Decline In All-cause Mortality Research Articles

Primary health care services for obesity and hypertension in sub-urban community: focus on nutrition

Medical nutrition therapy (MNT) is a major clinical care concept, especially for non-communicable diseases such as obesity and hypertension. Primary healthcare (PHC) centers are the first point of contact with health services and provide a point of entry for the entire health system. Research has revealed that access to primary healthcare services is associated with improved health outcomes, such as an improvement in self-rated health and a decline in all-cause mortality. However, the integration of MNT in hypertension and obesity management at PHC level is unclear. The aim of this study is to establish PHC services for obese and hypertensive individuals with a focus on nutrition, and the need for further research. Awareness of dietary approach to stop hypertension (DASH) among health workers, obese and hypertensive individuals and it utilization in practice was low in PHC centers this is due to lack of registered dietitians’ nutritionists who are trained in MNT which is complicated by lack of ministerial funding of PHC facilities.

The temporal trend of cause-specific mortality: comparing Estonia and Lithuania, 2001 – 2019

BackgroundDespite being two Baltic countries with similar histories, Estonia and Lithuania have diverged in life expectancy trends in recent years. We investigated this divergence by comparing cause-specific mortality trends.MethodsWe obtained yearly mortality data for individuals 20 + years of age from 2001–2019 (19 years worth of data) through Statistics Lithuania, the Lithuanian Institute for Hygiene, and the National Institute for Health Development (Estonia). Using ICD-10 codes, we analyzed all-cause mortality rates and created eight major disease categories: ischemic heart disease, cerebrovascular disease, all other cardiovascular disease, cancers (neoplasms), digestive diseases, self-harm and interpersonal violence, unintentional injuries and related conditions, and other mortality (deaths per 100,000 population). We used joinpoint regression analysis, and analyzed the proportional contribution of each category to all-cause mortality.ResultsThere was a steeper decline in all-cause mortality in Estonia (average annual percent change, AAPC = -2.55%, 95% CI: [-2.91%, -2.20%], P < .001) as compared to Lithuania (AAPC = -1.26%, 95% CI: [-2.18%, -0.57%], P = .001). For ischemic heart disease mortality Estonia exhibited a relatively larger decline over the 19-year period (AAPC = -6.61%, 95% CI: [-7.02%, -6.21%], P < .001) as compared to Lithuania (AAPC = -2.23%, 95% CI: [-3.40%, -1.04%], P < .001).ConclusionEstonia and Lithuania showed distinct mortality trends and distributions of major disease categories. Our findings highlight the role of ischemic heart disease mortality. Differences in public health care, management and prevention of ischemic heart disease, alcohol control policies may explain these differences.

Association Between Early Left Ventricular Ejection Fraction Improvement After Transcatheter Aortic Valve Replacement and 5-Year Clinical Outcomes

In patients with severe aortic stenosis and left ventricular ejection fraction (LVEF) less than 50%, early LVEF improvement after transcatheter aortic valve replacement (TAVR) is associated with improved 1-year mortality; however, its association with long-term clinical outcomes is not known. To examine the association between early LVEF improvement after TAVR and 5-year outcomes. This cohort study analyzed patients enrolled in the Placement of Aortic Transcatheter Valves (PARTNER) 1, 2, and S3 trials and registries between July 2007 and April 2015. High- and intermediate-risk patients with baseline LVEF less than 50% who underwent transfemoral TAVR were included in the current study. Data were analyzed from August 2020 to May 2021. Early LVEF improvement, defined as increase of 10 percentage points or more at 30 days and also as a continuous variable (ΔLVEF between baseline and 30 days). All-cause death at 5 years. Among 659 included patients with LVEF less than 50%, 468 (71.0%) were male, and the mean (SD) age was 82.4 (7.7) years. LVEF improvement within 30 days following transfemoral TAVR occurred in 216 patients (32.8%) (mean [SD] ΔLVEF, 16.4 [5.7%]). Prior myocardial infarction, diabetes, cancer, higher baseline LVEF, larger left ventricular end-diastolic diameter, and larger aortic valve area were independently associated with lower likelihood of LVEF improvement. Patients with vs without early LVEF improvement after TAVR had lower 5-year all-cause death (102 [50.0%; 95% CI, 43.3-57.1] vs 246 [58.4%; 95% CI, 53.6-63.2]; P = .04) and cardiac death (52 [29.5%; 95% CI, 23.2-37.1] vs 135 [38.1%; 95% CI, 33.1-43.6]; P = .05). In multivariable analyses, early improvement in LVEF (modeled as a continuous variable) was associated with lower 5-year all-cause death (adjusted hazard ratio per 5% increase in LVEF, 0.94 [95% CI, 0.88-1.00]; P = .04) and cardiac death (adjusted hazard ratio per 5% increase in LVEF, 0.90 [95% CI, 0.82-0.98]; P = .02) after TAVR. Restricted cubic spline analysis demonstrated a visual inflection point at ΔLVEF of 10% beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement. There were no statistically significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire Overall Summary score at 5 years in patients with vs without early LVEF improvement. In subgroup analysis, the association between early LVEF improvement and 5-year all-cause death was consistent regardless of the presence or absence of coronary artery disease or prior myocardial infarction. In patients with severe aortic stenosis and LVEF less than 50%, 1 in 3 experience LVEF improvement within 1 month after TAVR. Early LVEF improvement is associated with lower 5-year all-cause and cardiac death.

Trends in Etiology-based Mortality From Chronic Liver Disease Before and During COVID-19 Pandemic in the United States

Background & AimsDuring the global coronavirus disease 2019 (COVID-19) pandemic, patients with pre-existing chronic liver disease may represent a vulnerable population. We studied the etiology-based temporal trends in mortality of chronic liver disease and the underlying cause of death in the United States before and during the COVID-19 pandemic.MethodsPopulation-based analyses were performed on United States national mortality records (2017–2020). Temporal trends in quarterly age-standardized mortality were obtained by joinpoint analysis with estimates of quarterly percentage change (QPC).ResultsQuarterly age-standardized all-cause mortality due to alcohol-related liver disease (ALD) initially increased at a quarterly rate of 1.1% before the COVID-19 pandemic, followed by a sharp increase during the COVID-19 pandemic at a quarterly rate of 11.2%. Likewise, steady increase in mortality of nonalcoholic fatty liver disease before the COVID-19 pandemic (QPC, 1.9%) accelerated during the COVID-19 pandemic (QPC, 6.6%). Although ALD-related mortality increased steeply compared with viral hepatitis-related mortality during the COVID-19 pandemic, the proportion of mortality due to COVID-19 among individuals with ALD was the lowest at 2.5%; more than 50% lower than viral hepatitis. The significant decline in all-cause mortality due to viral hepatitis before the COVID-19 pandemic plateaued during the COVID-19 pandemic due to increase in COVID-19-related mortality in individuals with viral hepatitis. Mortality due to cirrhosis increased markedly during the COVID-19 pandemic, mainly attributable to ALD.ConclusionAll-cause mortality for ALD and nonalcoholic fatty liver disease rapidly accelerated during the COVID-19 pandemic compared with the pre-COVID-19 era. There has been a significant decline in viral hepatitis; however, a significant increase in COVID-related death in this population.

Sex stratification of the trends and risk of mortality among individuals living with HIV under different transmission categories

We retrospectively examined 33,142 persons living with HIV (PLWH) in Taiwan from a nationwide database to assess sex-stratified trends and risk of all-cause mortality under different transmission categories from 1984 to 2016. Overall, 61.25% were men who have sex with men (MSM), 14.37% were men who have sex with women (MSW), 18.32% were male persons who inject drugs (M-PWID), 3.30% were women who have sex with men (WSM), and 2.74% were female PWID (F-PWID). All-cause mortality (per 100 person-years) among heterosexual people and PWID was higher in men (4.04 and 3.39, respectively) than in women (2.93 and 2.18, respectively). In each sex-stratified transmission category, the all-cause mortality reduced substantially from 1984–1996 to 2012–2016, but evolved distinctly from 2007–2011 to 2012–2016. Since 2007–2011, the decline in all-cause mortality has slowed notably in the groups with sexually transmitted HIV, but has increased in PWID, surpassing even that among groups with sexually transmitted HIV in 2012–2016. PLWH with sexually transmitted HIV had lower risks of all-cause mortality than PWID, regardless of sex. Sex and transmission category did not interact significantly on all-cause mortality. Understanding the reasons for the distinct evolving trends of all-cause mortality in each transmission category serves as a reference for developing strategies to reduce mortality in PLWH in Taiwan further.

Decomposing County-Level Working-Age Mortality Trends in the United States Between 1999–2001 and 2015–2017

Studies have documented significant geographic divergence in U.S. mortality in recent decades. However, few studies have examined the extent to which county-level trends in mortality can be explained by national, state, and metropolitan-level trends, and which county-specific factors contribute to remaining variation. Combining vital statistics data on deaths and Census data with time-varying county-level contextual characteristics, we use a spatially explicit Bayesian hierarchical model to analyze the associations between working-age mortality, state, metropolitan status and county-level socioeconomic conditions, family characteristics, labor market conditions, health behaviors, and population characteristics between 2000 and 2017. Additionally, we employ a Shapley decomposition to illustrate the additive contributions of each changing county-level characteristic to the observed mortality change in U.S. counties between 1999–2001 and 2015–2017 over and above national, state, and metropolitan–nonmetropolitan mortality trends. Mortality trends varied by state and metropolitan status as did the contribution of county-level characteristics. Metropolitan status predicted more of the county-level variance in mortality than state of residence. Of the county-level characteristics, changes in percent college-graduates, smoking prevalence and the percent of foreign-born population contributed to a decline in all-cause mortality over this period, whereas increasing levels of poverty, unemployment, and single-parent families and declines manufacturing employment slowed down these improvements, and in many nonmetropolitan areas were large enough to overpower the positive contributions of the protective factors.

Reduction in Late Mortality after Autologous Blood or Marrow Transplantation (autoBMT) in Childhood - a Report from the Blood or Marrow Transplant Survivor Study-2 (BMTSS-2)

Background: AutoBMT is used with a curative intent for several types of childhood cancer. However, there is paucity of information regarding the long-term outcome after autoBMT performed in childhood, and whether mortality rates have changed over the past 4 decades. We address these gaps by examining all-cause, relapse-related [RRM] and non-relapse-related [NRM] mortality in patients undergoing autoBMT between 1980 and 2010 at City of Hope, University of Minnesota or University of Alabama at Birmingham. Methods: To be included in this analysis, patients had to have received a single autoBMT before age 22y, and survived ≥2y after transplantation. Vital status information was ascertained as of December 31, 2016, using medical records, the National Death Index (NDI), and Accurint databases. Information on the cause of death was obtained from the NDI Plus program and medical records. Using Kaplan-Meier techniques, we describe overall survival conditional on surviving 2y and 15y from autoBMT. We describe cumulative incidence of RRM and NRM using competing risk methods. We also describe trends in all-cause mortality over 3 time periods: <1990, 1990-1999 and 2000-2010. Standardized mortality ratio (SMR) was used to compare the mortality of this cohort to the age- sex-, and calendar-specific mortality of the US general population. Proportional subdistribution hazards model (Fine-Gray) for competing risks was used for identifying predictors of late mortality (demographics, primary disease, conditioning agents, and disease status at autoBMT). Results: In this cohort of 364 2+y survivors of autoBMT performed in childhood, the most common primary diagnoses were Hodgkin lymphoma (HL: 26%), neuroblastoma (23%), acute myeloid leukemia (AML: 13%), acute lymphoblastic leukemia (ALL: 12%), and non-Hodgkin lymphoma (NHL: 9%). The distribution of the cohort over the 3 time periods was: <1990 (20%); 1990-1999 (37%); 2000-2010 (43%). After a median follow-up of 14.2y, 104 deaths were observed in this 2+y survivor cohort. The leading causes of death included primary disease (49.5%), subsequent malignant neoplasms (21.0%) and infection (18.2%). The 10y cumulative incidence of RRM (13.6%) exceeded that of NRM (10.2%) (Fig 1). Overall, the cohort was at a 23-fold higher risk of late mortality (SMR 23.6, 95% CI 19.3-28.6), when compared with the general population. The SMR was significantly increased in all groups of primary diagnoses; ALL (SMR 27.0), AML (SMR 7.8), HL (SMR 15.1), NHL (SMR 13.5), and neuroblastoma (SMR 60.7). Conditional on surviving 2y, 5y, 10y and 15y, the overall survival was 81.9%, 91.4%, 95.6% and 99.4%, respectively. Mortality rates continued to remain higher than the general population among those who had survived at least 10y after autoBMT (SMR 12.4, 95% CI 4.9-25.1), but approached those of the general population among the 15+y survivors (SMR 3.0, 95%CI, 0.5-9.4). The all-cause 10y cumulative mortality rate declined over the 3 eras (<1990: 35.1%, 1990-1999: 24.4%; 2000-2010: 20.6%, p=0.02) (Fig 2). Adjusting for demographic and clinical variables, as well as preparative regimens, the hazard ratio (HR) of all-cause mortality declined in the more recent treatment eras (<1990 (referent group): HR=1.0; 1990-1999: HR=0.5, 95%CI, 0.3-0.9, p=0.02; 2000-2010: HR=0.4, 95%CI, 0.2-0.8, p=0.007). Conclusion: Taken together, these findings suggest that the mortality rates of autoBMT recipients are significantly higher than those of the general population. Relapse is the leading cause of death for the first 10y after autoBMT. Importantly, there has been a significant decline in all-cause mortality in children undergoing autoBMT over the past 4 decades. [Display omitted] DisclosuresArora:Takeda Oncology: Consultancy.

Target: Stroke Was Associated With Faster Intravenous Thrombolysis and Improved One-Year Outcomes for Acute Ischemic Stroke in Medicare Beneficiaries.

The benefit of intravenous thrombolytic therapy for acute ischemic stroke is time dependent. To assist hospitals in providing faster thrombolytic treatment, the American Heart Association launched target: stroke quality initiative in January 2010 which disseminated feasible strategies to shorten door-to-needle times for thrombolytic therapy. This study aimed to examine whether target: stroke was associated with improved door-to-needle times and 1-year outcomes. We analyzed Medicare beneficiaries aged ≥65 years receiving intravenous thrombolytic treatment for acute ischemic stroke at 1490 Get With The Guidelines-Stroke hospitals during January 2006 and December 2009 (preintervention, n=10 804) and January 2010 and December 2014 (postintervention, n=31 249). The median age was 80 years and 42.7% were male. The median door-to-needle times decreased from 80 minutes for the preintervention to 68 minutes for the postintervention (P<0.001). The proportion of patients receiving intravenous thrombolysis with door-to-needle times 45 minutes and 60 minutes increased from 9.6% and 24.8% for preintervention to 17.1% and 40.6% for postintervention, respectively (P<0.001). The annual rate of increase in the door-to-needle times of 60 minutes or less accelerated from 0.20% (95% CI, -0.43% to 0.83%) per each 4 quarters for preintervention to 5.68% (95% CI, 5.23%-6.13%) for postintervention (P<0.001) which was further confirmed in piecewise multivariable generalized estimating analysis (adjusted odds ratio, 1.27 [95% CI, 1.19-1.35]). Cox proportional hazards analysis, after adjusting for patient and hospital characteristics and within-hospital clustering, showed that target: stroke was associated with lower all-cause readmission (40.4% versus 44.1%; hazard ratio, 0.91 [95% CI, 0.88-0.95]), cardiovascular readmission (19.7% versus 22.9%; hazard ratio, 0.85 [95% CI, 0.80-0.89]), and composite of all-cause mortality or readmission (56.0% versus 58.4%; hazard ratio, 0.96 [95% CI, 0.93-1.00]). The risk decline in all-cause mortality dissipated after risk adjustment (adjusted hazard ratio, 0.98 [95% CI, 0.94-1.02]). Target: stroke quality initiative was associated with faster thrombolytic treatment times for acute ischemic stroke and modestly lower 1-year all-cause and cardiovascular readmissions.

Adolescent Health and Healthy China 2030: A Review

PurposeThis article explores differences between the current health status of adolescents and the targets set in Healthy China 2030 (HC2030). MethodsGlobal and domestic policies and strategies relating to adolescent health were reviewed. Data from the Global Burden of Disease Study (1990–2016) and the Chinese National Survey on Students' Constitution and Health (1985–2014) were used to analyze time trends and geographical distributions of health indicators for adolescents aged 10–19 years in China. ResultsThe Chinese government has released many health policies over the past 3 decades. In this context, there has been a major decline in all-cause mortality and stunting. However, gaps between the current health status of adolescents and the targets set in HC2030 were numerous. The prevalence of obesity and poor vision increased rapidly, and few adolescents meet the physical activity and fitness targets set in HC2030. Urban/rural differences were marked for some indicators such as obesity, whereas for other indicators (e.g., stunting), there remained notable differences across provinces. ConclusionsMany long-standing health problems of adolescents have improved, but new problems related to noncommunicable disease risks have emerged and should be a prominent focus for policy action under HC2030.

Effect of convalescent blood products for patients with severe acute respiratory infections of viral etiology: A systematic review and meta-analysis

ObjectivesThe aim of this study was to determine whether convalescent blood products (CBPs) offer a survival advantage for patients with severe acute respiratory infections of viral etiology. MethodsUp-to-date trials were identified by the authors through searches of the MEDLINE, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and medRxiv databases from inception up to September 14, 2020. Meta-analyses were performed using a random-effects model. ResultsAccording to the observational studies, patients who received CBPs showed a decline in all-cause mortality compared with patients who did not receive CBPs (odds ratio (OR) 0.36, 95% confidence interval (CI) 0.23–0.56; p < 0.00001). However, the randomized controlled trials (RCTs) showed no difference between the intervention group and the control group regarding all-cause mortality (OR 0.82, 95% CI 0.57–1.19; p = 0.30). The use of CBPs did not increase the risk of adverse events (OR 0.88, 95% CI 0.60–1.29; p = 0.51). Using CBPs earlier compared with using CBPs later was associated with a significant reduction in all-cause mortality (OR 0.18, 95% CI 0.08–0.40; p < 0.0001). ConclusionsBased on the outcomes of RCTs, CBPs may not decrease all-cause mortality. Furthermore, compared with later initiation of CBP therapy, earlier initiation of this therapy may decrease the rate of mortality.

Mortality in working-age population during the Great Recession and austerity in Spain.

ObjectiveTo analyze the mortality trend in Spain before, during and after the economic crisis and austerity policies in the working-age population.MethodsFrom 2005 to 2016 we calculated the annual all-cause mortality rate and the annual mortality rate from the main causes of death in the population aged 15 to 64. We also estimated the linear trends in mortality rates during four time intervals—2005–2007 (before crisis), 2008–2010 (first part of the crisis), 2011–2013 (second part of the crisis and implementation of austerity policies) and 2014–2016 (after the crisis)- by the annual percentage change (APC).ResultsThe all-cause mortality rate in men and women showed the greatest decline in 2008–2010 and the smallest decline in 2014–2016. The decline in 2011–2013 was higher than in 2014–2016. The APCs in 2005–2007, 2008–2010, 2011–2013 and 2014–2016 were -2.8, -4.1, -3.0 and -1.5 in men and -1.0. -2.1, -1.1 and -0.6 in women, respectively, although the APC in 2014–2016 in women was not significant. In 2014–2016, cancer mortality showed the largest decrease, mortality from cardiovascular diseases (men), respiratory diseases and traffic accidents reversed and showed an upward trend, and the downward trend in mortality from infectious diseases and digestive diseases was equal to or greater than that observed before the crisis.ConclusionThe decline in all-cause mortality in the working-age population during the economic crisis and the introduction of austerity measures was greater than that observed before and after the economic crisis. The slowing of the decline after the crisis was due to the reversal of the trend in mortality from cardiovascular and respiratory diseases.

2265. The Changing Landscape of AIDS Defining CNS Infections in S. Alberta, Canada Over 30 Years

BackgroundThe incidence of AIDS defining CNS infections declined significantly with HAART; however, the longitudinal change in factors and effects of disease has not been well described. We characterized the changing incidence and outcomes in AIDS defining CNS infections over the past 30 years in the geographically defined, well-characterized southern Alberta HIV Cohort (SAC).MethodsAll episodes of cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), toxoplasma encephalitis (TE) and cryptococcal meningitis (CM) between January 1, 1987 and January 1, 2017 were identified from the SAC database. Mycobacterium Tuberculosis CNS infections were excluded due to <5 cases. CD4 most proximal to CNS infection and the length of survival to date of death or January 1, 2017 were determined. We compared incidence and outcomes before and after implementation of highly active antiretroviral therapy (HAART), defined as January 1, 1997.ResultsOf the 3,633 patients followed at SAC between January 1, 1987 and December 31, 2016, with 27,776 years of follow-up, 256 cases of AIDS defining CNS infections occurred in 241 individuals including; 150 episodes of CMV retinitis, 50 of TE, 21 of CM and 35 of PML. Two or more concurrent CNS infections were identified in 30 cases. Pre-HAART, the overall incidence rate of CNS infections was 40.5/1,000 patient-years (163 cases), declining to 6.5/1,000 patient-years (53 cases) from 1997 to 2007 and to 3.1/1,000 patient-years (48 cases) after 2007 (Figure 1). CNS infection occurred an average of 52 months (SD: ±49.1 months) following HIV diagnosis. Of note, 14% of CM, 26% of PML and 32% of TE cases were diagnosed within 3 months of HIV. The median CD4 count at diagnosis of CMV retinitis was 19 /mm3, PML 29 /mm3, CM 60 /mm3 and TE 77 /mm3. Pre-HAART 5-year all-cause mortality for AIDS defining CNS infections was 88.0%; with post-HAART decreasing to 38.7% (Figure 2). Of people who died, survival pre-HAART was 10.4 months and post-HAART was 18.5 months. ConclusionWith the widespread use of HAART, the incidence of AIDS defining CNS infections decreased more than tenfold leading to a significant decline in all-cause mortality. The survival differences and legacy from functional impairment is currently under further examination.Disclosures All authors: No reported disclosures.

The Impact of Cancer Screening on All-Cause Mortality.

It is a matter of debate whether, and if so, to what extent, cancer screening programs reduce all-cause mortality. Against this backdrop, we analyzed potential effects of several cancer screening approaches on all-cause mortality in two representative Western European populations. We used mortality data from the UK (England &Wales) and Germany from 2015 and published figures from screening studies on relative reduction in mortality for screened cancers to calculate the expected decline in all-cause mortality in these countries. We determined the required sample size for demonstrating a 3% reduction in all-cause mortality with a narrow (95%) confidence interval in a hypothetical screening trial. A relative 20% reduction in breast cancer mortality can be accompanied by a maximum 1.7-1.8% reduction in all-cause mortality in England & Wales and Germany, respectively. Expected declines are smaller for sigmoidoscopy screening (1.0-1.2%), prostate-specific antigen (PSA) screening (0.4-0.6%), and skin cancer screening (0.2%). To obtain a 95% confidence interval of +/-1% for demonstrating a 3% decline in all-cause mortality, a study size of 596 200 persons is required. Because the proportion of cancer deaths in all deaths in Western Europe is relatively low, cancer screening procedures can reduce all-cause mortality by only 1-3%. However, this reduction is relevant to public health.

Decline in Late Mortality after Allogeneic Blood or Marrow Transplantation (alloBMT) Performed in Childhood: a Report from the BMT Survivor Study-2 (BMTSS-2)

Background: AlloBMT is a curative option for children with malignant and non-malignant diseases. Nonetheless, the high intensity of therapeutic exposures at a young age increases the risk of organ compromise and may lead to premature death. However, there remains a gap in knowledge regarding cause-specific late mortality experienced by children undergoing alloBMT. Furthermore, it is not clear whether mortality rates have changed over the past 4 decades. We address these gaps by examining premature death (all-cause, relapse-related mortality [RRM] and non-relapse-related mortality [NRM]) in patients undergoing alloBMT between 1974 and 2010 at City of Hope, University of Minnesota or University of Alabama at Birmingham. Methods: To be included in this analysis, the patients had to have received alloBMT before age 22, and survived for ≥2y after transplantation. Vital status information was ascertained as of Dec 31, 2016, using medical records, the National Death Index (NDI), and Accurint databases. Information on cause of death was obtained from the NDI Plus program and medical records. Using Kaplan-Meier techniques, we describe overall survival conditional on surviving 2+ and 20+y from alloBMT. We describe cumulative incidence of RRM and NRM using competing risk methods. We also describe all-cause late mortality for patients transplanted over 3 time periods: <1990; 1990-1999; 2000-2010. Standardized mortality ratio (SMR) was used to compare the mortality experienced by this cohort to the age- sex-, and calendar-specific mortality of the US general population. Proportional subdistribution hazards model (Fine-Gray) for competing risks was used for identifying predictors of late mortality, including demographics, primary disease, conditioning agents, disease status at alloBMT and GvHD prophylaxis. Results: In this cohort of 1,411 recipients of alloBMT performed in childhood and surviving ≥2y, the most common primary diagnoses were acute lymphoblastic leukemia (ALL: 25%), acute myeloid leukemia/myelodysplastic syndrome (AML/MDS: 24%), inborn errors of metabolism (IEM: 14%) and severe aplastic anemia (SAA: 11%). The distribution of the cohort over the 3 time periods was: <1990 (23%); 1990-1999 (29%); 2000-2010 (48%). After a median follow-up of 14.9y, we observed 295 deaths in this 2y survivor cohort, yielding an overall survival rate of 79.6% at 20y from alloBMT. The leading causes of premature death were infection (32.0%), primary disease (24.6%) and subsequent malignant neoplasms (18.4%). Overall, the cohort was at a 15-fold increased risk for premature death (SMR 15.3, 95% CI 13.6-17.2), when compared with the general population. Conditional on surviving 20y, the 5y overall survival was 96.0% for the entire cohort, and 98.4% for SAA, 96.0% for AML/MDS, 90.3% for ALL and 85.8% for IEM. Relative mortality declined with time from alloBMT, but remained significantly elevated at 25y after transplantation (SMR 1.9, 95% CI 1.1-2.9). The cumulative incidence of NRM exceeded that due to RRM (fig 1); the 20y cumulative incidence of NRM and RRM were 13.0% and 4.4%, respectively. The all-cause 10y cumulative mortality rate declined over the 3 eras (<1990: 18.9%, 1990-1999: 12.5%; >2000: 10.7%, p=0.001) (Fig 2). Adjusting for demographic and clinical variables, as well as conditioning, the hazard ratio (HR) of all-cause death decreased with more recent treatment eras (<1990: HR=1.0; 1990-1999: HR=0.7, 95%CI, 0.5-0.9, p=0.01; 2000-2010: HR=0.6, 95%CI, 0.4-0.8, p=0.004). Conclusions: This study demonstrates that compared with the general population, 2y survivors of alloBMT performed in childhood remain at an elevated risk of premature death, even after 25y from alloBMT. While the risk of relapse-related mortality plateaus with time, non-relapse-related mortality continues to increase and remains the major cause of late death in this population. However, we make an encouraging observation i.e., there has been a significant decline in all-cause mortality experienced by children undergoing alloBMT over the past 4 decades. [Display omitted] DisclosuresArora:Takeda Oncology: Consultancy.

Population Trends in Incidence of Second Malignant Neoplasm and Cause-Specific Mortality in Patients with Multiple Myeloma

Background: The management of patients with multiple myeloma (MM) has evolved significantly over the last two decades with increased utilization of autologous hematopoietic cell transplantation (AHCT) and introduction of proteasome inhibitors (PIs) and immunomodulatory agents (IMIDs) and concomitant improvement in survival, particularly in younger patients. Both AHCT and the IMID lenalidomide have been associated with increased risk of second malignant neoplasms (SMN) in clinical trials, with the risk reaching 6.9% at 5 years in a recent meta-analysis. We intended to assess whether an increase in incidence of SMN was evident at the population level and the impact of the changing SMN risk on survival of MM patients. Methods: We utilized the Surveillance, Epidemiology and End Results 13 (SEER 13) registries to analyze three cohorts of patients: those diagnosed during 1995-1999 (pre-thalidomide, limited use of AHCT, 15 years of follow up), 2000-2004 (post-thalidomide, pre lenalidomide and bortezomib, increased utilization of AHCT, 10 years of follow up) and 2005-2009 (post-lenalidomide and bortezomib, higher utilization of AHCT, 5 years of follow up). Follow up is current to the end of 2014. We included patients younger than 65 years at the time of diagnosis of MM as first malignant neoplasm to focus the analysis in patients more likely to receive AHCT and presumably prolonged lenalidomide exposure. For each cohort, we calculated the incidence of SMN considering death from any cause as a competing risk. Since comparison by era is subject to confounding by attained age, we analyzed and compared standardized incidence ratios (SIRs) for SMN and causes of death (COD) in intervals of 5 years: years 1-5 and years 6-10 from diagnosis. Results: There were 2,720 patients in the 1995-1999, 3,246 in the 2000-2004 and 3,867 in the 2005-2009 cohort. Median age of diagnosis was 56 years and 56.6% of the patients were males with no differences across cohorts. Non-Hispanic Whites were 55.9%, non-Hispanic Blacks 23.2%, Hispanics 12.6% and individuals of other race/ethnicities 8.2%. Median follow up of survivors was 198 months (range 1-239), 141 months (range 1-179) and 81 months (range 0-119) in the 1995-1999, 2000-2004 and 2005-2009 cohorts respectively. Cumulative incidences of SMN at 90 months were 4.7% (95% C.I. 4.0-5.6%), 6.0% (95% C.I. 5.2%-6.8%) and 6.3% (95% C.I. 5.5%-7.1%), respectively in the 3 consecutive cohorts, P=0.0008. The statistically significant, yet small increase in SMN is accompanied with decline in all-cause mortality in the same period from 69.9% for the 1995-1999 cohort to 60.4% for the 2000-2004 cohort to 52.8% for the 2005-2009 cohort, P&amp;lt;0.0001. During years 1-5 after MM diagnosis, the risk of another cancer of any type evolved from lower than expected in an age, gender and race-matched population for patients diagnosed in 1995-1999 (SIR=0.77, 95% C.I. 0.59-0.99) to similar to expected for patients diagnosed in 2005-2009 (SIR=1.15, 95% C.I. 0.97-1.36), driven particularly by increase in hematologic malignancies from SIR=1.28 (95% C.I. 0.47-2.78) to SIR=2.17 (95% C.I. 1.27-3.48),(Figure). For years 6-10, the overall risk of subsequent malignancy in MM survivors is similar to the matched population for both the 1995-1999 and the 2000-2004 cohorts (most recent cohort with 10-year follow up). However, the risk of subsequent hematologic malignancy is increased in both periods with the most substantial change being in the risk of lymphomas evolving from SIR=0.59 (95% C.I. 0.01-3.29) for the 1995-1999 cohort to SIR=3.31 (95% C.I. 1.51-6.27) for the 2000-2004 cohort. As expected, overall mortality in years 1-5 declined sharply across the three cohorts (Table), driven by decline in both MM-associated (from 159.4 to 91.7/1,000 patient-year) and cardiovascular mortality (from 12.6 to 9.1/1,000 patient-year). Importantly, there was no discernible increase in risk of death from SMN (from 4.5 to 3.9/1,000 patient-year). Conclusions: This population study confirms that the evolution of MM therapy in the US in the last 20 years is associated with a small, statistically significant increase in the risk of SMN in patients &amp;lt;65 years. Such increase is driven mostly by the increased incidence of hematologic malignancies. The study also demonstrates that the mortality from SMN is modest, has not significantly increased over time and is obscured by the robust reduction in mortality from MM. Disclosures No relevant conflicts of interest to declare.

The Evolving Demographic and Health Transition in Four Low- and Middle-Income Countries: Evidence from Four Sites in the INDEPTH Network of Longitudinal Health and Demographic Surveillance Systems.

This paper contributes evidence documenting the continued decline in all-cause mortality and changes in the cause of death distribution over time in four developing country populations in Africa and Asia. We present levels and trends in age-specific mortality (all-cause and cause-specific) from four demographic surveillance sites: Agincourt (South Africa), Navrongo (Ghana) in Africa; Filabavi (Vietnam), Matlab (Bangladesh) in Asia. We model mortality using discrete time event history analysis. This study illustrates how data from INDEPTH Network centers can provide a comparative, longitudinal examination of mortality patterns and the epidemiological transition. Health care systems need to be reconfigured to deal simultaneously with continuing challenges of communicable disease and increasing incidence of non-communicable diseases that require long-term care. In populations with endemic HIV, long-term care of HIV patients on ART will add to the chronic care needs of the community.

Age-specific mortality analysis helps to explain all-cause mortality decline in Kazakhstan

Background In Kazakhstan, all-cause mortality declined by almost 20% between 2007 and 2012. This steep decline was the first sustained improvement in all-cause mortality in the country since the steep increases in mortality after the collapse of the Soviet Union in 1991. We hypothesize that reduced alcohol consumption was a major reason for the observed improvements. Methods Age-specific mortality rates in Kazakhstan from all-cause …

Age-related mortality trends in Italy from 1901 to 2008.

We stratified the Italian population according to age and gender in order to evaluate mortality trends over more than one century. Data covering the 1901–2008 period were used to study the yearly variations in mortality. Fluctuations in age-adjusted mortality curves were analyzed by Join Point Regression Models, identifying Join Points and Annual Percent Changes. A consistent decline in all-cause mortality occurred across the whole period, the most striking variations being observed in the 0–49 years population. In 1901, other and undefined diseases were the main causes of death, followed by infectious, digestive, and respiratory diseases in the 0–49 years population and by respiratory, cardiovascular, and cerebrovascular diseases in the ≥50 years population groups. In 2008 the main causes of death were accidents (males) and tumors (females) in the 0–49 age class, tumors in the 50–69 age class (both genders), and tumors (males) and cardiovascular diseases (females) in the elderly. The results highlight the interplay between age and gender in affecting mortality trends and reflect the dramatic progress in nutritional, lifestyle, socioeconomic, medical, and hygienic conditions.

Exercise and life expectancy

Chi Pang Wen and colleagues (Oct 1, p 1244) report on the minimum amount of physical activity necessary for reduced mortality and extended life expectancy. Compared with individuals in the inactive group, those in the low-volume activity group reportedly had a 14% reduced risk of all-cause mortality and a 3-year longer life expectancy. We agree that any additional physical activity is worthwhile, but the reported decline in all-cause mortality and increase in life expectancy are not compatible. On the basis of the 2009 Taiwan life tables, and using Wen and colleagues’ mortality hazard ratios for the low activity group compared with the inactive group, we estimate that the life expectancy extension at age 30 years is 1·85 years for men and 0·96 years for women. Wen and colleagues therefore overestimate by 38% for men and 223% for women.

Pharmacologic Prevention of Microvascular and Macrovascular Complications in Diabetes Mellitus

Observational epidemiologic data indicate that lower blood glucose levels, blood pressure (BP), and lipid parameters are associated with a lower incidence of micro- and macrovascular complications in people with diabetes. While no threshold for this effect is discernible in these observational studies, intervention studies do not mirror this finding. The earliest glycemia target study in type 2 diabetes mellitus, UKPDS, demonstrated unequivocal benefits of tight glucose control on microvascular complications, but needed a prolonged follow-up to demonstrate a benefit on macrovascular outcomes and mortality. Recently, three major studies, ACCORD, ADVANCE, and VADT, evaluated the impact of attaining euglycemia (ACCORD) or near-euglycemia (ADVANCE, VADT) in older patients with diabetes and high cardiovascular (CV) risk. None of these studies, either individually or on pooled analysis, demonstrated any reduction in all-cause or CV mortality, although the meta-analyses revealed 15-17% reductions in the incidence of non-fatal myocardial infarction in those exposed to tight glucose control. A higher mortality was observed in the intensive glucose control arm of ACCORD, resulting in the premature termination of the glucose-lowering component of this study. Also, the occurrence of hypoglycemic episodes (total and major) was significantly higher in the intensive glucose control arm. ADVANCE and ACCORD also had BP-lowering components. While data from ADVANCE demonstrated a benefit of routine use of a combination of perindopril and indapamide, with a decline in all-cause mortality, CV mortality, and new-onset microalbuminuria, reducing systolic BP to <120 mmHg in ACCORD did not result in any incremental benefits over a systolic BP<140 mmHg. A residual CV risk observed in people with diabetes even after low-density lipoprotein (LDL) cholesterol lowering has led to trials evaluating additional therapy with fibric acid derivatives to reduce triglyceride levels. The lipid-lowering arm of ACCORD failed to demonstrate any benefit of add-on therapy with fibric acid derivatives to LDL-lowering treatment with HMG-CoA reductase inhibitors (statins) on vascular outcomes in patients with diabetes. However, data from earlier studies, and also from the subgroup analysis of ACCORD, indicate a probable benefit of adding treatment with fibric acid derivatives to individuals with persistently elevated triglyceride levels despite statin therapy. The most compelling evidence comes from studies assessing the impact of multiple risk factors - glucose, BP, and cholesterol. Studies like the Steno study unequivocally demonstrate the benefit of aggressive control of all three parameters on vascular outcomes in patients with diabetes. In conclusion, attempts to achieve euglycemia in older patients with type 2 diabetes with co-morbidities are not associated with any survival benefit, but may reduce the occurrence of non-fatal CV events. There is a significant risk of major hypoglycemia with this approach, thereby probably limiting its utility to younger patients with new-onset disease. Similarly, lowering systolic BP below 120 mmHg in high CV risk people with diabetes is associated with significant excess adverse events, limiting the utility of such an intervention. However, a clear benefit, which is also cost effective, is observed with strategies for multiple risk-factor control, which should be universally adopted in clinical practice.