Association of oxaliplatin-containing adjuvant duration with post-treatment fall-related injury and fracture in patients with stage III colon cancer: a population-based retrospective cohort study.

PURPOSE: Oxaliplatin-containing adjuvant chemotherapy yields a significant survival benefit in stage III colon cancer and is the standard of care. Simultaneously, it causes dose-dependent peripheral neuropathy that may increase the risk of fall-related injury (FRI) such as fracture and laceration. Because these events carry significant morbidity and the global burden of colon cancer is on the rise, we examined the association between treatment with a full versus shortened course of adjuvant chemotherapy and post-treatment FRI and fracture. METHODS: In this overlap propensity score weighted, retrospective cohort study, we included patients aged ≥ 18 years with resected stage III colon cancer diagnosed 2007-2019 and treated with oxaliplatin-containing adjuvant chemotherapy (oxaliplatin plus a fluoropyrimidine; capecitabine [CAPOX] or 5-fluorouracil and leucovorin [FOLFOX]). Propensity score methods facilitate the separation of design from analysis and comparison of baseline characteristics across the weighted groups. Treatment groups were defined as 50% (4 cycles CAPOX/6 cycles FOLFOX) and > 85% (7-8 cycles CAPOX/11-12 cycles FOLFOX) of a maximal course of adjuvant chemotherapy to approximate the treatment durations received in the IDEA collaboration. The main outcomes were time to any FRI and time to fracture. We determined the subdistribution hazard ratios (sHR) estimating the association between FRI/fracture and treatment group, accounting for the competing risk of death. RESULTS: We included 3,461 patients; 473 (13.7%) received 50% and 2,988 (86.3%) received > 85% of a maximal course of adjuvant therapy. For post-treatment FRI, median follow-up was 4.6 years and total follow-up was 17,968 person-years. There were 508 FRI, 301 fractures, and 692 deaths. Treatment with > 85% of a maximal course of therapy conferred a sHR of 0.84 (95% CI 0.62-1.13) for post-treatment FRI and a sHR of 0.72 (95% CI 0.49-1.06) for post-treatment fracture. CONCLUSION: For patients with stage III colon cancer undergoing treatment with oxaliplatin-containing adjuvant chemotherapy, any potential neuropathy associated with longer durations of treatment was not found to result in greater rates of FRI and fracture. Within the limits of this retrospective study, our findings suggest concern about FRI, while mechanistically plausible, ought not to determine treatment duration.

A population-based analysis of the impact of the COVID-19 pandemic on common abdominal and gynecological emergency department visits.

BACKGROUND: Reduced use of the emergency department during the COVID-19 pandemic may result in increased disease acuity when patients do seek health care services. We sought to evaluate emergency department visits for common abdominal and gynecologic conditions before and at the beginning of the pandemic to determine whether changes in emergency department attendance had serious consequences for patients. METHODS: We conducted a population-based analysis using administrative data to evaluate the weekly rate of emergency department visits pre-COVID-19 (Jan. 1-Mar. 10, 2020) and during the beginning of the COVID-19 pandemic (Mar. 11-June 30, 2020), compared with a historical control period (Jan. 1-July 1, 2019). All residents of Ontario, Canada, presenting to the emergency department with appendicitis, cholecystitis, ectopic pregnancy or miscarriage were included. We evaluated weekly incidence rate ratios (IRRs) of emergency department visits, management strategies and clinical outcomes. RESULTS: Across all study periods, 39 691 emergency department visits met inclusion criteria (40.2 % appendicitis, 32.1% miscarriage, 21.3% cholecystitis, 6.4% ectopic pregnancy). Baseline characteristics of patients presenting to the emergency department did not vary across study periods. After an initial reduction in emergency department visits, presentations for cholecystitis and ectopic pregnancy quickly returned to expected levels. However, presentations for appendicitis and miscarriage showed sustained reductions (IRR 0.61-0.80), with 1087 and 984 fewer visits, respectively, after the start of the pandemic, relative to 2019. Management strategies, complications and mortality rates were similar across study periods for all conditions. INTERPRETATION: Although our study showed evidence of emergency department avoidance in Ontario during the first wave of the COVID-19 pandemic, no adverse consequences were evident. Emergency care and outcomes for patients were similar before and during the pandemic.

Hyaluronate carboxymethylcellulose sheets for the prevention of adhesive complications: a model-based cost-utility analysis.

AIM: Clinical trials suggest that hyaluronate carboxymethylcellulose (HA/CMC) prevents adhesion-related complications after intra-abdominal surgery, but at a high upfront cost. This study evaluated the cost-effectiveness of HA/CMC for patients undergoing curative-intent open colorectal cancer surgery. METHODS: Using a Markov Monte Carlo microsimulation model, we conducted a cost-utility analysis comparing the cost-effectiveness of HA/CMC at curative-intent open colorectal cancer surgery versus standard management. We considered a scenario where HA/CMC was used at the index operation only, as well as where it was used at the index operation and any subsequent operations. The perspective was that of the third-party payer. Costs and utilities were discounted 1.5% annually, with a 1-month cycle length and 5-year time horizon. Model input data were obtained from a literature review. Outcomes included cost, quality-adjusted life-years (QALYs), small bowel obstructions (SBOs) and operations for SBO. RESULTS: Using HA/CMC at the index operation results in an incremental cost increase of CA$316 and provides 0.001 additional QALYs, for an incremental cost-effectiveness ratio of CA$310,000 per QALY compared to standard management. In our simulated cohort of 10,000 patients, HA/CMC prevented 460 SBOs and 293 surgeries for SBO. Probabilistic sensitivity analysis found that HA/CMC was cost-effective in 18.5% of iterations, at a cost-effectiveness threshold of CA$50,000 per QALY. Results of the scenario analysis where HA/CMC was used at the index operation and any subsequent operations were similar. CONCLUSIONS: Hyaluronate carboxymethylcellulose prevents adhesive bowel obstruction after open colorectal cancer surgery but is unlikely to be cost-effective given minimal long-term impact on healthcare costs and QALYs.

Building Environmentally Sustainable Health Systems in Canada: The Time Is Now for Emergent and Strategic Leadership.

Canada's healthcare sector produces the third highest healthcare-related emissions per capita globally. However, Canada has no national strategy toward environmentally sustainable healthcare. Transforming Canada's health systems to be environmentally sustainable requires leadership from many stakeholders and collaboration between trainees and health leaders. This article provides an overview of student and trainee leadership among health-related fields in response to the climate crisis and highlights the formation of a trainee-led organization focused on building capacity among emerging leaders in healthcare. We share key lessons learned by this group that are essential for all leaders seeking to leverage interdisciplinary action toward sustainable health systems in Canada.

Metrics used in quality improvement publications addressing environmental sustainability in healthcare: A scoping review protocol.

Quality improvement approaches are increasingly being used to address the problem of healthcare's climate and ecological impact. While sustainability is increasingly recognized as a domain of quality, consensus is lacking on the most appropriate measures and metrics for those looking to reduce ecological impacts through quality improvement initiatives. We propose a scoping review to summarize approaches for selecting and quantifying ecological impacts in the published quality improvement literature. We will search multiple electronic databases (MEDLINE, EMBASE, CINAHL, and Scopus) from 2000 onwards, to identify published quality improvement initiatives in the human healthcare setting intended to address ecological impact with at least one quantitative measure of ecological impact, such as kilograms of carbon dioxide equivalent greenhouse gas. Two independent reviewers working in parallel will screen studies for inclusion and abstract study data, including publication, study, and ecological impact characteristics. Charted data will be synthesized narratively as well as with descriptive tables, figures, and summary statistics. In doing so, we will map areas of relative focus as well as gaps in the measurement of ecological impact across quality improvement initiatives. This map can in turn be used to raise awareness of ecological impacts requiring broader consideration, encouraging holistic and clinically relevant approaches to measuring ecological impact in future quality improvement work.

Trends and Prescriber Variation in the Duration of Oxaliplatin-Containing Adjuvant Chemotherapy for Stage III Colon Cancer From 2007 to 2019: A Population-Based Retrospective Cohort Study.

INTRODUCTION: The International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration in 2017 established 3 months of adjuvant therapy as an alternative to 6 months of therapy for stage III colon cancer. We determined the association between the IDEA publication, changes in clinical practice, and prescriber variation. PATIENTS AND METHODS: Using linked databases, we identified Ontarians aged ≥18 years at diagnosis of stage III colon cancer between 2007 and 2019 who received oxaliplatin-containing adjuvant therapy. The outcome was duration of therapy, categorized as ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% of a 6-month course of therapy to approximate treatment durations in the IDEA collaboration. We examined trends in duration over time using an interrupted time series regression model. We analyzed treatment duration after accounting for patient and prescriber characteristics, using multivariable mixed effects logistic regression models to quantify between-prescriber variation. RESULTS: We included 4695 patients with stage III colon cancer who received oxaliplatin-containing adjuvant chemotherapy, of whom 77.5% initiated treatment pre-IDEA and 22.5% initiated treatment post-IDEA. Post-IDEA, there was a 16.4% (95% CI, 12.5%-20.3%) absolute increase in the proportion of patients treated with ≤50% of a maximal course of therapy. This trend was greatest among patients with low-risk tumors. Prescriber variation increased pre-IDEA to 15.6% post-IDEA (variance partition coefficient 5.4% pre-IDEA and 15.6% post-IDEA). CONCLUSION: The publication of IDEA was associated with increases in short duration adjuvant therapy and prescriber-level practice variation for stage III colon cancer. Clinicians should be better supported to make consistent recommendations about adjuvant duration under conditions of uncertainty and trade-offs.

The Association of Oxaliplatin-Containing Adjuvant Chemotherapy Duration with Overall and Cancer-Specific Mortality in Individuals with Stage III Colon Cancer: A Population-Based Retrospective Cohort Study.

PURPOSE: Few studies have examined the relationship between duration of oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer and mortality in routine practice. We examined the association between treatment with 50% versus >85% of a maximal course of adjuvant therapy (eight cycles of CAPOX, twelve cycles of FOLFOX) and mortality in stage III colon cancer. METHODS: Using linked databases, we identified Ontarians aged ≥18 years at diagnosis of stage III colon cancer between 2007 and 2019. In the primary comparison, we compared patients who received 50% or >85% of a maximal course of adjuvant therapy; in a secondary comparison, we evaluated a dose effect across patients who received FOLFOX in one-cycle increments from six to ten cycles against >85% (more than ten cycles) of a maximal course of FOLFOX. The main outcomes were overall and cancer-specific mortality. Follow-up began 270 days after adjuvant treatment initiation and terminated at the first of the outcome of interest, loss of eligibility for Ontario's Health Insurance Program, or study end. Overlap propensity score weights accounted for baseline between-group differences. We determined the hazard ratio, estimating the association between mortality and treatment. Non-inferiority was concluded in the primary comparison for either outcome if the upper limit of the two-sided 95% CI was ≤1.11, which is the margin used in the International Duration Evaluation of Adjuvant Chemotherapy Collaboration. RESULTS: We included 3546 patients in the analysis of overall mortality; 486 (13.7%) received 50% and 3060 (86.3%) received >85% of a maximal course of therapy. Median follow-up was 5.4 years, and total follow-up was 20,510 person-years. There were 833 deaths. Treatment with 50% of a maximal course of adjuvant therapy was associated with a hazard ratio of 1.13 (95% CI 0.88 to 1.47) for overall mortality and a subdistribution hazard ratio of 1.31 (95% CI 0.91 to 1.87) for cancer-specific mortality versus >85% of a maximal course of therapy. In the secondary comparison, there was a trend toward higher overall mortality in patients treated with shorter durations of therapy, though confidence intervals overlapped considerably. CONCLUSION: We could not conclude that treatment with 50% of a maximal course is non-inferior to >85% of a maximal course of adjuvant therapy for mortality in stage III colon cancer. Clinicians and patients engaging in decision-making around treatment duration in this context should carefully consider the trade-off between treatment effectiveness and adverse effects of treatment.

Randomised controlled trials of non-pharmacological interventions to improve patient-reported outcomes of colonoscopy: a scoping review.

BACKGROUND AND AIMS: Non-pharmacological interventions to improve patient-reported outcomes of colonoscopy may be effective at mitigating negative experiences and perceptions of the procedure, but research to characterise the extent and features of studies of these interventions is limited. METHODS: We conducted a scoping review searching multiple databases for peer-reviewed publications of randomised controlled trials conducted in adults investigating a non-pharmacological intervention to improve patient-reported outcomes of colonoscopy. Study characteristics were tabulated and summarised narratively and graphically. RESULTS: We screened 5939 citations and 962 full texts, and included 245 publications from 39 countries published between 1992 and 2022. Of these, 80.8% were full publications and 19.2% were abstracts. Of the 41.9% of studies reporting funding sources, 11.4% were unfunded. The most common interventions were carbon dioxide and/or water insufflation methods (33.9%), complementary and alternative medicines (eg, acupuncture) (20.0%), and colonoscope technology (eg, magnetic scope guide) (21.6%). Pain was as an outcome across 82.0% of studies. Studies most often used a patient-reported outcome examining patient experience during the procedure (60.0%), but 42.9% of studies included an outcome without specifying the time that the patient experienced the outcome. Most intraprocedural patient-reported outcomes were measured retrospectively rather than contemporaneously, although studies varied in terms of when outcomes were assessed. CONCLUSION: Research on non-pharmacological interventions to improve patient-reported outcomes of colonoscopy is unevenly distributed across types of intervention and features high variation in study design and reporting, in particular around outcomes. Future research efforts into non-pharmacological interventions to improve patient-reported outcomes of colonoscopy should be directed at underinvestigated interventions and developing consensus-based guidelines for study design, with particular attention to how and when outcomes are experienced and measured. PROSPERO REGISTRATION NUMBER: 42020173906.

Clinical Delays and Comparative Outcomes in Younger and Older Adults with Colorectal Cancer: A Systematic Review.

Outcome disparities between adults <50 with colorectal cancer (CRC) and older adults may be explained by clinical delays. This study synthesized the literature comparing delays and outcomes between younger and older adults with CRC. Databases were searched until December 2021. We included studies published after 1990 reporting delay in adults <50 that made comparisons to older adults. Comparisons were described narratively and stage between age groups was meta-analyzed. 39 studies were included representing 185,710 younger CRC patients and 1,422,062 older patients. Sixteen delay intervals were compared. Fourteen studies (36%) found significantly longer delays among younger adults, and nine (23%) found shorter delays among younger patients. Twelve studies compared time from symptom onset to diagnosis (N younger = 1538). Five showed significantly longer delays for younger adults. Adults <50 years also had higher odds of advanced stage (16 studies, pooled OR for Stage III/IV 1.76, 95% CI 1.52-2.03). Ten studies compared time from diagnosis to treatment (N younger = 171,726) with 4 showing significantly shorter delays for younger adults. All studies showing longer delays for younger adults examined pre-diagnostic intervals. Three studies compared the impact of delay on younger versus older adult. One showed longer delays were associated with advanced stage and worse survival in younger but not older adults. Longer delays among younger adults with CRC occur in pre-diagnostic intervals.

Time to diagnosis and treatment in younger adults with colorectal cancer: A systematic review.

BACKGROUND: The incidence of colorectal cancer is rising in adults <50 years of age. As a primarily unscreened population, they may have clinically important delays to diagnosis and treatment. This study aimed to review the literature on delay intervals in patients <50 years with colorectal cancer (CRC), and explore associations between longer intervals and outcomes. METHODS: MEDLINE, Embase, and LILACS were searched until December 2, 2021. We included studies published after 1990 reporting any delay interval in adults <50 with CRC. Interval measures and associations with stage at presentation or survival were synthesized and described in a narrative fashion. Risk of bias was assessed using the Newcastle-Ottawa Scale, Institute of Health Economics Case Series Quality Appraisal Checklist, and the Aarhus Checklist for cancer delay studies. RESULTS: 55 studies representing 188,530 younger CRC patients were included. Most studies used primary data collection (64%), and 47% reported a single center. Sixteen unique intervals were measured. The most common interval was symptom onset to diagnosis (21 studies; N = 2,107). By sample size, diagnosis to treatment start was the most reported interval (12 studies; N = 170,463). Four studies examined symptoms onset to treatment start (total interval). The shortest was a mean of 99.5 days and the longest was a median of 217 days. There was substantial heterogeneity in the measurement of intervals, and quality of reporting. Higher-quality studies were more likely to use cancer registries, and be population-based. In four studies reporting the relationship between intervals and cancer stage or survival, there were no clear associations between longer intervals and adverse outcomes. DISCUSSION: Adults <50 with CRC may have intervals between symptom onset to treatment start greater than 6 months. Studies reporting intervals among younger patients are limited by inconsistent results and heterogeneous reporting. There is insufficient evidence to determine if longer intervals are associated with advanced stage or worse survival. OTHER: This study's protocol was registered with the Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42020179707).

Non-pharmacological interventions to improve the patient experience of colonoscopy under moderate or no sedation: a systematic review protocol.

INTRODUCTION: The patient experience is a critical dimension of colonoscopy quality. Sedative and analgesic drugs are commonly used to improve the patient experience of colonoscopy, with predominant regimens being deep sedation, typically achieved with propofol, and moderate sedation, typically achieved with an opioid and a benzodiazepine. However, non-pharmacological interventions exist that may be used to improve patient experience. Furthermore, by identifying non-pharmacological interventions to increase the quality of patient experience under moderate sedation, jurisdictions facing rising use of deep sedation for colonoscopy and its significant associated costs may be better able to encourage patients and clinicians to adopt moderate sedation. Advancing either of these aims requires synthesising the evidence and raising awareness around these non-pharmacological interventions to improve the patient experience of colonoscopy. METHODS AND ANALYSIS: A systematic review will be conducted that searches multiple electronic databases from inception until 2020 to identify randomised controlled trials evaluating what, if any, non-pharmacological interventions are effective compared with placebo or usual care for improving the patient experience of routine colonoscopy under moderate or no sedation. Two reviewers will independently perform a three-stage screening process and extract all study data using piloted forms. Study quality will be assessed using the Cochrane Risk of Bias Tool V.2.0. Where multiple studies evaluate a single intervention, evidence will be quantitatively synthesised using pairwise meta-analysis, otherwise narrative syntheses will be undertaken. ETHICS AND DISSEMINATION: This is a review of existing literature not requiring ethics approval. The review findings will be included in future efforts to develop an implementation strategy to reduce the use of deep sedation for routine colonoscopy. They will also be published in a peer-reviewed journal, presented at conferences and contribute to a doctoral thesis. PROSPERO REGISTRATION NUMBER: CRD42020173906.