Healthcare provider's perceptions of bleeding in patients with acute leukaemia undergoing induction chemotherapy: A qualitative study.

BACKGROUND: Bleeding is a primary outcome for many transfusion-related trials in acute leukaemia (AL) patients, typically graded using the World Health Organisation (WHO) bleeding scale (clinically significant bleed (CSB) is ≥grade 2). This composite outcome fails to differentiate minor bleeds that may not be significant, poorly represents the total burden of bleeding and lacks input from healthcare providers (HCPs) and patients. As part of a multi-step project to create a better bleeding tool for trials, our objective was to identify HCPs' perspectives on the components of CSB in AL patients. STUDY DESIGN AND METHODS: Using qualitative description, we interviewed 19 physicians and nurses who care for AL patients undergoing induction chemotherapy. Participants were recruited from professional organisations, networks and social media. An inductive approach to conventional content analysis was used. RESULTS: HCPs identified features of CSB as the anatomical site of bleeding, amount of bleeding, need for intervention and changes in vital signs. Using these characteristics, bleeding events were categorised into three groups: clinically significant, could evolve into a CSB and not clinically significant. HCPs considered the patient's condition, bleeding history and clinical intuitions when deciding whether a bleed could escalate into serious bleeding. DISCUSSION: Using data from HCPs, we categorised bleeds as clinically significant, could evolve into a CSB, and not significant. A study of patients' perspectives on the importance of different kinds of bleeding is the next step to creating a bleeding definition that is informed by evidence, clinicians and patients.

Implementation and evaluation of a national quality improvement initiative in cancer surgery.

BACKGROUND: In 2017, the Canadian Partnership Against Cancer, a Canadian federally sponsored organisation, initiated a national multijurisdictional quality improvement (QI) initiative to maximise the use of synoptic data to drive cancer system improvements, known as the Evidence for Surgical Synoptic Quality Improvement Programme. The goal of our study was to evaluate the outcomes, determinants and learning of this nationally led initiative across six jurisdictions in Canada, integrating a mix of cancer surgery disease sites and clinicians. METHODS: A mixed-methods evaluation (surveys, semistructured interviews and focus groups) of this initiative was focused on the ability of each jurisdiction to use synoptic reporting data to successfully implement and sustain QI projects to beyond the completion of the initiative and the lessons learnt in the process. Resources provided to the jurisdictions included operational funding, training in QI methodology, national forums, expert coaches, and ad hoc monitoring and support. The programme emphasised foundational concepts of the QI process including data literacy, audit and feedback reports, communities of practice (CoP) and positive deviance methodology. RESULTS: 101 CoP meetings were held and 337 clinicians received feedback reports. There were 23 projects, and 22 of 23 (95%) showed improvements with 15 of 23 (65%) achieving the proposed targets. Enablers of effective data utilisation/feedback reports for QI included the need for clinicians to trust the data, have comparative data for feedback, and the engagement of both data scientists and clinicians in designing feedback reports. Enablers of sustainability of QI within each jurisdiction included QI training for clinicians, the ability to continue CoP meetings, executive and broad stakeholder engagement, and the ability to use pre-existing organisational infrastructures and processes. Barriers to continue QI work included lack of funding for core team members, lack of automated data collection processes and lack of clinician incentives (financial and other). CONCLUSION: Success and sustainability in data-driven QI in cancer surgery require skills in QI methodology, data literacy and feedback, dedicated supportive personnel and an environment that promotes the process of collective learning and shared accountability. Building these capabilities in jurisdictional teams, tailoring interventions to facility contexts and strong leadership engagement will create the capacity for continued success in QI for cancer surgery.

How a Canadian federal organization integrated synoptic reporting and quality improvement tools to drive a national learning health system in cancer surgery.

Accurate and complete surgical and pathology reports are the cornerstone of treatment decisions and cancer care excellence. Synoptic reporting is a process for reporting specific data elements in a specific format in surgical and pathology reports. Since 2007, the Canadian Partnership Against Cancer has led the implementation of synoptic reporting mechanisms across multiple cancer disease sites and jurisdictions across Canada. While the implementation of synoptic reporting has been successful, its use to drive improvements in the quality of cancer care delivery has been lacking. Here we describe the 4-year, national multi-jurisdictional quality improvement initiative to catalyse the use synoptic data to drive cancer system improvements. Resources provided to the jurisdictions included operational funding, training in quality improvement methodology, national forums, expert coaches, and ad hoc monitoring and support. The program emphasized foundational concepts including data literacy, audit and feedback reports, communities of practice, and positive deviance methodology.

Diagnosis and Management of Cardiovascular Effects of Bruton's Tyrosine Kinase Inhibitors.

PURPOSE OF REVIEW: Bruton's tyrosine kinase inhibitors (BTKis) have changed the treatment and prognosis of several B-cell malignancies. However, since the approval of the first BTKi, ibrutinib, reports of cardiovascular adverse events especially atrial fibrillation have arisen. In this review, we discuss the cardiovascular side effects of BTKis and the management of these toxicities in clinical practice. RECENT FINDINGS: BTKIs increase the risks of atrial fibrillation, bleeding, hypertension, heart failure, and potentially ventricular arrhythmia. Newer second and third-generation BTKis appear to have a lower risk of cardiovascular adverse events; however, long-term follow-up data are not available for these new BTKis. BTKis are an effective treatment for some B-cell malignancies; however, they can cause cardiovascular side effects. The best preventive strategies to minimize cardiovascular complications remain undefined. Currently, a practical approach for managing patients receiving BTKis includes the management of cardiovascular risk factors and side effects of BTKis to prevent interruption of cancer treatment.

Optimizing Cancer Survivorship Care: Examination of Factors Associated with Transition to Primary Care.

Healthcare systems in Canada and elsewhere have identified the need to develop methods to effectively and safely transition appropriate cancer survivors to primary care. It is generally accepted that survivors with a low risk of adverse events, including recurrence and toxicity, should be more systematically identified and offered transition. There remains a lack of clarity about what constitutes an appropriate profile that would assist greater application in practice. To address this gap, we examined the clinical profiles of patients that were transitioned from a large regional cancer centre to the community. The factors examined included disease site, clinical stage, time since diagnosis/first consult, cancer treatments, and Edmonton Symptom Assessment System (ESAS) scores. In total, 2604 patients were identified as transitioned between 2013 and 2020. These patients tended to have common cancers (e.g., breast, endometrium, colorectal) that were generally of lower stage. Half of the patients had received chemotherapy and/or radiation treatment. Nearly one-third of survivors were transitioned within a year of first consult and a third after five years. Most patients reported minimal symptoms based on ESAS scores prior to being transitioned. This study represents one of the first to analyze the types of cancer patients that are being selected for transition to primary care.

A Survey of Patient Experience in CML: American and Canadian Perspectives.

Purpose: With treatment, chronic myeloid leukemia (CML) has a favorable prognosis, however, individuals with CML experience impairment to their quality of life (QoL). The aim of this study was to examine the perspectives and experiences of individuals with CML and to understand their challenges communicating with their CML physician. Patients and Methods: An online survey in adults with CML (n=100) in the US and Canada assessed QoL, patient-provider relationships, treatment satisfaction, and understanding of CML and treatment goals via the MD Anderson Symptom Inventory, the Cancer Therapy Satisfaction Questionnaire and de novo survey questions. Participants were recruited via an external patient recruiter and CML Patient Groups. Results: Many participants reported hardships due to CML and its treatment. The main impacts were on the ability to work (21%), engage in personal activities (e.g., hobbies, 28%), and to enjoy sexual relations (median=2.00, IQR=8.50). A substantial proportion (21-39%) wished to discuss additional topics with their providers (e.g., management of CML and/or its impacts). While participants reported satisfaction with therapy overall (median=85.71, IQR=17.86), they indicated low to moderate treatment satisfaction with specific components, including concerns regarding side effects (median=43.75, IQR=43.75). Participants generally had a good understanding of CML (97%) and its treatment goals (92%). Conclusion: These findings advance our understanding of issues that need improvement to support QoL for individuals living with CML. Future work is needed to improve patient-provider relationships, address treatment-related side effects, and provide clinical information that is easier for patients to understand.

The Cost Effectiveness of Axicabtagene Ciloleucel Versus Best Supportive Care in the Treatment of Adult Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL) After Two or More Lines of Systemic Therapy in Canada.

BACKGROUND AND OBJECTIVE: Axicabtagene ciloleucel (axi-cel) received marketing authorisation in Canada for the treatment of relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, and the clinical and economic value of axi-cel to patients and the healthcare system should be examined. The objective of this analysis is to determine, from societal and public healthcare payer perspectives, the cost effectiveness of axi-cel versus best supportive care for patients with relapsed or refractory large B-cell lymphoma in Canada. METHODS: A pharmacoeconomic model was developed and populated with clinical data derived from the ZUMA-1 and SCHOLAR-1 studies using a propensity score-matched comparison. A partitioned survival mixture-cure modelling approach was taken to characterise the potential curative effect of axi-cel therapy in large B-cell lymphoma. Healthcare resource utilisation and adverse event data were based on results from ZUMA-1, and utility values were derived from ZUMA-1 data supplemented with published literature. Costs (in 2021 Canadian dollars) were taken from publicly available Canadian cost databases and published literature. Benefits and costs were discounted at 1.5% per year, and sensitivity analyses were conducted to assess the robustness of the results. RESULTS: In the base case, axi-cel generated an incremental 6.2 life-years compared to best supportive care, corresponding to 4.6 additional quality-adjusted life-years, and was associated with $606,010 in additional costs. The incremental cost-utility ratio was $132,747 per quality-adjusted life-year gained compared with best supportive care from a societal perspective ($106,392 per quality-adjusted life-year gained from a public healthcare payer perspective). Key drivers of the analysis included progression-free survival and overall survival values for axi-cel. CONCLUSIONS: The results of this analysis suggest that axi-cel may be considered a cost-effective allocation of resources compared with best supportive care for the treatment of adult patients with relapsed or refractory large B-cell lymphoma in Canada.

Identification and Adjudication of Adverse Events Following Rectal Cancer Surgery: Observational Case Series in a Region of Ontario, Canada.

BACKGROUND: For patients undergoing rectal cancer surgery, we evaluated whether suboptimal preoperative surgeon evaluation of resection margins is a latent condition factor-a factor that is common, unrecognized, and may increase the risk of certain adverse events, including local tumour recurrence, positive surgical margin, nontherapeutic surgery, and in-hospital mortality. METHODS: In this observational case series of patients who underwent rectal cancer surgery during 2016 in Local Health Integrated Network 4 region of Ontario (population 1.4 million), chart review and a trigger tool were used to identify patients who experienced the adverse events. An expert panel adjudicated whether each event was preventable or nonpreventable and identified potential contributing factors to adverse events. RESULTS: Among 173 patients, 25 (14.5%) had an adverse event and 13 cases (7.5%) were adjudicated as preventable. Rate of surgeon awareness of preoperative margin status was low at 50% and similar among cases with and without an adverse event (p = 0.29). Suboptimal surgeon preoperative evaluation of surgical margins was adjudicated a contributing factor in all 11 preventable local recurrence, positive margin, and nontherapeutic surgery cases. Failure to rescue was judged a contributing factor in the two cases with preventable in-hospital mortality. CONCLUSIONS: Suboptimal surgeon preoperative evaluation of surgical margins in rectal cancer is likely a latent condition factor. Optimizing margin evaluation may be an efficient quality improvement target.

Bruton's tyrosine kinase Inhibitors and Cardiotoxicity: More Than Just Atrial Fibrillation.

PURPOSE OF REVIEW: The purpose of this review is to summarize the epidemiology, mechanisms, and management of cardiovascular complications of Bruton's Tyrosine Kinase inhibitors (BTKIs). RECENT FINDINGS: Ibrutinib increases the risk of atrial fibrillation, bleeding, and hypertension compared with non-BTKI therapies. The evidence to support an association between ibrutinib and other cardiovascular complications including ventricular tachyarrhythmias or cardiomyopathy is limited. Ibrutinib metabolism can be inhibited by some medications used to treat cardiovascular complications. The cardiovascular effects of more selective BTKIs, such as acalabrutinib, remain to be determined. Future research should address the mechanisms underlying the cardiovascular complications of BTKIs and how best to manage them. The risks and benefits of more selective BTKIs as compared with ibrutinib require further evaluation.

A pneumococcal pneumonia and influenza vaccination quality improvement program for women receiving chemotherapy for gynecologic cancers at a major tertiary cancer Centre.

OBJECTIVE: International guidelines recommend pneumococcal pneumonia and influenza vaccination for all patients with solid organ malignancies prior to initiating chemotherapy. Baseline vaccination rates (March 2019) for pneumococcal pneumonia and influenza at our tertiary cancer centre were 8% and 40%, respectively. The aim of this study was to increase the number of gynecologic chemotherapy patients receiving pneumococcal and influenza vaccinations to 80% by March 2020. METHODS: We performed an interrupted time series study using structured quality improvement methodology. Three interventions were introduced to address vaccination barriers: an in-house vaccination program, a staff education campaign, and a patient care bundle (pre-printed prescription, information brochure, vaccine record booklet). Process and outcome data were collected by patient survey and pharmacy audit and analyzed on statistical process control charts. RESULTS: We identified 195 eligible patients. Pneumococcal and influenza vaccination rates rose significantly from 5% to a monthly mean of 61% and from 36% to a monthly mean of 67%, respectively. The 80% target was reached for both vaccines during one or more months of study. The in-house vaccination and staff education programs were major contributors to the improvement, whereas the information brochure and record booklet were minor contributors. CONCLUSIONS: Three interventions to promote pneumococcal and influenza vaccination among chemotherapy patients resulted in significantly improved vaccination rates. Lessons learned about promoting vaccine uptake may be generalizable to different populations and vaccine types. In response to the global COVID-19 pandemic, initiatives to expand the program to all chemotherapy patients at our centre are underway.

Tyrosine kinase inhibitors in chronic myeloid leukaemia and emergent cardiovascular disease.

OBJECTIVES: (1) Describe how the risk of major adverse cardiovascular events (MACE) in individuals with chronic myeloid leukaemia (CML) has evolved; (2) evaluate the risk of MACE associated with the prescription of different CML tyrosine kinase inhibitors (TKI). METHODS: A population-based retrospective study including all patients (n=4238) diagnosed with CML in Ontario, Canada between 1986 and 2017 and and age-matched and sex-matched individuals who received healthcare but who did not have CML (controls: n=42 380). The cohort was divided into those entering before 2001 vs from 2001 onwards (when TKIs were introduced). We developed competing risks models to compare time-to-event in CML cases versus controls. We adjusted for baseline comorbidities and present subdistribution HRs and 95% CIs. The relationship between TKI use and MACE was assessed by logistic regression. RESULTS: Before 2001 and from 2001 on, patients with CML had a higher crude incidence of MACE than patients without CML (19.8 vs 15.3 and 20.3 vs 12.6 per 1000 person-years, respectively). After adjustment for cardiovascular risk factors, patients with CML had a lower subdistribution hazard for MACE (0.59, 95% CI 0.46 to 0.76) before 2001; but from 2001, the adjusted subdistribution HR for MACE (1.27, 95% CI 0.96 to 1.43) was similar to age-matched and sex-matched patients. The incidence (9.3 vs 13.8 per 1000 person-years) and subdistribution hazard for cardiovascular death (0.43, 95% CI 0.36 to 0.52) were lower in patients with CML than controls before 2001. From 2001 on, the incidence (6.3 vs 5.4 per 1000 person-years) and subdistribution hazard for cardiovascular death (0.99, 95% CI 0.84 to 1.18) were similar to age-matched and sex-matched patients without CML with a higher risk of cerebrovascular events (8.6 vs 5.6 per 1000 person-years; 1.35, 95% CI 1.00 to 1.83) and peripheral arterial events (6.9 vs 3.0 per 1000 person-years; 1.66 95% CI, 1.15 to 2.39) in patients with CML than patients without CML. Compared with imatinib, there was no difference in the risk of MACE among those prescribed dasatinib (OR 0.67, 95% CI 0.41 to 1.10) or nilotinib (OR 1.22, 95% CI 0.70 to 1.97). CONCLUSIONS: In a contemporary CML population, the risk of MACE and cardiovascular death is at least as high as among age-matched and sex-matched patients without CML and may be higher for cerebrovascular and peripheral arterial events. No difference in the risk of MACE between imatinib, dasatinib and nilotinib was observed.

Patterns of Ruxolitinib Therapy Failure and Its Management in Myelofibrosis: Perspectives of the Canadian Myeloproliferative Neoplasm Group.

Ruxolitinib improves splenomegaly and other disease-related symptoms in patients with myelofibrosis, but over time, many patients lose this benefit. It is difficult to determine whether this is due to resistance or intolerance to the drug; thus, we have used the more inclusive term of ruxolitinib failure. The survival of patients with myelofibrosis after ruxolitinib failure is poor but varies significantly by the pattern of the failure, underlining the need for a clinically appropriate classification. In this review, we propose diagnostic guidance for early recognition of the pattern of ruxolitinib failure and we recommend treatment options. The most frequent patterns of ruxolitinib failure are loss or failure to obtain a significant reduction in splenomegaly or symptom response, and the development or persistence of clinically significant cytopenias. Ruxolitinib dose modification and other ancillary therapies are sometimes helpful, and splenectomy is a palliative option in selected cases. Stem-cell transplantation is the only curative option for these patterns of failure, but its restricted applicability due to toxicity highlights the importance of ongoing clinical trials in this area. Recent approval of fedratinib by the US Food and Drug Administration provides an alternative option for patients with suboptimal or loss of spleen response. The transformation of myelofibrosis to accelerated or blast phase is an infrequent form of failure with an extremely poor prognosis, whereby patients who are ineligible for transplantation have limited treatment options.

Evaluating the endometabolic and bone health effects of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukaemia: a systematic review protocol.

INTRODUCTION: Chronic Myeloid Leukaemia (CML) constitutes 15% of new adult leukaemia cases as well as 2%-3% of leukaemia in children under 15% and 9% of leukaemias in adolescents 15-19 years of age annually. The introduction of Tyrosine Kinase Inhibitors (TKI) therapy has dramatically improved survival in these patients, yet the off-target effects of this treatment may have long-term health impacts on CML survivors. The risk of adverse health outcomes is especially important in children, where TKI exposure may occur during critical windows of growth and puberty, and patients require treatment for prolonged periods of time. The aim of this systematic review protocol is to report on the methods used to conduct a systematic review to investigate the endometabolic and bone health effects of TKI therapy in CML. METHODS AND ANALYSIS: Searches will be conducted in the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception on August 1st, 2019. Searches may be updated while performing the systematic review to ensure new evidence is included if applicable. Grey literature search will include ClinicalTrials.gov and ProQuest Dissertations and Theses A&I. We will perform a meta-analysis if there are at least two studies reporting similar populations, interventions, methods and tracking the same outcome measures. The studies should also have similar age and sex distributions. ETHICS AND DISSEMINATION: As this is a systematic review protocol, it does not include patient data; therefore, Research Ethics Board approval is not indicated. The systematic review will be published in a peer-reviewed journal and presented at international conferences. PROSPERO REGISTRATION NUMBER: CRD42018091175.

Sex-mismatched red blood cell transfusions and mortality: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Selection of a compatible red blood cell (RBC) unit does not include matching for donor sex. This systematic review and meta-analysis aims to summarize the evidence examining the impact of sex-mismatched RBC transfusion on recipient mortality. MATERIALS AND METHODS: Ovid MEDLINE, Ovid EMBASE, CINAHL, PubMed, Web of Science and the Cochrane Database of Systematic Reviews were searched from inception up to 23 November 2018. Randomized controlled trials and observational studies were included in the search. Eligible studies reported on the impact of sex-matched compared to sex-mismatched RBC transfusion on recipient mortality. Two investigators independently extracted data and assessed study quality. A three-level meta-analytic model was applied to emphasize the unknown dependence among the effect sizes. RESULTS: Five retrospective observational studies (n = 86 737) were included; no RCTs were found. Sex-mismatched RBC transfusions were associated with a higher risk of death compared with sex-matched transfusions (pooled hazard ratio [HR]: 1·13; 95% confidence interval [CI]: 1·02-1·24). In the subgroup of cardiovascular surgery (n = 57 712), there was no significant increase in mortality with sex-mismatched transfusions (pooled HR: 1·08; 95% CI: 0·95-1·22). The data were prone to confounding, selection bias and reporting bias. Certainty of the evidence was very low. CONCLUSION: Sex-mismatched RBC transfusions were associated with an increased risk of death in this pooled analysis. However, the certainty of the evidence was very low from observational studies. The need to match donor and recipient sex for transfusions requires further investigation because of the potential widespread impact.

The real-world outcomes of treating Polycythemia Vera: Physician adherence to treatment guidelines.

Therapy in Polycythemia Vera (PV), a myeloproliferative neoplasm, focuses on reducing cardiovascular (CV) risk without increasing bleeding or hematological progression. However, the real-world practice of treating PV in North America is understudied. We performed a retrospective cohort study of newly diagnosed PV (JAK2V617F mutation positive) patients in Hamilton, Canada to fill this knowledge gap. Out of 108 patients included, (n = 45, 41.7%) patients did not receive therapy consistent with contemporary treatment guidelines. Multivariable analysis showed increased white blood cell count at diagnosis (HR, 1.09; 95% CI, 1.04-1.14; p < 0.001), older age (HR, 1.15; 95% CI, 1.07-1.23; p < 0.001) and diabetic history (HR, 3.71; 95% CI, 1.27-10.78; p = 0.012) associated with greater mortality. Not receiving pharmacological treatment according to guidelines was also independently associated with increased mortality (HR, 3.12; 95% CI, 1.13-8.65; p = 0.029).