Predictors of high-intensity care at the end of life among older adults with solid tumors: A population-based study.

INTRODUCTION: High-intensity end-of-life (EoL) care can be burdensome for patients, caregivers, and health systems and does not confer any meaningful clinical benefit. Yet, there are significant knowledge gaps regarding the predictors of high-intensity EoL care. In this study, we identify risk factors associated with high-intensity EoL care among older adults with the four most common malignancies, including breast, prostate, lung, and colorectal cancer. MATERIALS AND METHODS: Using SEER-Medicare data, we conducted a retrospective analysis of Medicare beneficiaries aged 65 and older who died of breast, prostate, lung, or colorectal cancer between 2011 and 2015. We used multivariable logistic regression to identify clinical, demographic, socioeconomic, and geographic predictors of high-intensity EoL care, which we defined as death in an acute care hospital, receipt of any oral or parenteral chemotherapy within 14 days of death, one or more admissions to the intensive care unit within 30 days of death, two or more emergency department visits within 30 days of death, or two or more inpatient admissions within 30 days of death. RESULTS: Among 59,355 decedents, factors associated with increased likelihood of receiving high-intensity EoL care were increased comorbidity burden (odds ratio [OR]:1.29; 95% confidence interval [CI]:1.28-1.30), female sex (OR:1.05; 95% CI:1.01-1.09), Black race (OR:1.14; 95% CI:1.07-1.23), Other race/ethnicity (OR:1.20; 95% CI:1.10-1.30), stage III disease (OR:1.11; 95% CI:1.05-1.18), living in a county with >1,000,000 people (OR:1.23; 95% CI:1.16-1.31), living in a census tract with 10%-<20% poverty (OR:1.09; 95% CI:1.03-1.16) or 20%-100% poverty (OR:1.12; 95% CI:1.04-1.19), and having state-subsidized Medicare premiums (OR:1.18; 95% CI:1.12-1.24). The risk of high-intensity EoL care was lower among patients who were older (OR:0.98; 95% CI:0.98-0.99), lived in the Midwest (OR:0.69; 95% CI:0.65-0.75), South (OR:0.70; 95% CI:0.65-0.74), or West (OR:0.81; 95% CI:0.77-0.86), lived in mostly rural areas (OR:0.92; 95% CI:0.86-1.00), and had poor performance status (OR:0.26; 95% CI:0.25-0.28). Results were largely consistent across cancer types. DISCUSSION: The risk factors identified in our study can inform the development of new interventions for patients with cancer who are likely to receive high-intensity EoL care. Health systems should consider incorporating these risk factors into decision-support tools to assist clinicians in identifying which patients should be referred to hospice and palliative care.

County-Level Mandates Were Generally Effective At Slowing COVID-19 Transmission.

Throughout the COVID-19 pandemic in the US, counties adopted numerous nonpharmaceutical interventions, such as mask mandates and stay-at-home orders, to slow COVID-19 transmission and prevent hospitals from reaching full capacity. Early evidence has been mixed about whether these interventions are effective. However, most studies only covered the early waves of COVID-19 and did not account for county-level variation in the adoption and repeal of such policies. Using daily county-level data from the Centers for Disease Control and Prevention, we evaluated the joint impact of bans on large gatherings, stay-at-home orders, mask mandates, and bar and restaurant closures on slowing COVID-19 transmission during waves 1-4 of the pandemic in the US (March 1, 2020-June 30, 2021). Our survival analysis showed that these interventions were generally effective at slowing COVID-19 transmission during this period. The mitigating effect was particularly strong during waves 2 and 3 and less substantial during waves 1 and 4. We also found strong evidence of the overall protective effect of mask mandates and, to a lesser degree, anticongregation policies. These study findings provide crucial evidence for public health officials to reference for support when using nonpharmaceutical interventions to flatten the curve of future waves of COVID-19 or other infectious disease outbreaks.

Functional status and therapy for older adults with diffuse large B-cell lymphoma in nursing homes: A population-based study.

OBJECTIVES: To characterize the prevalence of functional and cognitive impairments, and associations between impairments and treatment among older patients with diffuse large B cell lymphoma (DLBCL) receiving nursing home (NH) care. METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify beneficiaries diagnosed with DLBCL 2011-2015 who received care in a NH within -120 ~ +30 days of diagnosis. Multivariable logistic regression was used to compare receipt of chemoimmunotherapy (including multi-agent, anthracycline-containing regimens), 30-day mortality, and hospitalization between NH and community-dwelling patients, estimating odds ratios (OR) and 95% confidence interval (CI). We also examined overall survival (OS). Among NH patients, we examined receipt of chemoimmunotherapy based on functional and cognitive impairment. RESULTS: Of the eligible 649 NH patients (median age: 82 years), 45% received chemoimmunotherapy; among the recipients, 47% received multi-agent, anthracycline-containing regimens. Compared with community-dwelling patients, those in a NH were less likely to receive chemoimmunotherapy (OR: 0.34, 95%CI: 0.29-0.41), had higher 30-day mortality (OR: 2.00, 95%CI: 1.43-2.78) and hospitalization (OR: 1.51, 95%CI: 1.18-1.93), and poorer OS (hazard ratio: 1.36, 95%CI: 1.11-1.65). NH patients with severe functional (61%) or any cognitive impairment (48%) were less likely to receive chemoimmunotherapy. CONCLUSIONS: High rates of functional and cognitive impairment and low rates of chemoimmunotherapy were observed among NH residents diagnosed with DLBCL. Further research is needed to better understand the potential role of novel and alternative treatment strategies and patient preferences for treatment to optimize clinical care and outcomes in this high-risk population.

Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium.

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

Rehabilitation for Total Knee Arthroplasty: A Systematic Review.

ABSTRACT: We sought to determine the comparative benefit and harm of rehabilitation interventions for patients who have undergone elective, unilateral total knee arthroplasty for the treatment of primary osteoarthritis. We searched PubMed, Embase, The Cochrane Register of Clinical Trials, CINAHL, PsycINFO, Scopus, and ClinicalTrials.gov from January 1, 2005, through May 3, 2021. We included randomized controlled trials and adequately adjusted nonrandomized comparative studies of rehabilitation programs reporting performance-based, patient-reported, or healthcare utilization outcomes. Three researchers extracted study data and assessed risk of bias, verified by an independent researcher. The team assessed strength of evidence. Evidence from 53 studies randomized controlled trials suggests that various rehabilitation programs after total knee arthroplasty may lead to comparable improvements in pain, range of motion, and activities of daily living. Rehabilitation in the acute phase may lead to increased strength but result in similar strength when delivered in the postacute phase. No studies reported evidence of risk of harms due to rehabilitation delivered in the acute period after total knee arthroplasty; risk of harms among various postacute rehabilitation programs seems comparable. All findings were of low strength of evidence. Evaluation of rehabilitation after total knee arthroplasty needs a systematic overhaul to sufficiently guide future practice or research including the use of standardized intervention components and core outcomes.

Prehabilitation for Total Knee or Total Hip Arthroplasty: A Systematic Review.

ABSTRACT: We sought to systematically review the evidence on the benefits and harms of prehabilitation interventions for patients who are scheduled to undergo elective, unilateral total knee arthroplasty or total hip arthroplasty surgery for the treatment of primary osteoarthritis. We searched PubMed, Embase, The Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, Scopus, and ClinicalTrials.gov from January 1, 2005, through May 3, 2021. We selected for inclusion randomized controlled trials and adequately adjusted nonrandomized comparative studies of prehabilitation programs reporting performance-based, patient-reported, or healthcare utilization outcomes. Three researchers extracted study data and assessed risk of bias, verified by an independent researcher. Experts in rehabilitation content and complex interventions independently coded rehabilitation interventions. The team assessed strength of evidence. While large heterogeneity across evaluated prehabilitation programs limited strong conclusions, evidence from 13 total knee arthroplasty randomized controlled trials suggest that prehabilitation may result in increased strength and reduced length of stay and may not lead to increased harms but may be comparable in terms of pain, range of motion, and activities of daily living (all low strength of evidence). There was no evidence or insufficient evidence for all other outcomes after total knee arthroplasty. Although there were six total hip arthroplasty randomized controlled trials, there was no evidence or insufficient evidence for all total hip arthroplasty outcomes.

Rehabilitation for Total Hip Arthroplasty: A Systematic Review.

ABSTRACT: We sought to determine the comparative benefits and harms of rehabilitation interventions for patients who have undergone elective, unilateral THA surgery for the treatment of primary osteoarthritis. We searched PubMed, Embase, The Cochrane Register of Clinical Trials, CINAHL, PsycINFO, Scopus, and ClinicalTrials.gov from January 1, 2005, through May 3, 2021. We included randomized controlled trials and adequately adjusted nonrandomized comparative studies of rehabilitation programs reporting performance-based, patient-reported, or healthcare utilization outcomes. Three researchers extracted study data and assessed risk of bias, verified by an independent researcher. Experts in rehabilitation content and complex interventions independently coded rehabilitation interventions. The team assessed strength of evidence. Large heterogeneity across evaluated rehabilitation programs limited conclusions. Evidence from 15 studies suggests that diverse rehabilitation programs may not differ in terms of risk of harm or outcomes of pain, strength, activities of daily living, or quality of life (all low strength of evidence). Evidence is insufficient for other outcomes. In conclusion, no differences in outcomes were found between different rehabilitation programs after THA. Further evidence is needed to inform decisions on what attributes of rehabilitation programs are most effective for various outcomes.

Comparison of Low-Value Care Among Commercial and Medicaid Enrollees.

BACKGROUND: Low-value healthcare is costly and inefficient and may adversely affect patient outcomes. Despite increases in low-value service use, little is known about how the receipt of low-value care differs across payers. OBJECTIVE: To evaluate differences in the use of low-value care between patients with commercial versus Medicaid coverage. DESIGN: Retrospective observational analysis of the 2017 Rhode Island All-payer Claims Database, estimating the probability of receiving each of 14 low-value services between commercial and Medicaid enrollees, adjusting for patient sociodemographic and clinical characteristics. Ensemble machine learning minimized the possibility of model misspecification. PARTICIPANTS: Medicaid and commercial enrollees aged 18-64 with continuous coverage and an encounter at which they were at risk of receiving a low-value service. INTERVENTION: Enrollment in Medicaid or Commercial insurance. MAIN MEASURES: Use of one of 14 validated measures of low-value care. KEY RESULTS: Among 110,609 patients, Medicaid enrollees were younger, had more comorbidities, and were more likely to be female than commercial enrollees. Medicaid enrollees had higher rates of use for 7 low-value care measures, and those with commercial coverage had higher rates for 5 measures. Across all measures of low-value care, commercial enrollees received more (risk difference [RD] 6.8 percentage points; CI: 6.6 to 7.0) low-value services than their counterparts with Medicaid. Commercial enrollees were also more likely to receive low-value services typically performed in the emergency room (RD 11.4 percentage points; CI: 10.7 to 12.2) and services that were less expensive (RD 15.3 percentage points; CI 14.6 to 16.0). CONCLUSION: Differences in the provision of low-value care varied across measures, though average use was slightly higher among commercial than Medicaid enrollees. This difference was more pronounced for less expensive services indicating that financial incentives may not be the sole driver of low-value care.

Supportive interventions for childhood cancer: An umbrella review of randomized evidence.

Therapeutic advancements have improved pediatric cancer prognosis, shifting the interest towards the management of psychosocial burden and treatment-related morbidity. To critically appraise the available evidence, we conducted an umbrella review of meta-analyses of randomized controlled trials on supportive interventions for childhood cancer. Thirty-four publications (92 meta-analyses, 1 network, 14,521 participants) were included. The most concrete data showed a reduction in procedure-related pain and distress through hypnosis. Moreover, exercise improved the functional mobility of the patients. Regarding pharmacological interventions, most of the meta-analyses pertained to the treatment of nausea/vomiting (ondansetron was effective) and infections/febrile neutropenia [granulocyte-(macrophage) colony-stimulating factors showed benefits]. Substantial heterogeneity was detected in 31 associations. Conclusively, supportive interventions for pediatric cancer are being thoroughly evaluated. However, most of the studies are small and of moderate quality, highlighting the need for more randomized evidence in order to increase precision in improving the quality of life of patients, survivors and their families.

US Black-White Differences in Mortality Risk Among Transgender and Cisgender People in Private Insurance, 2011-2019.

Objectives. To compare survival by gender and race among transgender and cisgender people enrolled in private insurance in the United States between 2011 and 2019. Methods. We examined Optum's Clinformatics Data Mart Database. We identified transgender enrollees using claims related to gender-affirming care. Our analytic sample included those we identified as transgender and a 10% random sample of cisgender enrollees. We limited our sample to those 18 years or older who were non-Hispanic Black or White. We identified 18 033 transgender and more than 4 million cisgender enrollees. We fit Kaplan-Meier survival curves and calculated standardized mortality ratios while adjusting for census region. Results. Black transfeminine and nonbinary people assigned male sex at birth were 2.73 times more likely to die than other Black transgender people and 2.38 and 3.34 times more likely than Black cisgender men and women, respectively; similar results were found when White transfeminine and nonbinary people assigned male sex at birth were compared with White cisgender cohorts. Conclusions. Our findings highlight glaring inequities in mortality risks among Black transfeminine and nonbinary people assigned male sex at birth and underscore the need to monitor mortality risks in transgender populations and address the social conditions that increase these risks. (Am J Public Health. 2022;112(10):1507-1514. https://doi.org/10.2105/AJPH.2022.306963).

Reproducibility of prediction models in health services research.

The field of health services research studies the health care system by examining outcomes relevant to patients and clinicians but also health economists and policy makers. Such outcomes often include health care spending, and utilization of care services. Building accurate prediction models using reproducible research practices for health services research is important for evidence-based decision making. Several systematic reviews have summarized prediction models for outcomes relevant to health services research, but these systematic reviews do not present a thorough assessment of reproducibility and research quality of the prediction modelling studies. In the present commentary, we discuss how recent advances in prediction modelling in other medical fields can be applied to health services research. We also describe the current status of prediction modelling in health services research, and we summarize available methodological guidance for the development, update, external validation and systematic appraisal of prediction models.

Differences in All-Cause Mortality Among Transgender and Non-Transgender People Enrolled in Private Insurance.

Few studies have analyzed mortality rates among transgender (trans) populations in the United States and compared them to the rates of non-trans populations. Using private insurance data from 2011 to 2019, we estimated age-specific all-cause mortality rates among a subset of trans people enrolled in private insurance and compared them to a 10% randomly selected non-trans cohort. Overall, we found that trans people were nearly twice as likely to die over the period as their non-trans counterparts. When stratifying by gender, we found key disparities within trans populations, with people on the trans feminine to nonbinary spectrum being at the greatest risk of mortality compared to non-trans males and females. While we found that people on the trans masculine to nonbinary spectrum were at a similar risk of overall mortality compared to non-trans females, their overall mortality rate was statistically smaller than that of non-trans males. These findings provide evidence that some trans and non-trans populations experience substantially different mortality conditions across the life course and necessitate further study.

Multivariable prediction models for health care spending using machine learning: a protocol of a systematic review.

BACKGROUND: With rising cost pressures on health care systems, machine-learning (ML)-based algorithms are increasingly used to predict health care costs. Despite their potential advantages, the successful implementation of these methods could be undermined by biases introduced in the design, conduct, or analysis of studies seeking to develop and/or validate ML models. The utility of such models may also be negatively affected by poor reporting of these studies. In this systematic review, we aim to evaluate the reporting quality, methodological characteristics, and risk of bias of ML-based prediction models for individual-level health care spending. METHODS: We will systematically search PubMed and Embase to identify studies developing, updating, or validating ML-based models to predict an individual's health care spending for any medical condition, over any time period, and in any setting. We will exclude prediction models of aggregate-level health care spending, models used to infer causality, models using radiomics or speech parameters, models of non-clinically validated predictors (e.g., genomics), and cost-effectiveness analyses without predicting individual-level health care spending. We will extract data based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS), previously published research, and relevant recommendations. We will assess the adherence of ML-based studies to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement and examine the inclusion of transparency and reproducibility indicators (e.g. statements on data sharing). To assess the risk of bias, we will apply the Prediction model Risk Of Bias Assessment Tool (PROBAST). Findings will be stratified by study design, ML methods used, population characteristics, and medical field. DISCUSSION: Our systematic review will appraise the quality, reporting, and risk of bias of ML-based models for individualized health care cost prediction. This review will provide an overview of the available models and give insights into the strengths and limitations of using ML methods for the prediction of health spending.

Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study.

BACKGROUND: The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection. METHODS: We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality. RESULTS: Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections. CONCLUSIONS: Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and Cancer Consortium.

BACKGROUND: Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer. METHODS: In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models. FINDINGS: 5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients. INTERPRETATION: The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality. FUNDING: US National Institutes of Health National Cancer Institute Cancer Center.

Functional Status and Survival in Older Nursing Home Residents With Advanced Non-Small-Cell Lung Cancer: A SEER-Medicare Analysis.

PURPOSE: Many older patients with advanced lung cancer have functional limitations and require skilled nursing home care. Function, assessed using activities of daily living (ADL) scores, may help prognostication. We investigated the relationship between ADL impairment and overall survival among older patients with advanced non-small-cell lung cancer (NSCLC) receiving care in nursing homes. METHODS: Using the SEER-Medicare database linked with Minimum Data Set assessments, we identified patients age 65 years and older with NSCLC who received care in nursing homes from 2011 to 2015. We used Cox regression and Kaplan-Meier survival curves to examine the relationship between ADL scores and overall survival among all patients; among patients who received systemic cancer chemotherapy or immunotherapy within 3 months of NSCLC diagnosis; and among patients who did not receive any treatment. RESULTS: We included 3,174 patients (mean [standard deviation] age, 77 [7.4] years [range, 65-102 years]; 1,664 [52.4%] of female sex; 394 [12.4%] of non-Hispanic Black race/ethnicity), 415 (13.1%) of whom received systemic therapy, most commonly with carboplatin-based regimens (n = 357 [86%] patients). The median overall survival was 3.1 months for patients with ADL score < 14, 2.8 months for patients with ADL score between 14 and 17, 2.3 months for patients with ADL score between 18-19, and 1.8 months for patients with ADL score 20+ (log-rank P < .001). The ADL score was associated with increased risk of death (hazard ratio [HR], 1.20; 95% CI, 1.16 to 1.25 per standard deviation). One standard deviation increase in the ADL score was associated with lower overall survival rate among treated (HR, 1.14; 95% CI, 1.02 to 1.27) and untreated (HR, 1.20; 95% CI, 1.15 to 1.26) patients. CONCLUSION: ADL assessment stratified mortality outcomes among older nursing home adults with NSCLC, and may be a useful clinical consideration in this population.

miR-579-3p Controls Hepatocellular Carcinoma Formation by Regulating the Phosphoinositide 3-Kinase-Protein Kinase B Pathway in Chronically Inflamed Liver.

Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas the 10-year incidence for HCC in patients with cirrhosis is approximately 20%, many of these patients remain tumor free for their entire lives. Clarifying the mechanisms that define the various outcomes of chronic liver inflammation is a key aspect in HCC research. In addition to a wide variety of contributing factors, microRNAs (miRNAs) have also been shown to be engaged in promoting liver cancer. Therefore, we wanted to characterize miRNAs that are involved in the development of HCC, and we designed a longitudinal study with formalin-fixed and paraffin-embedded liver biopsy samples from several pathology institutes from Switzerland. We examined the miRNA expression by nCounterNanostring technology in matched nontumoral liver tissue from patients developing HCC (n = 23) before and after HCC formation in the same patient. Patients with cirrhosis (n = 26) remaining tumor free within a similar time frame served as a control cohort. Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed a down-regulation of miR-579-3p as an early step in HCC development, which was further confirmed in a validation cohort. Correlation with messenger RNA expression profiles further revealed that miR-579-3p directly attenuated phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) expression and consequently protein kinase B (AKT) and phosphorylated AKT. In vitro experiments and the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology confirmed that miR-579-3p controlled cell proliferation and cell migration of liver cancer cell lines. Conclusion: Liver tissues from patients developing HCC revealed changes in miRNA expression. miR-579-3p was identified as a novel tumor suppressor regulating phosphoinositide 3-kinase-AKT signaling at the early stages of HCC development.

Global Risk Indicator and Therapy for Older Patients With Diffuse Large B-Cell Lymphoma: A Population-Based Study.

PURPOSE: To examine the impact of global risk, a measure comprising age, comorbidities, function, and cognitive statuses, on treatment selection and outcomes among older home care recipients with diffuse large B-cell lymphoma. METHODS: From SEER-Medicare, we selected home care recipients diagnosed with diffuse large B-cell lymphoma in 2011-2015, who had pretreatment Outcome and Assessment Information Set (OASIS) evaluations. We created a global risk indicator categorizing patients as low-, moderate-, or high-risk on the basis of OASIS assessments. We examined the association of global risk with receipt of therapy and among chemotherapy recipients, with mortality, emergency department visits, hospitalization, and intensive care unit admission within 30 days from first treatment in logistic models, reporting adjusted odds ratios (OR) with 95% CI. We compared overall survival across risk groups estimating adjusted hazard ratios. RESULTS: Of the 1,232 patients (median age, 80 years), 65% received chemotherapy. High-risk patients (v moderate-risk) were less likely to receive any chemotherapy (OR, 0.50; 95% CI, 0.39 to 0.64) and curative regimens (OR, 0.59; 95% CI, 0.40 to 0.86) if treated, although even in the moderate-risk group, only 61% received curative regimens. High-risk patients were more likely to experience acute mortality (OR, 2.24; 95% CI, 1.43 to 3.52), emergency department visits (OR, 1.35; 95% CI, 1.00 to 1.83), hospitalization (OR, 1.60; 95% CI, 1.19 to 2.17), or intensive care unit admission (OR, 1.52; 95% CI, 1.04 to 2.22) and had inferior overall survival (hazard ratio, 1.41; 95% CI, 1.11 to 1.78). CONCLUSION: Global risk on the basis of OASIS is easily available, suggesting a potential way to improve patient selection for curative treatment and institution of preventive measures.

Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers.

This review has been withdrawn because it has been found to be in breach of the Cochrane Commercial Sponsorship policy clause 2:  'Individuals who are currently employed or where employed any time in the last three years by a company that has a real or potential financial interest in the outcome of the review (including but not limited to drug companies or medical device manufacturers); or who hold or have applied for a patent related to the review are prohibited from being Cochrane Review authors. In most cases, current or previous employment would be characterized by the affiliation statement made by the author at the title registration, protocol, or review stage of the review'.

Comparison of COVID-19 outcomes in organ transplant recipients (OTr) and non-transplant patients: a study protocol for rapid review.

BACKGROUND: The COVID-19 pandemic has devastated the global community with nearly 4.9 million deaths as of October 2021. While organ transplant (OT) recipients (OTr) may be at increased risk for severe COVID-19 due to their chronic immunocompromised state, outcomes for OTr with COVID-19 remain disputed in the literature. This review will examine whether OTr with COVID-19 are at higher risk for severe illness and death than non-immunocompromised individuals. METHODS: MEDLINE (via Ovid and PubMed) and EMBASE (via Embase.com ) will be searched from December 2019 to October 2021 for observational studies (including cohort and case-control) that compare COVID-19 clinical outcomes in OTr to those in individuals without history of OT. The primary outcome of interest will be mortality as defined in each study, with possible further analyses of in-hospital mortality, 28 or 30-day mortality, and all-cause mortality versus mortality attributable to COVID-19. The secondary outcome of interest will be the severity of COVID-19 disease, most frequently defined as requiring intensive care unit admission or mechanical ventilation. Two reviewers will independently screen all abstracts and full-text articles. Potential conflicts will be resolved by a third reviewer and potentially discussion among all investigators. Methodological quality will be appraised using the Newcastle-Ottawa Scale. If data permit, we will perform random-effects meta-analysis with the Sidik-Jonkman estimator and the Hartung-Knapp adjustment for confidence intervals to estimate a summary measure of association between histories of transplant with each outcome. Potential sources of heterogeneity will be explored using meta-regression. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., subgroup analysis) considering least minimal adjustment for confounders. DISCUSSION: This rapid review will assess the available evidence on whether OTr diagnosed with COVID-19 are at higher risk for severe illness and death compared to non-immunocompromised individuals. Such knowledge is clinically relevant and may impact risk stratification, allocation of organs and healthcare resources, and organ transplantation protocols during this, and future, pandemics. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (OSF) registration DOI: https://doi.org/10.17605/osf.io/4n9d7 .