Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology.

BACKGROUND: Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD). METHODS: Retrospective study of patients with PAD referred for rheumatologic evaluation prior to starting or during immunotherapy between January 2013 and July 2019 from 10 academic sites across Canada. Data were extracted by chart review using a standardized form. RESULTS: Twenty-seven patients with PAD on ICI therapy were identified. The most common PADs were rheumatoid arthritis (30%), psoriasis/psoriatic arthritis (30%), inflammatory bowel disease (IBD, 15%) and axial spondyloarthritis (11%), and the most frequently observed cancers were lung cancer and melanoma. All patients received anti-PD-1 therapies, and 2 received additional sequential anti-CTLA-4 therapy. PAD exacerbations occurred in 52% over a median (IQR) follow-up of 11.0 (6.0-17.5) months, with 14% being severe, 57% requiring corticosteroids, 50% requiring immunosuppression and 14% requiring ICI discontinuation. Flares were generally more frequent and severe in patients who previously required more intensive immunosuppression (i.e., biologics). Flares occurred despite background immunosuppression at the time of ICI initiation. In patients with preexisting psoriasis, IBD and axial spondyloarthritis, rheumatic immune-related adverse events (irAEs), mostly polyarthritis and tenosynovitis, were frequently observed. Tumor progression was not associated with exposure to immunosuppressive drugs before or after ICI initiation and was numerically less frequent in patients with irAEs. CONCLUSION: PAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy.

Palliative care provision at a tertiary cancer center during a global pandemic.

COVID-19 was first reported in Wuhan, China, in December 2019; it rapidly spread around the world and was declared a global pandemic by the World Health Organization in March 2020. The palliative care program at the Princess Margaret Cancer Centre, Toronto, Canada, provides comprehensive care to patients with advanced cancer and their families, through services including an acute palliative care unit, an inpatient consultation service, and an ambulatory palliative care clinic. In the face of a global pandemic, palliative care teams are uniquely placed to support patients with cancer who also have COVID-19. This may include managing severe symptoms such as dyspnea and agitation, as well as guiding advance care planning and goals of care conversations. In tandem, there is a need for palliative care teams to continue to provide care to patients with advanced cancer who are COVID-negative but who are at higher risk of infection and adverse outcomes related to COVID-19. This paper highlights the unique challenges faced by a palliative care team in terms of scaling up services in response to a global pandemic while simultaneously providing ongoing support to their patients with advanced cancer at a tertiary cancer center.

Palliative medicine outpatient clinic 'no-shows': retrospective review.

OBJECTIVES: Patients who do not attend outpatient palliative care clinic appointments ('no-shows') may have unmet needs and can impact wait times. We aimed to describe the characteristics and outcomes associated with no-shows. METHODS: We retrospectively reviewed new no-show referrals to the Princess Margaret Cancer Centre Oncology Palliative Care Clinic (OPCC) in Toronto, Canada, between January 2017 and December 2018, compared with a random selection of patients who attended their first appointment, in a 1:2 ratio. We collected patient information, symptoms, performance status (Eastern Cooperative Oncology Group (ECOG) and outcomes. Univariable and multivariable logistic regression analyses were used to identify significant factors. RESULTS: Compared with those who attended (n=214), no-shows (n=103), on multivariable analysis, were at higher odds than those who attended of being younger (OR 0.98, 95% CI 0.96 to 1.00, p=0.019), living outside Toronto (OR 2.67, 95% CI 1.54 to 4.62, p<0.001) and having ECOG ≥2 (OR 2.98, 95% CI 1.41 to 6.29, p=0.004). No-shows had a shorter median survival compared with those who attended their first appointment (2.3 vs 8.7 months, p<0.001). CONCLUSION: Compared with patients who attended, no-shows lived further from the OPCC, were younger, and had a poorer ECOG. Strategies such as virtual visits should be explored to reduce no-shows and enable attendance at OPCCs.

Rheumatic immune-related adverse events associated with cancer immunotherapy: A nationwide multi-center cohort.

OBJECTIVE: Although immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, their use is associated with immune toxicities referred to as immune-related adverse events (irAE). Here we describe the clinical presentation and management of rheumatic immune-related adverse events (Rh-irAE) in a national multi-center cohort. METHODS: All patients presenting with Rh-irAE at 9 academic sites across Canada between January 2013 and January 2019 were identified and included in this retrospective cohort study. Standardized data were extracted by chart review. RESULTS: 117 patients who developed 136 Rh-irAE were identified. The most frequent Rh-irAE was symmetric polyarthritis (n = 45). Other Rh-irAE included non-inflammatory musculoskeletal symptoms (n = 18), polymyalgia rheumatica (n = 17) and myositis (n = 9). Prednisone was the most commonly used treatment (n = 76) with a mean maximum dose of 60 ± 74 mg/d and duration of treatment of 8.4 ± 11 months. Forty-two patients required conventional synthetic disease-modifying anti-rheumatic drugs (DMARD) and two required biologic DMARD to control the Rh-irAE. ICI was discontinued due to the Rh-irAE in 22 patients. There were no deaths related to Rh-irAE. Treatment of the Rh-irAE did not appear to negatively impact the tumor response to immunotherapy with 23 patients experiencing tumor progression prior to treatment of the Rh-irAE and 13 following treatment. CONCLUSION: In this largest multi-center cohort of Rh-irAE described to date, symmetric polyarthritis was the most common Rh-irAE. There was considerable heterogeneity of treatment, although this did not appear to negatively impact the anti-tumor response. This study can inform the development of evidence-based recommendations to optimize Rh-irAE and cancer outcomes in patients treated with ICI.

Team-based outpatient early palliative care: a complex cancer intervention.

BACKGROUND: Although the effectiveness of early palliative care for patients with advanced cancer has been demonstrated in several trials, there has been no detailed published description of an early palliative care intervention. METHOD: In this paper, we delineate the iterative conception and systematic evaluation of a complex intervention called team-based outpatient early palliative care (TO-EPC), and describe the components of the intervention. The intervention was developed based on palliative care theory, review of previous palliative care interventions and practice guidelines. We conducted feasibility testing and piloting of TO-EPC in a phase 2 trial, followed by evaluation in a large cluster randomised trial and qualitative research with patients and caregivers. The qualitative research informed the iterative refinement of the intervention. RESULTS: Four principles and four domains of care constitute a conceptual framework for TO-EPC. The main domains of care are: coping and support, symptom control, decision-making and future planning. The main principles are that care is flexible, attentive, patient-led and family-centred. The most prominent domain for the initial consultation is coping and support; follow-up visits focus on symptom control, decision-making to maximise quality of life and future planning according to patient readiness. Key tasks are described in relation to each domain. CONCLUSION: The description of our intervention may assist palliative care teams seeking to implement it, researchers wishing to replicate or build on it and oncologists hoping to adapt it for their patients.

Variability in physician care practices for glucose treatment in stroke patients.

BACKGROUND: Hyperglycemia is noted in up to 60% of stroke patients. Practice guidelines recommend glucose monitoring following stroke but provide few management recommendations. We examined physician care practices for glucose management in stroke patients. METHODS: Emergency physicians, family physicians, general internists, intensive care specialists and neurologists in Ontario comprised the study population. A mailed, self-administered survey inquired about glucose management practices. Proportions of responses for survey questions were determined. Chi-square analysis was used for comparing physician groups. RESULTS: Surveys were mailed to 2,280 physicians; 26.8% returned surveys. There were 278 respondents who reported providing stroke patient care. For physicians treating glucose in stroke patients, 16.6% targeted glucose 4.0-6.0 mmol/l, 52% targeted 6.1-8.0 mmol/l, 13.6% targeted 8.1-12.0 mmol/l, 0.8% targeted 12.1-15.0 mmol/l, and 7.5% were unsure. Comparing specialties, 32% of intensivists, 17.5% of neurologists, 13% of general internists, 14% of emergency physicians, and 0% of family physicians reported targeting 4.0-6.0 mmol/l (p=0.026). Overall, 44% reported aiming for target glucose within 12 hours and 77% within 24 hours from hospital presentation. Intensive care specialists treated glucose most aggressively, including 20% treating, with insulin infusion, patients with no diabetes and initial glucose 6.0-8.0 mmol/l. Emergency physicians were most conservative when treating glucose in stroke patients. CONCLUSION: There is variability in the aggressiveness of glucose management in stroke patients by different physician specialty groups, reflecting the lack of evidence available to guide hyperglycemia management in this setting. These results highlight an important gap in knowledge and recommendations for stroke patient care that must be addressed to ensure optimal patient outcomes.

The association between rural residence and stroke care and outcomes.

BACKGROUND: Little is known about stroke care and outcomes in those residing in rural compared to urban areas. METHODS: We conducted a cohort study on a population-based sample of patients with stroke or transient ischemic attack seen at 153 acute care hospitals in the province of Ontario, Canada, between April 1, 2008 and March 31, 2011. Based on their primary residence, patients were categorized as residing in a rural (population<10,000), medium urban (population 10,000-99,999) or large urban (population≥100,000) area. In the study sample of 15,713, we compared processes of stroke care (use of thrombolysis, stroke unit care, investigations, consultations and treatments) and outcomes (30-day mortality, disability at discharge) in those from rural and urban areas, with multivariable models constructed to evaluate the association between rural residence and outcomes after adjustment for potential confounders. RESULTS: Patients from rural areas were less likely than those from urban areas to receive stroke unit care, brain imaging within 24 h, carotid imaging, and consultations from neurologists, physiotherapists, occupational therapists and speech language pathologists, and were less likely to be transferred to inpatient rehabilitation facilities. Use of antithrombotic agents and lipid lowering therapy was similar in rural and urban residents, as was disability at discharge. There was a trend toward higher 30-day mortality in rural compared to urban residents (adjusted hazard ratio 1.14; 95% confidence interval 0.99-1.32). CONCLUSION: Rural residence is associated with lower use of key stroke care interventions after stroke. Future work should focus on developing interventions to address gaps in stroke care in rural areas.

Care and Outcomes of Patients With In-Hospital Stroke.

IMPORTANCE: A sizeable minority of strokes occur in hospitalized patients. However, little is known about the presentation, care, and outcomes of stroke in this subgroup of patients. OBJECTIVE: To examine stroke care delivery and outcomes for patients with in-hospital vs community-onset stroke. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of all patients older than 18 years with acute stroke seen in the emergency department or admitted to the hospital at participating centers (all regional stroke centers in Ontario, Canada) between July 1, 2003, and March 31, 2012, including those with stroke onset during hospitalization for another cause. MAIN OUTCOMES AND MEASURES: We compared processes of stroke care delivery, including time to neuroimaging and rates of thrombolysis, as well as outcomes, including death and disability, in those with in-hospital vs community-onset stroke. We used multiple logistic regression models to adjust for age, sex, comorbid conditions, and stroke type and severity. RESULTS: The study sample included 973 patients with in-hospital stroke and 28 837 with community-onset stroke. Patients with in-hospital stroke compared with those with community-onset stroke had significantly longer waiting times from symptom recognition to neuroimaging (median, 4.5 vs 1.2 hours; P < .001; for <2 hours, 32% vs 63%; adjusted odds ratio [AOR] = 0.21; 95% CI, 0.18-0.24), lower use of thrombolysis (12% vs 19% of those with ischemic stroke; AOR = 0.54; 95% CI, 0.43-0.67; P < .001), and longer time from stroke recognition to administration of thrombolysis (median, 2.0 vs 1.2 hours; P < .001). After adjustment for age, stroke severity, and other factors, mortality rates at 30 days and 1 year after stroke were similar in those with in-hospital stroke and community-onset stroke; however, those with in-hospital stroke had a longer median length of stay following stroke onset (17 vs 8 days; P < .001), were more likely to be dead or disabled at discharge (77% vs 65% with modified Rankin Scale score of 3-6; AOR = 1.64; 95% CI, 1.38-1.96; P < .001), and were less likely to be discharged home from the hospital (35% vs 44%; AOR = 0.76; 95% CI, 0.64-0.90; P < .001). CONCLUSIONS AND RELEVANCE: Compared with those with community-onset stroke, patients with in-hospital stroke had delays in investigations and treatment, suggesting a need for a standardized approach to the recognition and management of in-hospital stroke, with the aim of ensuring access to rapid acute stroke care.

HIV/AIDS research conducted in the developing world and sponsored by the developed world: reporting of research ethics committee review in two countries.

We explored how often journal articles reporting HIV research sponsored by a developed country, but conducted in a developing country, mention research ethics committee (REC) approval from both countries, and what factors are involved. Of all such 2007 articles on Medline conducted in one of four developing countries (N = 154), only 52% mentioned such dual approval. Mention of dual vs. single approval was more likely among articles with ≥ 50% sponsor country authors, and the United States as the sponsor country. Also, dual approval was more likely among articles that mentioned informed consent and funding, had ≥ 50% sponsor country authors, were biomedical (vs. psychosocial), and appeared in journals adopting International Committee Medical Journal Editors (ICMJE) guidelines. Dual approval was thus obtained in only half of the articles and was associated with ethical and logistic issues, indicating the need for clearer and more universally accepted guidelines.