Effect of vertical central plication on vertical deviations.

PURPOSE: To evaluate the surgical effect of the Wright central plication on vertical rectus muscles to correct vertical strabismus. METHODS: In this multicenter, retrospective, observational outcomes study, data were collected from two surgeons in different practice settings (2017-22). All patients who underwent vertical rectus central plication were included; those undergoing any concurrent strabismus surgery for vertical strabismus were excluded. Primary outcome was amount of strabismus correction in prism diopters per vertical rectus central plication. Secondary outcome was to determine factors associated with better or worse surgical outcomes and patient and patient responses. Data were analyzed using descriptive and bivariate statistics. RESULTS: A total of 36 patients were included. Mean age was 60 years. Mean follow-up was 8.4 months. Of the 36 patients, 11 (31%) had idiopathic strabismus, and 7 (19%) had congenital superior oblique palsy. The remainder had a history that included prior ocular surgery, trauma, and Brown syndrome; 16 (44 %) had prior strabismus surgery. Of 31 patients with preoperative diplopia, 23 (74%) had postoperative resolution of diplopia, and 10 of 16 patients with preoperative prisms (63%) no longer required prisms postoperatively. Mean vertical deviation change was 4.7Δ. Subgroup analysis removing patients with congenital superior oblique palsy showed a larger response of 5.5Δ. 78% of patients had a final deviation <5Δ. No complications or induced postoperative diplopia was reported. CONCLUSIONS: In our study cohort, vertical rectus central plication corrected approximately 5Δ (range, 4.5Δ-5.5Δ) of vertical strabismus due to a variety of causes.

Sedentary behavior does not predict low BMD nor fracture-population-based Canadian Multicentre Osteoporosis Study.

Sedentary behavior (SB) or sitting is associated with multiple unfavorable health outcomes. Bone tissue responds to imposed gravitational and muscular strain with there being some evidence suggesting a causal link between SB and poor bone health. However, there are no population-based data on the longitudinal relationship between SB, bone change, and incidence of fragility fractures. This study aimed to examine the associations of sitting/SB (defined as daily sitting time), areal BMD (by DXA), and incident low trauma (fragility) osteoporotic fractures (excluding hands, feet, face, and head). We measured baseline (1995-7) and 10-yr self-reported SB, femoral neck (FN), total hip (TH), and lumbar spine (L1-L4) BMD in 5708 women and 2564 men aged 25 to 80+ yr from the population-based, nationwide, 9-center Canadian Multicentre Osteoporosis Study. Incident 10-yr fragility fracture data were obtained from 4624 participants; >80% of fractures were objectively confirmed by medical records or radiology reports. Vertebral fractures were confirmed by qualitative morphological methods. All analyses were stratified by sex. Multivariable regression models assessed SB-BMD relationships; Cox proportional models were fit for fracture risk. Models were adjusted for age, height, BMI, physical activity, and sex-specific covariates. Women in third/fourth quartiles had lower adjusted FN BMD versus women with the least SB (first quartile); women in the SB third quartile had lower adjusted TH BMD. Men in the SB third quartile had lower adjusted FN BMD than those in SB first quartile. Neither baseline nor stable 10-yr SB was related to BMD change nor to incident fragility fractures. Increased sitting (SB) in this large, population-based cohort was associated with lower baseline FN BMD. Stable SB was not associated with 10-yr BMD loss nor increased fragility fracture. In conclusion, habitual adult SB was not associated with subsequent loss of BMD nor increased risk of fracture.

The number of hours of sitting in a day (often called "sedentary behavior") is currently understood to be "bad for bone health" both because of increased bone loss and a higher risk for fractures. Very few studies in randomly sampled men and women from a whole population have consistently asked about hours of sitting and examined baseline bone density. Fewer still have compared hours of sitting and its changes over 10 yr with changes in bone density and the number of new fractures that occurred. The Canadian Multicentre Osteoporosis Study obtained sitting hours from 5708 women and 2564 men aged 25 to 80+ yr and compared it with the spine, total hip (TH), and femoral neck (FN) bone density values. The average sitting at 7.4 h in men was associated with slightly lower adjusted femoral neck bone density; in women, sitting 6.7 h/d was associated with slightly lower adjusted FN and TH bone density. Ten-year follow-up data (now in about 5000 people) showed no relationship between the slightly longer sitting (an increase of 18% in men and 22% in women) and bone loss or new bone fractures. In this large country-wide population-based study, hours of sitting each day were not associated with 10-yr BMD loss in women or men nor did sitting more associate with new bone fractures. These data are reassuring; women and men who walk regularly and have some moderate-vigorous physical activity each day, despite more sitting, do not seem to be at greater risk for osteoporosis.

Incidence and risk factors of venous and arterial thromboembolic events among patients with ovarian cancer- data from a large Canadian database.

OBJECTIVES: To determine the incidence of thromboembolic events (TEEs) in ovarian cancer patients and to identify risk factors that are significantly associated with the development of venous thromboembolism (VTE), arterial thromboembolism (ATE), or overall TEEs in this population. METHODS: This is a retrospective cohort study of 4491 patients with epithelial ovarian cancer identified in the British Columbia cancer registry between 1996 and 2017. The presence of TEEs and risk factors were identified in administrative health records from fee-for-service provider visits and hospital data using ICD-9-CM and ICD-10-CM billing codes. Statistical analysis was performed using Chi-squared test and Fischer's exact test. RESULTS: Of 4491 patients with epithelial ovarian cancer included in this study, 1.74% experienced ATE and (9.44%) experienced VTE. There was a significant association found between the occurrence of TEEs and all-cause mortality. Sepsis was significantly associated with both venous and arterial thromboembolism. The top three risk factors for arterial thromboembolism included peripheral vascular disease (PVD), open wound, and aneurysm. CONCLUSIONS: Risk factors predictive of thrombosis in ovarian cancer patients are not consistent between ATE and VTE, thus thrombotic events should not be combined for analysis. Differential thrombosis risk assessment is needed to improve prevention strategies and guide thromboprophylaxis for these patients.

Financial Toxicity: Unveiling the Burden of Cancer Care on Patients in Rwanda.

INTRODUCTION: Cancer is a major public health problem in Rwanda and other low- and middle-income countries (LMICs). While there have been some improvements in access to cancer treatment, the cost of care has increased, leading to financial toxicity and treatment barriers for many patients. This study explores the financial toxicity of cancer care in Rwanda. METHODS: This prospective cross-sectional study was conducted at 3 referral hospitals in Rwanda, which deliver most of the country's cancer care. Data were collected over 6 months from June 1 to December 1, 2022 by trained research assistants (RAs) using a modified validated data collection tool. RAs interviewed consecutive eligible patients with breast cancer, cervical cancer, colorectal cancer, Hodgkin's and non-Hodgkin's lymphoma who were on active systemic therapy. The study aimed to identify sources of financial burden. Data were analyzed using descriptive statistics. RESULTS: 239 patients were included; 75% (n = 180/239) were female and mean age was 51 years. Breast, cervix, and colorectal cancers were the most common diagnoses (42%, 100/239; 24%, 58/239; and 24%, 57/239, respectively) and 54% (n = 129/239) were diagnosed with advanced stage (stages III-IV). Financial burden was high; 44% (n = 106/239) of respondents sold property, 29% (n = 70/239) asked for charity from public, family, or friends, and 16% (n = 37/239) took loans with interest to fund cancer treatment. CONCLUSION: Despite health insurance which covers many elements of cancer care, a substantial proportion of patients on anti-cancer treatment in Rwanda experience major financial toxicity. Novel health financing solutions are needed to ensure accessible and affordable cancer care.

Challenges in building radiotherapy capacity: A longitudinal study evaluating eight years of the Brazilian radiotherapy expansion plan.

BACKGROUND: In 2012, the Brazilian government launched a radiotherapy (RT) expansion plan (PER-SUS) to install 100 linear accelerators. This study assesses the development of this program after eight years. METHODS: Official reports from the Ministry of Health (MoH) were reviewed. RT centres projects status, timeframes, and cost data (all converted to US dollars) were extracted. The time analysis was divided into seven phases, and for cost evaluation, there were five stages. The initial predicted project time (IPPT) and costs (estimated by the MoH) for each phase were compared between the 18 operational RT centres (able to treat patients) and 30 non-operational RT centres using t-tests, ANOVA, and the Mann-Whitney U. A p-value < 0.05 indicates statistical significance. RESULTS: A significant delay was observed when comparing the IPPT with the overall time to conclude each 48 RT centres project (p < 0.001), with considerable delays in the first five phases (p < 0.001 for all). Moreover, the median time to conclude the first 18 operational RT centres (77.4 months) was shorter compared with the 30 non-operational RT centres (94.0 months), p < 0.001. The total cost of 48 RT services was USD 82,84 millions (mi) with a significant difference in the per project median total cost between 18 operational RT centres, USD1,34 mi and 30 non-operational RT centres USD2,11 mi, p < 0.001. All phases had a higher cost when comparing 30 non-operational RT centres to 18 operational RT centres, p < 0.001. The median total cost for expanding existing RT centres was USD1,30 mi versus USD2,18 mi for new RT services, p < 0.0001. CONCLUSION: After eight years, the PER-SUS programs showed a substantial delay in most projects and their phases, with increased costs over time. POLICY SUMMARY: Our findings indicate a need to act to increase the success of this plan. This study may provide a benchmark for other developing countries trying to expand RT capacity.

Retraction speed and chronic poststernotomy pain: A randomized controlled trial.

OBJECTIVES: Approximately 30% of patients develop chronic poststernotomy pain (CPSP) following cardiac surgery with sternal retraction. Risk factors have been described but no causal determinants identified. Investigators hypothesized that opening the sternum slowly would impart less force (and thereby less nerve/tissue damage) and translate to a reduced incidence of CPSP. The main objectives were to determine whether or not slower sternal retraction would reduce the incidence of CPSP and improve health-related quality of life. METHODS: Patients undergoing coronary artery bypass graft surgery were recruited to this randomized controlled trial. Patients were randomized to slow or standard retraction (ie, sternum opened over 15 minutes vs 30 seconds, respectively). Although the anesthesiologist and surgeon were aware of the randomization, the patients, assessors, and postoperative nursing staff remained blinded. Sternotomy pain and analgesics were measured in hospital. At 3, 6, and 12 months postoperatively, all patients completed the Medical Outcomes Survey Short Form and reported on CPSP and complications requiring rehospitalization. Thirty-day rehospitalizations and mortality were recorded. RESULTS: In total, 326 patients consented to participate and 313 were randomized to slow (n = 159) versus standard retraction (n = 154). No clinically relevant differences were detected in acute pain, analgesic consumption, or the incidence of CPSP or health-related quality of life. Although the slow group had significantly more hospitalizations at 3 and 12 months postoperatively, the reasons were unrelated to retraction speed. No differences were observed in 30-day rehospitalizations or mortality. CONCLUSIONS: All outcomes were consistent with previous reports, but no clinically significant differences were observed with retraction speed.

Dobutamine and Goal-Directed Fluid Therapy for Improving Tissue Oxygenation in Deep Inferior Epigastric Perforator (DIEP) Flap Breast Reconstruction Surgery: Protocol for a Randomized Controlled Trial.

BACKGROUND: Breast reconstruction is an integral part of breast cancer care. There are 2 main types of breast reconstruction: alloplastic (using implants) and autologous (using the patient's own tissue). The latter creates a more natural breast mound and avoids the long-term need for surgical revision-more often associated with implant-based surgery. The deep inferior epigastric perforator (DIEP) flap is considered the gold standard approach in autologous breast reconstruction. However, complications do occur with DIEP flap surgery and can stem from poor flap tissue perfusion/oxygenation. Hence, the development of strategies to enhance flap perfusion (eg, goal-directed perioperative fluid therapy) is essential. Current perioperative fluid therapy is traditionally guided by subjective criteria, which leads to wide variations in clinical practice. OBJECTIVE: The main objective of this trial is to determine whether the use of minimally invasive cardiac output (CO) monitoring for guiding intravenous fluid administration, combined with low-dose dobutamine infusion (via a treatment algorithm), will increase tissue oxygenation in patients undergoing DIEP flap surgery. METHODS: With appropriate institutional ethics board and Health Canada approval, patients undergoing DIEP flap surgery are randomly assigned to receive CO monitoring for the guidance of intraoperative fluid therapy in addition to a low-dose dobutamine infusion (which potentially improves flap oxygenation) versus the current standard of care. The primary outcome is tissue oxygenation measured via near-infrared spectroscopy at the perfusion zone furthest from the perforator vessels 45 minutes after vascular reanastomosis of the DIEP flap. Low dose (2.5 µg/kg/hr) dobutamine infusion continues for up to 4 hours postoperatively, provided there are no associated complications (ie, persistent tachycardia). Flap oxygenation, hemodynamic parameters, and any medication-associated side effects/complications are monitored for up to 48 hours postoperatively. Complications, rehospitalizations, and patient satisfaction are also collected until 30 days postoperatively. RESULTS: Funding and regulatory approvals were obtained in 2019, but the study recruitment was interrupted by the COVID-19 pandemic. As of October 4, 2023, 34 participants have been recruited. Because of the significant delays associated with the pandemic, the expected completion date was extended. We expect the study to be completed and ready for potential news release (as appropriate) and publication by July 2024. No patients have suffered any adverse effects/complications from participating in this study, and none have been lost to follow-up. CONCLUSIONS: CO-directed fluid therapy in combination with a low-dose dobutamine infusion via a treatment algorithm has the potential to improve DIEP flap tissue oxygenation and reduce complications following DIEP flap breast reconstruction surgery. However, given that the investigators remain blinded to group randomization, no comment can be made regarding the efficacy of this intervention for improving tissue oxygenation at this time. Nevertheless, no patients have been withdrawn for safety concerns thus far, and compliance remains high. TRIAL REGISTRATION: Clinicaltrials.gov NCT04020172; https://clinicaltrials.gov/study/NCT04020172.

Randomised controlled trials evaluating anticancer therapies in haematological cancers: an overview of global research activity.

Background: Design, results, and interpretation of oncology randomised controlled trials (RCTs) have changed substantially over the past decade. In this study, we describe all RCTs evaluating anticancer therapies in haematological cancers published globally during 2014-2017 with comparisons with solid tumours RCTs. Methods: A PubMed literature search identified all phase 3 RCTs of anticancer therapy for haematological cancers and solid tumours published globally during 2014-2017. Descriptive statistics, chi-square tests and the Kruskal-Wallis test were used to compare RCT design results, and output between haematological cancers and solid tumours as well as for different haematological cancer subtypes. Results: 694 RCTs were identified; 124 in haematological cancers and 570 in solid tumours. Overall survival (OS) was the primary endpoint in only 12% (15/124) of haematological cancer trials compared to 35% (200/570) in solid tumours (p < 0.001). Haematological cancer RCTs evaluated the systemic novel therapy more often than the solid tumour RCT (98% versus 84%, p = 0.002). Use of surrogate endpoints like progression-free survival (PFS) and time to treatment failure (TTF) were more common in haematological cancers than solid tumours (47% versus 31%, p < 0.001). Within haematological cancers, the use of PFS and TTF was more prevalent in chronic lymphocytic leukaemia and multiple myeloma as compared to others (80%-81% versus 0%-41%, p < 0.001). Seventy-eight percent of haematologic trials were funded by industry as compared to 70% of solid tumour trials. Only 4% (5/124) of haematologicalcancer trials were led by investigators in upper-middle and lower-middle-income countries as compared to the 9% of solid tumour trials. Conclusion: The fact that only 12% of haematological cancer RCTs are designed to show improvements in OS is of grave concern for the field and the care of future patients. This is further compounded by the highly prevalent use of alternative primary endpoints that are rarely valid surrogates for OS in haematological cancers.

Allocation of authorship and patient enrollment among global clinical trials in oncology.

BACKGROUND: Oncology randomized controlled trials (RCTs) are increasingly global in scope. Whether authorship is equitably shared between investigators from high-income countries (HIC) and low-middle/upper-middle incomes countries (LMIC/UMIC) is not well described. The authors conducted this study to understand the allocation of authorship and patient enrollment across all oncology RCTs conducted globally. METHODS: A cross-sectional retrospective cohort study of phase 3 RCTs (published 2014-2017) that were led by investigators in HIC and recruited patients in LMIC/UMIC. FINDINGS: During 2014-2017, 694 oncology RCTs were published; 636 (92%) were led by investigators from HIC. Among these HIC-led trials, 186 (29%) enrolled patients in LMIC/UMIC. One-third (33%, 62 of 186) of RCTs had no authors from LMIC/UMIC. Forty percent (74 of 186) of RCTs reported patient enrollment by country; in 50% (37 of 74) of these trials, LMIC/UMIC contributed <15% of patients. The relationship between enrollment and authorship proportion is very strong and is comparable between LMIC/UMIC and HIC (Spearman's ρ LMIC/UMIC 0.824, p < .001; HIC 0.823, p < .001). Among the 74 trials that report country enrollment, 34% (25 of 74) have no authors from LMIC/UMIC. CONCLUSIONS: Among trials that enroll patients in HIC and LMIC/UMIC, authorship appears to be proportional to patient enrollment. This finding is limited by the fact that more than half of RCTs do not report enrollment by country. Moreover, there are important outliers as a significant proportion of RCTs had no authors from LMIC/UMIC despite enrolling patients in these countries. The findings in this study reflect a complex global RCT ecosystem that still underserves cancer control outside high-income settings.

Management of heavy menstrual bleeding in women with bleeding disorders in a tertiary care center.

Background: Heavy menstrual bleeding (HMB) affects a significant number of women with bleeding disorders and has a negative impact on their quality of life. Objective: This retrospective study examined the management of patients with inherited bleeding disorders who used medical treatments, alone or in combination, for HMB. Methods: Chart review was performed on women attending the Women with Bleeding Disorders Clinic in Kingston, Ontario, between 2005 and 2017. Data collected included patient demographics, the reason for presentation and diagnosis, medical history, treatments, and patient satisfaction. Results: One hundred nine women were included in this cohort. Of these, only 74 (68%) were satisfied with medical management, and only 18 (17%) with first-line therapy. Treatments included combined contraceptives (oral pill, transdermal patch, and vaginal ring), progesterone-only pills, tranexamic acid, 52-mg levonorgestrel intrauterine system (LIUS), depomedroxyprogesterone acetate, and desmopressin, either alone or in combination. Satisfactory control of HMB occurred most often with the LIUS. Conclusion: In this cohort, managed in a tertiary care Women with Bleeding Disorders Clinic, only 68% of patients had successful control of HMB with medical treatment, and a minority were satisfied with first-line therapy. These data clearly highlight the need for additional research, including treatment approaches and novel therapies for this population.

Missed appointments in a tertiary academic pediatric ophthalmology and adult strabismus service: cross-sectional study and literature review.

PURPOSE: To investigate the rate of missed appointments in a Canadian academic hospital-based pediatric ophthalmology and adult strabismus practice and the demographic and clinical factors associated with missed appointments. METHODS: This cross-sectional study included all consecutive patients seen from June 1, 2018, to May 31, 2019. Multivariable logistic regression model assessed associations between clinical and demographic variables with no-show status. A literature review on evidence-based interventions to reduce no-show appointments in ophthalmology was performed. RESULTS: Of 3,922 visits, 718 (18.3%) were no-shows. Characteristics associated with no-shows included new patient (OR = 1.4; 95% CI, 1.1-1.7 [P = 0.001]), age 4-12 years (OR = 1.6; 95% CI, 1.1-2.3 [P = 0.011]) or age 13-18 years (OR = 1.8; 95% CI, 1.2-2.7 [P = 0.007]) compared with age 19+ years, history of previous no-shows (OR = 2.2; 95% CI, 1.8-2.7 [P = 0.001]), referrals from nurse practitioners (OR = 1.8; 95% CI, 1.0-3.2 [P = 0.037]), nonsurgical diagnoses such as retinopathy of prematurity (OR = 3.2; 95% CI, 1.8-5.6 [P < 0.001]), and winter season (OR = 1.4; 95% CI, 1.2-1.7 [P < 0.001]). CONCLUSIONS: Missed appointments in our pediatric ophthalmology and strabismus academic center are more likely new patient referrals, prior no-shows, referrals from nurse practitioners, and nonsurgical diagnoses. These findings may facilitate targeted strategies to help improve utilization of healthcare resources.

Assessing the utilization of cancer medicines in Rwanda: an analysis of treatment patterns.

Introduction: Cancer is a growing public health concern in Africa, especially in low- and middle-income countries (LMICs) like Rwanda. Increased cancer incidences translate into increased utilisation of cancer medicine. Access to affordable cancer medicines in Rwanda is a pressing issue as the National Health Insurance plan does not provide coverage for cancer medicines. In this study, we investigated the utilisation patterns of cancer medicines in Rwanda. Methods: This retrospective cross-sectional study was conducted at all referral hospitals (n = 3) capable of delivering chemotherapy in Rwanda. The data collection was over a period of 6 months, during which a team of trained research assistants reviewed a convenience sample of selected patient charts. Both paper charts and electronic medical records were used to collect patients' data, including cancer type, stage, treatment setting, type of drugs or regimen used and completed cycles. Data were analysed using descriptive statistics. Results: A total of 630 patients received chemotherapy during the study period and were included. Seventy-seven percent (n = 486) were female and mean age was 51 (SD ± 13). Among all patients receiving chemotherapy, 43% (n = 270) had breast cancer, 22% (n = 140) had cervical cancer and 19% (n = 121) had colorectal cancer. The majority of patients (71%) had a community-based insurance. Butaro Cancer Centre treated the most patients (48%, n = 303). Thirty-six percent (221/630) had stage III cancer. The most common regimens within the cohort were adriamycin, cyclophosphamide and taxane, capecitabine and oxaliplatin (CAPOX), paclitaxel + carboplatin and a single agent cisplatin given concurrently with radiotherapy. The proportion of chemotherapy that was given in the curative and palliative setting was 72% and 28% respectively. Conclusion: Access to affordable cancer medicines remains a challenge in Rwanda. The study's findings provide valuable information on the utilisation patterns of cancer medicines in Rwanda, which can be used to guide policy decisions and improve cancer care in the country.

Plasma bupivacaine levels (total and free/unbound) during epidural infusion in liver resection patients: a prospective, observational study.

INTRODUCTION: Liver resection patients may be at an increased risk of local anesthetic (LA) toxicity because the liver is essential for metabolizing LA and producing proteins (mainly α1-acid glycoprotein (AAG)) that bind to it and reduce the free (and pharmacologically active/toxic) levels in circulation. The liver resection itself, manipulation during surgery, and pre-existing liver disease may all interfere with normal hepatic protein synthesis and result in an attenuation of the increased AAG (a positive acute-phase protein) that normally occurs postoperatively. The purpose of this study was to determine whether the AAG response is attenuated postoperatively following liver resection and whether patients approach toxicity thresholds with continuous postoperative epidural infusion of bupivacaine. METHODS: Prospective, observational study with blood drawn preoperatively, in the postanesthetic care unit, on postoperative day (POD) 2, and prior to discontinuation of epidural analgesia on POD3/POD4. Plasma was analyzed for total and unbound bupivacaine via liquid chromatography-mass spectrometry and AAG via ELISA. Signs/symptoms of local anesthetic systemic toxicity (LAST), pain, and sedation scores were also recorded. RESULTS: For the 19 patients completed, total plasma bupivacaine was correlated with total administered, but unbound levels were not associated with the total administered. Unlike non-hepatectomy surgery where unbound LA plasma levels remain stable (or decrease) with continuous postoperative epidural administration, we observed an overall increase. Several patients approached toxicity thresholds and 47% reported at least one symptom of LAST, but no epidurals were discontinued because of LAST. In contrast to the AAG response reported following major non-liver surgery where AAG levels increase twofold, we observed a reduction until POD2 and the magnitude was proportional to resection weight. DISCUSSION: Our results are supported by the literature in suggesting that major liver resection patients may be at an increased vulnerability for LAST. Factors such as the extent of liver disease, resection and intraoperative blood loss should be considered when using continuous postoperative epidural infusion of bupivacaine and vigilance should be used in monitoring, for signs/symptoms of LAST, even for those subtle and non-specific. Future research will be required to verify these findings. TRIAL REGISTRATION NUMBER: NCT03145805.

Participation of Lower and Upper Middle-Income Countries in Clinical Trials Led by High-Income Countries.

Importance: Many randomized clinical trials (RCTs) led by high-income countries (HICs) now enroll patients from lower middle-income countries (LMICs) and upper middle-income countries (UMICs). Although enrolling diverse populations promotes research collaborations, there are issues regarding which countries participate in RCTs and how this participation may contribute to global research. Objective: To describe which UMICs and LMICs participate in RCTs led by HICs. Design, Setting, and Participants: A cross-sectional study of all oncology RCTs published globally during January 1, 2014, to December 31, 2017, was conducted. The study cohort was restricted to RCTs led by HICs that enrolled participants from LMICs and UMICs. Study analyses were conducted in November 1, 2021, to May 31, 2022. Main Outcomes and Measures: A bibliometric approach (Web of Science 2007-2017) was used to explore whether RCT participation was proportional to other measures of cancer research activity. Participation in RCTs (ie, percentage of RCTs in the cohort in which each LMIC and UMIC participated) was compared with country-level cancer research bibliometric output (ie, percentage of total cancer research bibliometric output from the same group of countries that came from a specific LMIC and UMIC). Results: Among the 636 HIC-led RCTs, 186 trials (29%) enrolled patients in LMICs (n = 84 trials involving 11 LMICs) and/or UMICs (n = 181 trials involving 26 UMICs). The most common participating LMICs were India (42 [50%]), Ukraine (39 [46%]), Philippines (23 [27%]), and Egypt (12 [14%]). The most common participating UMICs were Russia (115 [64%]), Brazil (94 [52%]), Romania (62 [34%]), China (56 [31%]), Mexico (56 [31%]), and South Africa (54 [30%]). Several LMICs are overrepresented in the cohort of RCTs based on proportional cancer research bibliometric output: Ukraine (46% of RCTs but 2% of cancer research bibliometric output), Philippines (27% RCTs, 1% output), and Georgia (8% RCTs, 0.2% output). Overrepresented UMICs include Russia (64% RCTs, 2% output), Romania (34% RCTs, 2% output), Mexico (31% RCTs, 2% output), and South Africa (30% RCTs, 1% output). Conclusions and Relevance: In this cross-sectional study, a substantial proportion of RCTs led by HICs enrolled patients in LMICs and UMICs. The LMICs and UMICs that participated in these trials did not match overall cancer bibliometric output as a surrogate for research ecosystem maturity. Reasons for this apparent discordance and how these data may inform future capacity-strengthening activities require further study.

Anxiety in adults with allergic rhinitis during the coronavirus disease 2019 pandemic: A Canadian perspective.

BACKGROUND: Despite the symptom overlap between allergic rhinitis (AR) and coronavirus disease 2019 (COVID-19), pandemic-time anxiety in people with AR remains an area of limited study. OBJECTIVE: To assess the AR-anxiety relationship in the unique context of the COVID-19 pandemic from a Canadian perspective. METHODS: The COVID-19 Associated Anxiety in patients with Asthma and AR Experiencing Symptoms survey was distributed on the "Qualtrics XM" platform, with 835 adult participants responding to the first iteration from April to August 2020. Anxiety was assessed on the Generalized Anxiety Disorder Assessment-7 (GAD-7), and AR burden of disease was assessed on the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). All analyses were conducted using IBM SPSS Statistics 27. RESULTS: High levels of anxiety were found, with 28.0% of the AR group and 27.5% of the control group meeting the diagnostic criteria for generalized anxiety disorder. After controlling for covariates, AR status had no significant predictive effect on GAD-7 in a hierarchal multiple regression model (ΔR2 = .00, P = .69). In the AR subgroup, there were significant positive correlations between anxiety and burden of disease for the total RQLQ score and all 7 domain scores (P < .001 for all), with the non-nose or eye symptom domain having the strongest correlation (r = .63). After controlling for covariates, total RQLQ score had a predictive effect on GAD-7 in a hierarchal multiple regression model (ΔR2 = .049, P < .001). CONCLUSION: High levels of anxiety exist during the COVID-19 pandemic regardless of AR status, indicating the importance of early anxiety screening in all patients. This study also highlights the importance of non-nose or eye symptoms in AR management.

Choosing Wisely Africa: Insights from the front lines of clinical care.

BACKGROUND: A multidisciplinary Task Force of African oncologists and patient representatives published the Choosing Wisely Africa (CWA) recommendations in 2020. These top 10 recommendations identify low-value, unnecessary, or harmful practices that are frequently used in Sub-Saharan Africa (SSA). In this study, we describe agreement and concordance with the recommendations from front-line oncologists across SSA. METHODS: An electronic survey was distributed to members of the African Organization for Research & Training in Cancer (AORTIC) and oncology groups within SSA using a hierarchical snowball method; each primary contact distributed the survey through their personal networks. The survey captured information about awareness of the CWA list, agreement with recommendations, and concordance with clinical practice. Descriptive statistics were used to summarize study results. RESULTS: 52 individuals responded to the survey; 64% (33/52) were female and 58% (30/52) were clinical oncologists. Respondents represented 15 countries in SSA; 69% (36/52) practiced exclusively in the public system. Only 46% (24/52) were aware of the CWA list and 89% (46/52) agreed it would be helpful if the list was displayed in their clinic. There was generally a high agreement with the recommendations (range 84-98%); the highest agreement was related to staging/defining treatment intent (98%). The proportion of oncologists who implemented these recommendations in routine practice was somewhat lower (range 68-100%). Lowest rates of concordance related to: the use of shorter schedules of radiotherapy (67%); discussion of active surveillance forlow-risk prostate cancer (67%); only performing breast surgery for a mass that was proven to be malignant (70%); and seeking multidisciplinary input for curative intent treatment plans (73%). CONCLUSION: While most frontline SSA oncologists agree with CWA recommendations, efforts are needed to disseminate the list. Agreement with the recommendations is high but there are gaps in implementation in routine practice. Further work is needed to understand the barriers and enablers of implementation.

Impact of the COVID-19 pandemic on the burnout rates of graduating Canadian Urology residents.

OBJECTIVE: To assess the impact of coronavirus disease 2019 (COVID-19) on burnout rates in Canadian Urology trainees. SUBJECTS AND METHODS: A total of 37 chief residents representing all 12 Canadian Urology residency programmes attended a preparatory examination in December 2019 pre-pandemic and 39 chief residents attended virtually in November 2020 during the pandemic. The Maslach Burnout Inventory (MBI) for medical professionals' questionnaire was administered anonymously to both groups. The MBI covers emotional exhaustion, depersonalisation, and personal accomplishment. Descriptive statistics were used to analyse the data. RESULTS: There was a 100% response rate in the convenience sample (n = 37) in 2019 and 64.1% response rate (n = 25) in 2020. Overall, 70% of chief residents in Canadian Urology programmes showed evidence of burnout in 2019 compared to 88% in 2020 (P = 0.101). There was a statistically significant difference between the two cohorts in emotional exhaustion (mean [sd] 16.2 [5.6] in 2019 and 20.2 [6.2] in 2020, P = 0.011) and personal accomplishment scores (mean [sd] 32.2 [4.5] in 2019 and 30.6 [3.6] in 2020, P = 0.039). CONCLUSIONS: This study is the first to examine the impact of the pandemic on burnout rates in Urology trainees. Burnout rates are high in trainees at baseline, and the pandemic appears to have exacerbated emotional exhaustion, and personal accomplishment, but not overall burnout rates. Vigilance and proactive steps need to be implemented to alleviate this crisis.

Randomized Controlled Trials in Lung, Gastrointestinal, and Breast Cancers: An Overview of Global Research Activity.

Background: In this study, we compared and contrasted design characteristics, results, and publications of randomized controlled trials (RCTs) in gastrointestinal (GI), lung, and breast cancer. Methods: A PUBMED search identified phase III RCTs of anticancer therapy in GI, lung, and breast cancer published globally during the period 2014−2017. Descriptive statistics, chi-square tests, and the Kruskal−Wallis test were used to compare RCT design, results, and output across the cancer sites. Results: A total of 352 RCTs were conducted on GI (36%), lung (29%), and breast (35%) cancer. Surrogate endpoints were used in 55% of trials; this was most common in breast trials (72%) compared to GI (47%) and lung trials (43%, p < 0.001). Breast trials more often met their primary endpoint (54%) than GI (41%) and lung trials (41%) (p = 0.024). When graded with the ESMO-MCBS, lung cancer trials (50%, 15/30) were more likely to meet the threshold for substantial benefit. GI trials were published in journals with a substantially lower impact factor (IF; median IF 13) than lung (median IF 21) and breast cancer trials (median IF 21) (p = 0.038). Conclusions: Important differences in RCT design and output exist between the three major cancer sites. Use of surrogate endpoints and the magnitude of benefit associated with new treatments vary substantially across cancer sites.

Real-World Evidence of Systemic Therapy Sequencing on Overall Survival for Patients with Metastatic BRAF-Mutated Cutaneous Melanoma.

Aim: To evaluate optimal systemic therapy sequencing (first-line targeted therapy (1L-TT) vs. first-line immunotherapy (1L-IO)) in patients with BRAF-mutated metastatic melanoma. Methods: Nation-wide prospective data of patients with newly diagnosed BRAF-mutated metastatic melanoma were retrieved from the Canadian Melanoma Research Network. Results: Our study included 79 and 107 patients in the 1L-IO and 1L-TT groups, respectively. There were more patients with ECOG 0−1 (91% vs. 72%, p = 0.023) in the 1L-IO group compared to the 1L-TT group. Multivariable Cox analysis suggested no OS differences between the two groups (HR 0.838, 95%CI 0.502−1.400, p = 0.500). However, patients who received 1L-TT then 2L-IO had the longest OS compared to 1L-IO without 2L therapy, 1L-IO then 2L-TT, and 1L-TT without 2L therapy (38.3 vs. 32.2 vs. 16.9 vs. 6.3 months, p < 0.001). For patients who received 2L therapy, those who received 2L-IO had a trend towards OS improvement compared with the 2L-TT group (21.7 vs. 8.9 months, p = 0.053). Conclusions: Our nation-wide prospective study failed to establish any optimal systemic therapy sequencing in advanced BRAF-mutant melanoma patients. Nevertheless, we provided evidence that immunotherapy has durable efficacy in advanced BRAF-mutant melanoma patients, regardless of treatment line, and that Canadian medical oncologists were selecting the appropriate treatment sequences in a real-world setting, based on patients' clinical and tumour characteristics.

Prioritising locations for radiotherapy equipment in Brazil: a cross-sectional, population-based study and development of a LINAC shortage index.

BACKGROUND: Similarly to several other upper-middle-income countries, there is a major shortfall in radiotherapy services for the treatment of cancer in Brazil. In this study, we developed the linear accelerator (LINAC) shortage index to assess the LINAC shortage and support the prioritisation of new LINAC distribution in Brazil. METHODS: This cross-sectional, population-based study used data from the National Cancer Institute 2020 Cancer estimates, the Ministry of Health 2019 radiotherapy census, the Minister of Health radiotherapy expansion programme progress reports, and the Fundação Oncocentro de São Paulo public database of the Cancer Hospital Registry of the State of São Paulo to calculate the LINAC shortage index. Data collected were number of new cancer cases in Brazil, number of LINACs per region and state, number of cancer cases treated with radiotherapy, patient state of residence, and radiotherapy treatment centre and location. National, regional, and state-level data were collected for analysis. LINAC numbers, cancer incidence, geographical distribution, and radiotherapy needs were estimated. A LINAC shortage index was calculated as a relative measure of LINAC demand compared with supply based on number of new cancer cases, number of patients requiring radiotherapy, and the number of LINCAS in the region or state. We then built a prioritisation framework using the LINAC shortage index, cancer incidence, and geographical factors. Finally, using patient-level public cancer registry data from the Fundação Oncocentro de São Paulo and Google maps, we estimated the geospatial distance travelled by patients with cancer from their state of residence to radiotherapy treatment in São Paulo from 2005-14. Non-parametric statistics were used for analysis. FINDINGS: Data were collected between Feb 2 and Dec 31, 2021. In 2020, there were 625 370 new cancer cases in Brazil and 252 LINAC machines. The number of LINACs was inadequate in all Brazilian regions, with a national LINAC shortage index of 221 (ie, 121% less than the required radiotherapy capacity). The LINAC shortage index was higher in the midwest (326), north (313), and northeast (237) regions, than the southeast (210) and south (192) regions. Four states (Tocantins, Acre, Amapá, and Roraima) in the north region were ranked first on the prioritisation rank due to no availability of LINACs. There was an association between LINAC shortage index and the number of patients who travelled to receive radiotherapy (p<0·0001). Patients living in the midwest (793 km), north (2835 km), and northeast (2415 km) regions travelled significantly longer average distances to receive radiotherapy treatment in São Paulo than patients living in the southeast or south regions (p=0·032). The reduced number of LINACs in these regions was associated with longer distance travelled (p=0·032). INTERPRETATION: There is substantial discordance between distribution of cancer cases and LINAC availability in Brazil. We developed a tool using the LINACs shortage index to help prioritise the development of radiotherapy infrastructure across Brazil; this approach might also be useful in other health systems. FUNDING: None.