Lower Hazard Of Death Research Articles

Opioid agonist treatment and risk of death or rehospitalization following injection drug use-associated bacterial and fungal infections: A cohort study in New South Wales, Australia.

Injecting-related bacterial and fungal infections are associated with significant morbidity and mortality among people who inject drugs (PWID), and they are increasing in incidence. Following hospitalization with an injecting-related infection, use of opioid agonist treatment (OAT; methadone or buprenorphine) may be associated with reduced risk of death or rehospitalization with an injecting-related infection. Data came from the Opioid Agonist Treatment Safety (OATS) study, an administrative linkage cohort including all people in New South Wales, Australia, who accessed OAT between July 1, 2001 and June 28, 2018. Included participants survived a hospitalization with injecting-related infections (i.e., skin and soft-tissue infection, sepsis/bacteremia, endocarditis, osteomyelitis, septic arthritis, or epidural/brain abscess). Outcomes were all-cause death and rehospitalization for injecting-related infections. OAT exposure was classified as time varying by days on or off treatment, following hospital discharge. We used separate Cox proportional hazards models to assess associations between each outcome and OAT exposure. The study included 8,943 participants (mean age 39 years, standard deviation [SD] 11 years; 34% women). The most common infections during participants' index hospitalizations were skin and soft tissue (7,021; 79%), sepsis/bacteremia (1,207; 14%), and endocarditis (431; 5%). During median 6.56 years follow-up, 1,481 (17%) participants died; use of OAT was associated with lower hazard of death (adjusted hazard ratio [aHR] 0.63, 95% confidence interval [CI] 0.57 to 0.70). During median 3.41 years follow-up, 3,653 (41%) were rehospitalized for injecting-related infections; use of OAT was associated with lower hazard of these rehospitalizations (aHR 0.89, 95% CI 0.84 to 0.96). Study limitations include the use of routinely collected administrative data, which lacks information on other risk factors for injecting-related infections including injecting practices, injection stimulant use, housing status, and access to harm reduction services (e.g., needle exchange and supervised injecting sites); we also lacked information on OAT medication dosages. Following hospitalizations with injection drug use-associated bacterial and fungal infections, use of OAT is associated with lower risks of death and recurrent injecting-related infections among people with opioid use disorder.

Comparing parametric and Cox regression models using HIV/AIDS survival data from a retrospective study in Ntcheu district in Malawi.

Background:The study was designed to compare parametric and Cox regression survival models. It was also aimed at determining risk factors of death due to HIV/AIDS.Design and methods:The models were fitted to time from ART initiation to death due to HIV/AIDS while using data that was collected from 6670 patients records who registered for ART from 2007 to 2012 at Ntcheu district hospital in Malawi. The best fitting model was used to determine risk factors of death due to HIV/AIDS.Results:The exponential and Gompertz model competed very well with the Cox regression. Patients in WHO clinical stage 4 (HR = 1.69, p-value <0.001) and males (HR = 1.74, p-value <0.001) were associated with increased hazard of death than those in WHO clinical stage 3 and females. Patients with high body mass index (HR = 0.82, p-value <0.001) were associated with lower hazard of death than those with lower body mass index.Conclusions:Parametric models may perform as good as the Cox regression and the plausibility of all models needs to be investigated to use the correct model for accurate inferences. Furthermore, strategies to limit deaths due to HIV/AIDS should initiate ART early before WHO clinical stage 4 and males should receive special attention. The strategies should also aim at improving the body mass index of patients.

Association Between Fat Mass to Lean Body Mass Ratio and All-Cause Mortality Among Middle-Aged and Elderly Cancer Patients Without Obesity: A Multi-Center Observational Study in China.

ObjectiveWe aimed to investigate the association between fat mass to lean body mass ratio (RFL), percentage of body fat (PBF), and fat mass (FM) with mortality among middle-aged and elderly cancer patients without obesity.MethodsThis prospective hospital-based cohort study comprised 3,201 patients with stage I to IV cancer aged 40 years or above (mean age: 58 years for female patients and 61 years for male patients; mean length of follow-up was 1.67 years; the maximal follow-up length was 6.42 years). FM and PBF were measured by bioelectrical impedance analysis (BIA). Cox proportional hazard models were used, and adjusted hazard ratios (HRs) were estimated.ResultsWe revealed a significant association between RFL and all-cause mortality among men aged ≥60 years after adjusting for confounders. Compared with those in the lowest tertile of RFL, elderly men in the medium and highest tertile had a 35 and 34% lower hazard of death from any cause, respectively. After additionally adjusted for C-reaction protein (CRP), HRs of medium and high tertile of RFL became short of statistical significance [medium tertile: adjusted HRs (95% CI) = 0.74 (0.46, 1.20); highest tertile: adjusted HRs (95% CI) = 0.84 (0.53, 1.33)]. Among elderly women, RFL was significantly related to all-cause mortality only when the additional adjustment for CRP [medium tertile: adjusted HRs (95% CI) = 2.08 (1.08, 4.01); highest tertile: adjusted HRs (95% CI) = 0.90 (0.45, 1.81)]. No significant association between RFL and all-cause mortality was observed among female participants or male participants aged less than 60 years.ConclusionOur findings showed a significant non-linear association between RFL and all-cause mortality, which was observed only in elderly men, and might be attenuated by their inflammation state.

The Relationship Between Change in Employment Status, Insurance Coverage, and Graft Failure or Death After Kidney Transplant.

Introduction: Early change of insurance coverage after kidney transplantation may be associated with worse graft outcomes. We examine how return to employment moderates the hazard of graft failure associated with exit from Medicare within 36 months after transplantation. Design: Patients undergoing kidney transplantation covered by Medicare between January 2005 and December 2016 were identified in the United Network for Organ Sharing (UNOS) database. A composite outcome of graft failure or death was analyzed across four groups: (1) no change in coverage within the first 3 years post-transplant, and no return to work (2) no change in coverage, return to work (3) change in coverage, no return to work (4) change in coverage, return to work. Results: The sample included 46 120 patients; 28% changed insurance coverage from Medicare posttransplant. Among patients who returned to work (36%), change in coverage from Medicare to other insurance was associated with lower hazard of death or graft failure (hazard ratio: 0.93; 95% confidence interval: 0.87, 0.99; P = 0.030). Conclusions: Exit from Medicare was associated with patient and graft survival greater than 3 years after transplant, depending on return to work. Among patients returning to work, changes in insurance from Medicare to private coverage were associated with favorable outcomes.

Medical nutrition therapy and clinical outcomes in critically ill adults: a European multinational, prospective observational cohort study (EuroPN)

BackgroundMedical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes.MethodsProspective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: < 10 kcal/kg, < 0.8 g/kg; moderate: 10–20 kcal/kg, 0.8–1.2 g/kg, high: > 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV).ResultsA total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (− 2.74 [− 3.28; − 2.21] and − 0.12 [− 0.15; − 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements.ConclusionsCalorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes.Trial registrationNCT04143503, registered on October 25, 2019.Graphical abstract

Indirect comparison of tisagenlecleucel and historical treatments for relapsed/refractory diffuse large B-cell lymphoma

AbstractNo head-to-head trials have compared the efficacy of tisagenlecleucel vs historical treatments for adults with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study indirectly compared the overall survival (OS) and overall response rate (ORR) associated with tisagenlecleucel, using data from the JULIET study (Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients; #NCT02445248), vs historical treatments assessed in the CORAL (Collaborative Trial in Relapsed Aggressive Lymphoma) study follow-up population. To assess treatment effects in the treated (full analysis set [FAS]) and enrolled (intention-to-treat [ITT]) study populations, the JULIET FAS vs the CORAL follow-up FAS and JULIET ITT vs CORAL follow-up ITT populations were separately compared. Propensity score weighting using standardized mortality ratio weight (SMRW) and fine stratification weight (FSW) was used to compare OS and ORR, adjusting for baseline confounders. The results indicated that tisagenlecleucel was associated with a lower hazard of death among the FAS (adjusted hazard ratio [95% confidence interval], both FSW and SMRW, 0.44 [0.32, 0.59]) and ITT populations (FSW, 0.60 [0.44, 0.77]; SMRW, 0.57 [0.44, 0.73]; all, P < .001). Median OS was 12.48 months (JULIET) vs 4.34 to 4.40 months (CORAL) for the FAS, and 8.25 (JULIET) months vs 4.04 to 4.86 (CORAL) months for the ITT populations. Tisagenlecleucel was associated with a significantly higher ORR compared with historical treatments among the FAS (adjusted response rate difference [95% confidence interval], both FSW and SMRW, 36% [22%, 0.48%]; P < .001) and among the ITT populations after SMRW adjustment (11% [0%, 22%]; P = .043). This analysis supports that improved response and OS are achieved in patients with r/r DLBCL treated with tisagenlecleucel compared with those treated with alternative historical treatments.

Survival and associated predictors for patients with pineoblastoma or pineal parenchymal tumors of intermediate differentiation older than 3 years: Insights from the National Cancer Database.

BackgroundThe management of pineal parenchymal tumors remains controversial.MethodsThe 2004-2017 National Cancer Database was queried for cases (age >3 years) with histologically confirmed pineal parenchymal tumors of intermediate differentiation (PPTID, n = 90) or pineoblastoma (n = 106).ResultsWithin the PPTID group, median age was 41 years; 49% were males. Five- and 10-year survival were 83% and 78%, respectively. Adjuvant radiation and chemotherapy were administered in 64% and 17% patients, respectively. The effect of radiation with or without chemotherapy (HR 1.15, P = .81, and HR 1.31, P = .72, respectively), and extent of resection (HR = 1.07, P = .93) was not significant. Within the pineoblastoma group, median age was 25 years; 51% were males. Five- and 10-year survival were 66% and 42%, respectively. Adjuvant radiation and chemotherapy were administered in 72% and 51%, respectively. In multivariable analysis, patients with pineoblastoma who received both radiation and chemotherapy (n = 39) had significantly lower hazard of death (HR 0.35, 95% CI 0.14-0.85, P = .02) compared to those who received radiation alone (n = 20) or no adjuvant treatment (n = 19). Finally, females in the pineoblastoma group were found to have a lower hazard of death compared to males (HR 0.24, 95% CI 0.10-0.58, P = .001); this comparison trended toward statistical significance in the PPTID subgroup (HR 0.40, 95% CI 0.14-1.08, P = .07).ConclusionsSurvival rates were higher in patients with PPTID vs patients with pineoblastoma. Adjuvant chemoradiation was associated with improved survival in pineoblastoma and females had lower hazards of death. Further research should identify specific patient profiles and molecular subgroups more likely to benefit from multimodality therapy.

Association of ABO blood type with mortality in hospitalized patients with COVID-19

Introduction. The novel SARS-CoV-2 infection (COVID-19) has generated a global crisis. It is necessary to find prognosis factors for hospitalized patients with SARS-CoV-2, that help us to understand the observed difference in disease severity in patients with similar characteristics. The aim of this study was to explore the relation between ABO groups and in-hospital mortality in Mexican patients admitted with COVID-19. Study design and Methods. We performed a retrospective study with 2369 hospitalized patients with SARS-CoV-2 confirmed infection in a tertiary referral hospital, admitted from March 27 and December 10, 2020. Results. Type A blood was associated with a lower hazard of death among COVID-19 patients compared to type O (adjusted HR=0.72, 95% IC 0.55-0.95, P-value=0.02). Conclusions We found evidence of a significant association between ABO blood type and COVID-19 in-patients’ death. The blood group A may be less likely to death during hospitalization compared with group O.

Indirect comparison of tisagenlecleucel and blinatumomab in pediatric relapsed/refractory acute lymphoblastic leukemia

AbstractIn the absence of head-to-head trials, an indirect-treatment comparison can estimate the treatment effect of tisagenlecleucel in comparison with blinatumomab on rates of complete remission (CR) and overall survival (OS) in patients with relapsed or primary refractory (R/R) acute lymphoblastic leukemia (ALL). Patient-level data from two pivotal trials, ELIANA (tisagenlecleucel; n = 79) and MT103-205 (blinatumomab; n = 70), were used in comparisons of CR and OS, controlling for cross-trial difference in available patient characteristics. Five different adjustment approaches were implemented: stabilized inverse probability of treatment weight (sIPTW); trimmed sIPTW; stratification by propensity score quintiles; adjustment for prognostic factors; and adjustment for both prognostic factors and propensity score. Comparative analyses indicate that treatment with tisagenlecleucel was associated with a statistically significant higher likelihood of achieving CR and lower hazard of death than treatment with blinatumomab. The tisagenlecleucel group exhibited a higher likelihood of CR than the blinatumomab group in every analysis regardless of adjustment approach (odds ratios: 6.71-9.76). Tisagenlecleucel was also associated with a lower hazard of death than blinatumomab in every analysis, ranging from 68% to 74% lower hazard of death than with blinatumomab, determined using multiple adjustment approaches (hazard ratios: 0.26-0.32). These findings support the growing body of clinical trials and real-world evidence demonstrating that tisagenlecleucel is an important treatment option for children and young adults with R/R ALL.

CLRM-09. INCORPORATING EXTERNAL CONTROL ARM IN MDNA55 RECURRENT GLIOBLASTOMA REGISTRATION TRIAL

BACKGROUNDDrug development in recurrent glioblastoma multiforme (rGBM) is challenging. For randomized controlled trials (RCTs) short survival horizons and limited life-prolonging treatment options may delay accrual and introduce bias through differential dropout of control patients. Comparing results of a single-arm Phase 2b trial of intratumoral delivery of MDNA55 (an interleukin-4 receptor targeted fusion protein) to an external control arm, we sought early efficacy insights and consideration by the FDA of incorporating an ECA in a Phase 3 registrational trial.METHODSUsing propensity score weighting, we compared rGBM patients from the Phase 2b trial (NCT02858895) (2017-2019) to patients from rGBM registries who had received standard of care therapies (2011-2019) and met eligibility requirements. Propensity scores were estimated using a logistic regression model with 11 covariates. We compared the propensity score weighted groups according to demographic and disease attributes before and after weighting and compared overall survival between the two groups.RESULTSThrough propensity score weighting, 43 (98%, 43/44) MDNA55 patients and 40.80 weighted ECA patients (from 62 unweighted registry patients) were identified for comparison. MDNA55 and ECA patients were balanced on all baseline characteristics (i.e., standardized mean difference ≤ 0.15). Compared to ECA patients, MDNA55 patients had a 37% lower hazard of death (hazard ratio 0.63, 95% confidence interval: 0.39,1.02).CONCLUSIONIn advance of a Phase 3 trial, comparison of Phase 2b trial results to an ECA suggests that MDNA55 may be efficacious in rGBM. In view of the known challenges associated with drug development for rGBM, these results provided a proof-of-concept for the design of a novel hybrid Phase 3 trial. This planned Phase 3 trial incorporates propensity score weighting to create a composite hybrid randomized and external control arm, an approach preferred by the FDA over full replacement of a randomized control with an external control.

Neoadjuvant versus Postoperative Chemoradiotherapy is Associated with Improved Survival for Patients with Resectable Gastric and Gastroesophageal Cancer

The optimal timing of chemoradiotherapy (CRT) for patients with localized gastric cancer remains unclear. This study aimed to compare the survival outcomes between neoadjuvant and postoperative CRT for patients with gastric and gastroesophageal junction (GEJ) cancer. This retrospective study analyzed 152 patients with gastric (42%) or GEJ (58%) adenocarcinoma who underwent definitive surgical resection and received either neoadjuvant or postoperative CRT between 2005 and 2017 at the authors' institution. The primary end point of the study was overall survival (OS). The median follow-up period was 37.5months. Neoadjuvant CRT was performed for 102patients (67%) and postoperative CRT for 50 patients (33%). The patients who received neoadjuvant CRT were more likely to be male and to have a GEJ tumor, positive lymph nodes, and a higher clinical stage. The median radiotherapy (RT) dose was 50.4Gy for neoadjuvant RT and 45.0Gy for postoperative RT (p<0.001). The neoadjuvant CRT group had a pathologic complete response (pCR) rate of 26% and a greater rate of R0 resection than the postoperative CRT group (95% vs. 76%; p=0.002). Neoadjuvant versus postoperative CRT was associated with a lower rate of any grade 3+ toxicity (10% vs. 54%; p<0.001). The multivariable analysis of OS showed lower hazards of death to be independently associated neoadjuvant versus postoperative CRT (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.36-0.91; p=0.020) and R0 resection (HR 0.50; 95% CI 0.27-0.90; p=0.021). Neoadjuvant CRT was associated with a longer OS, a higher rate of R0 resection, and a lower treatment-related toxicity than postoperative CRT. The findings suggest that neoadjuvant CRT is superior to postoperative CRT in the treatment of gastric and GEJ cancer.

Association between procurement biopsy findings and deceased donor kidney outcomes: a paired kidney analysis.

Unfavourable procurement biopsy findings are the most common reason for deceased donor kidney discard in the United States. We sought to assess the association between biopsy findings and post-transplant outcomes when donor characteristics are accounted for. We used registry data to identify 1566 deceased donors of 3132 transplanted kidneys (2015-2020) with discordant right/left procurement biopsy classification and performed time-to-event analyses to determine the association between optimal histology and hazard of death-censored graft failure or death. We then repeated all analyses using a local cohort of 147 donors of kidney pairs with detailed procurement histology data available (2006-2016). Among transplanted kidney pairs in the national cohort, there were no significant differences in incidence of delayed graft function or primary nonfunction. Time to death-censored graft failure was not significantly different between recipients of optimal versus suboptimal kidneys. Results were similar in analyses using the local cohort. Regarding recipient survival, analysis of the national, but not local, cohort showed optimal kidneys were associated with a lower hazard of death (adjusted HR 0.68, 95% CI 0.52-0.90, P=0.006). In conclusion, in a large national cohort of deceased donor kidney pairs with discordant right/left procurement biopsy findings, we found no association between histology and death-censored graft survival.

Sex Difference in the Case Fatality of Older Myocardial Infarction Patients.

BackgroundThe female sex is associated with poorer outcomes after myocardial infarction (MI), although current evidence in older patients is limited and mixed. We sought to evaluate sex-based differences in outcome after MI in older patients.MethodConsecutive older (≥70 years) all-comer patients with out-of-hospital MI admitted to 20 hospitals in Finland between 2005 and 2014 were studied using national registries (n = 40 654, mean age 80 years, 50% women). The outcome of interest was death within 1 year after MI. Differences between sexes (age, baseline features, medication, comorbidities, revascularization, and treating hospital) were balanced by inverse probability weighting.ResultsAdjusted all-cause case fatality was lower in women than in men at 30 days (16.0% vs 19.0%, respectively) and at 1 year (27.7% vs 32.4%, respectively) after MI (hazard ratio: 0.83; confidence interval [CI]: 0.80–0.86; p < .0001). Excess 1-year case fatality after MI compared to the corresponding general population was 22.1% (CI: 21.4%–22.8%) in women and 24.1% (CI: 23.4%–24.9%) in men. Women had a lower adjusted hazard of death after MI in subgroups of patients aged 70–79 years and ≥80 years, patients with and without ST elevation MI, revascularized and non-revascularized patients, patients with and without atrial fibrillation, and patients with and without diabetes. The sex difference in case fatality remained similar during the study period.ConclusionsOlder women were found to have a lower hazard of death after an out-of-hospital MI when compared to older men with similar features and treatments. This finding was consistent in several subgroups.

Prognostic Significance of Computed Tomography Findings in Pulmonary Vein Stenosis.

(1) Pulmonary vein stenosis (PVS) can be a severe, progressive disease with lung involvement. We aimed to characterize findings by computed tomography (CT) and identify factors associated with death; (2) Veins and lung segments were classified into five locations: right upper, middle, and lower; and left upper and lower. Severity of vein stenosis (0–4 = no disease–atresia) and lung segments (0–3 = unaffected–severe) were scored. A PVS severity score (sum of all veins + 2 if bilateral disease; maximum = 22) and a total lung severity score (sum of all lung segments; maximum = 15) were reported; (3) Of 43 CT examinations (median age 21 months), 63% had bilateral disease. There was 30% mortality by 4 years after CT. Individual-vein PVS severity was associated with its corresponding lung segment severity (p < 0.001). By univariate analysis, PVS severity score >11, lung cysts, and total lung severity score >6 had higher hazard of death; and perihilar induration had lower hazard of death; (4) Multiple CT-derived variables of PVS severity and lung disease have prognostic significance. PVS severity correlates with lung disease severity.

Risk factors for dementia development, frailty, and mortality in older adults with epilepsy – A population-based analysis

ObjectiveAlthough the prevalence of comorbid epilepsy and dementia is expected to increase, the impact is not well understood. Our objectives were to examine risk factors associated with incident dementia and the impact of frailty and dementia on mortality in older adults with epilepsy. MethodsThe CALIBER scientific platform was used. People with incident epilepsy at or after age 65 were identified using Read codes and matched by age, sex, and general practitioner to a cohort without epilepsy (10:1). Baseline cohort characteristics were compared using conditional logistic regression models. Multivariate Cox proportional hazard regression models were used to examine the impact of frailty and dementia on mortality, and to assess risk factors for dementia development. ResultsOne thousand forty eight older adults with incident epilepsy were identified. The odds of having dementia at baseline were 7.39 [95% CI 5.21–10.50] times higher in older adults with epilepsy (n = 62, 5.92%) compared to older adults without epilepsy (n = 88, 0.86%). In the final multivariate Cox model (n = 326), age [HR: 1.20, 95% CI 1.09–1.32], Charlson comorbidity index score [HR: 1.26, 95% CI 1.10–1.44], and sleep disturbances [HR: 2.41, 95% CI 1.07–5.43] at baseline epilepsy diagnosis were significantly associated with an increased hazard of dementia development over the follow-up period. In a multivariate Cox model (n = 1047), age [HR: 1.07, 95% CI 1.03–1.11], baseline dementia [HR: 2.66, 95% CI 1.65–4.27] and baseline e-frailty index score [HR: 11.55, 95% CI 2.09–63.84] were significantly associated with a higher hazard of death among those with epilepsy. Female sex [HR: 0.77, 95% CI 0.59–0.99] was associated with a lower hazard of death. SignificanceThe odds of having dementia were higher in older adults with incident epilepsy. A higher comorbidity burden acts as a risk factor for dementia, while prevalent dementia and increasing frailty were associated with mortality.

Association between primary caregiver type and mortality among Chinese older adults with disability: a prospective cohort study

BackgroundSocio-demographic transitions have dramatically changed the traditional family care settings in China, caused unmet care needs among older adults. However, whether different primary caregiver types have different influences on disabled older adults’ health outcomes remain poorly understood. We aimed to examine the association between the type of primary caregiver (e.g., spouse and children) and death among community-dwelling Chinese older adults disabled in activities of daily living.MethodsWe used data from Chinese Longitudinal Healthy Longevity Survey. The analytic sample comprised 4278 eligible adults aged ≥ 80 years. We classified primary caregiver type into five categories: spouse, son/daughter-in-law, daughter/son-in-law, grandchildren, and domestic helper. We used Cox regression model to examine the association between primary caregiver type and all-cause mortality. Covariates included age, sex, residence, years of education, co-residence status, financial independence, whether living with children, number of ADL disability, number of chronic conditions, and self-reported health, cognitive impairment, and caregiving quality.ResultsMarried older adults whose primary caregivers were son/daughter-in-law had a 38% higher hazard of death than those who had spouse as the primary caregiver. Married men who received care primarily from son/daughter-in-law or daughter/son-in-law had a 64 and 68% higher hazard of death, respectively, than those whose primary caregiver was spouse. The association between primary caregiver type and mortality among widowed older adults differed between urban and rural areas. Urban residents who had domestic helpers as the primary caregiver had an 16% lower hazard of death, while those living in rural areas had a 50% higher hazard of death, than those having son/daughter-in-law as the primary caregiver.ConclusionsThe quality of care of the primary caregiver may be a risk factor for mortality of disabled older adults in China. Interventions are necessary for reducing unmet needs and managing care burden.

Outcomes After Use of a Lymph Node Collection Kit for Lung Cancer Surgery: A Pragmatic, Population-Based, Multi-Institutional, Staggered Implementation Study

IntroductionSuboptimal pathologic nodal staging prevails after curative-intent resection of lung cancer. We evaluated the impact of a lymph node specimen collection kit on lung cancer surgery outcomes in a prospective, population-based, staggered implementation study. MethodsFrom January 1, 2014, to August 28, 2018, we implemented the kit in three homogeneous institutional cohorts involving 11 eligible hospitals from four contiguous hospital referral regions. Our primary outcome was pathologic nodal staging quality, defined by the following evidence-based measures: the number of lymph nodes or stations examined, proportions with poor-quality markers such as nonexamination of lymph nodes, and aggregate quality benchmarks including the National Comprehensive Cancer Network criteria. Additional outcomes included perioperative complications, health care utilization, and overall survival. ResultsOf 1492 participants, 56% had resection with the kit and 44% without. Pathologic nodal staging quality was significantly higher in the kit cases: 0.2% of kit cases versus 9.8% of nonkit cases had no lymph nodes examined; 3.2% versus 25.3% had no mediastinal lymph nodes; 75% versus 26% attained the National Comprehensive Cancer Network criteria (p < 0.0001 for all comparisons). Kit cases revealed no difference in perioperative complications or health care utilization except for significantly shorter duration of surgery, lower proportions with atelectasis, and slightly higher use of blood transfusion. Resection with the kit was associated with a lower hazard of death (crude, 0.78 [95% confidence interval: 0.61–0.99]; adjusted 0.85 [0.71–1.02]). ConclusionsLung cancer surgery with a lymph node collection kit significantly improved pathologic nodal staging quality, with a trend toward survival improvement, without excessive perioperative morbidity or mortality.

Abstract PS1-06: High-risk breast cancer in oldest old: Exploring the effect of different treatments on outcomes

Abstract Background: Octogenarians and nonagenarians diagnosed with breast cancer have a competing risk of death from other causes and their management is frequently found to be discordant with guidelines in comparison to the younger patients, particularly with low-risk disease. There is limited information about the disease trajectory and outcomes of patients with high-risk disease. Thus, this study was conducted. Methods: This is a retrospective, population-based observational study. Women aged 80 years of age or older and diagnosed with non-metastatic, high-risk breast cancer in Alberta, Canada between January 2004 and December 2017 were identified from the Alberta Cancer Registry. High-risk disease was defined as having any of the following; T3/4, any N positive, triple negative, or Her-2 positive disease. A risk scoring system was generated based on the presence of two anatomical and one biological high-risk features to generate 3 risk levels. Patients’ characteristics (age, Charlson comorbidity index, residence, education-, and income- quintiles), disease characteristics (stage, grade, receptor status,) treatment patterns (treatment delivered, facility) and survival were determined from linkage with administrative databases (Discharge Abstract Data, National Ambulatory Care Reporting System, and Vital statistics). Treatments were stratified into; none, hormonal treatment only (HT), surgery only (S), and surgery with any adjuvant treatment (S+A). Statistical methods included chi-square and Cox regression models. Association between patient, tumor and treatment variables and survival were assessed with uni- and multivariable analysis. Primary outcome was breast cancer specific survival (BCSS) in patients stratified by different risk levels in relation to the treatment delivered. Results: 1369 patients met the inclusion criteria. The median age was 84 years (interquartile range [IQR] 82-88). After a median follow-up of 35 months (m), 873 (64%) patients had died; 405 (46%) of deaths were due to breast cancer. On multivariable analysis, patients had a lower hazard of death from cancer if they were treated with S (HR = 0.51, 95%CI: 0.34, 0.77, p = 0.001) or S+A (HR = 0.41, 95%CI: 0.28, 0.6, p &amp;lt; 0.001) in comparison to HT alone. Patients who did not receive any form of treatment were more likely to die from breast cancer (HR 2.14 95%CI: 1.38, 3.31, p = 0.0006). Patients who had 1 or 2 risk features had higher cancer specific and overall survival if they had S or S+A (49/31m, 92/66m median differences respectively p &amp;lt; .0001). Those with 3 risk features showed longer survival if they received S+A (29/25m median differences p &amp;lt; .0001). Conclusions and Relevance: Our findings suggest that a significant proportion of older patients with breast cancer patients with high-risk features may have increased disease-specific mortality risk. Based on a priori risk levels, and in properly selected patients, treatment options including surgery and adjuvant treatment may be associated in longer survival. Table 1 - Population and Treatment CharacteristicsVariablesCategoryTotal (N=1369)Age group80-85817 (59.7 %)86-90388 (28.3 %)91-95146 (10.7 %)&amp;gt;9518 (1.3 %)Charlson Comorbidity Index0453 (33.1 %)1361 (26.4 %)&amp;gt;=2555 (40.5 %)TNM stageI239 (17.5 %)II663 (48.4 %)III422 (30.8 %)T stageT1416 (30.4 %)T2601 (43.9 %)T3163 (11.9 %)T4169 (12.3 %)Unknown20 (1.5 %)N stageN0526 (38.4 %)N1548 (40 %)N2159 (11.6 %)N385 (6.2 %)Unknown51 (3.7 %)Receptor statusER+orPR+andHer2-1071 (78.2 %)Her2+130 (9.5 %)ER-andPR-andHer2-123 (9 %)Unknown45 (3.3 %)Risk levels1922 (67.3 %)2371 (27.1 %)376 (5.6 %)Surgery typeNo surgery215 (15.7 %)BCS364 (26.6 %)Mastectomy790 (57.7 %)Sentinel surgeryno938 (68.5 %)yes431 (31.5 %)Chemotherapyno1337 (97.7 %)yes32 (2.3 %)Radiotherapyno991 (72.4 %)yes378 (27.6 %)Hormonotherapyno659 (48.1 %)yes710 (51.9 %) Citation Format: Abdulla Al-Rashdan, Yuan Xu, Lisa Barbera, Jeffrey Cao, Winson Cheung, Antoine Bouchard-Fortier, MayLynn Quan. High-risk breast cancer in oldest old: Exploring the effect of different treatments on outcomes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-06.

Motor function is the primary driver of the associations of sarcopenia and physical frailty with adverse health outcomes in community-dwelling older adults.

BackgroundThis study tested the hypothesis that sarcopenia and its constituent components, reduced lean muscle mass and impaired motor function, are associated with reduced survival and increased risk of incident disabilities.Methods1466 community-dwelling older adults underwent assessment of muscle mass with bioelectrical impedance analysis (BIA), grip strength, gait speed and other components of physical frailty and annual self-report assessments of disability. We used Cox proportional hazards models that controlled for age, sex, race, education and height to examine the associations of a continuous sarcopenia metric with the hazard of death and incident disabilities.ResultsMean baseline age was about 80 years old and follow-up was 5.5 years. In a proportional hazards model controlling for age, sex, race, education and baseline sarcopenia, each 1-SD higher score on a continuous sarcopenia scale was associated with lower hazards of death (HR 0.70, 95%CI [0.62, 0.78]), incident IADL (HR 0.80,95%CI [0.70, 0.93]), incident ADL disability (HR 0.80 95%CI [71, 91]) and incident mobility disability (HR 0.81, 95%CI [0.70, 0.93]). Further analyses suggest that grip strength and gait speed rather than muscle mass drive the associations with all four adverse health outcomes. Similar findings were observed when controlling for additional measures used to assess physical frailty including BMI, fatigue and physical activity.ConclusionsMotor function is the primary driver of the associations of sarcopenia and physical frailty with diverse adverse health outcomes. Further work is needed to identify other facets of muscle structure and motor function which together can identify adults at risk for specific adverse health outcomes.

Prognostic impact of chemoradiation-related lymphopenia in patients with locally advanced pancreatic cancer.

439 Background: Chemoradiation (CRT) induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. The objective of this study was to evaluate the prognostic impact of lymphopenia in patients with nonmetastatic, unresectable pancreatic ductal adenocarcinoma (PDAC) treated by neoadjuvant FOLFIRINOX (5-fluorouracil [5FU]/leucovorin/irinotecan/oxaliplatin) followed by CRT. We hypothesized that severe lymphopenia would correlate with worse survival. Methods: The inclusion criteria for this single-institution retrospective study were: 1) biopsy-proven diagnosis of unresectable PDAC, 2) absence of distant metastasis, 3) receipt of neoadjuvant FOLFIRINOX followed by CRT, and 4) absolute lymphocyte count (ALC) available prior to and two months after initiating CRT. In general, CRT consisted of 5FU or capecitabine and RT with 58.8 Gy over 28 fractions. Lymphopenia was graded according to CTCAE v5.0. The primary variable of interest was lymphopenia at two months, dichotomized by ALC of &lt; 0.5/μl (Grade 3 lymphopenia). The primary endpoint was overall survival (OS). Cox modeling and Kaplan-Meier methods were used to perform survival analyses. Results: A total of 138 patients were identified. Median follow-up for the entire cohort was 16 months. Median age was 65. Fifty-six percent were female, 86% were Caucasian, and 97% had ECOG ≤1. Median tumor size was 3.8 cm. Tumor location was pancreatic head in 63%, body in 22%, tail in 8%, and neck in 7%. Median baseline ALC for the entire cohort was 1.5 k/ul. Two months after initiating CRT, 106 (77%) had severe (Grade 3 or worse) lymphopenia. While there were no significant differences in baseline patient or disease characteristics, patients with severe lymphopenia received higher doses of RT with longer duration of treatment compared to those without severe lymphopenia. On multivariable Cox model, severe lymphopenia at two months was significantly associated with increased hazards of death (HR = 4.00 [95% CI 2.03-7.89], p &lt; 0.001). Greater number of neoadjuvant FOLFIRINOX cycles received prior to CRT was associated with lower hazards of death (HR = 0.84 [95% CI 0.77-0.92], p &lt; 0.001). The 12-month OS was 73% vs. 90% in the cohort with vs. without severe lymphopenia, respectively (log-rank p &lt; 0.001). Conclusions: Treatment-related lymphopenia is common and severe lymphopenia may be a prognostic marker of poorer survival in locally advanced pancreatic cancer. Closer observation in high-risk patients and minimization of RT dose and duration are potential approaches to mitigating CRT-related lymphopenia. Our findings also suggest an important role of the host immunity in pancreatic cancer outcomes, supporting the ongoing efforts of immunotherapy trials in pancreatic cancer.