Low-dose naltrexone for post-COVID fatigue syndrome: a study protocol for a double-blind, randomised trial in British Columbia.

INTRODUCTION: A significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-viral fatigue syndromes. There remains no clear pharmacological therapy for patients with this subtype of PCC, which can be referred to as post-COVID fatigue syndrome (PCFS). A low dose of the opioid antagonist naltrexone (ie, low-dose naltrexone (LDN)) has emerged as an off-label treatment for treating fatigue and other symptoms in PCC. However, only small, non-controlled studies have assessed LDN in PCC, so randomised trials are urgently required. METHODS AND ANALYSIS: A prospective, randomised, double-blind, parallel arm, placebo-controlled phase II trial will be performed to assess the efficacy of LDN for improving fatigue in PCFS. The trial will be decentralised and open to eligible individuals throughout the Canadian province of British Columbia (BC). Participants will be recruited through the province-wide Post-COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN) and research volunteer platform (REACH BC). Eligible participants will be 19-69 years old, have had a confirmed or physician-suspected SARS-CoV-2 infection at least 3 months prior and meet clinical criteria for PCFS adapted from the Institute of Medicine ME/CFS criteria. Individuals who are taking opioid medications, have a history of ME/CFS prior to COVID-19 or history of significant liver disease will be excluded. Participants will be randomised to an LDN intervention arm (n=80) or placebo arm (n=80). Participants in each arm will be prescribed identical capsules starting at 1 mg daily and follow a prespecified schedule for up-titration to 4.5 mg daily or the maximum tolerated dose. The trial will be conducted over 16 weeks, with assessments at baseline, 6, 12 and 16 weeks. The primary outcome will be fatigue severity at 16 weeks evaluated by the Fatigue Severity Scale. Secondary outcomes will include pain Visual Analogue Scale score, overall symptom severity as measured by the Patient Phenotyping Questionnaire Short Form, 7-day step count and health-related quality of life measured by the EuroQol 5-Dimension questionnaire. ETHICS AND DISSEMINATION: The trial has been authorised by Health Canada and approved by The University of British Columbia/Children's and Women's Health Centre of British Columbia Research Ethics Board. On completion, findings will be disseminated to patients, caregivers and clinicians through engagement activities within existing PCC and ME/CFS networks. Results will be published in academic journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT05430152.

Patient-Physician Sex Discordance and "Before Medically Advised" Discharge from Hospital: A Population-Based Retrospective Cohort Study.

BACKGROUND: Patient-physician sex discordance (when patient sex does not match physician sex) has been associated with reduced clinical rapport and adverse outcomes including post-operative mortality and unplanned hospital readmission. It remains unknown whether patient-physician sex discordance is associated with "before medically advised" hospital discharge (BMA discharge; commonly known as discharge "against medical advice"). OBJECTIVE: To evaluate whether patient-physician sex discordance is associated with BMA discharge. DESIGN: Retrospective cohort study using 15 years (2002-2017) of linked population-based administrative health data for all non-elective, non-obstetrical acute care hospitalizations from British Columbia, Canada. PARTICIPANTS: All individuals with eligible hospitalizations during study interval. MAIN MEASURES: Exposure: patient-physician sex discordance. OUTCOMES: BMA discharge (primary), 30-day hospital readmission or death (secondary). RESULTS: We identified 1,926,118 eligible index hospitalizations, 2.6% of which ended in BMA discharge. Among male patients, sex discordance was associated with BMA discharge (crude rate, 4.0% vs 2.9%; adjusted odds ratio [aOR] 1.08; 95%CI 1.03-1.14; p = 0.003). Among female patients, sex discordance was not associated with BMA discharge (crude rate, 2.0% vs 2.3%; aOR 1.02; 95%CI 0.96-1.08; p = 0.557). Compared to patient-physician sex discordance, younger patient age, prior substance use, and prior BMA discharge all had stronger associations with BMA discharge. CONCLUSIONS: Patient-physician sex discordance was associated with a small increase in BMA discharge among male patients. This finding may reflect communication gaps, differences in the care provided by male and female physicians, discriminatory attitudes among male patients, or residual confounding. Improved communication and better treatment of pain and opioid withdrawal may reduce BMA discharge.

Physician financial incentives to reduce unplanned hospital readmissions: A propensity score weighted cohort study.

BACKGROUND: Unplanned hospital readmissions are associated with adverse patient outcomes and substantial healthcare costs. It remains unknown whether physician financial incentives for enhanced discharge planning can reduce readmission risk. METHODS: In 2012, policymakers in British Columbia, Canada, introduced a $75 fee-for-service physician payment to incentivize enhanced discharge planning (the 'G78717' fee code). We used population-based administrative health data to compare outcomes among G78717-exposed and G78717-unexposed patients. We identified all non-elective hospitalizations potentially eligible for the incentive over a five-year study interval. We examined the composite risk of unplanned readmission or death and total direct healthcare costs accrued within 30 days of discharge. Propensity score overlap weights and adjustment were used to account for differences between exposed and unexposed patients. RESULTS: A total of 5262 of 24,787 G78717-exposed and 28,096 of 136,541 unexposed patients experienced subsequent unplanned readmission or death, suggesting exposure to the G78717 incentive did not reduce the risk of adverse outcomes after discharge (crude percent, 21.1% vs 20.6%; adjusted odds ratio, 0.97; 95%CI, 0.93-1.01; p=0.23). Mean direct healthcare costs within 30 days of discharge were $3082 and $2993, respectively (adjusted cost ratio, 1.00; 95%CI, 0.95-1.05; p=0.93). CONCLUSIONS: A physician financial incentive that encouraged enhanced hospital discharge planning did not reduced the risk of readmission or death, and did not significantly increase or decrease direct healthcare costs. Policymakers should consider the baseline prevalence and effectiveness of enhanced discharge planning, the magnitude and design of financial incentives, and whether auditing of incentivized activities is required when implementing similar incentives elsewhere. TRIAL REGISTRATION: ClinicalTrials.gov ID, NCT03256734.

Long-term Health-related Quality of Life in Working-age COVID-19 Survivors: A Cross-sectional Study.

BACKGROUND: Most working-age (18-64) adults have been infected with SARS-CoV-2, and some may have developed post-COVID-19 condition (PCC). However, health-related quality of life (HRQOL) greater than 2 years following infection remains uncharacterized. METHODS: In this cross-sectional study, COVID-19 survivors from throughout British Columbia (BC), Canada, completed a questionnaire greater than 2 years post-infection. PCC status was self-reported, and HRQOL was assessed using the EuroQol 5-dimension 5-level (EQ-5D-5L) instrument. We compared HRQOL in those with current PCC, those with recovered PCC, and those without a history of PCC. Iterative proportional fitting was used to weight analyses to be representative of COVID-19 survivors in BC. Multivariable regression models were used to adjust for confounders. RESULTS: Of the 1,135 analyzed participants, 19.2% had current PCC, and 27.6% had recovered PCC. Compared to those without a history of PCC, participants with recovered PCC had a similar weighted mean EQ-5D health utility (adjusted difference -0.02 [95%CI -0.03, 0.00]), but those with current PCC had a lower health utility (adjusted difference -0.08 [95%CI -0.12, -0.05]). Compared to those without a history of PCC, participants with current PCC were more likely to report problems with mobility (adjusted odds ratio (aOR) 6.00 [95%CI 2.88-12.52]), self-care (aOR 5.96 [95%CI 1.84-19.32]), usual activities (aOR 8.00 [95%CI 4.27-14.99]), pain/discomfort (aOR 4.28 [95%CI 2.46-7.48]), and anxiety/depression (aOR 3.45 [95%CI 1.90-6.27]). CONCLUSIONS: In working-age adults who have survived greater than 2 years following COVID-19, HRQOL is high among those who have never had PCC or have recovered from PCC. However, individuals with ongoing symptoms of PCC have lower HRQOL and are more likely to have deficits in multiple functional domains. These findings underscore the importance of implementing targeted healthcare interventions to improve HRQOL in adults with long-term PCC.

Psychiatric Symptoms, Treatment Uptake, and Barriers to Mental Health Care Among US Adults With Post-COVID-19 Condition.

Importance: Psychiatric symptoms are reportedly common among adults with post-COVID-19 condition (PCC). However, nationally representative data regarding symptom prevalence, treatment uptake, and barriers to care are needed to inform the development of care models. Objectives: To evaluate the prevalence of psychiatric symptoms in US adults with PCC compared with those without PCC and assess treatment uptake and cost-related barriers to treatment. Design, Setting, and Participants: Data from the 2022 National Health Interview Survey (NHIS), a nationally representative US cross-sectional survey, were analyzed between October 2023 and February 2024. Exposure: Current PCC, defined as new symptoms following SARS-CoV-2 infection lasting more than 3 months and ongoing at the time of interview. Main Outcomes and Measures: Depression symptoms were evaluated by the Patient Health Questionnaire-8 and anxiety symptoms were assessed using the General Anxiety Disorder-7 instrument. Participants were classified as having received treatment if they received mental health counseling or therapy or medications for mental health. Sleep difficulties, cognitive difficulties, disabling fatigue, and cost-related barriers were assessed from additional NHIS questions. Results: Of the 25 122 participants representing approximately 231 million US adults (median [IQR] age, 46 [32-61] years; 49.8% male and 50.2% female participants), a weighted prevalence (wPr) of 3.4% (95% CI, 3.1%-3.6%) had current PCC. Compared with other US adults, participants with current PCC were more likely to have depression symptoms (wPr, 16.8% vs 7.1%; adjusted odds ratio [AOR], 1.96; 95% CI, 1.51-2.55), anxiety symptoms (wPr, 16.7% vs 6.3%; AOR, 2.21; 95% CI, 1.53-3.19), sleep difficulties (wPr, 41.5% vs 22.7%; AOR 1.95; 95% CI, 1.65-2.29), cognitive difficulties (wPr, 35.0% vs 19.5%; AOR, 2.04; 95% CI, 1.66-2.50), and disabling fatigue (wPr, 4.0% vs 1.6%; AOR, 1.85; 95% CI, 1.20-2.86). Among participants who had depression or anxiety symptoms, those with PCC had a similar likelihood of not having received treatment (wPr, 28.2% vs 34.9%; AOR, 1.02; 95% CI, 0.66-1.57). However, participants with current PCC were more likely to report a cost-related barrier to accessing mental health counseling or therapy (wPr, 37.2% vs 23.3%; AOR, 2.05; 95% CI, 1.40-2.98). Conclusions and Relevance: The findings of this study suggest that people with PCC have a higher prevalence of psychiatric symptoms than other adults but are more likely to experience cost-related barriers to accessing therapy. Care pathways for PCC should consider prioritizing mental health screening and affordable treatment.

Population-Based Trends in Complexity of Hospital Inpatients.

Importance: Clinical experience suggests that hospital inpatients have become more complex over time, but few studies have evaluated this impression. Objective: To assess whether there has been an increase in measures of hospital inpatient complexity over a 15-year period. Design, Setting and Participants: This cohort study used population-based administrative health data from nonelective hospitalizations from April 1, 2002, to January 31, 2017, to describe trends in the complexity of inpatients in British Columbia, Canada. Hospitalizations were included for individuals 18 years and older and for which the most responsible diagnosis did not correspond to pregnancy, childbirth, the puerperal period, or the perinatal period. Data analysis was performed from July to November 2023. Exposure: The passage of time (15-year study interval). Main Outcomes and Measures: Measures of complexity included patient characteristics at the time of admission (eg, advanced age, multimorbidity, polypharmacy, recent hospitalization), features of the index hospitalization (eg, admission via the emergency department, multiple acute medical problems, use of intensive care, prolonged length of stay, in-hospital adverse events, in-hospital death), and 30-day outcomes after hospital discharge (eg, unplanned readmission, all-cause mortality). Logistic regression was used to estimate the relative change in each measure of complexity over the entire 15-year study interval. Results: The final study cohort included 3 367 463 nonelective acute care hospital admissions occurring among 1 272 444 unique individuals (median [IQR] age, 66 [48-79] years; 49.1% female and 50.8% male individuals). Relative to the beginning of the study interval, inpatients at the end of the study interval were more likely to have been admitted via the emergency department (odds ratio [OR], 2.74; 95% CI, 2.71-2.77), to have multimorbidity (OR, 1.50; 95% CI, 1.47-1.53) and polypharmacy (OR, 1.82; 95% CI, 1.78-1.85) at presentation, to receive treatment for 5 or more acute medical issues (OR, 2.06; 95% CI, 2.02-2.09), and to experience an in-hospital adverse event (OR, 1.20; 95% CI, 1.19-1.22). The likelihood of an intensive care unit stay and of in-hospital death declined over the study interval (OR, 0.96; 95% CI, 0.95-0.97, and OR, 0.81; 95% CI, 0.80-0.83, respectively), but the risks of unplanned readmission and death in the 30 days after discharge increased (OR, 1.14; 95% CI, 1.12-1.16, and OR, 1.28; 95% CI, 1.25-1.31, respectively). Conclusions and Relevance: By most measures, hospital inpatients have become more complex over time. Health system planning should account for these trends.

Forecasting ward-level bed requirements to aid pandemic resource planning: Lessons learned and future directions.

During the COVID-19 pandemic, there has been considerable research on how regional and country-level forecasting can be used to anticipate required hospital resources. We add to and build on this work by focusing on ward-level forecasting and planning tools for hospital staff during the pandemic. We present an assessment, validation, and deployment of a working prototype forecasting tool used within a modified Traffic Control Bundling (TCB) protocol for resource planning during the pandemic. We compare statistical and machine learning forecasting methods and their accuracy at one of the largest hospitals (Vancouver General Hospital) in Canada against a medium-sized hospital (St. Paul's Hospital) in Vancouver, Canada through the first three waves of the COVID-19 pandemic in the province of British Columbia. Our results confirm that traditional statistical and machine learning (ML) forecasting methods can provide valuable ward-level forecasting to aid in decision-making for pandemic resource planning. Using point forecasts with upper 95% prediction intervals, such forecasting methods would have provided better accuracy in anticipating required beds on COVID-19 hospital units than ward-level capacity decisions made by hospital staff. We have integrated our methodology into a publicly available online tool that operationalizes ward-level forecasting to aid with capacity planning decisions. Importantly, hospital staff can use this tool to translate forecasts into better patient care, less burnout, and improved planning for all hospital resources during pandemics.

Evaluating fatigue in patients recovering from COVID-19: validation of the fatigue severity scale and single item screening questions.

BACKGROUND: Fatigue is a common symptom in hospitalized and non-hospitalized patients recovering from COVID-19, but no fatigue measurement scales or questions have been validated in these populations. The objective of this study was to perform validity assessments of the fatigue severity scale (FSS) and two single-item screening questions (SISQs) for fatigue in patients recovering from COVID-19. METHODS: We examined patients ≥ 28 days after their first SARS-CoV-2 infection who were hospitalized for their acute illness, as well as non-hospitalized patients referred for persistent symptoms. Patients completed questionnaires through 1 of 4 Post COVID-19 Recovery Clinics in British Columbia, Canada. Construct validity was assessed by comparing FSS scores to quality of life and depression measures. Two SISQs were evaluated based on the ability to classify fatigue (FSS score ≥ 4). RESULTS: Questionnaires were returned in 548 hospitalized and 546 non-hospitalized patients, with scores computable in 96.4% and 98.2% of patients respectively. Cronbach's alpha was 0.96 in both groups. The mean ± SD FSS score was 4.4 ± 1.8 in the hospitalized and 5.2 ± 1.6 in the non-hospitalized group, with 62.5% hospitalized and 78.9% non-hospitalized patients classified as fatigued. Ceiling effects were 7.6% in the hospitalized and 16.1% in non-hospitalized patients. FSS scores negatively correlated with EQ-5D scores in both groups (Spearman's rho - 0.6 in both hospitalized and non-hospitalized; p < 0.001) and were higher among patients with a positive PHQ-2 depression screen (5.4 vs. 4.0 in hospitalized and 5.9 vs. 4.9 in non-hospitalized; p < 0.001). An SISQ asking whether there was "fatigue present" had a sensitivity of 70.6% in hospitalized and 83.2% in non-hospitalized patients; the "always feeling tired" SISQ, had a sensitivity of 70.5% and 89.6% respectively. CONCLUSIONS: Fatigue was common and severe in patients referred for post COVID-19 assessment. Overall, the FSS is suitable for measuring fatigue in these patients, as there was excellent data quality, strong internal consistency, and construct validity. However, ceiling effects may be a limitation in the non-hospitalized group. SISQs had good sensitivity for identifying clinically relevant fatigue in non-hospitalized patients but only moderate sensitivity in the hospitalized group, indicating that there were more false negatives.

Repeat virological and serological profiles in hospitalized patients initially tested by nasopharyngeal RT-PCR for SARS-CoV-2.

Real-time polymerase chain reaction (PCR) for SARS-CoV-2 is the mainstay of COVID-19 diagnosis, yet there are conflicting reports on its diagnostic performance. Wide ranges of false-negative PCR tests have been reported depending on clinical presentation, the timing of testing, specimens tested, testing method, and reference standard used. We aimed to estimate the frequency of discordance between initial nasopharyngeal (NP) PCR and repeat NP sampling PCR and serology in acutely ill patients admitted to the hospital. Panel diagnosis of COVID-19 infection is further utilized in discordance analysis. Included in the study were 160 patients initially tested by NP PCR with repeat NP sampling PCR and/or serology performed. The percent agreement between initial and repeat PCR was 96.7%, while the percent agreement between initial PCR and serology was 98.9%. There were 5 (3.1%) cases with discordance on repeat testing. After discordance analysis, 2 (1.4%) true cases tested negative on initial PCR. Using available diagnostic methods, discordance on repeat NP sampling PCR and/or serology is a rare occurrence.

Internet Interest in Colon Cancer Following the Death of Chadwick Boseman: Infoveillance Study.

BACKGROUND: Compared with White Americans, Black Americans have higher colon cancer mortality rates but lower up-to-date screening rates. Chadwick Boseman was a prominent Black American actor who died of colon cancer on August 28, 2020. As announcements of celebrity diagnoses often result in increased awareness, Boseman's death may have resulted in greater interest in colon cancer on the internet, particularly among Black Americans. OBJECTIVE: This study aims to quantify the impact of Chadwick Boseman's death on web-based search interest in colon cancer and determine whether there was an increase in interest in regions of the United States with a greater proportion of Black Americans. METHODS: We conducted an infoveillance study using Google Trends (GT) and Wikipedia pageview analysis. Using an autoregressive integrated moving average algorithm, we forecasted the weekly relative search volume (RSV) for GT search topics and terms related to colon cancer that would have been expected had his death not occurred and compared it with observed RSV data. This analysis was also conducted for the number of page views on the Wikipedia page for colorectal cancer. We then delineated GT RSV data for the term colon cancer for states and metropolitan areas in the United States and determined how the RSV values for these regions correlated with the percentage of Black Americans in that region. Differences in these correlations before and after Boseman's death were compared to determine whether there was a shift in the racial demographics of the individuals conducting the searches. RESULTS: The observed RSVs for the topics colorectal cancer and colon cancer screening increased by 598% and 707%, respectively, and were on average 121% (95% CI 72%-193%) and 256% (95% CI 35%-814%) greater than expected during the first 3 months following Boseman's death. Daily Wikipedia page view volume during the 2 months following Boseman's death was on average 1979% (95% CI 1375%-2894%) greater than expected, and it was estimated that this represented 547,354 (95% CI 497,708-585,167) excess Wikipedia page views. Before Boseman's death, there were negative correlations between the percentage of Black Americans living in a state or metropolitan area and the RSV for colon cancer in that area (r=-0.18 and r=-0.05, respectively). However, in the 2 weeks following his death, there were positive correlations between the RSV for colon cancer and the percentage of Black Americans per state and per metropolitan area (r=0.73 and r=0.33, respectively). These changes persisted for 4 months and were all statistically significant (P<.001). CONCLUSIONS: There was a significant increase in web-based activity related to colon cancer following Chadwick Boseman's death, particularly in areas with a higher proportion of Black Americans. This reflects a heightened public awareness that can be leveraged to further educate the public.

Learning from the first wave: Lessons about managing patient flow and resource utilization on medical wards at providence health during the COVID-19 pandemic.

We report the successful implementation of a modified Traffic Control Bundling (TCB) protocol called "Red, Yellow and Green" on the inpatient medical units at St. Paul's Hospital in Vancouver, Canada during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. The modified TCB protocol demonstrates an important example on how hospitals can rapidly reorganize operational and clinical processes to reallocate existing capacity to minimize exposure, improve traffic flow and reduce nosocomial transmissions of COVID-19 to health care workers (HCWs) and other patients. Preliminary evidence demonstrates the benefits on how an existing facility can be redesigned for adjustable ward capacity to provide disease containment under a context of uncertainty of disease transmission and varying patient load. Important lessons in preparation for the evolution of the pandemic fall into categories of risk management, capacity and demand management.

Emotional distress and psychosocial needs in patients with breast cancer in British Columbia: younger versus older adults.

PURPOSE: This study evaluates the prevalence of emotional distress and psychosocial needs in young adult (YA, age 18-39) patients at the time of their breast cancer diagnosis compared to older patients. METHODS: Through a province-wide program, BC Cancer patients complete the PsychoSocial Scan for CANcer-Revised (PSSCAN-R) questionnaire, which screens for the presence of symptoms of anxiety and depression and assesses psychosocial needs using the Canadian Problem Checklist (CPC). The study population comprised all breast cancer patients who completed the questionnaire within 6 months of their cancer diagnosis between 2011 and 2016. Clinical information was retrospectively collected from electronic health records. Univariate and multivariate analyses using the X2, Fisher's exact test, and logistical regression were used to compare patient age groups. RESULTS: The cohort included 10,734 breast cancer patients: median age 62, 4% YA, 99% female, and 96% presented with non-metastatic disease. After adjusting for clinical and demographic variables, YA patients were more likely to report depression (33.6% vs. 25.5%, OR 1.47, p = 0.001) and anxiety symptoms (58.6% vs. 35.7%, OR 2.49, p < 0.001) than older patients. Psychosocial needs regarding work/school (OR 3.79, p < 0.001), intimacy/sexuality (OR 2.82, p < 0.001), and finances (OR 2.78, p < 0.001) were more common among YA than older adults. CONCLUSIONS: After a breast cancer diagnosis, YAs have higher levels of emotional distress compared to older patients. Differences in specific psychosocial needs likely reflect differences in life stage between these age groups. The data suggest that YAs warrant specific attention with respect to early psychosocial assessment and tailored intervention.

Acceptability of Routine Evaluations Using Patient-Reported Outcomes of Common Terminology Criteria for Adverse Events and Other Patient-Reported Symptom Outcome Tools in Cancer Outpatients: Princess Margaret Cancer Centre Experience.

BACKGROUND: Recent studies have demonstrated improved outcomes with real-time patient-reported outcome questionnaires (PRO questionnaires) using questions adapted for patient use from the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). Outside of the clinical trial setting, limited information exists on factors affecting the completion of PRO questionnaires in routine practice. The primary aim of this prospective cross-sectional study was to evaluate patient willingness to complete PRO questionnaires on a regular basis and to better understand responder biases to improve patient feedback. MATERIALS AND METHODS: Patients performing PRO-CTCAE toxicity and symptom PRO questionnaires in oncology clinics at Princess Margaret Cancer Centre from 2013 to 2016 were assessed for their willingness to complete PRO questionnaires using a nine-item, tablet-based acceptability survey. Patient-reported characteristics (i.e., age, sex, language, marital status, education, occupation, etc.), cancer type, treatment modalities, and health metrics (i.e., Eastern Cooperative Oncology Group) were also collected. Characteristics were evaluated by logistic regression (odds ratios [OR]) using the primary outcome with prespecified levels of significance for univariate (p ≤ .10), and additional multivariate (p ≤ .05) testing. RESULTS: A total of 1,792 patients (median age 60 years; range 18-97) with various cancer diagnoses were assessed. A greater proportion of female (56%) and white (74%) respondents with an annual household income of <$100,000 (69%) participated. More than half (58%) of respondents were willing to complete PRO questionnaires at every clinic visit, and a high proportion (77%) found utility in reporting physical and emotional feelings to clinicians using PRO questionnaires. In general, patients did not find that PRO questionnaires made clinic visits more difficult (93%). In uni- and multivariable testing, patients were more willing to complete sleep- and fatigue-related PRO questionnaires relative to chemotoxicity-based PRO questionnaires (OR 1.52; p = .012). Patients aged 40-65 versus 18-40 years were also more likely to report high PRO questionnaire acceptability (OR 1.49; p = .025). Additional patient characteristics such as white ethnicity (OR 1.76), Canada as country of birth (OR 1.66), and English language (OR 2.15) relative to other had higher acceptability on uni- (p < .001) and multivariable (p < .001) analyses. Patients reporting treatment intent as palliative (OR 0.69; p = .0013) or hematological (OR 0.73; p = .027) were less likely to report high PRO questionnaire acceptability on univariable analysis; however, only palliative patients (OR 0.72) maintained this effect on multivariable testing (p = .012). Patients reporting higher health utility scores (per change in .05) also had significantly increased PRO questionnaire acceptability in uni- (OR 1.06; p < .001) and multivariable (OR 1.05; p = .008) analyses. No significant differences in PRO questionnaire acceptability were seen between cancer types, education level, household income, employment status, or treatment modality. CONCLUSION: Routine assessment using PRO questionnaires is associated with moderate acceptability by patients with cancer. Specific patient characteristics are associated with higher completion willingness. Additional research is necessary to identify factors associated with low acceptability of PRO questionnaires and to develop site-, ethnicity-, and treatment-specific instruments to assess the value of PRO questionnaires for symptom monitoring in clinical practice. IMPLICATIONS FOR PRACTICE: This study will help to identify the clinical, demographic, and survey characteristics associated with willingness to complete patient-reported outcome questionnaires regularly in the cancer outpatient setting.

The Impact of Brain Metastases and Associated Neurocognitive Aspects on Health Utility Scores in EGFR Mutated and ALK Rearranged NSCLC: A Real World Evidence Analysis.

BACKGROUND: In lung cancer, brain metastases (BM) and their treatment are associated with high economic burden and inferior health-related quality of life. In the era of targeted therapy, real world evidence through health utility scores (HUS) is critical for economic analyses. MATERIALS AND METHODS: In a prospective observational cohort study (2014-2016), outpatients with stage IV lung cancer completed demographic and EQ-5D-3L surveys (to derive HUS). Health states and clinicopathologic variables were obtained from chart abstraction. Patients were categorized by the presence or absence of BM; regression analyses identified factors that were associated with HUS. A subset of patients prospectively completed neurocognitive function (NCF) tests and/or the FACT-brain (FACT-Br) questionnaire, which were then correlated with HUS (Spearman coefficients; regression analyses). RESULTS: Of 519 patients with 1,686 EQ-5D-3L-derived HUS, 94 (18%) completed NCF tests and 107 (21%) completed FACT-Br; 301 (58%) never developed BM, 24 (5%) developed first BM during study period, and 194 (37%) had BM at study entry. The sample was enriched (46%) for EGFR mutations (EGFRm) and ALK-rearrangements (ALKr). There were no HUS differences by BM status overall and in subsets by demographics. In multivariable analyses, superior HUS was associated with having EGFRm/ALKr (p < .0001), no prior radiation for extracranial disease (p < .001), and both intracranial (p = .002) and extracranial disease control (p < .01). HUS correlated with multiple elements of the FACT-Br and tests of NCF. CONCLUSION: Having BM in lung cancer is not associated with inferior HUS in a population enriched for EGFRm and ALKr. Patients exhibiting disease control and those with oncogene-addicted tumors have superior HUS. IMPLICATIONS FOR PRACTICE: In the setting of EGFR mutations or ALK rearrangement non-small cell lung cancer (NSCLC), a diagnosis of brain metastases no longer consigns the patient to an inferior health state suggesting that new economic analyses in NSCLC are needed in the era of targeted therapies. Additionally, the EQ-5D questionnaire is associated with measures of health-related quality of life and neurocognitive scores suggesting this tool should be further explored in prospective clinical studies.

Impact of immigration status on health behaviors and perceptions in cancer survivors.

BACKGROUND: Health behaviors including smoking cessation, physical activity (PA), and alcohol moderation are key aspects of cancer survivorship. Immigrants may have unique survivorship needs. We evaluated whether immigrant cancer survivors had health behaviors and perceptions that were distinct from native-born cancer survivors. METHODS: Adult cancer patients from Princess Margaret Cancer Centre were surveyed on their smoking, PA, and alcohol habits and perceptions of the effects of these behaviors on quality of life (QoL), 5-year survival, and fatigue. Multivariable models evaluated the association of immigration status and region-of-origin on behaviors and perceptions. RESULTS: Of the 784 patients, 39% self-identified as immigrants. Median time of survey was 24 months after histological diagnosis. At baseline, immigrants had trends toward not meeting Canadian PA guidelines or being ever-drinkers; patients from non-Western countries were less likely to smoke (aORcurrent  = 0.46, aORex-smoker  = 0.47, P = 0.02), drink alcohol (aORcurrent  = 0.22, aORex-drinker  = 0.52, P < 0.001), or meet PA guidelines (aOR = 0.44, P = 0.006). Among immigrants, remote immigrants (migrated ≥40 years ago) were more likely to be consuming alcohol at diagnosis (aOR = 5.70, P < 0.001) compared to recent immigrants. Compared to nonimmigrants, immigrants were less likely to perceive smoking as harmful on QoL (aOR = 0.58, P = 0.008) and survival (aOR = 0.56, P = 0.002), and less likely to perceive that PA improved fatigue (aOR = 0.62, P = 0.04) and survival (aOR = 0.64, P = 0.08). CONCLUSIONS: Immigrants had different patterns of health behaviors than nonimmigrants. Immigrants were less likely to perceive continued smoking as harmful and were less likely to be aware of PA benefits. Culturally tailored counselling may be required for immigrants who smoke or are physically sedentary at diagnosis.

Favourable health-related quality of life reported in survivors of thymic malignancies.

OBJECTIVES: The management of patients with locally advanced thymic malignancies remains controversial. Differing combinations of surgical resection, chemotherapy and radiation are used in the management of initial and relapsed disease. Treatment-related toxicities and quality of life could inform therapeutic options. This study describes health utility scores (HUS) in survivors with locally advanced thymic malignancies and investigates the impact of multimodality regimens on HUS. METHODS: In a cross-sectional study (2014-2017), patients with Masaoka Stage II-IVa thymic malignancies completed various self-reported questionnaires, including EuroQol-5-Dimensions with visual analogue scale (VAS), Eastern Cooperative Oncology Group (ECOG) and Edmonton Symptom Assessment Scale tools. Trimodality versus uni- or bimodality regimens and aggressive versus non-aggressive management of recurrent disease were compared using regression analyses. RESULTS: Of the 72 patients, 43 (60%) were male with a median age of 58 years, 65 (90%) had thymoma while 7 (10%) had thymic carcinomas; and median time since diagnosis was 50.5 months (range: 3-266). Median HUS and VAS did not differ between groups (trimodality n = 24 vs uni- or bimodality n = 48: HUS = 0.77 vs 0.80, P = 0.29; VAS = 80 vs 75, P = 0.79, respectively). The distributions of patient-reported ECOG were also similar (P = 0.86). Edmonton Symptom Assessment Scale scores for every assessed symptom were similar for different modalities of therapy. Median scores on these tools were also similar regardless of recurrence status or management of relapsed disease (aggressive versus non-aggressive). CONCLUSION: Survivors with Stage II-IVa thymic malignancies report favourable HUS, VAS and self-reported ECOG with minimal symptom burden. These outcomes may be independent of number and type of initial treatment modalities or management of recurrence.

Patterns, perceptions, and perceived barriers to physical activity in adult cancer survivors.

PURPOSE: Physical activity (PA) during and after cancer treatment is associated with improved cancer- and non-cancer-related outcomes. We assessed for predictors of change in PA levels among cancer survivors. METHODS: Adult cancer survivors from a comprehensive cancer center completed a one-time questionnaire retrospectively assessing PA levels before, during, and after cancer treatment along with their perceptions of PA. Multivariable logistic regression models evaluated the association of clinico-demographics variables and perceptions of PA with changes in whether patients were meeting PA guidelines after cancer diagnosis. RESULTS: Among the 1003 patients, 319 (32%) met moderate to vigorous PA (MVPA) guidelines before diagnosis. Among those meeting guidelines before diagnosis, 50% still met guidelines after treatment; 12% not meeting MVPA guidelines initially met them after treatment/at follow-up. Among patients meeting guidelines before diagnosis, better ECOG performance status at follow-up, receiving curative therapy, and spending a longer time on PA initially were each associated with meeting guidelines at follow-up. After controlling for other variables, perceiving that PA improves quality of life (adjusted odds ratio, aOR = 11.09, 95%CI [1.42-86.64], P = 0.02) and overall survival (aOR = 8.52, 95%CI [1.12-64.71], P = 0.04) was each associated with meeting MVPA guidelines during/after treatment, in patients who did not meet guidelines initially. Only 13% reported receiving counseling, which was not associated with PA levels. Common reported barriers to PA included fatigue, lacking motivation, and being too busy. CONCLUSIONS: Patient perceptions of PA benefits are strongly associated with improving PA levels after a cancer diagnosis. Clinician counseling should focus on patient education and changing patient perceptions.