Low Standardized Mortality Ratios Research Articles

Impact of age on long-term relative survival benefit of radiotherapy for early-stage grade I–II follicular lymphoma from the SEER database (2000–2015)

The aim of this study was to investigate the effect of age on long-term mortality and net survival benefit of radiotherapy (RT) for early-stage grade I–II FL. Five thousand three hundred and five patients with early-stage grade I–II FL in the SEER database (2000–2015) were identified. Primary therapy included RT alone (RT, 20.7%), chemotherapy alone (CT, 27.6%), combined modality therapy (CMT, 5.9%), and observation (45.8%). Inverse probability of treatment weighting (IPTW) was conducted to balance the treatment arms. Relative survival (RS), the standardized mortality ratio (SMR), and transformed Cox regression were used to compare survival differences between treatments. RT with or without CT had significantly higher 10-year OS (approximately 78%) and RS (>95%), but lower SMR (1.47–1.76), compared with CT (67.8%; 86.3%; 2.35; ps < .001), observation (70.2%; 91.2%; 1.82; ps < .05). RT was an independent predictor of better OS and RS in multivariate analyses (p < .001). No significant interaction between age and RT was identified for RS (P interaction = .509) or OS (P interaction = .769), indicating similar survival benefits across all-ages patients. RT was associated with long-term OS and net survival benefits in patients with early-stage grade I–II FL, irrespective of age. Highlights The pattern and incidence of mortality varied by age-group as elderly patients often die of other diseases other than FL beyond 5 years. Radiotherapy was associated with higher long-term OS/RS and better SMR compared with other approaches, regardless of age.

An International Multicohort Study of Conditional Survival and Cause of Death after Achieving Event-Free Survival at 24 Months in Patients with Mantle Cell Lymphoma

Background: Event-free survival at 24 months (EFS24) after frontline immunochemotherapy (IC) is an important endpoint in diffuse large B-cell lymphoma and follicular lymphoma, and patients who achieve EFS24 have similar survival compared to age- and sex-matched general population. The role of EFS24 in predicting subsequent survival has not been established in mantle cell lymphoma (MCL), possibly due to perceived poor survival historically. In the last decade, the outcomes of MCL are improving in the evolving treatment landscape. In this international multicenter study, we investigated conditional survival and cause of death in patients with MCL who achieved EFS24 after frontline IC in the older and more recent eras. Methods: Outcomes after frontline IC were evaluated in 5 independent cohorts that included over 3000 patients in total: Mayo/Iowa MER prospective cohort, BC Cancer retrospective population-based cohort, US 12-center retrospective cohort, Swedish Lymphoma Registry, and Danish National Lymphoma Registry. For each cohort, 2 treatment eras were defined based on cohort-specific shifts in treatment patterns (Table 1). Overall survival (OS) after diagnosis and after achieving EFS24 were compared to the background age- and sex-matched general population using a standardized mortality ratio (SMR). Cumulative incidences of cause-specific deaths were analyzed using a competing risk model. Results: In the MER cohort, patients treated in Era M1 (2002-2009; n=147) and Era M2 (2010-2015; n=153) both had inferior OS compared to the general US population. A lower SMR in Era M2 vs M1 (2.25 vs 3.46) suggests a narrower gap in OS compared to the general US population. Lymphoma was the leading cause of death in both eras. In Era M1, patients who achieved EFS24 still had inferior OS compared to the general US population (SMR=2.40, 95% CI 1.76-3.19), and lymphoma remained the leading cause of death. For patients in Era M2 who achieved EFS24, the difference in OS compared to the general US population was not statistically significant with current follow-up (SMR=1.43, 95% CI 0.93-2.09), and lymphoma was no longer the leading cause of death (Table 2). In the BC cohort, patients treated in Era B2 (6/2013-2019; n=188) vs Era B1 (2003-5/2013; n=250) had a narrower gap in OS compared to the general British Columbia population (SMR 4.53 vs 6.69). Lymphoma was the leading cause of death in both eras. For patients achieving EFS24, the gap in OS was narrower in Era B2 vs B1 (SMR 3.56 vs 4.99). After achieving EFS24, lymphoma was the single leading cause of death for patients in Era B1 but not in Era B2 (Table 2). In the US 12-center cohort, patients treated in Era U1 (2002-2011; n=312) and Era U2 (2012-2016; n=417) both had inferior OS compared to the general US population (SMR 2.68 and 2.92, respectively). In patients who achieved EFS24, with current follow up, the difference in OS compared to the general US population was statistically significant in Era U1 (SMR=2.01, 95% CI 1.50-2.64) but not in Era U2 (SMR=1.44, 95% CI 0.82-2.34). Lymphoma was not the leading cause of death after achieving EFS24 (Table 2). In the Swedish cohort, the gap in OS compared to the general Swedish population was narrower in Era S2 (2013-2018; n=439) vs S1 (2006-2012; n=442), both after frontline IC (SMR 4.8 vs 5.4) and after achieving EFS24 (SMR 2.6 vs 3.4). After achieving EFS24, lymphoma was the leading cause of death for patients in Era S1 but not in Era S2 (Table 2). In the Danish cohort, patients treated in Era D2 (2014-2020; n=370) vs Era D1 (2004-2013; n=461) had a slightly narrower gap in OS compared to the general Danish population (SMR 1.90 vs 2.10). For patients who achieved EFS24, those in Era D1 still had inferior OS compared to the general Danish population (SMR=1.44, 95% CI 1.22-1.68), but the OS difference compared to the general Danish population in Era D2 was not statistically significant (SMR=1.27, 95% CI 0.92-1.72) with current follow-up (Table 2). Cause of death data were not available in this cohort. Conclusion: Survival in patients with MCL who achieved EFS24 after frontline IC improved in the more recent treatment era and moved closer to the background expected survival. After achieving EFS24, lymphoma-related mortality was no longer the leading cause of death in the more recent era. EFS24 following frontline treatment may become a critical endpoint for predicting subsequent outcomes in patients with MCL in the modern era.

Cohort profile: ORICAMs, a French cohort of medical workers exposed to low-dose ionizing radiation.

Medical personnel represent the largest group of workers occupationally exposed to ionizing radiation. Although the health risks associated with occupational exposure to low doses of ionizing radiation in the medical field have been investigated in several national cohorts, no study has been conducted in France to date. The ORICAMs (Occupational Radiation Induced Cancer in Medical staff) cohort is a nationwide French longitudinal cohort of medical workers exposed to ionizing radiation aiming to investigate the risk of radiation-associated cancer and non-cancer mortality. The ORICAMs cohort was set up in 2011 and includes all medical personnel monitored for ionizing radiation exposure with at least one dosimetric record in the SISERI database (the national registry for monitoring ionizing radiation exposure in workers) over the period 2002-2012. Causes of death were abstracted from death certificates and coded according to ICD-10. The follow-up ended on 31/12/2013. Standardized mortality ratios (SMRs) were calculated by cause of death to compare the mortality in the cohort to that in the French population, by gender, age group and calendar period. Among the 164,015 workers included in the cohort (60% women) a total of 1,358 deaths (892 in male and 466 in female) were reported. The observed number of all-cause deaths was significantly lower than expected based on national rates in both male (SMR = 0.35; 95% CI: 0.33, 0.38; ndeaths = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; ndeaths = 466). This analysis leads to the conclusion that mortality in French workers exposed to medical radiation is significantly lower than the national reference rates. However, these results based on a comparative analysis with national rates may be impacted by the healthy worker effect towards low SMRs, and do not enable to establish a potential relationship between occupational exposure and mortality risk, even if we may suspect an impact of high SES of these professionals on the observed decreased mortality. Thus, further dose-response analyses based on individual ionizing radiation exposure and job's type will be conducted to characterize correlation between risk of cancer mortality and occupational exposure.

Multicohort Study of Conditional Survival and Cause of Death After Achieving Event‐Free Survival at 24 Months (EFS24) in Patients With Mantle Cell Lymphoma (MCL)

Background: MCL is considered incurable, but outcomes are improving in the evolving treatment landscape. Event-free survival status at a landmark (e.g., 24 months) after frontline IC may help identify patients who will subsequently do well, which would be useful for patient counseling, care planning, and trial design. We evaluated conditional survival and cause of death in MCL patients who achieve EFS24 after frontline immunochemotherapy (IC). Methods: Outcomes after frontline IC were evaluated in 3 cohorts: Mayo/Iowa MER prospective clinic-based cohort, BC Cancer retrospective population-based cohort, and Swedish Lymphoma Register. For each cohort, 2 treatment eras were defined based on the specifics of local treatment patterns (Figure 1 A). Overall survival (OS) after diagnosis and after achieving EFS24 was compared to the background age and sex matched general population using a standardized mortality ratio (SMR). Cumulative incidences of cause-specific deaths were analyzed using a competing risk model. Results: In the MER, patients treated in Era M1 (2002–2009; n = 110) and M2 (2010–2015; n = 127) both had inferior OS compared to the US general population. A lower SMR (2.43 vs. 3.95) in Era M2 suggested a narrower gap in OS versus the general population. Lymphoma was the leading cause of death in both eras. In Era M1, patients achieving EFS24 still had inferior OS compared to the general population (SMR = 2.81, 95% CI: 1.98–3.88), and lymphoma remained the leading cause of death. However, in Era M2, patients achieving EFS24 had similar OS compared to the general population (SMR = 1.35, 95% CI: 0.83–2.09), and lymphoma was no longer the leading cause of death (Figure 1 B&E). In the BC cohort, patients treated in Era B2 (6/2013–2019; n = 188) versus Era B1 (2003–5/2013; n = 250) had a narrower gap in OS compared to the British Columbia population (SMR 4.53 vs. 6.69). Lymphoma was the leading cause of death in both eras. For patients achieving EFS24, the gap in OS was narrower in Era B2 versus B1 (SMR 3.56 vs. 4.99). After achieving EFS24, lymphoma was the leading cause of death for patients in Era B1 but not in Era B2 (Figure 1 C&E). Similar results were seen in the Swedish cohort. The gap in OS compared to the general Swedish population was narrower in Era S2 (2013–2018; n = 439) vs. S1 (2006–2012; n = 442), both after frontline IC (SMR 4.8 vs. 5.4) and after achieving EFS24 (SMR 2.6 vs. 3.4). After achieving EFS24, lymphoma was the leading cause of death for patients in Era S1 but not in Era S2 (Figure 1 D&E). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. Y. Wang Consultant or advisory role: Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene (all compensation to my institution) Honoraria: Kite (to my institution) Research funding: Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab (all to my institution) B. K Link Consultant or advisory role: Genentech, MEI Inc V. Diego Consultant or advisory role: Janssen, BeiGene, AstraZeneca, Merck, Kite/Gilead, BMS/Celgene, AbbVie, ONO therapeutics, Zetagen, Roche Honoraria: Janssen, BeiGene, AstraZeneca, Merck, Kite/Gilead, BMS/Celgene, AbbVie, ONO therapeutics, Zetagen, Roche Research funding: Roche, AstraZeneca (to institution)

Impact of Age on Long-Term Mortality and Net Survival Benefit of Radiotherapy for Early-Stage Follicular Lymphoma from the SEER Database (2000-2015)

<h3>Purpose/Objective(s)</h3> This study's aim was to analyze the effect of age on long-term mortality and the net survival benefit of radiotherapy (RT) for early-stage follicular lymphoma (FL). <h3>Materials/Methods</h3> A total of 8,803 patients with early-stage FL in the Surveillance, Epidemiology, and End Results (SEER) database (2000-2015) were identified for this study. Primary therapy included RT (27.0%), chemotherapy (CT, 29.3%), observation (24.1%), and other/unknown treatments (19.6%). Relative survival (RS), the standardized mortality ratio (SMR), and transformed Cox regression were used to compare survival differences between treatments. <h3>Results</h3> The risk of dying from FL than other causes over time was higher among younger patients (¡Ü60 years) and within 5 years among older patients (>60 years), who had a higher risk of dying from FL beyond 5 years. Overall survival (OS) rates continuously decreased regardless of treatment; the survival difference widened between RT and non-RT over 10 years. The RS rates for RT remained high (∼95%) over 10 years, but progressively decreased for other treatments. RT had significantly higher 10-year OS (77.2%) and RS (96.1%), but lower SMR (1.77), compared with CT (65.2%; 82.6%; 2.92; Ps < 0.001), observation (65.5%; 90.1%; 2.18; Ps < 0.001), and other/unknown treatments (66.5%, P < 0.001; 89.9%, P = 0.136; 2.05, P < 0.001). RT was an independent predictor of better RS and OS (P < 0.001). No significant interaction between age and RT was identified for RS (Pinteraction = 0.305) or OS (Pinteraction = 0.272), indicating similar survival benefits among patients of all ages. <h3>Conclusion</h3> RT provides significant long-term net survival benefits in early-stage FL, and remains a mainstay first-line treatment for early-stage FL.

Role of Radiation Therapy in Mortality among Adolescents and Young Adults with Lymphoma: Differences According to Cause of Death.

Simple SummaryDespite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. However, the most current research studying the association between RT and outcome is based only on groups of lymphoma patients and is not compared with the general population, which could more accurately reveal the impact of RT on outcomes. This population-based analysis showed that after adjusting for potential confounders, RT administration is associated with a low risk of cause-specific mortality, including death due to the original diagnosis, second malignant neoplasms (SMNs), and noncancer causes, among AYA patients with lymphoma. This analysis may play a guiding role in the design of future lymphoma studies and the formulation of healthcare policies regarding the widespread use of RT, especially for AYA survivors.Background: Despite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. Few long-term follow-up studies have examined the association between RT and outcomes. Methods: Lymphoma patients aged 15–39 years were identified in the Surveillance, Epidemiology and End Results (SEER) database from 1992 to 2016. Mortality was assessed by comparing those with and without RT using the Fine–Gray competing risk model. Standardized mortality ratios (SMRs) were used to assess the relative risk of death compared with the general U.S. population. Results: In total, 29,686 patients were included; 10,708 (36.07%) received RT. Cause-specific mortality was compared between patients with and without RT while considering other competing events, including death due to index cancer, second malignant neoplasms (SMNs), and noncancer causes. Patients with RT had a lower probability of death and crude 5-year cumulative incidence of death. Moreover, there were significantly lower SMRs in patients with RT than in patients without RT. Differences between the two groups were greatest for mortality due to hematological malignancies and infections. Additionally, in the RT cohort, the SMR for index-cancer-related death was highest in the first year after diagnosis and gradually decreased. Hematological malignancies and infections were the most common specific SMN and noncancer causes of death, respectively. Conclusions: RT did not increase mortality from index cancer, SMNs, or noncancer causes in AYA patients with lymphoid malignancies. The current analysis may serve as a reference for healthcare providers monitoring RT application for AYA lymphoid malignancy survivors.

An Update on the Healthy Soldier Effect in U.S. Veterans.

The healthy soldier effect (HSE) describes a phenomenon of enduring health and lower mortality among veterans due in part to initial screening procedures and health care access. Although early data were supportive of a broad HSE among former military members, more recent investigations have suggested a possible attenuation of the effect with older age. The present study aimed to provide an update of the HSE using an expansive Veterans Health Administration (VHA)-wide sample with a particular focus on age and sex effects. Mortality data for veterans within the VHA were obtained from the VHA Support Service Center program office and compared to mortality data from the general U.S. population spanning FY2014 to the second quarter of FY2020. The standardized mortality ratio (SMR) was calculated for the overall sample and for age- and sex-specific cohorts. Mortality rate ratios were also calculated and compared across sexes. Lower SMRs were observed in veterans compared to the general U.S. population (SMR 0.866). This effect was most prominent in younger and very old veterans, although a higher mortality was seen in the 55- to 64-year age cohort (SMR 1.371 for males and 1.074 for females). The HSE in females was lower than that in males in the <55-year age group but became higher in older cohorts. This is the largest investigation to date examining the HSE in U.S. veterans and includes younger veterans from more recent military eras. Higher mortality among the 55- to 74-year age groups merits further investigation, as does the relatively higher mortality among older female veterans. Our findings have implications for the provision of health care and preventative care to these veterans most at risk for higher mortality.

126-LB: Type 2 Diabetes Mellitus (T2DM) Has Greater Adverse Effect on Mortality in Females than Males—Results of 10-Year Cohort Study

Females are more prone to obesity than males. This may lead to different outcomes. We studied if sex differences were seen in mortality outcomes in a longitudinal T2D cohort study. Data from a regional UK database (Salford) was taken between 2010-2020. Standardised Mortality Ratio (SMR) was established from actual versus expected deaths calculated from national annual statistics for mortality rate by sex and age. The SMR was then calculated for by each sex, year, age group, HbA1c level, and diabetes medication as taken by a patient in previous years. We included 9,558 patients with 88,102 patient years and 2,909 recorded deaths against 1,851 expected, SMR men 1.46 and women 1.72 (18% higher than men) . SMR increased slightly over time (Figure 1a) . SMR in younger females (&amp;lt;75 years) was higher than older females (Figure 1b) . SMR in females with high HbA1c (&amp;gt;86mmol/mol) was higher (Figure 1c) than lower HbA1c. Patients currently on insulin and GLP1 had much higher SMR than oral alone (Figure 1d) .SMR analysis of the oral drug use had SGLT2i 1.28; metformin 1.50; thiazolinedione 1.61; DPP4i 1.74; sulphonylurea 1.78. Note that average age and HbA1c varied across therapies. Diabetes has greater impact on women’s mortality than men for both age, and HbA1c. Indication bias will impact drug choice but lower SMR with SGLT2i and higher with sulphonylureas concords with trial data. Despite newer therapies, SMR for diabetes has not improved over time. Disclosure A. H. Heald: None. M. Stedman: None. I. Laing: None. A. Robinson: None. G. Rayman: None. M. B. Whyte: Consultant; AstraZeneca, Research Support; AstraZeneca, Sanofi.

Epidemiology of hereditary transthyretin amyloidosis in the northernmost region of Sweden: a retrospective cohort study

Introduction Epidemiological data on hereditary transthyretin (ATTRv) amyloidosis from the northernmost region of Sweden (Norrbotten) are sparse. Methods We reviewed the medical records of all incident cases of ATTRv amyloidosis in Norrbotten between 2006 and 2018. Official population and mortality statistics were used to estimate incidence rates and standardised mortality ratios (SMRs). Results Ninety-three patients were diagnosed with ATTRv amyloidosis between 2006 and 2018 (median age, 72.8 years; 68.8% men; 95.7% Val30Met [p.Val50Met] mutation). The incidence rate per 100,000 persons and year increased from 1.50 (95% confidence interval [CI], 0.84–2.47) cases in 2006–2009 to 4.92 (95%CI, 3.46–6.78) cases in 2016–2018. The SMR in the ATTRv amyloidosis cohort was 2.64 times higher than in the general population in 2006–2018 (95%CI, 1.78–3.77). However, there were indications of lower SMRs over time (2006–2012, 2.96 [95%CI, 1.73–4.74]; 2013–2018, 2.32 [95%CI, 1.23–3.96]) and by use of disease-modifying drugs (no, 3.21 [95%CI, 1.87–5.13]; yes, 2.09 [95%CI, 1.08–3.64]). Conclusion The incidence of ATTRv amyloidosis increased 3-fold in Norrbotten between 2006 and 2018, most likely due to a previous underdiagnosis – with suggestions of lowered mortality during later years, possibly due to the introduction of disease-modifying drugs.

Geographical Differences and Their Associated Factors in Chronic Obstructive Pulmonary Disease Mortality in Japan: An Ecological Study Using Nationwide Data.

Geographical differences in chronic obstructive pulmonary disease (COPD) mortality have not been determined using municipal-specific data in Japan. This study determined the geographical differences in COPD mortality in Japan using municipal-specific data and identified associated factors. Data on COPD mortality from 2013 to 2017 for each municipality were obtained from the Vital Statistics of Japan. We calculated the standardized mortality ratio (SMR) of COPD by an empirical Bayes method for each municipality and located the SMRs on a map of Japan. In addition, an ecological study was conducted to identify factors associated with the SMR using demographic, socioeconomic, and medical characteristics of municipalities by a spatial statistics model. Geographical differences in the SMR were different in men and women, and municipalities with a low SMR tended to be more frequent in women. Spatial regression analysis identified that the total population and taxable income per capita were negatively associated with the SMR in men. In women, population density, the proportion of fatherless households, and the number of clinics per capita were positively associated with the SMR, whereas taxable income per capita was negatively associated with the SMR. There were some differences in regional characteristics associated with COPD mortality by sex.

Socioeconomic Predictors of Diabetes Mortality in Japan: An Ecological Study Using Municipality-specific Data.

ObjectivesThe aim of this study was to examine the geographic distribution of diabetes mortality in Japan and identify socioeconomic factors affecting differences in municipality-specific diabetes mortality.MethodsDiabetes mortality data by year and municipality from 2013 to 2017 were extracted from Japanese Vital Statistics, and the socioeconomic characteristics of municipalities were obtained from government statistics. We calculated the standardized mortality ratio (SMR) of diabetes for each municipality using the empirical Bayes method and represented geographic differences in SMRs in a map of Japan. Multiple linear regression was conducted to identify the socioeconomic factors affecting differences in SMR. Statistically significant socioeconomic factors were further assessed by calculating the relative risk of mortality of quintiles of municipalities classified according to the degree of each socioeconomic factor using Poisson regression analysis.ResultsThe geographic distribution of diabetes mortality differed by gender. Of the municipality-specific socioeconomic factors, high rates of single-person households and unemployment and a high number of hospital beds were associated with a high SMR for men. High rates of fatherless households and blue-collar workers were associated with a high SMR for women, while high taxable income per-capita income and total population were associated with low SMR for women. Quintile analysis revealed a complex relationship between taxable income and mortality for women. The mortality risk of quintiles with the highest and lowest taxable per-capita income was significantly lower than that of the middle-income quintile.ConclusionsSocioeconomic factors of municipalities in Japan were found to affect geographic differences in diabetes mortality.

Shedding Light on Tuberculosis Deaths in Children and Adolescents.

Tuberculosis (TB) kills ∼1.5 million people worldwide each year.1 Among children and adolescents infected with TB, those <5 years old and those with HIV coinfection have a higher risk of death.2–4 Not only have few researchers quantified the impact of antiretroviral therapy (ART) regarding those with coinfected with HIV,4–6 there are important gaps in our overall knowledge for adolescents treated for TB. Numerous observational studies conducted before the availability of anti-TB antibiotics revealed that TB disease and death peaked in the first 2 years of life and then decreased until adolescence, after which it rose steeply.7 Some reports revealed sex-based differences in incidence and mortality during adolescence.8–11 In recent decades, however, adolescents have received little attention in TB research, and their vulnerability to the disease has been largely forgotten, mostly because TB surveillance systems group individuals <15 years with children and those ≥15 years with adults.1,12 Disaggregated TB data have not been reported routinely for adolescents, although this practice will change in 2021 after the World Health Organization’s request for countries to disaggregate TB data by 5-year age bands for people <25 years old.In this issue of Pediatrics, Osman et al13 address these research gaps by analyzing the South African Electronic Treatment Register, a national surveillance database of individuals treated for drug-susceptible TB. The study includes ∼85 000 HIV coinfected children and adolescents, of whom nearly one-half were not receiving ART at TB diagnosis. The authors found that, compared with HIV-uninfected children and adolescents, those with HIV on ART were >5 times as likely to die within 6 months of TB diagnosis, whereas those with HIV not on ART were >8 times more likely to die. These findings highlight the importance of TB preventive therapy and timely ART initiation in HIV-infected children and adolescents.4,5Using finely age-disaggregated case fatality ratios (CFRs), Osman et al13 found that the risk of death was high in the first year of life for both sexes (4.1%), early adolescence for boys (4.3%), and late adolescence for girls (4.2%). Estimating standardized mortality ratios (SMRs), the authors found that, in 2016, observed TB deaths occurred at 4 to 5 times the rate of expected deaths in children <5 years of age. In contrast, in 2016, TB deaths occurred at 77 to 92 times the rate of expected deaths in adolescents 10 to 14 years old. Notably, SMRs were much higher for adolescent girls than for adolescent boys. As the authors hypothesize, lower SMRs in young children may reflect their susceptibility to other diseases, and the discrepancy between adolescent boys and girls may reflect the high risk of death from injury and violence among boys in South Africa. Nonetheless, SMRs reveal the impact of TB on specific groups and should be incorporated into future research to inform public health decisions.Another strength of this study is its examination of time trends between 2004 and 2016. The authors observed similar CFRs in all age groups in 2004. Thereafter, CFRs declined in children <10 years old (most steeply in those <5 years old) but remained stable in adolescents. This discrepancy is consistent with a global trend of sharp mortality declines in young children, compared with adolescents.14 Taken together, the study observations underscore the need to devote more resources to adolescents: identifying and addressing their risk factors for TB mortality, prioritizing them in TB-contact investigations and screening activities, and increasing the prescription of and adherence to TB preventive treatment in this age group.A key consideration is that the data available for this study do not include people who are diagnosed with TB but do not initiate treatment, are never diagnosed with TB at all, or have drug-resistant TB. Because an estimated 20% of children <15 years old with untreated TB disease die within 1 year and treatment outcomes for those with drug-resistant TB are likely worse,4 the findings represent the “best case scenario” for child and adolescent TB mortality in South Africa.In the study, Osman et al13 clarify the impact of HIV and ART on TB mortality in children and adolescents and expose adolescents’ overall high risk of poor TB outcomes. In future research efforts, researchers should incorporate the study’s granular age categories and innovative use of both CFRs and SMRs to examine TB deaths in children and adolescents in diverse settings. For example, in former Soviet republics, where >15% of adolescents have rifampin-resistant TB, characterizing the impact of drug-resistance on TB mortality is particularly important.15 The World Health Organization’s recent request for data disaggregation by 5-year age bands will facilitate more detailed evaluations of TB deaths among children and adolescents around the world. By analyzing these disaggregated data, researchers can help improve outcomes for the most vulnerable children and adolescents.

Mortality among U.S. military participants at eight aboveground nuclear weapons test series

Background Approximately 235,000 military personnel participated at one of 230 U.S. atmospheric nuclear weapons tests from 1945 through 1962. At the Nevada Test Site (NTS), the atomic veterans participated in military maneuvers, observed nuclear weapons tests, or provided technical support. At the Pacific Proving Ground (PPG), they served aboard ships or were stationed on islands during or after nuclear weapons tests. Material and methods Participants at seven test series, previously studied with high-quality dosimetry and personnel records, and the first test at TRINITY formed the cohort of 114,270 male military participants traced for vital status from 1945 through 2010. Dose reconstructions were based on Nuclear Test Personnel Review records, Department of Defense. Standardized mortality ratios (SMR) and Cox and Poisson regression models were used in the analysis. Results Most atomic veterans were enlisted men, served in the Navy at the PPG, and were born before 1930. Vital status was determined for 96.8% of the veterans; 60% had died. Enlisted men had significantly high all-causes mortality SMR (1.06); officers had significantly low all-causes mortality SMR (0.71). The pattern of risk over time showed a diminution of the ‘healthy soldier effect’: the all-causes mortality SMR after 50 years of follow-up was 1.00. The healthy soldier effect for all cancers also diminished over time. The all-cancer SMR was significantly high after 50 years (SMR 1.10) primarily from smoking-related cancers, attributed in part to the availability of cigarettes in military rations. The highest SMR was for mesothelioma (SMR 1.56) which was correlated with asbestos exposure in naval ships. Prostate cancer was significantly high (SMR 1.13). Ischemic heart disease was significantly low (SMR 0.84). Estimated mean doses varied by organ were low; e.g., the mean red bone marrow dose was 6 mGy (maximum 108 mGy). Internal cohort dose–response analyses provided no evidence for increasing trends with radiation dose for leukemia (excluding chronic lymphocytic leukemia (CLL)) [ERR (95% CI) per 100 mGy −0.37 (−1.08, 0.33); n = 710], CLL, myelodysplastic syndrome, multiple myeloma, ischemic heart disease, or cancers of the lung, prostate, breast, and brain. Conclusion No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65 years. The 95% confidence limits were narrow and excluded mortality risks per unit dose that are two to four times higher than those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships.

Academyhealth annual Research Meeting (ARM): A Selection of Abstracts accepted for Oral Presentation, 2020.

Research ObjectiveIn 2016, the 1% of Medicare beneficiaries with end‐stage renal disease (ESRD) constituted &gt; 7% of total Medicare spending ($35 billion). To improve the value of care for the ESRD population, the Centers for Medicare and Medicaid Services (CMS) implemented an alternative payment model (APM) for ESRD care, the ESRD Seamless Care Organization (ESCO). This model shares savings with organizations that reduce spending for their ESRD patients below a defined benchmark. This study evaluated the relationship between key organizational, provider, community characteristics, and ESCO performance.Study DesignWe constructed a novel, linked ESCO‐level data set capturing key information for all 37 Wave 2 (2017) ESCOs. After describing the organizational diversity of 2017 ESCOs, we performed bivariate comparisons of high‐ and low‐performing (eg, above versus below median) ESCOs based on three key outcomes: gross savings/losses, composite quality score, and standardized mortality ratio. Subsequently, we estimated generalized logistic regression models of ESCO performance as a function of organizational (number and type of participating facilities, and beneficiary‐to‐provider ratio), ESCO‐participating provider (credential and specialty), and community (percent Hispanic, non‐Hispanic black, percent Medicaid eligible, and median household income) characteristics.Population StudiedThe 37 ESCOs of 2017 were characterized using information from CMS reports, the National Plan and Provider Enumeration System National Provider Identification registry, and the Area Health Resource File. Combined, these ESCOs represented 40 162 Medicare beneficiaries.Principal FindingsESCO performance on the three outcomes was highly varied (ranges: savings/losses, −3.9% to 10.2%; quality, 76.4% to 100.0%; standardized mortality, 0.75 to 1.14), as were the ESCOs’ characteristics. Bivariate analysis showed that ESCOs with above (vs below) median savings had more aligned physicians (57.8 vs 28.6, P = .06), fewer dialysis facilities (8.66 vs 17.2, P = .07), a smaller non‐Hispanic black population (14.1% vs 21.9%, P = .06), and higher median household income ($55 532 vs $48 952, P &lt; .001). Facilities reporting a composite quality score of 100% (vs &lt;100%) had fewer aligned practices (22.3 vs 42.6, P = .05) and smaller non‐Hispanic black (16.3% vs 21.3%, P = .06) and Medicaid‐eligible (6.47% vs 8.9%, P = .14) populations. Low standardized mortality ratio (vs above median) was associated with higher median household income ($58 162 vs $45 810, P &lt; .001). Logistic regression model results were broadly consistent with these findings, though small sample size prevented finding statistically significant estimates.ConclusionsESCOs are highly diverse with respect to organizational composition and community characteristics; this variation partially explained the observed variation in ESCO performance. Among 2017 ESCOs, larger ESCOs (eg, with more affiliated physicians) and those in higher SES communities performed better with respect to savings and mortality. Quality measure performance was greater among smaller ESCOs, perhaps because of the difficulty of managing quality measure reporting efforts among larger physician groups.Implications for Policy or PracticeDrawing on data from the only ESRD‐specific APM effective to date, we offer the first evidence of the impact of organizational composition and social disparities on ESCO performance. This study provides crucial evidence that will inform policy deliberations about the design and implementation of APMs in specialty care, and the organizational decisions of provider groups considering whether to participate.

Comparison of lung cancer risk in black-coal miners based on mortality and incidence.

Cancer risk (especially as regards lung cancer) in black-coal miners is mainly analyzed on the basis of mortality. The risk calculated based on mortality may differ from the values based on incidence. The aim of the study was to compare cancer risk in black-coal miners with and without coal workers' pneumoconiosis (CWP), based on data on mortality and the incidence of lung cancer in the Czech Republic in 1992-2013. The cohort without CWP was composed of 6687 miners, and the cohort with CWP of 3476 miners. Information on the incidence of lung cancer was obtained from the Czech National Oncological Register (NOR), and information on mortality from the National Population Register. The risk of lung cancer incidence was compared with the general male population in the Czech Republic using the standardized incidence ratio (SIR), and the risk of lung cancer mortality using the standardized mortality ratio (SMR), with the 95% CI. In miners with CWP, a lower SMR value was found, SMR = 1.70 (95% CI: 1.41-2.04), compared with the SIR value, SIR = 2.01 (95% CI: 1.70-2.36). In miners without CWP, this was opposite, the value of SIR = 0.81 (95% CI: 0.69-0.94) was lower than the value of SMR = 0.83 (95% CI: 0.70-0.98). In miners without CWP, 17 cases of lung cancer (out of 176 cases in total) were not registered in NOR. In miners with CWP, the share of not registered cases was significantly lower (p = 0.018), and it was represented by 3% of not registered lung cancer cases, out of 156 cases with the diagnosis of lung cancer. In spite of the difference between SIR and SMR, the results of both indicators were consistent with the resulting relationship between the lung cancer risk and CWP. Med Pr. 2020;71(5):513-8.

Late mortality and chronic health conditions in long-term survivors of early-adolescent and young adult cancers: a retrospective cohort analysis from the Childhood Cancer Survivor Study.

Treatment outcomes among survivors of cancer diagnosed during adolescence and early young adulthood have not been characterised independently of survivors of cancers diagnosed during childhood. We aimed to describe chronic health conditions and all-cause and cause-specific mortality among survivors of early-adolescent and young adult cancer. The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study with longitudinal follow-up of 5-year survivors diagnosed with cancer before the age of 21 years at 27 academic institutions in the USA and Canada between 1970 and 1999. We evaluated outcomes among survivors of early-adolescent and young adult cancer (aged 15-20 years at diagnosis) and survivors diagnosed at age younger than 15 years (matched on primary cancer diagnosis, including leukaemia, lymphoma, CNS tumours, neuroblastoma, Wilms tumour, soft-tissue sarcomas, and bone cancer) by comparing both groups to siblings of the same age. Mortality was ascertained with the National Death Index. Chronic health conditions were classified with the Common Terminology Criteria for Adverse Events. Standardised mortality ratios (SMRs) were estimated with age-specific, sex-specific, and calendar year-specific US rates. Cox proportional hazard models estimated hazard ratios (HRs) for chronic health conditions and 95% CIs. Among 5804 early-adolescent and young adult survivors (median age 42 years, IQR 34-50) the SMR compared to the general population for all-cause mortality was 5·9 (95% CI 5·5-6·2) and among 5804 childhood cancer survivors (median age 34 years; 27-42), it was 6·2 (5·8-6·6). Early-adolescent and young adult survivors had lower SMRs for death from health-related causes (ie, conditions that exclude recurrence or progression of the primary cancer and external causes, but include the late effects of cancer therapy) than did childhood cancer survivors (SMR 4·8 [95% CI 4·4-5·1] vs 6·8 [6·2-7·4]), which was primarily evident more than 20 years after cancer diagnosis. Early-adolescent and young adult cancer survivors and childhood cancer survivors were both at greater risk of developing severe and disabling, life-threatening, or fatal (grade 3-5) health conditions than siblings of the same age (HR 4·2 [95% CI 3·7-4·8] for early adolescent and young adult cancer survivors and 5·6 [4·9-6·3] for childhood cancer survivors), and at increased risk of developing grade 3-5 cardiac (4·3 [3·5-5·4] and 5·6 [4·5-7·1]), endocrine (3·9 [2·9-5·1] and 6·4 [5·1-8·0]), and musculoskeletal conditions (6·5 [3·9-11·1] and 8·0 [4·6-14·0]) when compared with siblings of the same age, although all these risks were lower for early-adolescent and young adult survivors than for childhood cancer survivors. Early-adolescent and young adult cancer survivors had higher risks of mortality and severe and life threatening chronic health conditions than the general population. However, early-adolescent and young adult cancer survivors had lower non-recurrent, health-related SMRs and relative risks of developing grade 3-5 chronic health conditions than childhood cancer survivors, by comparison with siblings of the same age, which were most notable more than 20 years after their original cancer. These results highlight the need for long-term screening of both childhood and early-adolescent and young adult cancer survivors. National Cancer Institute and American Lebanese-Syrian Associated Charities.

Relationship between the manpower of full-time and part-time public health nurses and standardized mortality ratios: An ecological study in municipalities in Japan

Objectives The purpose of this ecological study was to clarify the relationship between the manpower of full-time and part-time public health nurses (PHNs) and standardized mortality ratios (SMRs) in municipalities in Japan.Methods We divided 1,225 municipalities with a population over 10,000 for which SMRs were officially published into two groups based on whether the municipality had established a public health center (PHC): general municipalities and PHC-established cities. A linear mixed model was used to examine the relationships among the number of full-time PHNs; cumulative total number of workdays for part-time PHNs; and other healthcare and social welfare resources for SMRs for all causes, malignant neoplasms, cerebrovascular disease, and heart disease.Results A higher cumulative total number of workdays for part-time PHNs was significantly associated with lower SMRs in both groups for all causes (males and females), lower SMRs in the general municipalities for malignant neoplasms (males) and heart disease (males), and lower SMRs in PHC-established cities for malignant neoplasms (males and females). The number of full-time PHNs had no effect on SMRs.Conclusion This study suggested that an increase in the manpower of municipal PHNs improves the health and wellbeing of residents.

Which urban land covers/uses are associated with residents’ mortality? A cross-sectional, ecological, pan-European study of 233 cities

​ObjectivesThe study aim was to determine whether the range and distribution of all, and proportions of specific, land covers/uses within European cities are associated with city-specific mortality rates.​Setting233 European cities...

Mortality trends for multiple sclerosis in Italy

Abstract Background Multiple sclerosis (MS) is the immune-mediated inflammatory disease affecting myelinated axons of the central nervous system with enormous socio-economic impact. The aim of this study was to analyze mortality trends for MS in Italy. Methods The mortality data relative to period 1980-2015 were provided by Italian Institute of Statistics, data were aggregated in 5 intervals (1980-1986; 1987-1993; 1994-2000; 2001-2008; 2008-2015). The Age-Standardized mortality Rates (SR) with respective 95% confidence intervals (95%CI) were calculated (using the European standard 2013) in order to evaluate the mortality trends (in confrontation to the initial period) and Standardized Mortality Ratios (SMR), in order to confront mortality in 5 major geographic areas: North-East (NE), North-West (NW), Central Italy (CI), South Italy (SI) and Islands (I). Results During the study period 4959 deaths for males and 7433 for females were observed. The SRs were significantly higher for females (0.71;95%CI:0.70-0.73 vs. 0.56; 95%CI:0.54-0.57). Significantly higher SMR were observed for both sexes in I (M:123.3 vs F:112.7), for females also in NE (106.5) and NW (115.8). Significantly lower SMR for both sexes were observed in SI (M:88.8; F:71.4) and for males in CI (90.9). The observed SRs during the five intervals for males were: 0.65(95%CI 0.60-0.69); 0.52 (95%CI 0.49-0.56); 0.46 (95%CI 0.43-0.49); 0.53 (95%CI 0.49-0.56); 0.59 (95%CI 0.56-0.62); and for females: 0.69 (0.65-0.73); 0.69 (0.65-0.73); 0.61 (0.58-0.65); 0.68 (0.65-0.72); 0.81(0.77-0.84); respectively. An initial decrease of SRs was observed for males until 2001-2007 in confrontation to the initial period (p &amp;lt; 0.05). For females significant increase of SRs was observed in 2008-2015 (p &amp;lt; 0.05). Conclusions An increase of mortality for MS, observed for females, especially after 2000 may reflect the raising prevalence of MS in Italy. Important geographical differences were observed for five main areas. Key messages During the study period an increase of mortality for MS was observed for females. Important differences were observed between five main Italian geographic areas.

Evaluating mortality outlier hospitals to improve the quality of care in emergency general surgery.

Expected performance rates for various outcome metrics are a hallmark of hospital quality indicators used by Agency of Healthcare Research and Quality, Center for Medicare and Medicaid Services, and National Quality Forum. The identification of outlier hospitals with above- and below-expected mortality for emergency general surgery (EGS) operations is therefore of great value for EGS quality improvement initiatives. The aim of this study was to determine hospital variation in mortality after EGS operations, and compare characteristics between outlier hospitals. Using data from the California State Inpatient Database (2010-2011), we identified patients who underwent one of eight common EGS operations. Expected mortality was obtained from a Bayesian model, adjusting for both patient- and hospital-level variables. A hospital-level standardized mortality ratio (SMR) was constructed (ratio of observed to expected deaths). Only hospitals performing three or more of each operation were included. An "outlier" hospital was defined as having an SMR with 80% confidence interval that did not cross 1.0. High- and low-mortality SMR outliers were compared. There were 140,333 patients included from 220 hospitals. Standardized mortality ratio varied from a high of 2.6 (mortality, 160% higher than expected) to a low of 0.2 (mortality, 80% lower than expected); 12 hospitals were high SMR outliers, and 28 were low SMR outliers. Standardized mortality was over three times worse in the high SMR outliers compared with the low SMR outliers (1.7 vs. 0.5; p < 0.001). Hospital-, patient-, and operative-level characteristics were equivalent in each outlier group. There exists significant hospital variation in standardized mortality after EGS operations. High SMR outliers have significant excess mortality, while low SMR outliers have superior EGS survival. Common hospital-level characteristics do not explain the wide gap between underperforming and overperforming outlier institutions. These findings suggest that SMR can help guide assessment of EGS performance across hospitals; further research is essential to identify and define the hospital processes of care which translate into optimal EGS outcomes. Epidemiologic Study, level III.