This study aimed to evaluate whether gait speed and grip strength predicted clinical outcomes among older adults with blood cancers. We prospectively recruited 448 patients aged 75 years and older presenting for initial consultation at the myelodysplastic syndrome/leukemia, myeloma, or lymphoma clinic of a large tertiary hospital, who agreed to assessment of gait and grip. A subset of 314 patients followed for ≥6 months at local institutions was evaluated for unplanned hospital or emergency department (ED) use. We used Cox proportional hazard models calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for survival, and logistic regression to calculate odds ratios (ORs) for hospital or ED use. Mean age was 79.7 (± 4.0 standard deviation) years. After adjustment for age, sex, Charlson comorbidity index, cognition, treatment intensity, and cancer aggressiveness/type, every 0.1-m/s decrease in gait speed was associated with higher mortality (HR, 1.20; 95% CI, 1.12-1.29), odds of unplanned hospitalizations (OR, 1.33; 95% CI, 1.16-1.51), and ED visits (OR, 1.34; 95% CI, 1.17-1.53). Associations held among patients with good Eastern Cooperative Oncology Group performance status (0 or 1). Every 5-kg decrease in grip strength was associated with worse survival (adjusted HR, 1.24; 95% CI, 1.07-1.43) but not hospital or ED use. A model with gait speed and all covariates had comparable predictive power to comprehensive validated frailty indexes (phenotype and cumulative deficit) and all covariates. In summary, gait speed is an easily obtained “vital sign” that accurately identifies frailty and predicts outcomes independent of performance status among older patients with blood cancers.

BACKGROUND/OBJECTIVES Cancer‐focused organizations now recommend routine assessment of instrumental activities of daily living (iADLs) for all older patients with cancer, along with assessment of basic activities of daily living (ADLs) if possible. However, little is known regarding the role of iADLs in predicting survival and acute‐care utilization in populations of older adults with different hematologic malignancies. DESIGN Prospective cohort study. SETTING AND PARTICIPANTS A screening geriatric assessment was conducted for adults 75 years and older with hematologic malignancies (n = 464) presenting for initial consultation at a large tertiary cancer hospital in Boston, MA. MEASUREMENTS Univariable and multivariable analyses assessed the association of dependency in ADLs and dependency in iADLs with survival and care utilization (emergency department [ED] visits and unplanned hospitalizations). RESULTS Subjects were a mean age of 79.7 years and had a mean follow‐up of 13.8 months. Overall, 11.4% had dependency in ADLs and 26.7% had dependency in iADLs. Only iADL dependency was associated with higher mortality (hazard ratio = 2.34 [95% confidence interval [CI] = 1.46‐3.74]) independently of age, comorbidity, cancer aggressiveness, and treatment intensity. The effect was dose dependent, and impairments in shopping, meal preparation, and housework were all independently associated with a higher hazard of death. iADL dependency was also associated with higher odds of ED visits (odds ratio [OR] = 2.76 [95% CI = 1.30‐5.84]) and hospitalizations (OR = 2.89 [95% CI = 1.37‐6.09]). Several geriatric domain impairments, including probable cognitive impairment and physical dysfunction, were associated with iADL dependency. CONCLUSION These findings suggest that older adults with hematologic malignancies and iADL dependency experience higher mortality and acute‐care utilization, arguing that iADLs should be formally assessed as part of routine oncology care. J Am Geriatr Soc 67:889–897, 2019.

BACKGROUND:Patients with blood cancers experience high-intensity medical care near the end of life (EOL) and low rates of hospice use; attributes of goals of care (GOC) discussions may partly explain these outcomes. METHODS: By using a retrospective cohort of patients with blood cancer who received care at Dana-Farber Cancer Institute and died in 2014, the authors assessed the potential relationship between timing, location, and the involvement of hematologic oncologists in the first GOC discussion with intensity of care near the EOL and timely hospice use. RESULTS: Among 383 patients, 39.2% had leukemia/myelodysplastic syndromes, 37.1% had lymphoma, and 23.7% had myeloma. Overall, 65.3% of patients had a documented GOC discussion. Of the first discussions, 33.2% occurred >30 days before death, 34.8% occurred in the outpatient setting, and 46.4% included a hematologic oncologist. In multivariable analyses, having the first discussion >30 days before death (odds ratio [OR], 0.37; 95% CI, 0.17-0.81), in the outpatient setting (OR, 0.21; 95% CI, 0.09-0.50), and having a hematologic oncologist present (OR, 0.40; 95% CI, 0.21-0.77) were associated with lower odds of intensive care unit admission ≤30 days before death. The presence of a hematologic oncologist at the first discussion (OR, 3.07; 95% CI, 1.58-5.96) also was associated with earlier hospice use (>3 days before death). CONCLUSIONS: In this large cohort of blood cancer decedents, most initial GOC discussions occurred close to death and in the inpatient setting. When discussions were timely, outpatient, or involved hematologic oncologists, patients were less likely to experience intensive health care use near death and were more likely to enroll in hospice. Cancer 2020;126:515-522.

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Patients with advanced myeloma experience a high symptom burden particularly near the end of life, making timely hospice use crucial. Little is known about the quality and determinants of end-of-life care for this population, including whether potential increases in hospice use are also accompanied by “late” enrollment (≤ 3 days before death). Using the Surveillance, Epidemiology, and End-Results-Medicare database, we identified patients ≥ 65 years diagnosed with myeloma between 2000 and 2013 who died by December 31, 2013. We assessed prevalence and trends in hospice use, including late enrollment. We also examined six established measures of potentially aggressive medical care at the end of life. Independent predictors of late hospice enrollment and aggressive end-of-life care were assessed using multivariable logistic regression analyses. Of 12,686 myeloma decedents, 48.2% enrolled in hospice. Among the 6111 who enrolled, 17.2% spent ≤ 3 days there. There was a significant trend in increasing hospice use, from 28.5% in 2000 to 56.5% by 2013 (Ptrend <0.001), no significant rise in late enrollment (12.2% in 2000 to 16.3% in 2013, Ptrend =0.19), and a slight decrease in aggressive end-of-life care (59.2% in 2000 to 56.7% in 2013, Ptrend =0.01). Patients who were transfusion-dependent, on dialysis, or survived for less than one year were more likely to enroll late in hospice and experience aggressive medical care at the end of life. Gains in hospice use for myeloma decedents were not accompanied by increases in late enrollment or aggressive medical care. These findings suggest meaningful improvements in end-of-life care for this population.

ORCID ID: 0000-0001-7054-794X (J.L.I.). AbstractElastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV 1 , 89 6 3% predicted) and 30 normal control subjects (FEV 1 , 102 6 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC 20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV 1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV 1 /FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts.

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Background: Uganda has successfully reduced pediatric HIV infections through prevention of mother-to-child transmission of HIV (PMTCT) programs, yet little is known about adherence to infant-specific components of interventions. We hypothesized that infants born to mothers receiving the WiseMama (WM) electronic drug monitoring (EDM)-based adherence intervention would have increased uptake of six-week post-natal nevirapine (NVP) infant prophylaxis and better adherence to six-week early infant diagnosis (EID) HIV testing. Methods: At two sites in Uganda, the Wise Infant Study (WIN) prospectively followed an infant cohort. Infants were born to women enrolled in an RCT testing the effect of real-time reminders delivered via EDM on maternal adherence to antiretroviral therapy. We assessed intrapartum and discharge receipt of NVP prophylaxis using pharmacy and infant HIV DNA testing laboratory data. Results: Of 121 women eligible for WIN, 97 (80%) consented and enrolled; 46 had been randomized to control and 51 to intervention. There were no differences in receipt of a six-week NVP supply (control 87%, intervention 82%, p = 0.53). Receipt of any NVP prophylaxis did not vary by delivery location (p = 0.35), and although 12% of infants were delivered at non-study health facilities, they were not less likely to receive NVP at discharge (p = 0.37). Among infants with a completed HIV test, there was no difference in mean time to first test (control 52 days (SD 18), intervention 51 days (SD 15), p = 0.86). Only one infant, in the control group, tested positive for HIV. Conclusion and Global Health Implications: We found no significant differences in adherence to infant PMTCT practices between intervention and control infants with relatively high rates of NVP receipt albeit with suboptimal adherence to six-week EID testing. Further work is needed to ensure improved access, uptake, and follow-up of HIV-exposed infants in the Option B+ era. Key words: • Prevention of maternal to child transmission of HIV • HIV • Nevirapine • Antiretroviral therapy prophylaxis • Early infant diagnosis • HIV-exposed infants   Copyright © 2020 Murillo et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in this journal, is properly cited.