The potential of integrating stereotactic ablative radiotherapy techniques with hyperfractionation for lung cancer.

BACKGROUND: Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity. METHODS: We utilized the linear-quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal-tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early-stage lung cancer. Mean lung BED, Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed-rank test. RESULTS: The transition point occurs when the tumor-to-normal tissue ratio (TNR) of the physical dose equals the TNR of α/ß in the BED dose-volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p < 0.01 for all). CONCLUSIONS: The hyperfractionated regimen has an advantage in the high-dose region of the lung but a disadvantage in the low-dose region. Further research is needed to determine the superiority between hypo- and hyperfractionation.

Machine learning-based comparison of factors influencing estimated glomerular filtration rate in Chinese women with or without non-alcoholic fatty liver.

BACKGROUND: The prevalence of non-alcoholic fatty liver (NAFLD) has increased recently. Subjects with NAFLD are known to have higher chance for renal function impairment. Many past studies used traditional multiple linear regression (MLR) to identify risk factors for decreased estimated glomerular filtration rate (eGFR). However, medical research is increasingly relying on emerging machine learning (Mach-L) methods. The present study enrolled healthy women to identify factors affecting eGFR in subjects with and without NAFLD (NAFLD+, NAFLD-) and to rank their importance. AIM: To uses three different Mach-L methods to identify key impact factors for eGFR in healthy women with and without NAFLD. METHODS: A total of 65535 healthy female study participants were enrolled from the Taiwan MJ cohort, accounting for 32 independent variables including demographic, biochemistry and lifestyle parameters (independent variables), while eGFR was used as the dependent variable. Aside from MLR, three Mach-L methods were applied, including stochastic gradient boosting, eXtreme gradient boosting and elastic net. Errors of estimation were used to define method accuracy, where smaller degree of error indicated better model performance. RESULTS: Income, albumin, eGFR, High density lipoprotein-Cholesterol, phosphorus, forced expiratory volume in one second (FEV1), and sleep time were all lower in the NAFLD+ group, while other factors were all significantly higher except for smoking area. Mach-L had lower estimation errors, thus outperforming MLR. In Model 1, age, uric acid (UA), FEV1, plasma calcium level (Ca), plasma albumin level (Alb) and T-bilirubin were the most important factors in the NAFLD+ group, as opposed to age, UA, FEV1, Alb, lactic dehydrogenase (LDH) and Ca for the NAFLD- group. Given the importance percentage was much higher than the 2nd important factor, we built Model 2 by removing age. CONCLUSION: The eGFR were lower in the NAFLD+ group compared to the NAFLD- group, with age being was the most important impact factor in both groups of healthy Chinese women, followed by LDH, UA, FEV1 and Alb. However, for the NAFLD- group, TSH and SBP were the 5th and 6th most important factors, as opposed to Ca and BF in the NAFLD+ group.

Association of cancer diagnosis with disability status among older survivors of colorectal cancer: a population-based retrospective cohort study.

Background: Older cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort. Methods: This retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. The study cohort consisted of 13,229 survivors of CRC diagnosed between 2005 and 2013 and an age-sex-matched, non-cancer cohort of 13,225 beneficiaries. The primary outcome was poor DS, determined by Davidoff's method, using predictors from 12 months of Medicare claims after cancer diagnosis. Multivariable Cox proportional hazards regression was used to identify risk factors associated with the development of poor DS. Results: Among the survivors of CRC, 97% were 65 years or older. After a 9-year follow-up, 54% of survivors of CRC developed poor DS. Significant factors associated with future poor DS included: age at diagnosis (hazard ratio [HR] = 3.50 for >80 years old), female sex (HR = 1.50), race/ethnicity (HR = 1.34 for Hispanic and 1.21 for Black), stage at diagnosis (HR = 2.26 for distant metastasis), comorbidity index (HR = 2.18 for >1), and radiation therapy (HR = 1.21). Having cancer (HR = 1.07) was significantly associated with developing poor DS in the pooled cohorts; age and race/ethnicity were also significant factors. Conclusions: Our findings suggest that a CRC diagnosis is independently associated with a small increase in the risk of developing poor DS after accounting for other known factors. The study identified risk factors for developing poor DS in CRC survivors, including Hispanic and Black race/ethnicity, age, sex, histologic stage, and comorbidities. These findings underscore the importance of consistent physical function assessments, particularly among subsets of older survivors of CRC who are at higher risk of disability, to prevent developing poor DS.

Repeat left ventricular-assisted device exchange and upgrade from second- to third-generation devices in a high-volume single center.

BACKGROUND: Pump exchange is an established strategy to treat LVAD-related complications such as thrombosis, infection, and driveline failure. Pump upgrades with an exchange to newer generation devices are being performed to the advantage of the patient on long-term support. The safety and efficacy of a repeat LVAD exchange with a concomitant upgrade to a third-generation pump have not been reported. METHODS: We performed a retrospective analysis of all consecutive patients who underwent a repeat LVAD device exchange and upgrade to HeartMate III (HMIII) at Houston Methodist Hospital between December 2018 and December 2020. RESULTS: Five patients underwent exchange and upgrade to HMIII within the specified timeframe. Four patients had already had two prior exchanges (all HMII to HMII), and one patient had one prior exchange (HVAD to HVAD). In all cases, implantation was performed as destination therapy. The surgical exchange was performed via redo median sternotomy on full cardiopulmonary bypass. No unplanned redo surgery of the device component was required. In-hospital mortality was 20% in this very high-risk population. At 1-, 3-, and 6-month follow-up, all discharged patients were on HMIII support, with no major LVAD-related adverse events reported. CONCLUSION: We report the feasibility and safety of a repeat pump exchange with an upgrade to HMIII in a high-volume center. The decision for medical therapy versus surgical exchange has to be tailored to individual cases based on risk factors and clinical stability but in expert hands, even a re-redo surgical approach grants options for good medium-term outcomes.

Trends in Diabetes Medication Taking and Incidence of Depression in Patients with Type 2 Diabetes: A Retrospective Cohort Study from 2010 to 2018.

BACKGROUND: This study examined the trends in diabetes medication taking and its association with the incidence of depression in patients with type 2 diabetes (T2D). METHOD: A retrospective cohort of Medicare enrollees with regular care in 2010 was defined from 100% Texas Medicare claims. The impact of medication taking on incident depression was evaluated from 2010 to 2018. Cox proportional hazards regressions were used to estimate the association between medication taking and depression. RESULTS: A total of 72,461 patients with T2D and with regular care were analyzed. Among 60,216 treated patients, the regular medication taking rate slightly increased from 60.8 to 63.2% during the study period. Patients with regular medication taking at baseline had a 9% lower risk of developing depression (hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.89-0.94), and the magnitude of the association increased after adjustment of the model for time-varied medication taking (HR: 0.82, 95% CI: 0.79-0.85). The presence of nephropathy had the greatest mediating effect (23.2%) on the association of medication taking and depression. CONCLUSION: We demonstrated a steady but modest increase in regular diabetes medication taking over a 9-year period and a significant relationship between medication taking and incident depression in patients with T2D.

A randomized, placebo-controlled study of givosiran in patients with acute hepatic porphyrias (ENVISION): Final (36-month) analysis of the Taiwan Cohort.

BACKGROUND/PURPOSE: Acute hepatic porphyrias (AHP) are rare genetic disorders associated with acute neurovisceral attacks and chronic symptoms. This analysis was conducted to examine the long-term efficacy and safety of givosiran in Taiwanese participants in the ENVISION study (NCT03338816). METHODS: Patients (age ≥12 years) with AHP and recurrent attacks were randomized to receive givosiran 2.5 mg/kg or placebo for 6 months during the double-blind period. Patients then switched from placebo to givosiran (placebo crossover group) or continued taking givosiran (continuous givosiran group) during a 30-month open-label extension period. The total study duration was 36 months. An analysis was conducted that included patients enrolled in Taiwan (N = 7). RESULTS: During the double-blind period and open-label extension period, the median annualized attack rates were 0.0 and 0.0, respectively, in the continuous givosiran group (n = 5) and 15.1 and 4.6, respectively, in the placebo crossover group (n = 2; 70 % decrease). Median annualized days of hemin use in the double-blind period and open-label extension period were 0.0 and 0.0, respectively, in the continuous givosiran group, and 23.8 and 5.0, respectively, in the placebo crossover group (79 % decrease). EQ-5D VAS scores remained relatively stable in both groups, and PPEQ responses indicated improved functioning and satisfaction in both groups. Delta-aminolevulinic acid and porphobilinogen levels remained low with long-term givosiran treatment. Serious adverse events were reported by 3 patients (43 %). CONCLUSIONS: Long-term efficacy and safety results in the Taiwan cohort are consistent with those in the global cohort.

Real-world outcomes of 18,186 metastatic solid tumor outpatients: Baseline blood cell counts correlate with survival after immune checkpoint inhibitor therapy.

BACKGROUND: Patient survival in advanced/metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) has improved with immune checkpoint inhibitors (ICI). Biomarkers' role in prognosis and treatment has been limited by conflicting trial results. METHODS: This retrospective, observational study analyzed baseline demographic, clinical, laboratory, and treatment data versus outcomes of The US Oncology Network adult outpatients. Patients with advanced/metastatic melanoma, NSCLC, or RCC treated between January 1, 2015 and November 30, 2020 were given ICI monotherapy or combination therapy with ipilimumab, pembrolizumab, nivolumab, or atezolizumab. Treatment outcomes (overall survival [OS], time to treatment discontinuation, time to next treatment) were followed longitudinally until May 31, 2021, last patient record, or date of death. Baseline blood cell counts, including absolute monocyte count (AMC), absolute lymphocyte count (ALC), monocyte-to-lymphocyte ratio (MLR), absolute neutrophil count (ANC), and eosinophil count, were subdivided into quintiles for univariate and multivariable Cox regression analyses. RESULTS: Data from 18,186 patients with advanced/metastatic melanoma (n = 3314), NSCLC (n = 12,416), and RCC (n = 2456) were analyzed. Better OS correlated with increased baseline serum albumin concentration, increased eosinophil and lymphocyte counts, and Western United States physician practice location. Decreased OS correlated with increased AMC, MLR, ANC, age, and worse Eastern Cooperative Oncology Group performance status. CONCLUSIONS: To our knowledge, this study is the largest to date to associate baseline survival indicators and outcomes in outpatients with advanced/metastatic melanoma, NSCLC, or RCC and receiving ICIs. Results may inform disease-specific prognostic models and help providers identify patients most likely to benefit from ICI therapy.

Extracorporeal Membrane Oxygenation in Postcardiotomy Cardiogenic Shock.

Postcardiotomy extracorporeal membrane oxygenation (PC-ECMO), the most frequent indication for ECMO in the United States, is increasingly used as the first-line mechanical circulatory support in patients who are refractory to conventional treatment. Despite increasing use of PC-ECMO, limited evidence is available regarding its safety, efficacy, and optimal timing for initiation and weaning. The decision to use PC-ECMO often is made in the absence of robust clinical data, leading to variability in patient selection, management, and outcomes across different institutions. This article summarizes current evidence on ECMO use in postcardiotomy cardiogenic shock and discusses its potential benefits, management, complications, and outcomes.

A vast evolutionarily transient translatome contributes to phenotype and fitness.

Translation is the process by which ribosomes synthesize proteins. Ribosome profiling recently revealed that many short sequences previously thought to be noncoding are pervasively translated. To identify protein-coding genes in this noncanonical translatome, we combine an integrative framework for extremely sensitive ribosome profiling analysis, iRibo, with high-powered selection inferences tailored for short sequences. We construct a reference translatome for Saccharomyces cerevisiae comprising 5,400 canonical and almost 19,000 noncanonical translated elements. Only 14 noncanonical elements were evolving under detectable purifying selection. A representative subset of translated elements lacking signatures of selection demonstrated involvement in processes including DNA repair, stress response, and post-transcriptional regulation. Our results suggest that most translated elements are not conserved protein-coding genes and contribute to genotype-phenotype relationships through fast-evolving molecular mechanisms.

Developing an AI-assisted planning pipeline for hippocampal avoidance whole brain radiotherapy.

BACKGROUND AND PURPOSE: Hippocampal avoidance whole brain radiotherapy (HA-WBRT) is effective for controlling disease and preserving neuro-cognitive function for brain metastases. However, contouring and planning of HA-WBRT is complex and time-consuming. We designed and evaluated a pipeline using deep learning tools for a fully automated treatment planning workflow to generate HA-WBRT radiotherapy plans. MATERIALS AND METHODS: We retrospectively collected 50 adult patients who received HA-WBRT. Using RTOG- 0933 clinical trial protocol guidelines, all organs-at-risk (OARs) and the clinical target volume (CTV) were contoured by experienced radiation oncologists. A deep-learning segmentation model was designed and trained. Next, we developed a volumetric-modulated arc therapy (VMAT) auto-planning algorithm for 30 Gy in 10 fractions. Automated segmentations were evaluated using the Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (95 % HD). Auto-plans were evaluated by the percentage of PTV volume that receives 30 Gy (V30Gy), conformity index (CI), and homogeneity index (HI) of planning target volume (PTV) and the minimum dose (D100%) and maximum dose (Dmax) for the hippocampus, Dmax for the lens, eyes, optic nerve, brain stem, and chiasm. RESULTS: We developed a deep-learning segmentation model and an auto-planning script. For the 10 cases in the independent test set, the overall average DSC and 95 % HD of contours were greater than 0.8 and less than 7 mm, respectively. All auto-plans met the RTOG- 0933 criteria. The HA-WBRT plan automatically created time was about 10 min. CONCLUSIONS: An artificial intelligence (AI)-assisted pipeline using deep learning tools can rapidly and accurately generate clinically acceptable HA-WBRT plans with minimal manual intervention and increase efficiency of this treatment for brain metastases.

Life-space mobility and post-hospitalization outcomes among older Mexican American Medicare beneficiaries.

BACKGROUND: Older adults with limited mobility are at an increased risk of adverse health outcomes, an outcome inadequately investigated in older Mexican Americans. We explored whether pre-admission life-space mobility predicts post-hospitalization outcomes among hospitalized Mexican American Medicare beneficiaries. METHODS: Life-space mobility, using the Life-Space Assessment (LSA), was analyzed using quartiles and 5-point intervals. Using the Hispanic Established Populations for the Epidemiologic Study of the Elderly (HEPESE) Waves 7 and 8 data linked to Medicare claims data, 426 older Mexican Americans with at least 2 months of Medicare coverage who were hospitalized within 2 years of completing the LSA were included. Logistic and Cox Proportional regression analyses estimated the association of pre-admission LSA with post-hospitalization outcomes. RESULTS: Prior to hospitalization, 85.4% reported limited life-space mobility. Most patients (n = 322, 75.6%) were hospitalized for medical reasons. About 65% were discharged to the community. Pre-admission LSA scores were not associated with community discharge (Odds Ratio [OR] = 1.02, 0.95-1.10). Higher pre-admission LSA scores were associated with 30-day readmission (OR = 1.11, 1.01-1.22). Patients in the highest pre-admission LSA quartile (i.e., greatest life-space mobility) were less likely to die within 2 years after hospital discharge (OR = 0.61, 0.39-0.97) compared to those with lower pre-admission LSA scores. CONCLUSIONS: Among older Mexican American Medicare beneficiaries, greater pre-admission LSA scores were associated with an increased risk of 30-day readmission and a decreased risk of mortality within 2 years following hospitalization. Future work should further investigate the relationship between LSA and post-hospitalization outcomes in a larger sample of Mexican American older adults.

Pain, obesity, and physical function in Mexican American older adults during 20 years of follow-up.

INTRODUCTION: Pain remains largely undertreated in older adults irrespective of health care setting. Mexican American adults in the United States have a high age-adjusted prevalence of obesity. However, the association of pain and obesity with physical function is understudied in this population. OBJECTIVE: To examine the association of co-occurring pain and obesity with physical function over 20 years of follow-up in a cohort of older Mexican Americans who scored ≥7 (moderate to high) in the Short Physical Performance Battery (SPPB) test and were nondisabled at baseline. DESIGN: Longitudinal population-based study. SETTING: Community-dwelling older adults from Southwestern United States. PARTICIPANTS: Mexican American adults age 65 years and older. INTERVENTIONS: Not Applicable. MAIN OUTCOME MEASURES: Physical function was assessed with the SPPB test (standing balance, timed 8-ft walk, and five repeated timed chair stands). Participants at baseline were divided into four groups: no pain-no obesity (n = 869), obesity only (n = 282), pain only (n = 216), and pain-obesity (n = 159). Generalized Estimating Equation models were used to estimate the odds ratio (OR) and 95% confidence interval (CI) of lower performance in physical function over 20 years as a function of pain-obesity grouping. RESULTS: Participants with pain only (OR = 1.61, 95% CI = 1.34-1.95) and with co-occurring pain and obesity (OR = 2.32, 95% CI = 1.83-2.95) had significantly greater odds of physical function impairment over those with no pain-no obesity or obesity only, after controlling for all covariates. CONCLUSION: Older Mexican American adults were at high risk for physical function impairment over time if they had pain or co-occurring pain and obesity. Early assessment and proper pain management as well as maintaining a healthy weight may reduce declines in physical function in older Mexican American adults.

Body mass index and physical frailty among older Mexican Americans: Findings from an 18-year follow up.

PURPOSES: The relationship between body mass index (BMI) and frailty in older Mexican Americans has not been previously studied. The objective of this study was to examine the relationship between BMI and frailty among non-frail older Mexican Americans at baseline over 18 years of follow up. METHODS: Longitudinal population-based study of 1,648 non-institutionalized Mexican Americans aged ≥ 67 years from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1995/96-2012/13). Frailty phenotype was defined as meeting three or more of the following: unintentional weight loss of >10 pounds, weakness, self-reported exhaustion, low physical activity, and slow walking speed. BMI (kg/m2) was classified as underweight (<18.5), normal weight (18.5-<25), overweight (25-< 30), obesity category I (30-<35), and obesity category II/morbid obesity (≥35). Covariates included socio-demographics, comorbidities, cognitive function, and depressive symptoms. Generalized Estimating Equation models were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of frailty as a function of BMI category. RESULTS: Participants with underweight or obesity category II/ morbid obesity had greater odds of frailty over time compared to those with normal weight (OR = 2.39, 95% CI = 1.29-4.44 and OR = 1.62, 95% CI = 1.07-2.44, respectively) after controlling for all covariates. Participants with BMIs in the overweight or category I obesity were at lower odds of frailty over time. CONCLUSIONS: Mexican American older adults with BMIs in the underweight or obesity category II/morbid obesity were at higher odds of frailty over time. This indicates that maintaining a healthy weight in this population may prevent future frailty.

Signal Detection of Adverse Events Associated with Trastuzumab in a Cohort of Elderly Patients with Breast Cancer.

AIM: Utilization of signal detection methods in longitudinal claims data can improve post-marketing drug surveillance, but to date there has been limited application. The aim of this study is to use 3 approaches, the proportional reporting ratio, Gamma Poisson Shrinker, and tree-based scan statistic in detecting adverse drug events (ADEs) attributed to trastuzumab using an administrative claims dataset. METHODS: Using data from the Texas Cancer Registry and SEER linked to Medicare from 2010 to 2013, we conducted 1:2 propensity score matching. Breast cancer HER2+ patients treated with trastuzumab in addition to standard chemotherapy were matched to HER2- patients treated with standard chemotherapy. Inpatient and outpatient encounters up to 6 months from start of therapy were used to identify adverse events. RESULTS: A total of 4191 patients were included in the study. Across all methods, use of trastuzumab generated signals on 9 distinct body systems. Cardiomyopathy and heart valve disease were the most consistently detected signals. Clinical review determined that most signals represented known ADEs. CONCLUSIONS: We showed that claims data can be used to complement current ADE monitoring using common data mining methods with propensity score matching. Our analysis identified all expected ADEs associated with trastuzumab, and additional signals of valvular heart disorders.

Cognitive impairment and low physical function among older Mexican Americans: findings from a 20-year follow-up☆.

PURPOSE: The aim of the study was to examine the association between cognitive impairment and low physical function over a 20-year follow-up period among older Mexican Americans. METHODS: The final sample included 1545 community-dwelling Mexican Americans age ≥ 65 years from the Hispanic Established Population for the Epidemiological Study of the Elderly, who scored moderate-high on Short Physical Performance Battery (SPPB) and were non-disabled at baseline (1993/94). Cognitive impairment was defined at each observation wave as less than equal to 21 points on the Mini Mental State Examination. General Estimating Equation was used to estimate the odds ratio of having low physical function (SPPB <7 points) over time as a function of cognitive impairment, adjusting for socio-demographics, self-reported medical conditions, body mass index, and depressive symptoms. All variables were time-varying, except sex and education. RESULTS: Participants with cognitive impairment had increased odds ratio of low physical function over time compared to those without cognitive impairment (Odds Ratio = 1.89; 95% Confidence Interval = 1.59-2.26, P <.0001), after controlling for all covariates. CONCLUSION: Despite having moderate to high physical function and being non-disabled at baseline, participants with cognitive impairment were more likely to decline in physical function over 20-years of follow-up.

Intelligent Bio-Impedance System for Personalized Continuous Blood Pressure Measurement.

Continuous blood pressure (BP) measurement is crucial for long-term cardiovascular monitoring, especially for prompt hypertension detection. However, most of the continuous BP measurements rely on the pulse transit time (PTT) from multiple-channel physiological acquisition systems that impede wearable applications. Recently, wearable and smart health electronics have become significant for next-generation personalized healthcare progress. This study proposes an intelligent single-channel bio-impedance system for personalized BP monitoring. Compared to the PTT-based methods, the proposed sensing configuration greatly reduces the hardware complexity, which is beneficial for wearable applications. Most of all, the proposed system can extract the significant BP features hidden from the measured bio-impedance signals by an ultra-lightweight AI algorithm, implemented to further establish a tailored BP model for personalized healthcare. In the human trial, the proposed system demonstrates the BP accuracy in terms of the mean error (ME) and the mean absolute error (MAE) within 1.7 ± 3.4 mmHg and 2.7 ± 2.6 mmHg, respectively, which agrees with the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). In conclusion, this work presents a proof-of-concept for an AI-based single-channel bio-impedance BP system. The new wearable smart system is expected to accelerate the artificial intelligence of things (AIoT) technology for personalized BP healthcare in the future.

Healthcare utilization and costs among high-need and frail Mexican American Medicare beneficiaries.

OBJECTIVES: To examine Medicare health care spending and health services utilization among high-need population segments in older Mexican Americans, and to examine the association of frailty on health care spending and utilization. METHODS: Retrospective cohort study of the innovative linkage of Medicare data with the Hispanic Established Populations for the Epidemiologic Study of the Elderly (H-EPESE) were used. There were 863 participants, which contributed 1,629 person years of information. Frailty, cognition, and social risk factors were identified from the H-EPESE, and chronic conditions were identified from the Medicare file. The Cost and Use file was used to calculate four categories of Medicare spending on: hospital services, physician services, post-acute care services, and other services. Generalized estimating equations (GEE) with a log link gamma distribution and first order autoregressive, correlation matrix was used to estimate cost ratios (CR) of population segments, and GEE with a logit link binomial distribution was applied to estimate odds ratios (OR) of healthcare use. RESULTS: Participants in the major complex chronic illness segment who were also pre-frail or frail had higher total costs and utilization compared to the healthy segment. The CR for total Medicare spending was 3.05 (95% CI, 2.48-3.75). Similarly, this group had higher odds of being classified in the high-cost category 5.86 (95% CI, 3.35-10.25), nursing home care utilization 11.32 (95% CI, 3.88-33.02), hospitalizations 4.12 (95% CI, 2.88-5.90) and emergency room admissions 4.24 (95% CI, 3.04-5.91). DISCUSSION: Our findings highlight that frailty assessment is an important consideration when identifying high-need and high-cost patients.

Modular evolution of secretion systems and virulence plasmids in a bacterial species complex.

BACKGROUND: Many named species as defined in current bacterial taxonomy correspond to species complexes. Uncertainties regarding the organization of their genetic diversity challenge research efforts. We utilized the Agrobacterium tumefaciens species complex (a.k.a. Agrobacterium biovar 1), a taxon known for its phytopathogenicity and applications in transformation, as a study system and devised strategies for investigating genome diversity and evolution of species complexes. RESULTS: We utilized 35 genome assemblies, including 14 newly generated ones, to achieve a phylogenetically balanced sampling of A. tumefaciens. Our genomic analysis suggested that the 10 genomospecies described previously are distinct biological species and supported a quantitative guideline for species delineation. Furthermore, our inference of gene content and core-genome phylogeny allowed for investigations of genes critical in fitness and ecology. For the type VI secretion system (T6SS) involved in interbacterial competition and thought to be conserved, we detected multiple losses and one horizontal gene transfer. For the tumor-inducing plasmids (pTi) and pTi-encoded type IV secretion system (T4SS) that are essential for agrobacterial phytopathogenicity, we uncovered novel diversity and hypothesized their involvement in shaping this species complex. Intriguingly, for both T6SS and T4SS, genes encoding structural components are highly conserved, whereas extensive diversity exists for genes encoding effectors and other proteins. CONCLUSIONS: We demonstrate that the combination of a phylogeny-guided sampling scheme and an emphasis on high-quality assemblies provides a cost-effective approach for robust analysis in evolutionary genomics. We show that the T6SS VgrG proteins involved in specific effector binding and delivery can be classified into distinct types based on domain organization. The co-occurrence patterns of VgrG-associated domains and the neighboring genes that encode different chaperones/effectors can be used to infer possible interacting partners. Similarly, the associations between plant host preference and the pTi type among these strains can be used to infer phenotype-genotype correspondence. Our strategies for multi-level investigations at scales that range from whole genomes to intragenic domains and phylogenetic depths from between- to within-species are applicable to other bacteria. Furthermore, modularity observed in the molecular evolution of genes and domains is useful for inferring functional constraints and informing experimental works.

Impact of State Nurse Practitioner Regulations on Potentially Inappropriate Medication Prescribing Between Physicians and Nurse Practitioners: A National Study in the United States.

BACKGROUND: The American Geriatrics Society regularly updates the Beers Criteria for Potentially Inappropriate Medication (PIM) to improve prescribing safety. PURPOSE: This study assessed the impact of nurse practitioner (NP) practices on PIM prescribing across states in the United States and compared the change in PIM prescribing rates between 2016 and 2018. METHODS: We used data from a random selection of 20% of Medicare beneficiaries (66 years or older) from 2015 to 2018 to perform multilevel logistic regression. A PIM prescription was classified as initial or refill on the basis of medication history 1 year before a visit. PIM use after an outpatient visit was the primary study outcome. RESULTS: We included 9 000 224 visits in 2016 and 9 310 261 in 2018. The PIM prescription rate was lower in states with full NP practice and lower among NPs than among physicians; these rates for both physicians and NPs decreased from 2016 to 2018. CONCLUSIONS: Changes could be due to individual state practices.

Arthritis, physical function, and disability among older Mexican Americans over 23 years of follow-up.

OBJECTIVE: Arthritis is a common chronic condition in the ageing population. Its impact on physical function varies according to sociodemographic and race/ethnic factors. The study objective was to examine the impact of arthritis on physical function and disability among non-disabled older Mexican Americans over time. DESIGN: A 23-year prospective cohort study of 2230 Mexican Americans aged 65 years and older from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1993/94-2016). The independent variable was self-reported physician-diagnosed arthritis, and the outcomes included Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), mobility, Short Physical Performance Battery (SPPB), and handgrip strength. Covariates were sociodemographic, medical conditions, body mass index, depressive symptoms, and cognitive function. General linear mixed models were performed to estimate the change in SPPB and muscle strength. General Equation Estimation models estimated the odds ratios (OR) of becoming ADL- or IADL- or mobility - disabled as a function of arthritis. All variables were used as time-varying except for sex, education, and nativity. RESULTS: Overall, participants with arthritis had higher odds ratio (OR) of any ADL [OR = 1.35, 95% Confidence Interval (CI) = 1.09-1.68] and mobility (OR = 1.34, 95% CI = 1.18-1.52) disability over time than those without arthritis, after controlling for all covariates. Women, but not men, reporting arthritis had increased risk for ADL and mobility disability. The total SPPB score declined 0.18 points per year among those with arthritis than those without arthritis, after controlling for all covariates (p-value < .010). CONCLUSIONS: Our study demonstrates the independent effect of arthritis in increasing ADL and mobility disability and decreased physical function in older Mexican Americans over 23-years of follow-up.