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.

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).

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.

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.

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.

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.

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'.

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

Treatment advancements in pediatric cancer have improved prognosis, but the strength of supporting evidence has not been thoroughly evaluated. To critically appraise it, we performed an umbrella review of meta-analyses of randomized controlled trials examining the efficacy and safety of therapeutic interventions for pediatric malignancies. Fourteen publications (68 meta-analyses, 31,496 participants) were eligible. Acute lymphoblastic leukemia (ALL) was investigated at most. Substantial heterogeneity was detected in 10 associations, with limited indications for small-study effects and excess-significance bias. The most concrete evidence pertained to the use of methotrexate and vincristine-prednisone pulses for ALL, improving event-free survival. Evidence regarding other cancers was relatively weak. Conclusively, we found few small meta-analyses focusing mainly on ALL. Randomized evidence stemming from adult populations still seems to serve as valuable indirect evidence backup. More randomized evidence and individual patient data meta-analyses are needed to increase certainty and precision in the care of pediatric cancer patients.

Prevalence of functional limitations and their associations with systemic cancer therapy among older adults in nursing homes with advanced non-small cell lung cancer.

OBJECTIVES: To determine the relationship of self-care task disabilities with the use of systemic cancer therapies for advanced non-small cell lung cancer (NSCLC) in nursing home patients. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database linked with Minimum Data Set assessments, we identified nursing home residents with advanced NSCLC from 2011 to 2015. We considered disability in activities of daily living (ADL) including dressing, personal hygiene, toilet use, locomotion on unit, transfer, bed mobility, and eating. We estimated the association between ADL disabilities and receipt of systemic cancer therapies within 3 months of diagnosis. RESULTS: Of the 3174 patients, 2702 (85.2%) experienced disability in one or more ADLs and 64.7% had disability in 5-7 ADLs. A total of 415 (13.1%) patients received systemic therapy. There was a strong association between disability in each ADL and receipt of therapy including dressing (OR, 0.52 [95% CI, 0.42-0.65]), toileting (odds ratio, OR, 0.52 [95% confidence interval, CI, 0.42-0.65]), personal hygiene (OR, 0.48 [95% CI, 0.39-0.59]), transfers (OR, 0.51 [95% CI, 0.41-0.64]), bed mobility (OR, 0.55 [95% CI, 0.44-0.69]), locomotion (OR, 0.57 [95% CI, 0.46-0.71]), or eating (OR, 0.45 [95% CI, 0.31-0.67]). Compared to patients having no ADL disability, patients were less likely to receive chemotherapy if they had disability in 1-2 ADLs (OR, 0.95 [95% CI, 0.66-1.37]), 3-4 ADLs (OR, 0.81 [95% CI, 0.56-1.15]), or 5-7 ADLs (OR, 0.43 [95% CI, 0.33-0.56]). CONCLUSIONS: Systemic cancer therapy is not commonly used in this population and is strongly predicted by disability in self-care tasks.

Temperature Screening for SARS-CoV-2 in Nursing Homes: Evidence from Two National Cohorts.

BACKGROUND/OBJECTIVES: Infection screening tools classically define fever as 38.0°C (100.4°F). Frail older adults may not mount the same febrile response to systemic infection as younger or healthier individuals. We evaluate temperature trends among nursing home (NH) residents undergoing diagnostic SARS-CoV-2 testing and describe the diagnostic accuracy of temperature measurements for predicting test-confirmed SARS-CoV-2 infection. DESIGN: Retrospective cohort study evaluating diagnostic accuracy of pre-SARS-CoV-2 testing temperature changes. SETTING: Two separate NH cohorts tested diagnostically (e.g., for symptoms) for SARS-CoV-2. PARTICIPANTS Veterans residing in Veterans Affairs (VA) managed NHs and residents in a private national chain of community NHs. MEASUREMENTS: For both cohorts, we determined the sensitivity, specificity, and Youden's index with different temperature cutoffs for SARS-CoV-2 polymerase chain reaction results. RESULTS: The VA cohort consisted of 1,301 residents in 134 facilities from March 1, 2020, to May 14, 2020, with 25% confirmed for SARS-CoV-2. The community cohort included 3,368 residents spread across 282 facilities from February 18, 2020, to June 9, 2020, and 42% were confirmed for SARS-CoV-2. The VA cohort was younger, less White, and mostly male. A temperature testing threshold of 37.2°C has better sensitivity for SARS-CoV-2, 76% and 34% in the VA and community NH, respectively, versus 38.0°C with 43% and 12% sensitivity, respectively. CONCLUSION: A definition of 38.0°C for fever in NH screening tools should be lowered to improve predictive accuracy for SARS-CoV-2 infection. Stakeholders should carefully consider the impact of adopting lower testing thresholds on testing availability, cost, and burden on staff and residents. Temperatures alone have relatively low sensitivity/specificity, and we advocate any threshold be used as part of a screening tool, along with other signs and symptoms of infection.

Adjuvant chemotherapy administration and survival outcomes of lymphoma survivors with common solid tumors: a population-based study†.

Using the Surveillance, Epidemiology, and End Results database (2004-2015), we compared adjuvant chemotherapy use and survival for three common solid tumors in patients with and without history of lymphoma (DLBCL: diffuse large B cell, HL: Hodgkin lymphoma). Among patients with breast (n = 531,243), colon (n = 108,196), and lung (n = 23,179) cancers, we identified 361, 134, and 37 DLBCL survivors, and 349, 73, and 25 HL survivors, respectively. We found no significant difference between lymphoma survivors and controls in the use of adjuvant chemotherapy, except HL survivors with colon cancer, who had a lower rate. Among chemotherapy recipients, OS was significantly worse among HL survivors with all three cancers, and DLBCL survivors with breast cancer (hazard ratio [HR] 1.57-2.28). HL survivors had significantly higher mortality from cardiovascular diseases in breast and lung cancers (sub-HR, 7.96-9.64), which suggests that worse survival in this population might be due to late or cumulative toxicities of cancer-directed treatment.

Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIGNIFICANCE: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.This article is highlighted in the In This Issue feature, p. 1426.

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.

BACKGROUND: Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. METHODS: In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. FINDINGS: Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53-2·21), male sex (1·63, 1·07-2·48), smoking status (former smoker vs never smoked: 1·60, 1·03-2·47), number of comorbidities (two vs none: 4·50, 1·33-15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11-7·18), active cancer (progressing vs remission: 5·20, 2·77-9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79-4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07-0·84) or the US-Midwest (0·50, 0·28-0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. INTERPRETATION: Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. FUNDING: American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Clinical Application of Computational Methods in Precision Oncology: A Review.

Importance: There is an enormous and growing amount of data available from individual cancer cases, which makes the work of clinical oncologists more demanding. This data challenge has attracted engineers to create software that aims to improve cancer diagnosis or treatment. However, the move to use computers in the oncology clinic for diagnosis or treatment has led to instances of premature or inappropriate use of computational predictive systems. Objective: To evaluate best practices for developing and assessing the clinical utility of predictive computational methods in oncology. Evidence Review: The National Cancer Policy Forum and the Board on Mathematical Sciences and Analytics at the National Academies of Sciences, Engineering, and Medicine hosted a workshop to examine the use of multidimensional data derived from patients with cancer and the computational methods used to analyze these data. The workshop convened diverse stakeholders and experts, including computer scientists, oncology clinicians, statisticians, patient advocates, industry leaders, ethicists, leaders of health systems (academic and community based), private and public health insurance carriers, federal agencies, and regulatory authorities. Key characteristics for successful computational oncology were considered in 3 thematic areas: (1) data quality, completeness, sharing, and privacy; (2) computational methods for analysis, interpretation, and use of oncology data; and (3) clinical infrastructure and expertise for best use of computational precision oncology. Findings: Quality control was found to be essential across all stages, from data collection to data processing, management, and use. Collecting a standardized parsimonious data set at every cancer diagnosis and restaging could enhance reliability and completeness of clinical data for precision oncology. Data completeness refers to key data elements such as information about cancer diagnosis, treatment, and outcomes, while data quality depends on whether appropriate variables have been measured in valid and reliable ways. Collecting data from diverse populations can reduce the risk of creating invalid and biased algorithms. Computational systems that aid clinicians should be classified as software as a medical device and thus regulated according to the potential risk posed. To facilitate appropriate use of computational methods that interpret high-dimensional data in oncology, treating physicians need access to multidisciplinary teams with broad expertise and deep training among a subset of clinical oncology fellows in clinical informatics. Conclusions and Relevance: Workshop discussions suggested best practices in demonstrating the clinical utility of predictive computational methods for diagnosing or treating cancer.