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Background: Nutritional impairment is associated with treatment toxicity and worse overall survival in patients with cancer. We aimed to (1) evaluate the association of nutritional impairment with psychological health and quality of life (QOL) and (2) examine which measures of nutrition had the strongest association with psychological health and QOL among older adults receiving cancer treatment with palliative intent. Methods: This secondary analysis was performed on baseline data from a nationwide cluster randomized clinical trial (ClinicalTrials.gov identifier: NCT02107443; PI: Mohile). Adults age ≥70 with advanced cancer and ≥1 geriatric assessment (GA) impairment were enrolled from 2014 to 2017. In line with geriatric oncology standards, we defined nutritional impairment as Mini Nutritional Assessment Short Form (MNA‐SF) ≤11, body mass index (BMI) <21 kg/m2, or >10% involuntary weight loss in the past 6 months. We conducted multivariable linear regressions to evaluate the association of nutritional impairment with each measure of psychological health and QOL: Geriatric Depression Scale (GDS‐15, range 0–15), Generalized Anxiety Disorder‐7 (GAD‐7, range 0–21), NCCN Distress Thermometer (NCCN DT, range 0–10), and Functional Assessment of Cancer Therapy‐General (FACT‐G, range 0–108). Analyses were adjusted for patient demographics, clinical characteristics, and GA. Results: Among 541 patients, the mean age was 77 (range 70–96) and 60% had nutritional impairment. Mean baseline scores: GDS‐15 3.1 (SD 2.7), GAD‐7 2.9 (SD 4.0), NCCN DT 2.9 (SD 2.7), and FACT‐G 80 (SD 15). In the adjusted model, compared to those with no nutritional impairment, older adults with nutritional impairment had greater depression (β = 0.79, 95% CI 0.36–1.23) and anxiety severity (β = 0.86, 95% CI 0.19–1.53), and worse QOL (β = −6.31, 95% CI −8.62 to −4.00). Of the measures of nutrition, MNA‐SF ≤11 demonstrated the strongest associations with depression, anxiety, distress, and QOL. Conclusion: Nutritional impairment is associated with impaired psychological health and worse QOL. Clinicians should use the MNA‐SF to screen older adults for nutritional impairment and offer tailored supportive interventions. [ABSTRACT FROM AUTHOR]

Maternal iron deficiency (ID) and environmental lead (Pb) exposure are co-occurring insults that both affect the neurodevelopment of offspring. Few studies have investigated how ID affects brain-region-specific Pb accumulations using human-relevant Pb concentrations. Furthermore, how these Pb exposures impact blood and brain Fe levels remains unclear. Importantly, we also wanted to determine whether the use of blood Pb levels as a surrogate for the brain Pb burden is affected by underlying iron status. We exposed virgin Swiss Webster female mice to one of six conditions differing by iron diet and Pb water concentration (0 ppm, 19 ppm, or 50 ppm lead acetate) and used Inductively Coupled Plasma Mass Spectrometry to measure the maternal and offspring circulating, stored, and brain Pb levels. We found that maternal ID rendered the offspring iron-deficient anemic and led to a region-specific depletion of brain Fe that was exacerbated by Pb in a dose-specific manner. The postnatal iron deficiency anemia also exacerbated cortical and hippocampal Pb accumulation. Interestingly, BPb levels only correlated with the brain Pb burden in ID pups but not in IN offspring. We conclude that ID significantly increases the brain Pb burden and that BPb levels alone are insufficient as a clinical surrogate to make extrapolations on the brain Pb burden. [ABSTRACT FROM AUTHOR]

Background The correlates of coronavirus disease 2019 (COVID-19) illness severity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are incompletely understood. Methods We assessed peripheral blood gene expression in 53 adults with confirmed SARS-CoV-2 infection clinically adjudicated as having mild, moderate, or severe disease. Supervised principal components analysis was used to build a weighted gene expression risk score (WGERS) to discriminate between severe and nonsevere COVID-19. Results Gene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus nonsevere illness, we identified >4000 genes differentially expressed (false discovery rate < 0.05). Biological pathways increased in severe COVID-19 were associated with platelet activation and coagulation, and those significantly decreased with T-cell signaling and differentiation. A WGERS based on 18 genes distinguished severe illness in our training cohort (cross-validated receiver operating characteristic-area under the curve [ROC-AUC] = 0.98), and need for intensive care in an independent cohort (ROC-AUC = 0.85). Dichotomizing the WGERS yielded 100% sensitivity and 85% specificity for classifying severe illness in our training cohort, and 84% sensitivity and 74% specificity for defining the need for intensive care in the validation cohort. Conclusions These data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity. [ABSTRACT FROM AUTHOR]

Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or [...]

A study of 2772 participants was conducted to identify risk factors associated with aborted cardiac arrest and sudden cardiac death during adolescence in patients with clinically suspected long-QT syndrome (LQTS). Findings indicate that the timing and frequency of syncope, the degree of QTc prolongation and sex are independent predictors of life-threatening events in adolescents with LQTS.

Purpose: The Program of All-Inclusive Care for the Elderly (PACE) is a community-based program providing primary, acute, and long-term care to frail elderly individuals. A central component of the PACE model is the interdisciplinary care team, which includes both professionals and non-professionals. The purpose of this study was to examine the association between the team's overall performance and the risk-adjusted health outcomes of program enrollees. Design and Methods: The study included interdisciplinary teams in 26 PACE programs and 3,401 individuals enrolled in them. We combined information about individuals' health, functional, and mental status from DataPACE with an overall measure of team performance. We used multivariate regression techniques to test the hypothesis that better team performance is associated with better risk-adjusted health outcomes: survival and short-term (within 3 months of enrollment) and long-term (within 12 months of enrollment) improvements in functional status and in urinary incontinence. Results: Team performance was significantly associated with better functional outcomes (both short and long term) and with better Iong-term urinary incontinence outcomes. There was no significant association with survival. Implications: This study provides empirical evidence for the relationship between team performance and patient outcomes in long-term care. It suggests that PACE programs can improve patient outcomes by improving the functioning of care teams. Key Words: Interdisciplinary teams, Risk-adjusted health outcomes, PACE, Long-term care, Managed care

Aims: Risk stratification of patients with long QT syndrome (LQTS) represents a difficult task. In 2018, we proposed a granular estimate of the baseline 5-year risk of life-threatening arrhythmias (LAE) for patients with LQTS, based on the genotype (long QT syndrome Type 1, long QT syndrome Type 2, and long QT syndrome Type 3) and the duration of the QTc interval. We sought to externally validate a novel risk score model (1-2-3-LQTS-Risk model) in a geographically diverse cohort from the USA and to evaluate its performance and assess potential clinical implication of this novel model.Methods and Results: The prognostic model (1-2-3-LQTS-Risk model) was derived using data from a prospective, single-centre longitudinal cohort study published in 2018 (discovery cohort) and was validated using an independent cohort of 1689 patients enrolled in the International LQTS Registry (Rochester NY, USA). The validation study revealed a C-index of 0.69 [95% confidence interval (CI): 0.61-0.77] in the validation cohort, when compared with C-index of 0.79 (95% CI: 0.70-0.88) in the discovery cohort. Adopting a 5-year risk ≥5%, as suggested by the ROC curve analysis as the most balanced threshold for implantable cardioverter-defibrillator (ICD) implantation, would result in a number needed to treat (NNT) of nine (NNT = 9; 95% CI: 6.3-13.6).Conclusion: The 1-2-3-LQTS-Risk model, the first validated 5-year risk score model for patients with LQTS, can be used to aid clinicians to identify patients at the highest risk of LAE who could benefit most from an ICD implant and avoid unnecessary implants. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) causes acute respiratory illness (ARI) and triggers exacerbations of cardiopulmonary disease. Estimates of incidence in hospitalized adults range widely, with few data on incidence in adults with comorbidities that increase the risk of severity. We conducted a prospective, population-based, surveillance study to estimate incidence of RSV hospitalization among adults overall and those with specific comorbidities. Methods Hospitalized adults aged ≥18 years residing in the surveillance area with ≥2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened during the 2017–2018, 2018–2019, and 2019–2020 RSV seasons in 3 hospitals in Rochester, New York and New York City. Respiratory specimens were tested for RSV using polymerase chain reaction assays. RSV incidence per 100 000 was adjusted by market share. Results Active and passive surveillance identified 1099 adults hospitalized with RSV. Annual incidence during 3 seasons ranged from 44.2 to 58.9/100 000. Age-group–specific incidence ranged from 7.7 to 11.9/100 000, 33.5 to 57.5/100 000, and 136.9 to 255.6/100 000 in patients ages 18–49, 50–64, and ≥65 years, respectively. Incidence rates in patients with chronic obstructive pulmonary disease, coronary artery disease, and congestive heart failure were 3–13, 4–7, and 4–33 times, respectively, the incidence in patients without these conditions. Conclusions We found a high burden of RSV hospitalization in this large prospective study. Notable was the high incidence among older patients and those with cardiac conditions. These data confirm the need for effective vaccines to prevent RSV infection in older and vulnerable adults. [ABSTRACT FROM AUTHOR]

Background: A total of 10%-20% of patients develop long-term toxicity following radiotherapy for prostate cancer. Identification of common genetic variants associated with susceptibility to radiotoxicity might improve risk prediction and inform functional mechanistic studies.Methods: We conducted an individual patient data meta-analysis of six genome-wide association studies (n = 3871) in men of European ancestry who underwent radiotherapy for prostate cancer. Radiotoxicities (increased urinary frequency, decreased urinary stream, hematuria, rectal bleeding) were graded prospectively. We used grouped relative risk models to test associations with approximately 6 million genotyped or imputed variants (time to first grade 2 or higher toxicity event). Variants with two-sided Pmeta less than 5 × 10-8 were considered statistically significant. Bayesian false discovery probability provided an additional measure of confidence. Statistically significant variants were evaluated in three Japanese cohorts (n = 962). All statistical tests were two-sided.Results: Meta-analysis of the European ancestry cohorts identified three genomic signals: single nucleotide polymorphism rs17055178 with rectal bleeding (Pmeta = 6.2 × 10-10), rs10969913 with decreased urinary stream (Pmeta = 2.9 × 10-10), and rs11122573 with hematuria (Pmeta = 1.8 × 10-8). Fine-scale mapping of these three regions was used to identify another independent signal (rs147121532) associated with hematuria (Pconditional = 4.7 × 10-6). Credible causal variants at these four signals lie in gene-regulatory regions, some modulating expression of nearby genes. Previously identified variants showed consistent associations (rs17599026 with increased urinary frequency, rs7720298 with decreased urinary stream, rs1801516 with overall toxicity) in new cohorts. rs10969913 and rs17599026 had similar effects in the photon-treated Japanese cohorts.Conclusions: This study increases the understanding of the architecture of common genetic variants affecting radiotoxicity, points to novel radio-pathogenic mechanisms, and develops risk models for testing in clinical studies. Further multinational radiogenomics studies in larger cohorts are worthwhile. [ABSTRACT FROM AUTHOR]