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 Partnership's 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.

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.

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.

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.

Devices to Reduce the Volume of Blood Taken for Laboratory Testing in ICU Patients: A Systematic Review.

BACKGROUND: Intensive care unit (ICU) patients are at high risk of anemia, which is associated with adverse clinical outcomes and death. Blood sampling for diagnostic testing is a potentially modifiable contributor to anemia. METHODS: We conducted a systematic review by searching MEDLINE and EMBASE from inception to October 5, 2017, for studies reporting the volume of blood taken for laboratory testing using blood sampling conservation devices compared to standard care or another intervention in adult ICU patients. RESULTS: We identified 8 eligible studies (n = 1204 patients) that used 2 types of devices: arterial access devices (n = 5) and reduced-volume blood collection tubes (n = 3). All studies reported a reduction in the volume of blood taken for laboratory testing with devices compared to standard practice (range 19%-80%). The studies were judged to have serious risk of bias, and due to heterogeneity, pooling for meta-analysis was not considered appropriate. CONCLUSIONS: Devices used to reduce the volume of blood taken for laboratory testing in ICU patients appear to be effective, although study heterogeneity limited our ability to calculate pooled estimates of efficacy for each device. Further assessment of clinical outcomes may establish clinical benefit with minimal negative consequences for hospitals and laboratories to facilitate the use of small-volume tubes.

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.

Strategies for eliciting and synthesizing evidence for guidelines in rare diseases.

BACKGROUND: Rare diseases are a global public health priority. Though each disease is rare, when taken together the thousands of known rare diseases cause significant morbidity and mortality, impact quality of life, and confer a social and economic burden on families and communities. These conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment. Clinical practice guidelines are necessary to support clinical and policy decisions. However, creating guidelines for rare diseases presents specific challenges, including a paucity of high certainty evidence to inform panel recommendations. METHODS: This paper draws from the authors' experience in the development of clinical practice guidelines for three rare diseases: hemophilia, sickle cell disease, and catastrophic antiphospholipid syndrome. RESULTS: We have summarized a number of strategies for eliciting and synthesizing evidence that are compatible with the rigorous, internationally accepted standards for guideline development set out by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. These strategies include: use of pre-existing and ad hoc qualitative research, use of systematic observation forms, use of registry data, and thoughtful use of indirect evidence. Their use in three real guideline development efforts, as well as their theoretical underpinnings, are discussed. Avenues for future research to improve clinical practice guideline creation for rare diseases - and any disease affected by a relative lack of evidence - are also identified. CONCLUSIONS: Rigorous clinical practice guidelines are needed to improve the care of the millions of people worldwide who suffer from rare diseases. Innovative evidence elicitation and synthesis methods will benefit not only the rare disease community, but also individuals with common diseases who have rare presentations, suffer rare complications, or require nascent therapies. Further refinement and improved uptake of these innovative methods should lead to higher quality clinical practice guidelines in rare diseases.

Impact of organizational interventions on reducing inappropriate intravenous immunoglobulin (IVIG) usage: A systematic review and meta-analysis.

BACKGROUND: With increasing global use of intravenous immunoglobulin (IVIG), there is interest in its appropriate usage. Efforts to regulate IVIG usage have primarily taken the form of organizational interventions implemented in hospitals to monitor and improve physician prescribing. Similar interventions have proven effective in reducing the inappropriate and total hospital usage of other blood products, but their efficacy on IVIG use is less understood. Thus, we performed a systematic review of studies reporting the change in inappropriate IVIG use following such interventions in hospitals or regions. METHODS: A systematic search was carried out using MEDLINE and EMBASE (1966-June 2016) for English language studies if they 1) were primary research, 2) described an organizational intervention to target plasma, IVIG, or albumin, and 3) reported appropriateness of usage and total usage preand post-intervention. Review Manager v5.0 was utilized to perform a random-effects meta-analysis on eligible IVIG studies, where the risk ratio (RR) of inappropriate IVIG transfusion comparing pre- and postintervention periods was calculated with 95% confidence intervals (CI). RESULTS: Our search retrieved three retrospective cohort studies, where metaanalysis encompassing 2100 episodes of IVIG transfusion demonstrated no decrease in inappropriate IVIG use (RR 1.55, 95% CI 0.78-3.07). Heterogeneity between studies was considerable (I2 = 89%). CONCLUSION: Organizational interventions were ineffective at changing inappropriate IVIG use, but more high-quality studies describing the effects of these interventions are required before any conclusions can be drawn. Futureresearch efforts should also be directed at evolving evidence-based IVIGguidelines to improve patient safety and burdens on healthcare systems.

Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review.

BACKGROUND: Patients with essential thrombocythemia (ET) are at high risk for both thrombosis and hemorrhage. PURPOSE: To evaluate the risks and benefits of antithrombotic therapy in adults with ET. DATA SOURCES: Multiple databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, through 4 March 2017. STUDY SELECTION: Randomized and observational studies of antiplatelet or anticoagulant therapy, published in any language and reporting thrombotic or hemorrhagic events. DATA EXTRACTION: Two reviewers independently extracted data, assessed risk of bias, and graded certainty of evidence. DATA SYNTHESIS: No relevant randomized trials were identified. Twenty-four observational studies (18 comparative and 6 single-group) involving 6153 patients followed for 31 711 patient-years were reviewed; most were deemed to have high risk of bias. Most patients receiving antiplatelet therapy (3613 of 4527 [80%]) received low-dose aspirin (50 to 150 mg/d); 914 (20%) received high-dose aspirin (300 to 600 mg/d), dipyridamole, or other agents. Overall, findings were inconsistent and imprecise. The reported incidence rates of thrombosis, any bleeding, and major bleeding without antiplatelet therapy ranged from 5 to 110 (median, 20), from 3 to 39 (median, 8), and from 2 to 53 (median, 6) cases per 1000 patient-years, respectively. The reported relative risks for thrombosis, any bleeding, and major bleeding with antiplatelet therapy compared with none ranged from 0.26 to 3.48 (median, 0.74), from 0.48 to 11.04 (median, 1.95), and from 0.48 to 5.17 (median, 1.30), respectively. Certainty of evidence was rated low or very low for all outcomes. LIMITATION: No randomized trials, no extractable data on anticoagulants, lack of uniform bleeding definitions, and systematic reporting of outcomes. CONCLUSION: Available evidence about the risk-benefit ratio of antiplatelet therapy in adults with ET is highly uncertain. PRIMARY FUNDING SOURCE: Regional Medical Associates. (PROSPERO: CRD42015027051).

The Canadian Choosing Wisely campaign: the Canadian Hematology Society's top five tests and treatments.

Choosing Wisely Canada (CWC), a medical stewardship campaign, encourages dialogue between physicians and patients to promote high-quality decision-making. Medical societies develop lists of tests, treatments, and procedures that are unnecessary, reduce value, and may cause harm. The Canadian Hematology Society (CHS) elicited suggestions for CWC recommendations from its members and received 35 unique suggestions. A working group rated these based on their potential for harm, benefit, frequency of use and value. Twelve highly ranked items were subjected to systematic evidence review. The final items were included in the list if they were of sufficient evidence base and met pre-defined core principles. The CHS-CWC recommendations are: to avoid IVIG treatment for asymptomatic immune thrombocytopenia, not bridge warfarin in low-risk patients going for procedures, not perform thrombophilia testing in the workup of early pregnancy loss, avoid fine-needle aspiration in lymphoma diagnosis, and not transfuse red blood cells for an arbitrary hemoglobin threshold. Through implementation of these recommendations, physicians will reduce potential harm to patients and increase the value of health care.

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.

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.

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.