Influence of oral microbiome on longitudinal patterns of oral mucositis severity in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck. METHODS: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit an average trend within each group and to assess the association between the longitudinal OM scores and longitudinal microbial abundances. RESULTS: Four latent groups (LGs) with differing patterns of OM severity were identified for 142 subjects. LG1 has an early onset of high OM scores. LGs 2 and 3 begin with relatively low OM scores until the eighth and 11th week, respectively. LG4 has generally flat OM scores. These LGs did not vary by treatment or clinical or demographic variables. Correlation analysis showed that the abundances of Bacteroidota, Proteobacteria, Bacteroidia, Gammaproteobacteria, Enterobacterales, Bacteroidales, Aerococcaceae, Prevotellaceae, Abiotrophia, and Prevotella_7 were positively correlated with OM severity across the four LGs. Negative correlation was observed with OM severity for a few microbial features: Abiotrophia and Aerococcaceae for LGs 2 and 3; Gammaproteobacteria and Proteobacteria for LGs 2, 3, and 4; and Enterobacterales for LGs 2 and 4. CONCLUSIONS: These findings suggest the potential to personalize treatment for OM. PLAIN LANGUAGE SUMMARY: Oral mucositis (OM) is a common and debilitating after effect for patients treated for squamous cell carcinoma of the head and neck. Trends in the abundance of specific microbial features may be associated with patterns of OM severity over time. Our findings suggest the potential to personalize treatment plans for OM via tailored microbiome interventions.

Attempts to Understand Oral Mucositis in Head and Neck Cancer Patients through Omics Studies: A Narrative Review.

Oral mucositis (OM) is a common and clinically impactful side effect of cytotoxic cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy with or without concomitant chemotherapy. The etiology and pathogenic mechanisms of OM are complex, multifaceted and elicit both direct and indirect damage to the mucosa. In this narrative review, we describe studies that use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) in attempts to elucidate the biological pathways associated with the development or severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host factors (genomics), host responses (transcriptomics, metabolomics), and the local environment (microbiomics).

"Triple Threat" Conditions Predict Mortality Among Patients With Advanced Cancer Who Present to the Emergency Department.

BACKGROUND: Delirium, poor performance status, and dyspnea predict short survival in the palliative care setting. OBJECTIVE: Our goal was to determine whether these three conditions, which we refer to as a "triple threat," also predict mortality among patients with advanced cancers in the emergency department (ED). METHODS: The study sample included 243 randomly selected, clinically stable patients with advanced cancer who presented to our ED. The analysis included patients who had delirium (Memorial Delirium Assessment Scale score ≥ 7), poor performance status (Eastern Cooperative Oncology Group performance status score of 3 or 4), or dyspnea as a presenting symptom. We obtained survival data from medical records. We calculated predicted probability of dying within 30 days and association with number of symptoms after the ED visit using logistic regression analysis. RESULTS: Twenty-eight patients died within 30 days after presenting to the ED. Death within 30 days occurred in 36% (16 of 44) of patients with delirium, 28% (17 of 61) of patients with poor performance status, and 14% (7 of 50) of patients with dyspnea, with a predicted probability of 30-day mortality of 0.38 (95% confidence interval [CI] 0.25-0.53), 0.28 (95% CI 0.18-0.40), and 0.15 (95% CI 0.07-0.29), respectively. The predicted probability of death within 30 days for patients with two or three of the conditions was 0.49 (95% CI 0.34-0.66) vs. 0.05 (95% CI 0.02-0.09) for patients with none or one of the conditions. CONCLUSIONS: Patients with advanced cancers who present to the ED and have at least two triple threat conditions have a high probability of death within 30 days.

Variations in pain prevalence, severity, and analgesic use by duration of survivorship: a cross-sectional study of 505 post-treatment head and neck cancer survivors.

BACKGROUND: Studies suggest a high prevalence of pain in head and neck cancer (HNC) patients at diagnosis, during and after treatment; however, these studies had small sample sizes and did not comprehensively assess factors known to influence pain. We surveyed a large cohort of HNC survivors to determine variations in the prevalence of pain, its treatment and management by duration of survivorship, and assessed a comprehensive list of risk factors. METHODS: A cross sectional survey of post-treatment survivors of HNC during routine follow-up clinic visits. RESULTS: A total of 505 HNC survivors with a median follow up of 3 years from cancer diagnosis were included in the study. Overall, 45% (n = 224) reported pain and 14.5, 22 and 7% reported use of prescribed pain medication, over-the-counter pain medication and alternative pain therapies, respectively. Prevalence of severe pain was 7.3% and did not vary significantly by years of survivorship (< 1 year = 5.7%; 1 to < 3 years = 7.1%; 3 to < 8 years = 7.6%; 8 years or more =9.7%; P = 0.392). However, use of prescribed pain medication significantly varied by years of survivorship (< 1 year = 45.7%; 1 to < 3 years = 24.6%; 3 to < 8 years = 18.9; 8 years or more = 18.3%; p < 0.001). Of note, a significant proportion of survivors reported moderate to severe pain (moderate to severe = 55.7% versus none to mild = 44.3%) despite step 3 analgesic use (p < 0.001). Multivariable regression shows that recurrent disease (OR 6.77, 95% CI [1.44, 31.80]), history of chemotherapy (OR 6.00, 95% CI [2.10, 17.14]), and depression (Mild-moderate OR 5.30, 95% CI [2.20, 12.78]; Major OR 8.00, 95% CI [2.67, 23.96]) were significant risk factors for severe pain. CONCLUSIONS: We identified a high prevalence of pain among HNC survivors and determined that analgesic use varied by the duration of survivorship. Therefore, routine surveillance for pain must be consistent throughout the course of survivorship.

Cancer pain management in the emergency department: a multicenter prospective observational trial of the Comprehensive Oncologic Emergencies Research Network (CONCERN).

PURPOSE: Many patients with cancer seek care for pain in the emergency department (ED). Prospective research on cancer pain in this setting has historically been insufficient. We conducted this study to describe the reported pain among cancer patients presenting to the ED, how pain is managed, and how pain may be associated with clinical outcomes. METHODS: We conducted a multicenter cohort study on adult patients with active cancer presenting to 18 EDs in the USA. We reported pain scores, response to medication, and analgesic utilization. We estimated the associations between pain severity, medication utilization, and the following outcomes: 30-day mortality, 30-day hospital readmission, and ED disposition. RESULTS: The study population included 1075 participants. Those who received an opioid in the ED were more likely to be admitted to the hospital and were more likely to be readmitted within 30 days (OR 1.4 (95% CI: 1.11, 1.88) and OR 1.56 (95% CI: 1.17, 2.07)), respectively. Severe pain at ED presentation was associated with increased 30-day mortality (OR 2.30, 95% CI: 1.05, 5.02), though this risk was attenuated when adjusting for clinical factors (most notably functional status). CONCLUSIONS: Patients with severe pain had a higher risk of mortality, which was attenuated when correcting for clinical characteristics. Those patients who required opioid analgesics in the ED were more likely to require admission and were more at risk of 30-day hospital readmission. Future efforts should focus on these at-risk groups, who may benefit from additional services including palliative care, hospice, or home-health services.

Oral microbiome and onset of oral mucositis in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC. METHODS: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM. RESULTS: Eighty-six percent of the patients developed OM (n = 57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n = 66), Cardiobacterium (P = .03) and Granulicatella (P = .04); 2) immediately before the development of OM (n = 57), Prevotella (P = .03), Fusobacterium (P = .03), and Streptococcus (P = .01); and 3) immediately before the development of severe OM (n = 24), Megasphaera (P = .0001) and Cardiobacterium (P = .03). There were no differences in α-diversity between the baseline samples and Human Microbiome Project data. CONCLUSIONS: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.

Clinical and Cancer-Related Predictors for Venous Thromboembolism in Cancer Patients Presenting to the Emergency Department.

BACKGROUND: The accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests. OBJECTIVE: We sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE. METHODS: We retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016. RESULTS: Cancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37-5.60], p < 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62-2.28], p < 0.001), active cancer (OR 1.35 [95% CI 1.10-1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01-1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32-2.27], p < 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort. CONCLUSIONS: Cancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.

Validation of the Emergency Severity Index (Version 4) for the Triage of Adult Emergency Department Patients With Active Cancer.

BACKGROUND: Patients with active cancer account for a growing percentage of all emergency department (ED) visits and have a unique set of risks related to their disease and its treatments. Effective triage for this population is fundamental to facilitating their emergency care. OBJECTIVES: We evaluated the validity of the Emergency Severity Index (ESI; version 4) triage tool to predict ED-relevant outcomes among adult patients with active cancer. METHODS: We conducted a prespecified analysis of the observational cohort established by the National Cancer Institute-supported Comprehensive Oncologic Emergencies Research Network's multicenter (18 sites) study of ED visits by patients with active cancer (N = 1075). We used a series of χ2 tests for independence to relate ESI scores with 1) disposition, 2) ED resource use, 3) hospital length of stay, and 4) 30-day mortality. RESULTS: Among the 1008 subjects included in this analysis, the ESI distribution skewed heavily toward high acuity (>95% of subjects had an ESI level of 1, 2, or 3). ESI was significantly associated with patient disposition and ED resource use (p values < 0.05). No significant associations were observed between ESI and the non-ED based outcomes of hospital length of stay or 30-day mortality. CONCLUSION: ESI scores among ED patients with active cancer indicate higher acuity than the general ED population and are predictive of disposition and ED resource use. These findings show that the ESI is a valid triage tool for use in this population for outcomes directly relevant to ED care.

MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients.

BACKGROUND: Genetic susceptibility plays an important role in the risk of developing pain in individuals with cancer. As a complex trait, multiple genes underlie this susceptibility. We used gene network analyses to identify novel target genes associated with pain in patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC). RESULTS: We first identified 36 cancer pain-related genes (i.e., focus genes) from 36 publications based on a literature search. The Ingenuity Pathway Analysis (IPA) analysis identified additional genes that are functionally related to the 36 focus genes through pathway relationships yielding a total of 82 genes. Subsequently, 800 SNPs within the 82 IPA-selected genes on the Illumina HumanOmniExpress-12v1 platform were selected from a large-scale genotyping effort. Association analyses between the 800 candidate SNPs (covering 82 genes) and pain in a patient cohort of 1368 patients with HNSCC (206 patients with severe pain vs. 1162 with non-severe pain) showed the highest significance for MAPK1/ERK2, a gene belonging to the MAP kinase family (rs8136867, p value = 8.92 × 10(-4); odds ratio [OR] = 1.33, 95 % confidence interval [CI]: 1.13-1.58). Other top genes were PIK3C2G (a member of PI3K [complex], rs10770367, p value = 1.10 × 10(-3); OR = 1.46, 95 % CI: 1.16-1.82), TCRA (the alpha chain of T-cell receptor, rs6572493, p value = 2.84 × 10(-3); OR = 0.70, 95 % CI: 0.55-0.88), PDGFC (platelet-derived growth factor C, rs6845322, p value = 4.88 × 10(-3); OR = 1.32, 95 % CI: 1.09-1.60), and CD247 (a member of CD3, rs2995082, p value = 7.79 × 10(-3); OR = 0.76, 95 % CI: 0.62-0.93). CONCLUSIONS: Our findings provide novel candidate genes and biological pathways underlying pain in cancer patients. Further study of the variations of these candidate genes could inform clinical decision making when treating cancer pain.

Immune-related adverse event in the emergency department: methodology of the immune-related emergency disposition index (IrEDi).

For many cancer patients, immune checkpoint inhibitors (ICIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICIs can be debilitating and can quickly become severe or even be fatal. Often, irAEs will precipitate visits to the emergency department (ED). Therefore, early recognition and the decision to admit, observe, or discharge these patients from the ED can be key to a cancer patient's morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe, or discharge) within 2-6 h from their patient's ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the absence of classic symptoms, the delayed availability of diagnostic tests during the ED encounter, and the fast pace in the ED setting. At present, there is no single sufficiently large ED data source with clinical, biological, laboratory, and imaging data that will allow for the development of a tool that will guide early recognition and appropriate ED disposition of patients with potential irAEs. We describe an ongoing federally funded project that aims to develop an immune-related emergency disposition index (IrEDi). The project capitalizes on a multi-site collaboration among 4 members of the Comprehensive Oncologic Emergency Research Network (CONCERN): MD Anderson Cancer Center, Ohio State University, Northwestern University, and University of California San Diego. If the aims are achieved, the IrEDi will be the first risk stratification tool derived from a large racial/ethnically and geographically diverse population of cancer patients. The future goal is to validate irEDi in general EDs to improve emergency care of cancer patients on ICIs.

Cardiovascular events after cancer immunotherapy as oncologic emergencies: Analyses of 610 head and neck cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Cardio-oncology and emergency medicine are closely collaborative, as many cardiac events in cancer patients require evaluation and treatment in the emergency department (ED). Immune checkpoint inhibitors (ICIs) have become a common treatment for patients with head and neck cancer (HNC). However, the immune-related adverse events (irAEs) from ICIs can be clinically significant. METHODS: We reviewed and analyzed cardiovascular diagnoses among HNC patients who received ICI during the period April 1, 2016-December 31, 2020 in a large tertiary cancer center. Demographics, clinical and cancer-related data were abstracted, and billing databases were queried for cardiovascular disease (CVD)-related diagnosis using International Classification of Disease-version10 (ICD-10) codes. We recorded receipt of care at the ED as one of the outcome variables. RESULTS: A total of 610 HNC patients with a median follow-up time of 12.3 months (median, interquartile range = 5-30 months) comprised our study cohort. Overall, 25.7% of patients had pre-existing CVD prior to ICI treatment. Of the remaining 453 patients without pre-existing CVD, 31.5% (n = 143) had at least one CVD-related diagnosis after ICI initiation. Tachyarrhythmias (91 new events) was the most frequent CVD-related diagnosis after ICI. The time to diagnosis of myocarditis from initiation of ICI occurred the earliest (median 2.5 months, 1.5-6.8 months), followed by myocardial infarction (3.7, 0.5-9), cardiomyopathy (4.5, 1.6-7.3), and tachyarrhythmias (4.9, 1.2-11.4). Patients with myocarditis and tachyarrhythmias mainly presented to the ED for care. CONCLUSION: The use of ICI in HNC is still expanding and the spectrum of delayed manifestation of ICI-induced cardiovascular toxicities is yet to be fully defined in HNC survivors.

Myocarditis, Myositis, and Myasthenia Gravis Overlap Syndrome Associated with Immune Checkpoint Inhibitors: A Systematic Review.

Immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment, but their use is linked to immune-related adverse events (irAEs), including the rare ICI-associated myocarditis, myositis, and myasthenia gravis (MMM) overlap syndrome. This systematic review aims to highlight MMM's clinical implications in emergency departments. PubMed and Embase were searched using a specific search strategy. Reports were eligible for inclusion if all three conditions were present and associated with the use of an ICI. Data were extracted by independent reviewers using the Rayyan web application for systematic reviews. Descriptive statistics and qualitative synthesis were used to summarize demographic, clinical, and treatment data for the reported cases. Among 50 cases, predominantly associated with melanoma, lung cancer, and renal cancer, the in-hospital mortality rate was 38.0%. The most commonly presenting symptoms were ptosis (58%), dyspnea (48%), diplopia (42%), or myalgia (36%). The median time from ICI initiation to MMM presentation was 21 days (interquartile range: 15-28 days). Corticosteroids were the primary treatment for the irAEs. MMM, a rare but potentially fatal complication of ICI therapy, requires prompt recognition in emergency settings. Corticosteroids should be initiated if suspected, without waiting for confirmation. Multidisciplinary collaboration is vital for diagnosis and treatment planning. Research on MMM's link to specific cancers and ICIs is imperative for better risk assessment and interventions.

Symptom clusters of pain, depressed mood, and fatigue in lung cancer: assessing the role of cytokine genes.

PURPOSE: Symptom clusters, the multiple, co-occurring symptoms experienced by cancer patients, are debilitating and affects quality of life. We assessed if a panel of immune-response genes may underlie the co-occurrence of severe pain, depressed mood, and fatigue and help identify patients with severe versus non-severe symptom clusters. METHODS: Symptoms were assessed at presentation, prior to cancer treatment in 599 newly diagnosed lung cancer patients. We applied cluster analyses to determine the patients with severe versus non-severe symptom clusters of pain, depressed mood, and fatigue. RESULTS: Two homogenous clusters were identified. One hundred sixteen patients (19 %) comprised the severe symptom cluster, reporting high intensity of pain, depressed mood, and fatigue and 183 (30 %) patients reported low intensity of these symptoms. Using Bayesian model averaging methodology, we found that of the 55 single nucleotide polymorphisms assessed, an additive effect of mutant alleles in endothelial nitric oxide synthase (-1474 T/A) (posterior probability of inclusion (PPI) = 0.78, odds ratio (OR) = 0.54, 95 % credible interval (CI) = (0.31, 0.93)); IL1B T-31C (PPI = 0.72, OR = 0.55, 95 % CI = (0.31, 0.97)); TNFR2 Met(196)Arg (PPI = 0.70, OR = 1.85, 95 % CI = (1.03, 3.36)); PTGS2 exon 10+837T > C (PPI = 0.69, OR = 0.54, 95 % CI = (0.28, 0.99)); and IL10RB Lys(47)Glu (PPI = 0.68; OR = 1.74; 95 % CI = (1.04, 2.92)) were predictive for symptom clusters. CONCLUSIONS: Genetic polymorphisms may facilitate identification of high-risk patients and development of individualized symptom therapies.

English proficiency, knowledge, and receipt of HPV vaccine in Vietnamese-American women.

Cervical cancer is one of the most important disease burdens experienced by Vietnamese-American women. Human papillomavirus (HPV) is the etiological agent in almost all cases of cervical cancer. We surveyed Vietnamese-American women to determine receipt of HPV vaccine and assessed if limited English proficiency and knowledge related to HPV vaccine were associated with HPV vaccine uptake. Of the 113 Vietnamese-American women who participated in the study, 58 % (n = 68) was born in Vietnam. The mean years of residency in the United States was 12.75 years. Only 16 (14 %) reported receiving HPV vaccine and 11 (9 %) reported receiving all three shots. Thirteen women responded that they are not at all likely to receive HPV vaccine. Of the whole sample, 47 % (n = 53) reported proficiency in spoken and written English. English proficiency was significantly associated with receipt of HPV vaccine (OR = 4.4; confidence interval (95 % CI) = 1.2; 16.50; p = 0.03). Of the knowledge items, 70 % (n = 79) responded correctly that HPV increases the risk for cervical cancer. However, as many as 60 % responded incorrectly, that HPV infection can be cured with medication. The item, "People infected with HPV can be cured with medication," was the most important variable associated with receipt of HPV vaccine. Specifically, those with correct response were 3.8 times more likely to report receiving the HPV vaccine (OR = 3.8; 95 % CI = 1.1; 13.5; p = 0.04). Important public health needs are the development and evaluation of educational programs on HPV and cervical cancer that are designed for Vietnamese-American women.

Consistency of symptom clusters among advanced cancer patients seen at an outpatient supportive care clinic in a tertiary cancer center.

OBJECTIVE: Advanced cancer patients often develop severe physical and psychological symptom clusters (SCs), but limited data exist on their consistency or severity after an outpatient interdisciplinary team consultation led by palliative care specialists. The primary aim of the study was to determine the consistency and severity of SCs in advanced cancer patients in this setting. METHOD: A total of 1373 patients with advanced cancer who were referred to The University of Texas MD Anderson Cancer Center's Outpatient Supportive Care Center between January 2003 and October 2008 with a complete Edmonton Symptom Assessment Scale (ESAS; 0-10 scale) occurred at initial and first follow-up visit were reviewed (median 14 days, range 1-4 weeks). We used a Wilcoxon signed-rank test to determine whether symptoms changed over time, and a principal components factor analysis with varimax rotation to determine SCs at baseline and at first follow-up. The number of factors calculated was determined based upon the number of eigenvalues. RESULTS: The patients' ratings of the following symptoms (mean, SD) at the initial and follow-up visits, respectively, were: fatigue 6.2 (2.3) and 5.7 (2.5, p < 0.0001), pain 5.4 (2.9) and 4.6 (3, p < 0.0001), nausea 2.2 (2.8) and 2.0 (2.6, p < 0.0001), depression 3.0 (2.9) and 2.5 (2.7, p < 0.0001), anxiety 3.4 (3.0) and 2.8 (2.8, p < 0.0001), drowsiness 4.8 (3.1) and 4.4 (3.1, p < 0.0001), dyspnea 3.0 (2.9) and 2.7 (2.8), p < 0.0001), loss of appetite 4.2 (2.7) and 3.9 (2.7, p < 0.0001), sleep disturbances 4.2 (2.6) and 3.8 (2.6, P < 0.0001), and well-being 4.3 (2.5) and 3.9 (2.3, p < 0.0001). Cluster composition differentiated into physical (fatigue, pain, nausea, drowsiness, dyspnea, and loss of appetite) and psychological (anxiety and depression) components at the initial visit, and these two SCs were consistent upon follow-up. SIGNIFICANCE OF RESULTS: We conclude that SCs remain constant between baseline and near-term follow-up but that the severity of those symptoms lessened during that interval. This knowledge may allow palliative care teams to provide more targeted and higher-quality care, but further studies are needed.

MyTPill: study protocol for a cross-over randomised controlled trial comparing novel strategies to monitor antiretroviral adherence among HIV+ prescription opioid users.

INTRODUCTION: Adherence to HIV antiretroviral therapy (ART) remains the cornerstone of HIV treatment. For individuals with suboptimal adherence, electronic adherence monitoring (EAM) technologies have become an important component of multimodal adherence support strategies. Most EAM technologies detect pillbox opening, and therefore, assume but cannot verify actual ingestion of oral medication. In contrast, a digital pill system (ID-capsule manufactured by etectRX, here named My/Treatment/Pill) measures directly ingestion of medications. Identifying the superior method to measure ART adherence would improve virological suppression by enabling the delivery of real-time interventions to support ART adherence, particularly in high-risk populations. METHODS AND ANALYSIS: Cross-over, randomised trial with 1:1 variable block size randomisation comparing two EAM systems in prescription opioid-using HIV+patient on once daily oral bictegravir, emtricitabine and tenofovir alafenamide regimens and detectable viral load >200 copies/mL within 30 days of screening (n=80). The primary outcome is once daily ART adherence measurement efficacy as assessed by comparing the accuracy of each EAM system as measured by concordance of the respective EAM systems to dried blood spot ART concentrations. Secondary outcomes are the identification of multilevel factors that are prevalent in the target population most closely linked to ART non-adherence and EAM non-adherence. ETHICS AND DISSEMINATION: This protocol was approved by the institutional review boards of participating sites (The Ohio State University, The Fenway Institute and the University of Miami). Data will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03978793.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.

Early referral to supportive care specialists for symptom burden in lung cancer patients: a comparison of non-Hispanic whites, Hispanics, and non-Hispanic blacks.

BACKGROUND: Effective management of symptoms in cancer patients requires early intervention. This study assessed whether the timing of referral to the Supportive Care Center (SCC) and symptom burden outcome varied by race or ethnicity in lung cancer patients who had been seen at a tertiary cancer center. METHODS: Non-Hispanic white (n = 752), Hispanic (n = 111), and non-Hispanic black (n = 117) patients with nonsmall cell lung cancer comprised this sample. Data on sociodemographic factors, stage of disease, comorbid conditions, and symptom severity (pain, depressed mood, fatigue) served as potential predictor variables. RESULTS: Whereas the mean time (15 months; median = 7 months) from initial presentation at the cancer center to referral to the SCC did not vary by race or ethnicity, we found that Hispanics and non-Hispanic blacks had higher symptom burden when they first presented at the cancer center than non-Hispanic whites. Severe pain, depressed mood, and fatigue were significant predictors for early referral (<7 months) of non-Hispanic whites, but only severe fatigue (P <.05) was predictive of early referral for Hispanics and non-Hispanic blacks. Furthermore, while the proportion of non-Hispanic white patients reporting severe pain, depressed mood, and fatigue significantly decreased (P <.001) at first follow-up visit after referral to the SCC; among Hispanics, improvement was only observed for depressed mood. No improvement in any of these symptoms was observed for non-Hispanic blacks. CONCLUSIONS: Whereas the timing of referral to supportive services did not vary by race, disparities in symptom burden outcomes persisted. Additional studies are needed to validate our findings.

Neuropathic pain prevalence and risk factors in head and neck cancer survivors.

BACKGROUND: Neuropathic pain (NP) is a debilitating symptom among head and neck cancer (HNC) survivors although few large studies report its prevalence and associated risk factors. METHODS: A cross-sectional survey assessing demographic, behavioral, and clinical risk factors for NP. NP was assessed using the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS). RESULTS: Forty-five percent (227/505) reported having pain including 13.7% (69/505) who were positive for S-LANSS. Reported pain sites were in the regions of the head and oral cavity (46.2%) and neck and throat (41.5%). Despite a higher self-reported use of analgesic medication (NP+ = 41.2%; NP- = 27.4%; p = 0.020) and alternative pain therapies (NP+ = 19.1%; NP- = 8.4%; p = 0.009), severe pain was more prevalent among those with NP (N+ = 23.2%; NP- = 13.3%; p = 0.004). Adjusted for opioid medications, ethnicity/race, age, surgery, depression, and comorbidities were risk factors for NP. CONCLUSION: NP remains prevalent in HNC survivors highlighting the importance of routine pain surveillance.

Characterization of older adults with cancer seeking acute emergency department care: A prospective observational study.

INTRODUCTION: Disparities in care of older adults in cancer treatment trials and emergency department (ED) use exist. This report provides a baseline description of older adults ≥65 years old who present to the ED with active cancer. MATERIALS AND METHODS: Planned secondary analysis of the Comprehensive Oncologic Emergencies Research Network observational ED cohort study sponsored by the National Cancer Institute. Of 1564 eligible adults with active cancer, 1075 patients were prospectively enrolled, of which 505 were ≥ 65 years old. We recruited this convenience sample from eighteen participating sites across the United States between February 1, 2016 and January 30, 2017. RESULTS: Compared to cancer patients younger than 65 years of age, older adults were more likely to be transported to the ED by emergency medical services, have a higher Charlson Comorbidity Index score, and be admitted despite no significant difference in acuity as measured by the Emergency Severity Index. Despite the higher admission rate, no significant difference was noted in hospitalization length of stay, 30-day mortality, ED revisit or hospital admission within 30 days after the index visit. Three of the top five ED diagnoses for older adults were symptom-related (fever of other and unknown origin, abdominal and pelvic pain, and pain in throat and chest). Despite this, older adults were less likely to report symptoms and less likely to receive symptomatic treatment for pain and nausea than the younger comparison group. Both younger and older adults reported a higher symptom burden on the patient reported Condensed Memorial Symptom Assessment Scale than to ED providers. When treating suspected infection, no differences were noted in regard to administration of antibiotics in the ED, admissions, or length of stay ≤2 days for those receiving ED antibiotics. DISCUSSION: We identified several differences between older (≥65 years old) and younger adults with active cancer seeking emergency care. Older adults frequently presented for symptom-related diagnoses but received fewer symptomatic interventions in the ED suggesting that important opportunities to improve the care of older adults with cancer in the ED exist.