Racial and Ethnic Disparities in COVID-19-Related Infections, Hospitalizations, and Deaths : A Systematic Review.

BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. DATA SOURCES: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence). LIMITATIONS: Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies. CONCLUSION: African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. (PROSPERO: CRD42020187078).

Disparities in H1N1 Vaccination Rates: a Systematic Review and Evidence Synthesis to Inform COVID-19 Vaccination Efforts.

BACKGROUND: Data suggest that there were disparities in H1N1 vaccine uptake, and these may inform COVID-19 vaccination efforts. We conducted a systematic review to evaluate disparities in H1N1 vaccine uptake, factors contributing to disparities, and interventions to reduce them. METHODS: We searched English-language articles in MEDLINE ALL, PsycINFO, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from database inception through May 8, 2020. Observational studies examining H1N1 vaccine uptake by race/ethnicity, socioeconomic status, rurality, and disability status in US settings were included. Two reviewers independently assessed study eligibility. Single-reviewer data abstraction was confirmed by a second reviewer. We conducted independent dual quality assessment, and collective strength of evidence assessment. RESULTS: We included 21 studies. African American/Black, Latino, and low-socioeconomic status participants had disproportionately lower H1N1 vaccination rates (low- to moderate-strength evidence). However, Latinos were more likely than Whites to intend to be vaccinated, and African American/Blacks and participants with lower-socioeconomic status were just as likely to intend to be vaccinated as their White and higher-socioeconomic status counterparts (low-strength evidence). Vaccine uptake for other groups has been insufficiently studied. Factors potentially contributing to disparities in vaccine uptake included barriers to vaccine access, inadequate information, and concerns about vaccine safety and efficacy. Studies were largely cross-sectional. Many of the studies are a decade old and were conducted in the context of a different pandemic. The categorization of racial and ethnic groups was not consistent across studies and not all groups were well-studied. DISCUSSION: Efforts to avoid disparities in COVID-19 vaccination uptake should prioritize vaccine accessibility and convenience in African American/Black, Latino, and low-SES communities; engage trusted stakeholders to share vaccine information; and address concerns about vaccine safety and efficacy. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. PROTOCOL REGISTRATION: PROSPERO CRD42020187078.

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study.

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials.

BACKGROUND: Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia. The aim of this systematic review is to determine the effectiveness of pharmacological treatments used to manage cachexia among adult cancer patients. METHODS: We performed literature searches of PubMed (NLM), Embase (Ovid), and Medline(Ovid) to identify clinical trials focused on pharmacological management of cancer cachexia among adult cancer patients from 2004 to 2018. Three reviewers screened a random selection of abstracts to measure for interrater reliability. After this step, each screener screened two-thirds of all abstracts and 177 studies were identified for full text review. The primary outcome was impact of pharmacological management on change in either weight or lean body mass in cancer patients. RESULTS: We identified 19 articles (representing 20 RCTs) that focused on pharmacological management of cancer cachexia. Agents showing promising results included Anamorelin and Enobosarm. Anamorelin at 50 or 100 mg per day for 12 weeks showed a consistent benefit across all studies and resulted in significant improvement in weight as compared to baseline among cancer patients. Enobosarm at 1 and 3 mg per day was also effective in improving lean body mass and QOL symptoms among advancer stage cancer patients. Finally, use of combination agents provide evidence for targeting multiple pathways underlying cachexia mechanism to achieve maximum benefit. No agents showed functional improvement in cancer patients. CONCLUSION: Anamorelin as a single agent shows promising results in improving cachexia related weight loss among cancer patients. Further research on combination therapies may be helpful to address critical gaps in cachexia management.

Local Control Modality and Outcome for Ewing Sarcoma of the Femur: A Report From the Children's Oncology Group.

BACKGROUND: The choice of a local control (LC) modality for Ewing sarcoma (EWS) of the femur is controversial. This study aimed to determine the effect of LC modality on tumor LC and patient outcomes. METHODS: The study reviewed the treatment and outcomes for 115 patients who had EWS of the femur treated with similar chemotherapy in three cooperative group trials. Patient outcomes were analyzed according to the LC modality using the log-rank test and the cumulative incidence of local or distant failure using competing risks regression. RESULTS: The median age of the patients was 13 years. The most common tumor location was the proximal femur followed by the mid femur. For 55 patients with available data, the tumor was larger than 8 cm in 29 patients and 8 cm or smaller in 26 patients. For 84 patients (73 %), surgery only was performed, whereas 17 patients (15 %) had surgery plus radiation, and 14 patients (12 %) had radiation only. The 5-year event-free survival (EFS) rate was 65 % (95 % confidence interval [CI], 55-73 %), and the 5-year overall survival (OS) rate was 70 % (95 % CI, 61-78 %). Patient outcomes did not differ significantly according to tumor location within the femur (proximal, mid or distal) or tumor size (<8 vs ≥8 cm). The findings showed no statistically significant differences in EFS, OS, cumulative incidence of local failure, or cumulative incidence of distant failure according to LC modality (surgery, surgery plus radiation, or radiation). CONCLUSIONS: The LC modality did not significantly affect disease outcome for EWS of the femur. Further study of treatment complications and functional outcome may help to define the optimal LC modality.

A proposed staging system and stage-specific interventions for familial adenomatous polyposis.

BACKGROUND AND AIMS: It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis. METHODS: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments. RESULTS: The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. CONCLUSIONS: The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.

Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis.

Importance: Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes. Objective: To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation. Data Sources: PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023. Study Selection: Studies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included. Data Extraction and Synthesis: Data extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model. Main Outcomes and Measures: Outcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis. Results: Of the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies). Conclusions and Relevance: In this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.

Stressors and Information-Seeking by Dialysis and Transplant Patients During COVID-19, Reported on a Telephone Hotline: A Mixed-Methods Study.

Rationale & Objective: In early 2020, we activated a telephone hotline, the coronavirus disease 2019 (COVID-19) Kidney or Transplant Listening and Resource Center, to learn more about the impact of the COVID-19 pandemic on the stress and information-seeking behaviors of dialysis and transplant patients. Study Design: A mixed-methods study including semi-structured, qualitative interviews probing about emotional, health, and financial challenges experienced and quantitative surveys assessing depression and anxiety levels and information-seeking behaviors. Setting & Participants: 99 participants (28 dialysis patients; 71 transplant patients), varying by race and ethnicity (Hispanic, 25.3%; White, 23.2%; Asian, 24.2%; Black, 24.2%), shared their COVID-19 pandemic experiences and information-seeking behaviors by telephone. Interviews and surveys were conducted from June 17, 2020, to November 24, 2020. Analytical Approach: Qualitative themes were identified using thematic analysis. Frequencies were calculated to assess levels of depression and anxiety using the Patient Health Questionnaire for Depression and Anxiety and types of information-seeking behaviors. Results: 7 themes and 16 subthemes emerged. Themes of commonly reported stressors include postponing medical visits; decreased accessibility of getting medication; difficulty in receiving up-to-date, patient-focused health information and dialysis supplies; and delays in medical appointments. Other stressors include losses of health insurance and income, and increased vigilance in behaviors to avoid contracting COVID-19. 15 participants had moderate to severe anxiety and depression symptoms and reported more frequent and severe panic attacks after the COVID-19 pandemic. Participants sought emotional support from family, friends, and faith communities. They also commonly obtained information from news media and reported needing more transplant-specific updates about COVID-19, and frequent communication from their kidney and transplant specialists. Limitations: This convenience sample of individuals willing to share their experiences through a telephone hotline may not generalize to all dialysis and transplant patients; stressors related to the COVID-19 pandemic for these patients continue to change. Conclusions: As the impact of the pandemic continues, needs-based interventions tailored for the kidney and transplant community, including access to mental health resources, education, and support for care transitions, should continue.

Factors Associated with Health Inequalities in Infectious Disease Pandemics Predating COVID-19 in the United States: A Systematic Review.

Objective: Previous pandemics may offer evidence on mediating factors that contributed to disparities in infection and poor outcomes, which could inform the effort to mitigate potential unequal outcomes during the current COVID-19 pandemic. This systematic review sought to examine those factors. Methods: We searched MEDLINE, PsycINFO, and Cochrane to May 2020. We included studies examining health disparities in adult U.S. populations during infectious disease epidemics or pandemics. Two investigators screened abstracts and full text. We assessed study quality using the Newcastle/Ottawa Scale or the Critical Appraisal Skills Programme Checklist for Qualitative Studies. Results: Sixteen articles were included, of which 14 focused on health disparities during the 2009 H1N1 influenza pandemic. Studies showed that disparities during the H1N1 pandemic were more related to differential exposure to the virus than to susceptibility or access to care. Overall, pandemic-related disparities emanate primarily from inequalities in social conditions that place racial and ethnic minorities and low socioeconomic status populations at greater risk of exposure and infection, rather than individual-level factors such as health behaviors and comorbidities. Conclusions: Policy- and systems-level interventions should acknowledge and address these social determinants of heightened risk, and future research should evaluate the effects of such interventions to avoid further exacerbation of health inequities during the current and future pandemics.

Findings of living donation experiences shared on a digital storytelling platform: A thematic analysis.

Objectives: To identify common experiences and emotional changes shared by living donors and kidney recipients about their living donation experiences on a digital storytelling platform. Methods: 82 donors and 36 recipients submitted prompt-guided videos to the platform. Two coders analyzed transcripts for motivations, common themes, and emotions expressed. Results: Storytellers shared their stories to advocate for living donation and contribute to others facing similar challenges. Pre-surgery, recipients recalled their dialysis experiences and how they sought living donors while donors discussed their motivations and common fears. Post-surgery, recipients discussed changes in their relationship with the donor and quality life, while donors described how they benefited. Learning they needed a transplant, recipients reported feeling fear (33.3%) while donors felt sadness (48.8%). Post-transplant, recipients and donors reported feeling happiness (85.4%, 38.9%) and relief (29.3%, 22.2%). Conclusion: Online digital storytelling libraries increase access to real-life living donation experiences. Since stories are highly personal, additional living donor kidney transplant risk-benefit education is needed. Innovation: Stories can supplement traditional education and be incorporated into advocacy efforts; campaigns could capitalize upon the personal aspect of stories to gently introduce and encourage living kidney donation among the general public.

Association of Prediagnosis Obesity and Postdiagnosis Aspirin With Survival From Stage IV Colorectal Cancer.

Importance: The potential relationship between obesity and colorectal cancer (CRC) outcome is poorly understood in patients with late-stage disease. Increased body mass index may negate aspirin use for cancer prevention, but its role as a factor on the effectiveness of postdiagnosis aspirin use is unclear. Objective: To evaluate how prediagnosis obesity and postdiagnosis aspirin use may be associated with overall survival in patients with late-stage colorectal cancer. Design, Setting, and Participants: This cross-sectional study used self-reported data from patients with metastatic or treatment-refractory disease who consented to a clinical protocol at MD Anderson Cancer Center, a large US cancer treatment center. Patients were enrolled between 2010 and 2018 and followed up for mortality through July 2020. Analyses were conducted through March 2022. Exposures: Body mass index in the decade prior to initial diagnosis and regular aspirin use at survey completion. Main Outcomes and Measures: Overall survival was measured from stage IV diagnosis until death or last follow-up. Cox proportional hazards models were constructed to estimate associations of prediagnosis obesity and postdiagnosis aspirin use with overall survival. Results: Of 656 patients included in this analysis, 280 (42.7%) were women, 135 (20.6%) were diagnosed with CRC before age 45 years, 414 (63.1%) were diagnosed between ages 45 and 65 years, and 107 (16.3%) were diagnosed at 65 years or older; 105 patients (16.0%) were Black or Hispanic, and 501 (76.4%) were non-Hispanic White. Controlling for age, sex, race, stage at initial diagnosis, and weight change between prediagnosis and survey date, patients with obesity in the decade prior to CRC diagnosis had significantly higher likelihood of death (hazard ratio, 1.45; 95% CI, 1.11-1.91) compared with those with normal prediagnosis body mass index. Furthermore, only patients with normal prediagnosis body mass index experienced significant survival benefit with postdiagnosis aspirin use (hazard ratio, 0.59; 95% CI, 0.39-0.90). Conclusions and Relevance: In this cross-sectional study, our findings suggest potentially differential tumor development in the long-term physiologic host environment of obesity. Confirmation and further evaluation are needed to determine whether prediagnosis body mass index may be used to estimate the benefit from postdiagnosis aspirin use.

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.

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Impact of Underlying Comorbidities on Mortality in SARS-COV-2 Infected Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The evidence has shown that SARS CoV-2 infected patients with comorbidities are more likely to have severe disease sequel and mortality. In SARS-CoV-2 infected cancer patients risks associated with other underlying comorbidities might vary from those in non-cancer SARS CoV-2 infected patients. The relative impact of different underlying health conditions among patients with cancer and SARS CoV-2 infection remains yet to be explored. This systematic review aims to explore the prevalence of comorbidities among cancer patients with SARS CoV-2 infection and their impact on mortality. METHODS: Online databases PubMed, Embase, Scopus and Web of science were searched for articles published between 9th July 2019 to July 8th 2020.Studies of cancer patients (>18 years) with diagnosis of SARS CoV-2 infection, published in English were included. A random-effects modelling for the meta-analyses was applied to assess the pooled prevalence and odds ratio for mortality due to comorbidities in SARS CoV-2 infected cancer patients. RESULTS: Total 31studies with 4086 SARS-CoV-2 infectedcancer patientsmet the inclusion criteria. Most prevalent co-morbidities in cancer patients with SARS CoV-2 infection were hypertension [42.3% (95%CI:37.5- 47.0)], diabetes [17.8% (95% CI: 15.3-20.4)] and cardiovascular diseases [16.7% (95%CI:12.9-20.4)].The risk of mortality (pOR) was significantly higher in individuals with hypertension[1.6(95%CI 1.24-2.00)], cardiovascular diseases [2.2 (95%CI 1.49- 3.27)], chronic obstructive pulmonary diseases [1.4(95% CI 1.05-2.00)] and diabetes [1.35(95%CI 1.06-1.73)]. CONCLUSION: Our results indicates that the mortality in SARS-CoV-2 infected cancer patients is affected by preexisting non-cancer comorbidities. By identifying the comorbidities predictive for mortality, clinicians can better stratify the risk of cancer patients presenting with SARS-COV-2, on their initial contact with health services.
.

Engaging Patients with Late-Stage Non-Small Cell Lung Cancer in Shared Decision Making about Treatment.

Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. Finally, we pilot tested the DSI among five patients with NSCLC at the beginning of an office visit scheduled to discuss treatment with an oncologist. Analyses of pilot study baseline and exit survey data showed that DSI use was associated with increased patient awareness of the alternatives' treatment options and benefits/risks. In contrast, patient concern about treatment costs and uncertainty in treatment decision making decreased. All patients expressed a treatment preference. Future randomized controlled trials are needed to assess DSI implementation feasibility and efficacy in clinical care.

Impartially Validated Multiple Deep-Chain Models to Detect COVID-19 in Chest X-ray Using Latent Space Radiomics.

The COVID-19 pandemic continues to spread globally at a rapid pace, and its rapid detection remains a challenge due to its rapid infectivity and limited testing availability. One of the simply available imaging modalities in clinical routine involves chest X-ray (CXR), which is often used for diagnostic purposes. Here, we proposed a computer-aided detection of COVID-19 in CXR imaging using deep and conventional radiomic features. First, we used a 2D U-Net model to segment the lung lobes. Then, we extracted deep latent space radiomics by applying deep convolutional autoencoder (ConvAE) with internal dense layers to extract low-dimensional deep radiomics. We used Johnson-Lindenstrauss (JL) lemma, Laplacian scoring (LS), and principal component analysis (PCA) to reduce dimensionality in conventional radiomics. The generated low-dimensional deep and conventional radiomics were integrated to classify COVID-19 from pneumonia and healthy patients. We used 704 CXR images for training the entire model (i.e., U-Net, ConvAE, and feature selection in conventional radiomics). Afterward, we independently validated the whole system using a study cohort of 1597 cases. We trained and tested a random forest model for detecting COVID-19 cases through multivariate binary-class and multiclass classification. The maximal (full multivariate) model using a combination of the two radiomic groups yields performance in classification cross-validated accuracy of 72.6% (69.4-74.4%) for multiclass and 89.6% (88.4-90.7%) for binary-class classification.

Prevalence and mortality of lung comorbidities among patients with COVID-19: A systematic review and meta-analysis.

COVID-19 infections are seen across all age groups, but they have shown to have a predisposition for the elderly and those with underlying comorbidities. Patients with severe COVID-19 infections and comorbidities are more prone to respiratory distress syndrome, mechanical ventilator use, and ultimately succumb to these complications. Little evidence exists of the prevalence of underlying lung comorbidities among COVID-19 patients and associated mortality. We performed a systematic review of the literature including PubMed (Medline), Embase (Ovid), Google Scholar, and Cochrane Library. The last date for our search was April 29, 2020. We included all original research articles on COVID-19 and calculated prevalence of chronic lung disease patients among COVID-19 patients using random effects model. Further, we assessed for mortality rates among COVID-19 patients associated with these lung comorbidities. The authors identified 29 articles that reported prevalence of chronic lung conditions among COVID-19 patients. Among those, 26 were from China and 3 from the United States. The pooled prevalence of lung comorbidities including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer was 3% (95% confidence interval [CI] = 0%-14%), 2.2% (95% CI = 0.02%-0.03%), and 2.1% (95% CI = 0.00%-0.21%), respectively. Mortality rates associated with these comorbidities was 30% (41/137) for COPD and 19% (7/37) for lung cancer respectively. No mortality rates were reported for patients with asthma. This study offers latest evidence of prevalence of chronic lung conditions among patients with COVID-19. Asthma, followed by COPD and lung cancer, was the most common lung comorbidity associated with COVID-19, while the higher mortality rate was found in COPD. Future studies are needed to assess other lung comorbidities and associated mortality among patients diagnosed with COVID-19.

Association of Breast Density With Breast Cancer Risk Among Women Aged 65 Years or Older by Age Group and Body Mass Index.

Importance: Breast density is associated with breast cancer risk in women aged 40 to 65 years, but there is limited evidence of its association with risk of breast cancer among women aged 65 years or older. Objective: To compare the association between breast density and risk of invasive breast cancer among women aged 65 to 74 years vs women aged 75 years or older and to evaluate whether the association is modified by body mass index (BMI). Design, Setting, and Participants: This prospective cohort study used data from the Breast Cancer Surveillance Consortium from January 1, 1996, to December 31, 2012, for US women aged 65 years or older who underwent screening mammography. Data were analyzed from January 1, 2018, to December 31, 2020. Exposures: Breast Imaging Reporting and Data System breast density category, age, and BMI. Main Outcomes and Measures: The 5-year cumulative incidence of invasive breast cancer by level of breast density (almost entirely fat, scattered fibroglandular densities, or heterogeneous or extreme density) and age (65-74 vs ≥75 years) was calculated using weighted means. Cox proportional hazards models were fit to estimate the association of breast density with invasive breast cancer risk. The likelihood ratio test was used to test the interaction between BMI and breast density. Results: A total of 221 714 screening mammograms from 193 787 women were included in the study; a total of 38% of the study population was aged 75 years or older. Of the mammograms, most were from women aged 65 to 74 years (64.6%) and non-Hispanic White individuals (81.4%). The 5-year cumulative incidence of invasive breast cancer increased in association with increasing breast density among women aged 65 to 74 years (almost entirely fatty breasts: 11.3 per 1000 women [95% CI, 10.4-12.5 per 1000 women]; scattered fibroglandular densities: 17.2 per 1000 women [95% CI, 16.1-17.9 per 1000 women]; extremely or heterogeneously dense breasts: 23.7 per 1000 women [95% CI, 22.4-25.3 per 1000 women]) and among those aged 75 years or older (fatty breasts: 13.5 per 1000 women [95% CI, 11.6-15.5]; scattered fibroglandular densities: 18.4 per 1000 women [95% CI, 17.0-19.5 per 1000 women]; extremely or heterogeneously dense breasts: 22.5 per 1000 women [95% CI, 20.2-24.2 per 1000 women]). Extreme or heterogeneous breast density was associated with increased risk of breast cancer compared with scattered fibroglandular breast density in both age categories (65-74 years: hazard ratio [HR], 1.39 [95% CI, 1.28-1.50]; ≥75 years: HR, 1.23 [95% CI, 1.10-1.37]). Women with almost entirely fatty breasts had a decrease of approximately 30% (range, 27%-34%) in the risk of invasive breast cancer compared with women with scattered fibroglandular breast density (65-74 years: HR, 0.66 [95% CI, 0.58-0.75]; ≥75 years: HR, 0.73; 95% CI, 0.62-0.86). Associations between breast density and breast cancer risk were not significantly modified by BMI (for age 65-74 years: likelihood ratio test, 2.67; df, 2; P = .26; for age ≥75 years, 2.06; df, 2; P = .36). Conclusions and Relevance: The findings suggest that breast density is associated with increased risk of invasive breast cancer among women aged 65 years or older. Breast density and life expectancy should be considered together when discussing the potential benefits vs harms of continued screening mammography in this population.

ARID1A Mutation May Define an Immunologically Active Subgroup in Patients with Microsatellite Stable Colorectal Cancer.

PURPOSE: AT-rich interactive domain 1A (ARID1A) is commonly mutated in colorectal cancer, frequently resulting in truncation and loss of protein expression. ARID1A recruits MSH2 for mismatch repair during DNA replication. ARID1A deficiency promotes hypermutability and immune activation in preclinical models, but its role in patients with colorectal cancer is being explored. EXPERIMENTAL DESIGN: The DNA sequencing and gene expression profiling of patients with colorectal cancer were extracted from The Cancer Genome Atlas and MD Anderson Cancer Center databases, with validation utilizing external databases, and correlation between ARID1A and immunologic features. IHC for T-cell markers was performed on a separate cohort of patients. RESULTS: Twenty-eight of 417 patients with microsatellite stable (MSS) colorectal cancer (6.7%) had ARID1A mutation. Among 58 genes most commonly mutated in colorectal cancer, ARID1A mutation had the highest increase with frameshift mutation rates in MSS cases (8-fold, P < 0.001). In MSS, ARID1A mutation was enriched in immune subtype (CMS1) and had a strong correlation with IFNγ expression (Δz score +1.91, P < 0.001). Compared with ARID1A wild-type, statistically significant higher expression for key checkpoint genes (e.g., PD-L1, CTLA4, and PDCD1) and gene sets (e.g., antigen presentation, cytotoxic T-cell function, and immune checkpoints) was observed in mutant cases. This was validated by unsupervised differential expression of genes related to immune response and further confirmed by higher infiltration of T cells in IHC of tumors with ARID1A mutation (P = 0.01). CONCLUSIONS: The immunogenicity of ARID1A-mutant cases is likely due to an increased level of neoantigens resulting from increased tumor mutational burden and frameshift mutations. Tumors with ARID1A mutation may be more susceptible to immune therapy-based treatment strategies and should be recognized as a unique molecular subgroup in future immune therapy trials.

Epidemiology and Molecular-Pathologic Characteristics of CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer.

BACKGROUND: CpG island methylator phenotype (CIMP) forms a distinct epigenetic phenotype in colorectal cancer (CRC). Though associated with distinct clinicopathologic characteristics, limited evidence exists of the association of CIMP with patient's reported lifestyle factors and tumor molecular characteristics. We assessed the associations of these characteristics in a pooled analysis of CRC patients. PATIENTS AND METHODS: We pooled data from 3 CRC patient cohorts: Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC), biomarker-based protocol (Integromics), and The Cancer Genome Atlas (TCGA). CIMP was measured using the classical 6-gene methylated-in-tumor (MINT) marker panel (MINT1, MINT2, MINT31, p14, p16, and MLH1) in ATTACC and genome-wide human methylation arrays in Integromics and TCGA, respectively. CIMP-High (CIMP-H) was defined as ≥ 3 of 6 methylated markers in ATTACC. In TCGA and Integromics, CIMP-H group was defined on the basis of clusters of methylation profiles and high levels of methylation in tumor samples. Baseline comparisons of characteristics across CIMP groups (CIMP-H vs. CIMP-0) were performed by Student t test or chi-square test for continuous or categorical variables, respectively. Further logistic regression analyses were performed to compute the odds ratio (OR) of these associations. RESULTS: Pooled prevalence of CIMP-H was 22% across 3 data sets. CIMP-H CRC tumors were associated with older age at diagnosis (OR, 1.02; 95% confidence interval [CI], 1.01, 1.03), microsatellite instability-high (MSI-H) status (OR, 9.15; 95% CI, 4.45, 18.81), BRAF mutation (OR, 7.70; 95% CI, 4.98, 11.87), right-sided tumor location (OR, 2.40; 95% CI, 1.78, 3.22), poor differentiation (OR, 2.94; 95% CI, 1.95, 4.45), and mucinous histology (OR, 2.47; 95% CI, 1.77, 3.47), as reported previously in the literature. CIMP-H tumors were also found to be associated with self-reported history of alcohol consumption (OR, ever vs. never, 1.58; 95% CI, 1.07, 2.34). Pathologically, CIMP-H tumors were associated with the presence of intraepithelial lymphocytes (OR, 3.31; 95% CI, 1.41, 7.80) among patients in the Integromics cohort. CONCLUSION: CIMP-H tumors were associated with history of alcohol consumption and presence of intraepithelial lymphocytes. In addition, we confirmed the previously known association of CIMP with age, MSI-H status, BRAF mutation, sidedness, and mucinous histology. Molecular pathologic epidemiology associations help us explore the underlying association of lifestyle and clinical factors with molecular subsets like CIMP and help guide cancer prevention and treatment strategies.