Efforts to Improve Naloxone Co-Prescription for Patients With Cancer Pain at Risk of Opioid Overdose.

Importance: Naloxone can be lifesaving in an opioid-related overdose (OD). However, the co-prescription of take-home naloxone (THN) is not widely adopted in routine clinical practice. We implemented a pilot program focused on increasing clinicians' awareness of THN and observed if this impacts THN prescriptions for our patients with cancer pain receiving opioids. Intervention: In January 2020, we initiated an educational program by twice-weekly video presentations and installed pamphlets in all clinic workstations highlighting the risk factors for ODs. We retrospectively reviewed electronic health records (EHR) of randomly selected patient visits, 200 each from eight weeks before intervention (BI) and eight weeks after the intervention (AI). Data on patient characteristics, risk factors for ODs, and THN prescriptions were collected. Results: In all, 380 unique patients were eligible for analysis. The median age was 60, 53% female, and 70% Caucasian. Eighty-two percent (152) BI and 73% (142) AI carried risk factors for ODs (p = 0.13). THN was prescribed to 21% (32/152) BI and 26% (37/142) AI (p = 0.53). Morphine-equivalent daily dose (MEDD) ≥100 mg (30%) and pulmonary disease (25%) were the most prevalent risk factors. The patient's likelihood of receiving a THN prescription increased by 0.9% for every 1-milligram increase in MEDD (p < 0.001, 95% confidence interval: 1.006-1.011). Conclusion: The educational intervention did not significantly increase the frequency of THN prescriptions. More direct interventions, including automatic EHR triggers, may need to be tested in future trials.

Levorphanol as a Second Line Opioid in Cancer Patients Presenting to an Outpatient Supportive Care Center: An Open-label Study.

CONTEXT: Levorphanol is a potent opioid agonist and NMDA receptor blocker with minimal drug interactions, and there are few reports of its use in cancer patients. OBJECTIVES: We aimed to determine the frequency of successful opioid rotation (OR) to levorphanol and the median opioid rotation ratio (ORR) from Morphine Equivalent Daily Dose (MEDD). METHODS: This is a prospective, single-group, interventional study. Cancer outpatients requiring an OR and receiving a MEDD of 60-300 mg were rotated to levorphanol using a ratio of 10:1 and assessed daily for 10-day. Successful OR was defined as a 2-point improvement in the Edmonton Symptom Assessment System (ESAS) pain score on day 10 or achieving the personalized pain goal between days 3-10 in patients with uncontrolled pain or resolution of opioid side effects (OSE) in those undergoing OR for OSE alone. The ORR to levorphanol was calculated using net-MEDD (MEDD before OR minus the MEDD of the breakthrough opioid used along with levorphanol after OR). RESULTS: Forty patients underwent OR to levorphanol, and uncontrolled pain 35/40 (87.5%) was the most common indication. The median net-MEDD and levorphanol doses were 95 and 10 mg, respectively, and 33/40 (82.5%) had a successful OR with a median (IQR) ORR of 8.56 (7.5-10). Successful OR was associated with significant improvement in ESAS and OSE scale scores. There was a strong association between MEDD and levorphanol dose. CONCLUSION: This study provided preliminary data that cancer patients could be successfully rotated to levorphanol using an ORR of 8.5. Levorphanol was associated with improved pain and symptom control and was well- tolerated.

Health Care Provider Attitudes and Beliefs Toward Nonmedical Opioid Use in Patients with Cancer Pain.

Background: Data on health care providers' (HCPs') perceptions about patients with cancer pain and nonmedical opioid use (NMOU) are lacking. We examined the perceptions and attitudes of HCPs and assessed the usefulness of an interdisciplinary opioid stewardship program (OSP) while caring for these patients. Methods: An anonymous cross-sectional survey was conducted among the supportive care HCPs between September and November 2021. Results: Of 85 HCPs, 64 responded (75%) to the survey. Participants perceived that NMOU is underdiagnosed (42/64; 67%), and caring for such patients is difficult (58/64, 91%) and time consuming (54/64, 87%). A majority (50/51, 98%) were aware of the OSP, and (48/51; 94%) found it helpful. Conclusion: HCPs reported that NMOU is underdiagnosed and is challenging to manage. They endorsed the utility of an OSP in managing patients with concurrent cancer pain and NMOU. Future research should identify ways to standardize care and integrate OSP in routine supportive oncology practice.

Effect of dexamethasone on dyspnoea in patients with cancer (ABCD): a parallel-group, double-blind, randomised, controlled trial.

BACKGROUND: Systemic corticosteroids are commonly prescribed for palliation of dyspnoea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone versus placebo on cancer-related dyspnoea. METHODS: The parallel-group, double-blind, randomised, controlled ABCD (Alleviating Breathlessness in Cancer Patients with Dexamethasone) trial was done at the at the University of Texas MD Anderson Cancer Center and the general oncology clinic at Lyndon B Johnson General Hospital (both in Houston, TX, USA). Ambulatory patients with cancer, aged 18 years or older, and with an average dyspnoea intensity score on an 11-point numerical rating scale (NRS; 0=none, 10=worst) over the past week of 4 or higher were randomly assigned (2:1) to receive dexamethasone 8 mg orally every 12 h for 7 days followed by 4 mg orally every 12 h for 7 days, or matching placebo capsules for 14 days. Pharmacists did permuted block randomisation with a block size of six, and patients were stratified by baseline dyspnoea score (4-6 vs 7-10) and study site. Patients, research staff, and clinicians were masked to group assignment. The primary outcome was change in dyspnoea NRS intensity over the past 24 h from baseline to day 7 (±2 days). Analyses were done by modified intention-to-treat (ie, including all patients who were randomly assigned and started the study treatment, regardless of whether they completed the study). Enrolment was stopped after the second preplanned interim analysis, when the futility criterion was met. This study is registered with ClinicalTrials.gov (NCT03367156) and is now completed. FINDINGS: Between Jan 11, 2018, and April 23, 2021, we screened 2867 patients, enrolled 149 patients, and randomly assigned 128 to dexamethasone (n=85) or placebo (n=43). The mean change in dyspnoea NRS intensity from baseline to day 7 (±2 days) was -1·6 (95% CI -2·0 to -1·2) in the dexamethasone group and -1·6 (-2·3 to -0·9) in the placebo group, with no significant between-group difference (mean 0 [95% CI -0·8 to 0·7]; p=0·48). The most common all-cause grade 3-4 adverse events were infections (nine [11%] of 85 patients in the dexamethasone group vs three [7%] of 43 in the placebo group), insomnia (seven [8%] vs one [2%]), and neuropsychiatric symptoms (three [4%] vs none [0%]). Serious adverse events, all resulting in hospital admissions, were reported in 24 (28%) of 85 patients in the dexamethasone group and in three (7%) of 43 patients in the placebo group. No treatment-related deaths occurred in either group. INTERPRETATION: High-dose dexamethasone did not improve dyspnoea in patients with cancer more effectively than placebo and was associated with a higher frequency of adverse events. These data suggest that dexamethasone should not be routinely given to unselected patients with cancer for palliation of dyspnoea. FUNDING: US National Cancer Institute.

Opioid Rotation and Conversion Ratios Used by Palliative Care Professionals: An International Survey.

Background: The opioid rotation ratios (ORRs) and conversion ratios (CRs) used worldwide among palliative care (PC) professionals to perform opioid rotations (ORs) and route conversions may have a wide variation. Methods: We surveyed PC professionals on opioid ratios used through email to the Multinational Association of Supportive Care in Cancer's PC study group and Twitter and Facebook posts between September and November 2020. Results: We received 370 responses from respondents from 53 countries: 276 (76%) were physicians, 46 (13%) advanced practice providers, 39 (11%) pharmacists, and 9 respondents did not report their profession. There were statistically significant variations in median CR from intravenous (IV) to oral morphine (2-3), IV to oral hydromorphone (2-4.5), ORR from IV hydromorphone to oral morphine (10-20), and ORR from transdermal fentanyl mcg/hour to oral morphine (2-3.5) across various groups. Conclusion: This survey highlights the wide variation in ORRs and CRs among PC clinicians worldwide and the need for further research to standardize practice.

Stay Home, Work Safe: Attitudes and Beliefs of Members of a Department of Palliative Care, Rehabilitation, and Integrative Medicine Regarding Remote Work during the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic compelled rapid transition to work from home for the University of Texas MD Anderson Cancer Center Palliative, Rehabilitation, and Integrative Medicine (PRIM) department to ensure social distancing and prevention of transmission. Objectives: To survey the attitudes and beliefs of personnel toward remote work during the COVID-19 pandemic. Methods: One hundred forty-eight clinical, research, and administrative PRIM department employees were invited to participate in an anonymous voluntary survey in May 2020, two months after the beginning of the COVID-19 pandemic and transition to work from home in the geographic location of Houston, Texas. The survey comprised 25 questions, including employee demographics and attitudes and beliefs toward working from home and the COVID-19 pandemic. Results: Ninety-four percent (139) of employees responded, with high response rates among all three employee arms. The majority of respondents were female (74%), between the ages of 30 and 59 years (87%), had broadband Internet (93%), and shared office space before working from home (59%). There were overall positive reports of experience (87%) and emotional response (79%) toward working from home, especially for those more concerned about COVID-19 illness and spread, shared office space, and those reporting adequate resources and equipment for remote work. Clinical role, however, was associated with a less positive response (80%), less productivity (29%), and higher levels of stress (62%). Most of the department also reported increased emotional exhaustion (68%). When surveyed about permanently working from home, most of the department responded favorably (69%). Conclusions: The PRIM rapid transition to remote work was associated with positive perceptions by most members of the clinical, research, and administrative teams. Insight from this survey can serve as a model for future rapid transitions in remote work and merits follow-up studies to prepare us for a postpandemic work environment. Clinical Trial Registration number NCI-2021-01265.

Rapid Transition to Virtual Care during the COVID-19 Epidemic: Experience of a Supportive Care Clinic at a Tertiary Care Cancer Center.

Background: COVID-19 pandemic necessitated rapid adoption of telemedicine at our supportive care center (SCC) to ensure continuity of care while maintaining social distancing. Objective: To document the process of transition from in-person to virtual care. Design: The charts of 1744 consecutive patients in our SCC located in the United States were retrospectively reviewed during the four weeks before transition (February 14-March 12), four weeks after transition (March 20-April 16), and transition week (March 13-March 19). Patient demographics, vital aspects of a supportive care visit such as assessments (Edmonton Symptom Assessment Scale-Financial and Spiritual [ESAS-FS], Cut-down, Annoyed, Guilty, Eye-opener Screen-Adapted to Include Drugs [CAGE-AID], and Memorial Delirium Assessment Scale [MDAS]), interdisciplinary team involvement, and visit type were recorded. Results: In total 763 patients were seen before transition, 168 during the transition week, and 813 after transitioning to virtual care. Patient characteristics, ESAS-FS, CAGE-AID, and nurse assessment did not significantly differ among the three groups. The after-transition group had a small reduction in counseling intervention compared with before (20.2% vs. 26.2%; p = 0.0068). MDAS completion was higher after transition (99.6% vs. 98%; p = 0.007). In-person visits decreased from 100% before to 12.7% after transition (p < 0.0001) and virtual visits increased to 49.3% (video) and 38% (telephone). In-person visits decreased to 49% in the week one, 3% in week two, and <2% in week four after transition (p < 0.0001). Conclusions: Our supportive care team transitioned from in-person care to virtual visits within weeks while maintaining a high patient volume, continuity of care, and adherence to social distancing. Our transition can serve as a model for other centers.

Fixed-Dose Netupitant and Palonosetron for Chronic Nausea in Cancer Patients: A Double-Blind, Placebo Run-in Pilot Randomized Clinical Trial.

CONTEXT: No clinical trials have examined the effect of netupitant/palonosetron (NEPA) on chronic nausea in patients with cancer. OBJECTIVES: In this pilot randomized trial, we assessed the efficacy of NEPA and placebo on chronic nausea. METHODS: This double-blind, parallel, randomized trial enrolled patients with cancer and chronic nausea for at least 1 month, intensity ≥4/10 and not on moderately or highly emetogenic systemic therapies. Patients started with a placebo run-in period from days 1 to 5; those without a placebo response proceeded to the double-blinded phase between days 6 to 15 (NEPA: placebo 2:1 ratio). The primary outcome was within-group change in average nausea over the 24 hours on a 0-10 numeric rating scale between day 5 and 15. RESULTS: Among the 53 enrolled patients, 46 proceeded to placebo run-in and 33 had blinded treatment (22 NEPA and 11 placebo). We observed a statistically significant within-group improvement in nausea numeric rating scale between day 5 and 15 in the NEPA group (mean change, -2.0; 95% CI, -3.1 to -0.8) and the placebo group (mean change, -2.3; 95% CI, -3.9 to -0.7). A complete response was achieved in 8 (38%) patients in the NEPA group and 2 (20%) in the placebo group by day 15. No grade 3-4 toxicities were attributed to NEPA. There were no statistically significant between-group differences for the primary/secondary outcomes. CONCLUSIONS: NEPA and placebo were associated with similar magnitude of within-group improvement in chronic nausea without significant between-group differences (Clinicaltrials.gov NCT03040726).

Knowledge matters and empowers: HPV vaccine advocacy among HPV-related cancer survivors.

PURPOSE: To describe knowledge about human papillomavirus (HPV), HPV-related care behavior, and advocacy intent (e.g., vaccine recommendation and willingness to become an advocate for vaccination) and to investigate associations between knowledge, HPV-related care behavior, and advocacy intent among HPV-related cancer survivors. METHODS: A cross-sectional online survey was offered through Qualtrics to HPV-related cancer survivors who were either volunteers at a cancer center or patients of survivorship clinics. RESULTS: A total of 200 survivors responded. Only 33.2% of respondents reported knowing their cancer was HPV-related and 56.8% reported HPV vaccine is safe. Participants who knew that their cancer was caused by HPV were more likely to have vaccinated their children (p < .001). Also, participants who knew that the vaccine is safe were more willing to recommend the vaccine (p < .001), to be a peer mentor for others with HPV-related cancers (43.2% vs. 14.0%, p < .001), and to act as an advocate for increasing vaccination rates (44.1% vs. 24.4%, p = 0.01). Finally, survivors who were aware of the vaccine's effectiveness in decreasing precancerous lesions were more likely to recommend the vaccine (45.7% vs. 12.0%, p = .002). CONCLUSIONS: Raising survivor awareness of the link between HPV and cancer and HPV vaccine safety may increase their willingness to serve as powerful opinion leaders and peer mentors to promote HPV vaccination. Providers may take the simple step of informing patients that their cancer is HPV-related and HPV vaccine is safe to increase the number of informed and empowered survivors.

Relationship Between Intent to Vaccinate and the Education and Knowledge of Human Papillomavirus Among Medical School Faculty and Students in Texas.

Little attention has been given to the state of human papillomavirus (HPV) education in medical schools and how this impacts future vaccination practices. We surveyed medical school faculty and students to assess the relationship between knowledge and willingness to recommend HPV vaccination.

Team-Based Learning Module for Undergraduate Medical Education: a Module Focused on the Human Papilloma Virus to Increase Willingness to Vaccinate.

Human papilloma virus (HPV) vaccination rates lag behind other vaccines, primarily because of weak provider recommendations, and are associated with nearly 30,000 new cancer diagnoses a year. Educating medical students about HPV using active, team-centered learning may increase assimilation of information and may increase vaccination rates. A team-based learning (TBL) module focused on HPV for first-year medical students about HPV will better increase knowledge and likeliness to vaccinate than traditional education methods. Baseline HPV knowledge in medical students across Texas was assessed by surveying all 4-year undergraduate medical schools. Students at one medical school then participated in a week-long TBL focused on basic and clinical concepts relating to HPV, and then were re-surveyed upon completion of the course module. At baseline assessment, first-year student at the intervention site performed at the same level as first-year medical students across the state of Texas on knowledge and satisfaction with their HPV-related medical school education. After the TBL implementation, students performed significantly better than similar-year students and equal to graduating seniors, on knowledge of HPV- and HPV-related cancers, and report significantly higher satisfaction with education measures. Students at the intervention site were significantly more likely to recommend the HPV vaccination in future practice. Short-term knowledge and willingness to recommend vaccination are improved with a targeted HPV TBL early in medical education, which may provide a basis of knowledge that could translate into improved vaccination rates.

Medical Care Costs Associated with Genital Warts for Commercially Insured US Patients.

INTRODUCTION: Genital warts are caused by infection with human papillomavirus (HPV) and are associated with significant morbidity. Primary prevention of genital warts is possible through HPV vaccination, but vaccination rates remain low in the USA. When deciding to implement HPV vaccination programs, public health officials and policy makers rely on cost-effectiveness studies that accurately reflect costs associated with morbidity and mortality. However, previous information on the cost of treating genital warts was outdated. OBJECTIVES: We estimated the mean direct medical care costs associated with genital warts in the USA. METHODS: This was a retrospective case-control study of patients diagnosed with genital warts and matched controls. We used commercial healthcare claims data from 2011 through 2014 to estimate total 1- and 2-year costs from date of diagnosis. We used a generalized linear model to identify factors associated with monthly costs. RESULTS: We identified 34,686 eligible cases of genital warts during the period 2011-2014. The first 2-year mean direct medical cost differences between cases and controls were US$6737 for the USA. Costs were significantly higher in the first 3 months following diagnosis and were higher among older individuals, women, those with co-morbidities or psychiatric illnesses, and those located in the south and southwest USA. CONCLUSIONS: The mean direct cost of treating genital warts is approximately US$6700 in the first 2 years after diagnosis in the USA. These data can assist policy makers in decisions with respect to allocation of resources to implement HPV vaccine programs.

Human Papillomavirus: From Basic Science to Clinical Management for Preclinical Medical Students.

Introduction: Human papillomavirus (HPV) is associated with 30,000 cancer diagnoses a year, but the HPV vaccination is administered less frequently than other vaccinations. Future providers are a potential target for improving rates, and this flipped classroom module was developed to educate future vaccinators on HPV virology, vaccination, and clinical management. Methods: Designed as a clinical correlation for a basic science curriculum on introductory virology and immunology, this weeklong module consisted of a 1-hour lecture and case presentation, assigned articles, and a 90-minute wrap-up session including individual and group quizzes over the assigned material, a group clinical application exercise, and a 20-minute lecture on the case and real-world applications. A pre-/posttest survey was done on general knowledge of HPV, satisfaction with education, and willingness to recommend vaccination for HPV. Results: This module was designed for first-year students, 491 of whom have performed well in it. Pre-/posttest surveys of 243 students indicated that they significantly improved their knowledge of HPV (from 66.3% premodule to 86.3% postmodule, p <.001) and their satisfaction with medical education on vaccination-related topics, as well as increasing their willingness to recommend vaccination (from 58% premodule to 100% postmodule, p <.001). Discussion: This module is an effective and satisfactory way to teach first-year medical students about HPV and HPV vaccination and improves reported willingness to recommend vaccination. With limited resources available to effectively teach HPV vaccination to preclinical medical students, this module fills a gap.

Mean direct medical care costs associated with cervical cancer for commercially insured patients in Texas.

OBJECTIVE: To determine the mean cervical cancer medical care costs for patients enrolled in commercial insurance in Texas. Cost is represented by insurer and patient payments for care. METHODS: We estimated the mean medical care costs during the first 2years after the index diagnosis date for patients with cervical cancer (cases). Cases were identified using claims-based International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9), diagnosis codes and matched to controls without a claims-based ICD-9 code for cancer using a 2-step propensity score matching method. Index dates for the cases were randomly assigned to potential controls, and cases and controls were matched by index date. Data for cancer cases and controls were obtained from the de-identified 2011-2014 U.S. MarketScan databases. A generalized linear model was employed to compute the cost for censored months during the 2-year follow-up period. Differential costs were assessed by subtracting the medical costs incurred by controls from those incurred by cases. RESULTS: During 2011-2014, 475 commercially insured Texas patients with newly diagnosed cervical cancer met the inclusion criteria. The first-year and second-year mean medical costs were $60,828 and $37,721 for cases and $9982 and $10,066 for controls, respectively. The differential costs of cervical cancer for the first and second years were $50,846 and $27,656, respectively. The major correlates of higher monthly cervical cancer costs were higher Charlson Comorbidity Index score during 6months period prior to diagnosis, higher healthcare costs between 6months and 3months prior to diagnosis, and residence in the western region of Texas. Costs for cervical cancer patients decreased steeply between month 1 and month 5 after diagnosis and then were stable, while costs for the control group were stable throughout the follow-up period. CONCLUSIONS: Mean direct medical costs associated with cervical cancer in Texas were substantial. These data will serve as key cost parameters in models of costs associated with human papillomavirus (HPV)-related cancers in Texas and the economic evaluation of HPV vaccination dissemination in Texas.