Occupational patterns of opioid-related harms comparing a cohort of formerly injured workers to the general population in Ontario, Canada.

OBJECTIVES: The role of work-related injuries as a risk factor for opioid-related harms has been hypothesized, but little data exist to support this relationship. The objective was to compare the incidence of opioid-related harms among a cohort of formerly injured workers to the general population in Ontario, Canada. METHODS: Workers' compensation claimants (1983-2019) were linked to emergency department (ED) and hospitalization records (2006-2020). Incident rates of opioid-related poisonings and mental and behavioural disorders were estimated among 1.7 million workers and in the general population. Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) were calculated, adjusting for age, sex, year, and region. RESULTS: Compared to the general population, opioid-related poisonings among this group of formerly injured workers were elevated in both ED (SIR = 2.41, 95% CI = 2.37-2.45) and hospitalization records (SIR = 1.54, 95% CI = 1.50-1.59). Opioid-related mental and behavioural disorders were also elevated compared to the general population (ED visits: SIR = 1.86, 95% CI = 1.83-1.89; hospitalizations: SIR = 1.42, 95% CI = 1.38-1.47). Most occupations and industries had higher risks of harm compared to the general population, particularly construction, materials handling, processing (mineral, metal, chemical), and machining and related occupations. Teaching occupations displayed decreased risks of harm. CONCLUSION: Findings support the hypothesis that work-related injuries have a role as a preventable risk factor for opioid-related harms. Strategies aimed at primary prevention of occupational injuries and secondary prevention of work disability and long-term opioid use are warranted.

RéSUMé: OBJECTIFS: Le rôle des accidents du travail en tant que facteur de risque pour les méfaits liés aux opioïdes a été supposé, mais il existe peu de données pour étayer cette relation. L'objectif était de comparer l'incidence des méfaits liés aux opioïdes dans une cohorte de travailleurs anciennement blessés à la population générale de l'Ontario, au Canada. MéTHODES: Les dossiers de demandes d'indemnisation des travailleurs (1983‒2019) ont été reliés aux dossiers des services d'urgence et d'hospitalisation (2006‒2020). Les taux d'incidence des empoisonnements liés aux opioïdes et des troubles mentaux et comportementaux ont été estimés parmi 1,7 million de travailleurs et dans la population générale. Les ratios d'incidence standardisés (RIS) et les intervalles de confiance (IC) à 95 % ont été calculés en tenant compte de l'âge, du sexe, de l'année et de la région. RéSULTATS: Comparativement à la population générale, les empoisonnements liés aux opioïdes chez ce groupe de travailleurs anciennement blessés étaient élevés dans les dossiers des services d'urgence (RIS = 2,41, IC à 95 % = 2,37-2,45) et d'hospitalisation (RIS = 1,54, IC à 95 % = 1,50-1,59). Les troubles mentaux et comportementaux liés aux opioïdes étaient également élevés par rapport à la population générale (visites aux urgences RIS = 1,86, IC à 95 % = 1,83-1,89; hospitalisations RIS = 1,42, IC à 95 % = 1,38-1,47). La plupart des professions et des secteurs d'activité présentaient des risques de méfaits plus élevés par rapport à la population générale, en particulier la construction, la manutention, le traitement (minéral, métallique, chimique) et l'usinage des matières premières et activités connexes. Les professions de l'enseignement présentaient des risques de méfaits moindres. CONCLUSION: Les résultats confirment l'hypothèse selon laquelle les accidents du travail constituent un facteur de risque évitable pour les méfaits liés aux opioïdes. Des stratégies visant la prévention primaire des accidents du travail et la prévention secondaire de l'incapacité de travail et de la consommation d'opioïdes à long terme sont justifiées.

TOward a comPrehensive supportive Care intervention for Older men with metastatic Prostate cancer (TOPCOP3): A pilot randomized controlled trial and process evaluation.

INTRODUCTION: Current management of metastatic prostate cancer (mPC) includes androgen receptor axis-targeted therapy (ARATs), which is associated with substantial toxicity in older adults. Geriatric assessment and management and remote symptom monitoring have been shown to reduce toxicity and improve quality of life in patients undergoing chemotherapy, but their efficacy in patients being treated with ARATs has not been explored. The purpose of this study is to examine whether these interventions, alone or in combination, can improve treatment tolerability and quality of life (QOL) for older adults with metastatic prostate cancer on ARATs. MATERIALS AND METHODS: TOPCOP3 is a multi-centre, factorial pilot clinical trial coupled with an embedded process evaluation. The study includes four treatment arms: geriatric assessment and management (GA + M); remote symptom monitoring (RSM); geriatric assessment and management plus remote symptom monitoring; and usual care and will be followed for six months. The aim is to recruit 168 patients between two cancer centres in Toronto, Canada. Eligible participants will be randomized equally via REDCap. Participants in all arms will complete a comprehensive baseline assessment upon enrollment following the Geriatric Core dataset, as well as follow-up assessments at 1.5, 3, 4.5, and 6 months. The co-primary outcomes will be grade 3-5 toxicity and QOL. Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. QOL will be measured by patient self-reporting using the EuroQol 5 dimensions of health questionnaire. Secondary outcomes include fatigue, insomnia, and depression. Finally, four process evaluation outcomes will also be observed, namely feasibility, fidelity, and acceptability, along with implementation barriers and facilitators. DISCUSSION: Data will be collected to observe the effects of GA + M and RSM on QOL and toxicities experienced by older adults receiving ARATs for metastatic prostate cancer. Data will also be collected to help the design and conduct of a definitive multicentre phase III randomized controlled trial. This study will extend supportive care interventions for older adults with cancer into new areas and inform the design of larger trials. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (registration number: NCT05582772).

Understanding the incidence, duration, and severity of symptoms through daily symptom monitoring among frail and non-frail older patients receiving metastatic prostate cancer treatments.

INTRODUCTION: Older adults with metastatic prostate cancer (mPC) experience high symptom burden associated with treatment. Frailty may exacerbate treatment toxicity. The aim of this study was to explore short-term treatment toxicity in patients with metastatic prostate cancer. MATERIALS AND METHODS: Older adults with metastatic prostate cancer starting chemotherapy, androgen-receptor-axis targeted therapies, or radium-223 participated in a prospective, multicentre, observational study. Participants self-reported symptoms daily using the Edmonton Symptom Assessment System for one treatment cycle via internet or telephone. The most common moderate-to-severe symptoms (score≥4), their duration, and the proportion of participants who experienced improvements in symptom severity (score<4) after reporting moderate-to-severe symptoms at baseline were determined using descriptive statistics. Once-weekly symptom questionnaires were administered and analyzed using linear mixed effect models. Symptom incidence, duration, and frailty associations were assessed using t-tests and chi-square tests. RESULTS: Ninety participants completed the study (mean age=77 years [standard deviation=6.1], 42% frail [Vulnerable Elders Survey≥3]). The most common moderate-to-severe symptoms across cohorts were fatigue (46.8%), insomnia (42.9%), poor wellbeing (41.2%), pain (37.5%), and decreased appetite (37.1%). Poor wellbeing had a higher incidence in frail participants (62.5% in frail vs. 31.4% in non-frail, p=0.039). Symptom duration varied across cohorts and between frail and non-frail participants. Among participants who reported moderate-to-severe symptoms at baseline, no more than 15% improved in any symptom. There were statistically significant improvements in weekly symptoms for fatigue, decreased appetite, and insomnia in the chemotherapy cohort only. DISCUSSION: Limitations include a short follow-up duration, lack of a control group, and few radium-223 participants. Regular symptom monitoring can help clinicians understand temporal patterns and durations of symptoms and inform supportive care approaches.

Experiences of people with multiple sclerosis and clinicians in using cognitive behavioural therapies for hidden symptoms: a systematic review and meta-aggregation.

PURPOSE: Cognitive behavioural therapies (CBTs) are a standard of care for treatment of many 'hidden symptoms' in people with MS (PwMS), such as stress, depression, and fatigue. However, these interventions can vary widely in formatting and may not be tailored for PwMS. To optimize CBTs for MS, understanding the experiences of PwMS and clinicians is essential. This systematic review and meta-aggregation synthesizes existing qualitative data on stakeholder perspectives of CBTs for PwMS. METHODS: Systematic searches across five major electronic databases were conducted. Studies reporting qualitative data were identified. Two reviewers performed screening, quality assessment, data extraction, and certainty of evidence assessments. Meta-aggregation was performed as per the Joanna Briggs Institute approach, entailing qualitative data extraction, developing categories, and synthesizing overall findings. RESULTS: Twenty-eight studies were included in this review, comprising data from 653 PwMS and 47 clinicians. In the meta-aggregation, 122 qualitative results were extracted and grouped into nine categories. Categories were then combined into six synthesized findings: (1) setting the context-life with MS, (2) reasons for participating in CBTs, (3) acceptability of and experiences with participating in CBTs, (4) perceived benefits of CBTs, (5) perceived challenges with CBTs, and (6) suggestions to improve CBTs for PwMS. CONCLUSIONS: A range of benefits including psychological, social, and lifestyle improvements were reported, but varied based on the design of the CBT intervention. Future CBT interventions should be tailored to participant needs, delivered in group settings, offer online options, and be delivered by a trained facilitator familiar with MS. Further exploration of the ideal CBT design for PwMS, as well as engagement with caregivers and clinicians treating MS, is warranted.

Daily physical activity monitoring in older adults with metastatic prostate cancer on active treatment: Feasibility and associations with toxicity.

INTRODUCTION: Physical activity may be associated with cancer treatment toxicity, but generalizability to geriatric oncology is unclear. As many older adults have low levels of physical activity and technology use, this area needs further exploration. We evaluated the feasibility of daily step count monitoring and the association between step counts and treatment-emergent symptoms. MATERIALS AND METHODS: Adults aged 65+ starting treatment (chemotherapy, enzalutamide/abiraterone, or radium-223) for metastatic prostate cancer were enrolled in a prospective cohort study. Participants reported step counts (measured via smartphone) and symptoms (Edmonton Symptom Assessment Scale) daily for one treatment cycle (i.e., 3-4 weeks). Embedded semi-structured interviews were performed upon completion of the study. The feasibility of daily monitoring was evaluated with descriptive statistics and thematic analysis. The predictive validity of a decline in daily steps (compared to pre-treatment baseline) for the emergence of symptoms was examined using sensitivity and positive predictive value (PPV). Associations between a 15% decline in steps and the emergence of moderate (4-6/10) to severe (7-10/10) symptoms and pain in the next 24 h were assessed using logistic regression. RESULTS: Of 90 participants, 47 engaged in step count monitoring (median age = 75, range = 65-88; 52.2% participation rate). Daily physical activity monitoring was found to be feasible (94% retention rate; 90.5% median response rate) with multiple patient-reported benefits including increased self-awareness and motivation to engage in physical activity. During the first treatment cycle, instances of a 15% decline in steps were common (n = 37, 78.7%), as was the emergence of moderate to severe symptoms overall (n = 40, 85.1%) and pain (n = 26, 55.3%). The predictive validity of a 15% decline in steps on the emergence of moderate to severe symptoms was good (sensitivity = 81.8%, 95% confidence interval [CI] = 68.7-95.0; PPV = 73.0%, 95% CI = 58.7-87.3), although the PPV for pain was poor (sensitivity = 77.8%, 95% CI = 58.6-97.0; PPV = 37.8%, 95% CI = 22.2-53.5). In the regression models, changes in daily physical activity were not associated with symptoms or pain. DISCUSSION: Changes in physical activity had modest ability to predict moderate to severe symptoms overall. Although participation was suboptimal, daily activity monitoring in older adults with cancer appears feasible and may have other uses such as improving physical activity levels. Further studies are warranted.

Symptom experiences of older adults during treatment for metastatic prostate cancer: A qualitative investigation.

INTRODUCTION: Exploring symptom experiences of older men during metastatic prostate cancer treatment can help clinicians identify unmet supportive care needs that, if addressed, could improve toxicity management and enhance patient wellbeing. Previous qualitative studies of older adults with advanced prostate cancer have focused on the psychological experience rather than the overall symptom experience. Therefore, the objective of this study was to understand the lived experience of symptoms and supportive care needs in older men undergoing treatment for metastatic prostate cancer. MATERIALS AND METHODS: Semi-structured interviews were conducted with older adults (aged 65+) who completed their first cycle of chemotherapy, androgen-axis targeted therapies, or radium-223 for metastatic castrate-resistant and sensitive prostate cancer at the Princess Margaret Cancer Centre, Toronto, Canada. Six coders worked in pairs to review interview transcripts and conduct a thematic analysis. A consensus was reached through team discussions. Topics of interest included symptom experiences, the impact of symptoms on daily life, symptom management strategies, and suggestions for external support. RESULTS: Thirty-six interviews were conducted with older adults (mean age: 76 years, 92% with metastatic castrate-resistant prostate cancer) who started chemotherapy (n = 11), androgen-axis targeted therapies (n = 19), or radium-223 (n = 6). The most common treatment-specific symptoms included: fatigue, pain, sleep disturbances, mood disturbances, and gastrointestinal symptoms. Four themes on the impact of symptoms on daily life emerged: resting more than usual, changes in mobility, changes in maintaining activities of daily living, and not feeling up to most things. It is important to note that participants who underwent chemotherapy have previously completed other lines of treatment and had more advanced disease, possibly contributing to higher prevalence of symptoms and greater impact on daily life. Four themes on symptom management strategies emerged: positive support systems, seeking help, interventions by healthcare providers, and self-management strategies. Suggestions for external support included building social support networks, improving health literacy, improving continuity of care, receiving support from healthcare providers, engaging in health-seeking behaviours, and addressing unmet supportive care needs. DISCUSSION: Exploring symptom experiences of older men with metastatic prostate cancer provides valuable insights for developing supportive care programs and improving patient care.

Feasibility and acceptability of remote symptom monitoring (RSM) in older adults during treatment for metastatic prostate cancer.

INTRODUCTION: Emerging data support multiple benefits of remote symptom monitoring (RSM) during chemotherapy to improve outcomes. However, these studies have not focused on older adults and do not include treatments beyond chemotherapy. Although chemotherapy, androgen receptor axis-targeted therapies (ARATs), and radium-223 prolong survival, toxicities are substantial and increased in older adults with metastatic prostate cancer (mPC). We aimed to assess RSM feasibility among older adults receiving life-prolonging mPC treatments. MATERIALS AND METHODS: Older adults aged 65+ starting chemotherapy, an ARAT, or radium-223 for mPC were enrolled in a multicentre prospective cohort study. As part of the RSM package, participants completed the Edmonton Symptom Assessment Scale (ESAS) daily and detailed questionnaires assessing mood, anxiety, fatigue, insomnia, and pain weekly online or by phone throughout one treatment cycle (3-4 weeks). Alerts were sent to the clinical oncology team for severe symptoms (ESAS ≥7). Participants also completed an end of study questionnaire that assessed study burden and satisfaction. Descriptive statistics were used to determine recruitment and retention rates, participant response rates to daily and weekly questionnaires, clinician responses to alerts, and participant satisfaction rates. An inductive descriptive approach was used to categorize open-ended responses about study benefits, challenges, and recommendations into relevant themes. RESULTS: Ninety males were included (mean age 77 years, 48% ARAT, 38% chemotherapy, and 14% radium-223). Approximately 38% of patients preferred phone-based RSM. Patients provided RSM responses in 1216 out of 1311 daily questionnaires (93%). Over 93% of participants were satisfied (36%), very satisfied (43%), or extremely satisfied (16%) with RSM, although daily reporting was reported by several (8%) as burdensome. Nearly 45% of patients reported severe symptoms during RSM. Most symptom alerts sent to the oncology care team were acknowledged (97%) and 53% led to follow-ups with a nurse or physician for additional care. DISCUSSION: RSM is feasible and acceptable to older adults with mPC, but accommodation needs to be made for phone-based RSM. The optimal frequency and duration of RSM also needs to be established.

Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer.

Importance: Older adults are at greater risk of cognitive decline with various oncologic therapies. Some commonly used therapies for advanced prostate cancer, such as enzalutamide, have been linked to cognitive impairment, but published data are scarce, come from single-group studies, or focus on self-reported cognition. Objective: To longitudinally examine the association between cognitive function and docetaxel (chemotherapy), abiraterone, enzalutamide, and radium Ra 223 dichloride (radium 223) in older men with metastatic castration-resistant prostate cancer. Design, Setting, and Participants: A multicenter, prospective, observational cohort study was conducted across 4 academic cancer centers in Ontario, Canada. A consecutive sample of 155 men age 65 years or older with metastatic castration-resistant prostate cancer starting any treatment with docetaxel, abiraterone acetate, enzalutamide, or radium Ra 223 dichloride (radium 223) were enrolled between July 1, 2015, and December 31, 2019. Exposures: First-line chemotherapy (docetaxel), abiraterone, enzalutamide, or radium 223. Main Outcomes and Measures: Cognitive function was measured at baseline and end of treatment using the Montreal Cognitive Assessment, the Trail Making Test part A, and the Trail Making Test part B to assess global cognition, attention, and executive function, respectively. Absolute changes in scores over time were analyzed using univariate and multivariable linear regression, and the percentages of individuals with a decline of 1.5 SDs in each domain were calculated. Results: A total of 155 men starting treatment with docetaxel (n = 51) (mean [SD] age, 73.5 [6.2] years; 34 [66.7%] with some postsecondary education), abiraterone (n = 29) (mean [SD] age, 76.2 [7.2] years; 18 [62.1%] with some postsecondary education), enzalutamide (n = 54) (mean [SD] age, 75.7 [7.4] years; 33 [61.1%] with some postsecondary education), and radium 223 (n = 21) (mean [SD] age, 76.4 [7.2] years; 17 [81.0%] with some postsecondary education) were included. Most patients had stable cognition or slight improvements during treatment. A cognitive decline of 1.5 SDs or more was observed in 0% to 6.5% of patients on each measure of cognitive function (eg, 3 of 46 patients [6.5%; 95% CI, 2.2%-17.5%] in the group receiving chemotherapy [docetaxel] had a decline of 1.5 SDs for Trails A and Trails B). Although patients taking enzalutamide had numerically larger declines than those taking abiraterone, differences were small and clinically unimportant. Conclusions and Relevance: These findings suggest that most older men do not experience significant cognitive decline in attention, executive function, and global cognition while undergoing treatment for advanced prostate cancer regardless of the treatment used.