable proportion of coronavirus disease-2019 (COVID-19) patients, however, evidence for the association of sex, age, and comorbidities on the risk of mortality is not well-aggregated yet. It was aimed to assess the association of sex, age, and comorbidities with mortality in COVID-2019 patients. Methods: Literatures were searched using different keywords in various databases. Relative risks (RRs) were calculated by RevMan software where statistical significance was set as p < 0.05. Results: COVID-19 male patients were associated with significantly increased risk of mortality compared to females (RR 1.86: 95% confidence interval [CI] 1.67–2.07; p < 0.00001). Patients with age ≥50 years were associated with 15.4-folds significantly increased risk of mortality compared to patients with age <50 years (RR 15.44: 95% CI 13.02–18.31; p < 0.00001). Comorbidities were also associated with significantly increased risk of mortality; kidney disease (RR 4.90: 95% CI 3.04–7.88; p < 0.00001), cereborovascular disease (RR 4.78; 95% CI 3.39–6.76; p < 0.00001), cardiovascular disease (RR 3.05: 95% CI 2.20–4.25; p < 0.00001), respiratory disease (RR 2.74: 95% CI 2.04–3.67; p < 0.00001), diabetes (RR 1.97: 95% CI 1.48–2.64; p < 0.00001), hypertension (RR 1.95: 95% CI 1.58–2.40; p < 0.00001), and cancer (RR 1.89; 95% CI 1.25–2.84; p = 0.002) but not liver disease (RR 1.64: 95% CI 0.82–3.28; p= 0.16). Conclusion: Implementation of adequate protection and interventions for COVID-19 patients in general and in particular male patients with age ≥50 years having comorbidities may significantly reduce risk of mortality associated with COVID-19.

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A Genotyped Case of Townes–Brocks Syndrome with Absent Pulmonary Valve Syndrome from Turkey

Journal of Pediatric Genetics ◽

10.1055/s-0041-1740371 ◽

2021 ◽

Author(s):

Ozkan Ilhan ◽

Evren Gumus ◽

Nilay Hakan ◽

Hande Istar ◽

Bugra Harmandar ◽

...

Keyword(s):

Surgical Repair ◽

Pulmonary Valve ◽

Heart Diseases ◽

Definitive Diagnosis ◽

Absent Pulmonary Valve ◽

Risk Of Mortality ◽

Increased Risk ◽

Conductive Hearing ◽

Absent Pulmonary Valve Syndrome

AbstractTownes–Brocks syndrome (TBS) is a rare syndrome characterized by triad of anal, ear, and thumb anomalies. Further malformations/anomalies include congenital heart diseases, foot malformations, sensorineural and/or conductive hearing impairment, genitourinary malformations, and anomalies of eye and nervous system. Definitive diagnosis for TBS is confirmed by molecular analysis for mutations in the SALL1 gene. Only one known case of TBS with absent pulmonary valve syndrome (APVS) has been previously described to our knowledge. Here, we report a newborn diagnosed with TBS with APVS and tetralogy of Fallot (TOF) who was found to carry the most common pathogenic SALL1 gene mutation c.826C > T (p.R276X), with its surgical repair and postoperative follow-up. To our knowledge, this is the first genotyped case of TBS from Turkey to date. TBS should be suspected in the presence of ear, anal, and thumb malformations in a neonate. If a patient with TBS and TOF-APVS needs preoperative ventilation within the first months of life, this implies prolonged postoperative intubation and increased risk of mortality.

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Hyperkalemia excursions are associated with an increased risk of mortality and hospitalizations in hemodialysis patients

Clinical Kidney Journal ◽

10.1093/ckj/sfaa208 ◽

2020 ◽

Author(s):

Angelo Karaboyas ◽

Bruce M Robinson ◽

Glen James ◽

Katarina Hedman ◽

Carol P Moreno Quinn ◽

...

Keyword(s):

Clinical Outcomes ◽

Cox Regression ◽

Target Range ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality ◽

Using Data ◽

Dialysis Outcomes ◽

Mortality Hazard Ratio ◽

New Strategies

Abstract Background Hyperkalemia is common among hemodialysis (HD) patients and has been associated with adverse clinical outcomes. Previous studies considered a single serum potassium (K) measurement or time-averaged values, but serum K excursions out of the target range may be more reflective of true hyperkalemia events. We assessed whether hyperkalemia excursions lead to an elevated risk of adverse clinical outcomes. Methods Using data from 21 countries in Phases 4–6 (2009–18) of the Dialysis Outcomes and Practice Patterns Study (DOPPS), we investigated the associations between peak serum K level, measured monthly predialysis, over a 4-month period (‘peak K’) and clinical outcomes over the subsequent 4 months using Cox regression, adjusted for potential confounders. Results The analysis included 62 070 patients contributing a median of 3 (interquartile range 2–6) 4-month periods. The prevalence of hyperkalemia based on peak K was 58% for >5.0, 30% for >5.5 and 12% for >6.0 mEq/L. The all-cause mortality hazard ratio for peak K (reference ≤5.0 mEq/L) was 1.15 [95% confidence interval (CI) 1.09, 1.21] for 5.1–5.5 mEq/L, 1.19 (1.12, 1.26) for 5.6–6.0 mEq/L and 1.33 (1.23, 1.43) for >6.0 mEq/L. Results were qualitatively consistent when analyzing hospitalizations and a cardiovascular composite outcome. Conclusions Among HD patients, we identified a lower K threshold (peak K 5.1–5.5 mEq/L) than previously reported for increased risk of hospitalization and mortality, with the implication that a greater proportion (>50%) of the HD population may be at risk. A reassessment of hyperkalemia severity ranges is needed, as well as an exploration of new strategies for effective management of chronic hyperkalemia.

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

Healthcare ◽

10.3390/healthcare9111402 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1402

Author(s):

Po-Feng Lee ◽

Chung-Yi Li ◽

Yen-Chin Liu ◽

Chang-Ta Chiu ◽

Wen-Hsuan Hou

Keyword(s):

General Population ◽

Opioid Analgesics ◽

Population Based ◽

Opioid Use ◽

Data Set ◽

Risk Of Mortality ◽

Increased Risk ◽

Underlying Causes ◽

Standardized Mortality Ratios

(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.

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Survival in Restless Legs Syndrome: An 11-Year Surveillance, Community-Based Population Study

Neuroepidemiology ◽

10.1159/000508855 ◽

2020 ◽

Vol 54 (5) ◽

pp. 375-382

Author(s):

Esther Cubo ◽

Carla Collazo Riobo ◽

Cesar Gallego-Nieto ◽

Miren Elizari-Roncal ◽

Teresa Barroso-Pérez ◽

...

Keyword(s):

Regression Analysis ◽

General Population ◽

Restless Legs Syndrome ◽

Cox Regression ◽

Cox Regression Analysis ◽

Restless Legs ◽

Risk Of Mortality ◽

Increased Risk ◽

Standardized Mortality Ratios

Background: A growing body of evidence relates restless legs syndrome (RLS) to an increased risk of mortality attributable to both cerebrovascular and cardiovascular events. The aim was to investigate survival in patients with RLS. Methods: This was an observational, retrospective longitudinal study of a cohort of patients followed up for 11 years. RLS was diagnosed by a physician using the International RLS Study Group criteria. Mortality was analyzed using age-standardized mortality ratios (SMR: observed/expected deaths) and Cox regression analysis. Results: Vital status was studied in a cohort of 232 patients: 181 women (78%), 96 with RLS (41.4%) with a mean age at baseline of 49.8 ± 15.0 years and a mean RLS duration of 14.1 ± 1.9 years, and 136 non-RLS (58.6%) with a mean age of 51.3 ± 14.9 years. This RLS cohort was followed up for a period of 10.4 ± 2.0 years. As of September 2019, 17 (7.3%) patients died (6 with RLS, 6.3%), and the most frequent cause was oncological (66.7%). A total of 944 person-years of observations were available for survival analysis. RLS was not associated with increased mortality in adjusted Cox regression analysis (HR = 1.12, 95% CI: 0.40–3.15), and survival was similar to that expected for the general population (SMR = 0.61, 95% CI: 0.27–1.36). Conclusions: RLS seems not to be associated with increased mortality compared to the general population. Still, studies with prospective data collection with large samples are needed to study the long-term mortality risk factors in RLS cohorts.

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Mortality in Patients with Pituitary Disease

Endocrine Reviews ◽

10.1210/er.2009-0033 ◽

2010 ◽

Vol 31 (3) ◽

pp. 301-342 ◽

Cited By ~ 212

Author(s):

Mark Sherlock ◽

John Ayuk ◽

Jeremy W. Tomlinson ◽

Andrew A. Toogood ◽

Aurora Aragon-Alonso ◽

...

Keyword(s):

Future Research ◽

Pituitary Hormone ◽

Clear Cut ◽

Pituitary Disease ◽

Risk Of Mortality ◽

Increased Risk ◽

Control Tumor Growth ◽

Control Tumor ◽

Standardized Mortality Ratios ◽

Reduction Of Mortality

Pituitary disease is associated with increased mortality predominantly due to vascular disease. Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing’s disease and acromegaly, retrospectively. For patients with acromegaly, the role of IGF-I is less clear-cut. Confounding pituitary hormone deficiencies such as gonadotropins and particularly ACTH deficiency (with higher doses of hydrocortisone replacement) may have a detrimental effect on outcome in patients with pituitary disease. Pituitary radiotherapy is a further factor that has been associated with increased mortality (particularly cerebrovascular). Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed. Craniopharyngioma patients have a particularly increased risk of mortality as a result of the tumor itself and treatment to control tumor growth; this is a key area for future research in order to optimize the outcome for these patients.

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