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.

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.

Identifying intraoperative events in a simulated laparotomy video: a multinational study of inattentional blindness among anesthesiologists.

PURPOSE: Medical errors may be occasionally explained by inattentional blindness (IB), i.e., failing to notice an event/object that is in plain sight. We aimed to determine whether age/experience, restfulness/fatigue, and previous exposure to simulation education may affect IB in the anesthetic/surgical setting. METHODS: In this multicentre/multinational study, a convenience sample of 280 anesthesiologists watched an attention-demanding video of a simulated trauma patient undergoing laparotomy and (independently/anonymously) recorded the abnormalities they noticed. The video contained four expected/common abnormalities (hypotension, tachycardia, hypoxia, hypothermia) and two prominently displayed unexpected/rare events (patient's head movement, leaky central venous line). We analyzed the participants' ability to notice the expected/unexpected events (primary outcome) and the proportion of expected/unexpected events according to age group and prior exposure to simulation education (secondary outcomes). RESULTS: Anesthesiologists across all ages noticed fewer unexpected/rare events than expected/common ones. Overall, younger anesthesiologists missed fewer common events than older participants did (P = 0.02). There was no consistent association between age and perception of unexpected/rare events (P = 0.28), although the youngest cohort (< 30 yr) outperformed the other age groups. Prior simulation education did not affect the proportion of misses for the unexpected/rare events but was associated with fewer misses for the expected/common events. Self-perceived restfulness did not impact perception of events. CONCLUSION: Anesthesiologists noticed fewer unexpected/rare clinical events than expected/common ones in an attention-demanding video of a simulated trauma patient, in keeping with IB. Prior simulation training was associated with an improved ability to notice anticipated/expected events, but did not reduce IB. Our findings may have implications for understanding medical mishaps, and efforts to improve situational awareness, especially in acute perioperative and critical care settings.

RéSUMé: OBJECTIF: Les erreurs médicales peuvent parfois s'expliquer par la cécité d'inattention, soit le fait de ne pas remarquer un événement/objet qui est à la vue de tous et toutes. Notre objectif était de déterminer si l'âge/l'expérience, le repos/la fatigue et l'exposition antérieure à l'enseignement par simulation pouvaient affecter la cécité d'inattention dans le cadre de l'anesthésie/chirurgie. MéTHODE: Dans cette étude multicentrique/multinationale, un échantillon de convenance de 280 anesthésiologistes ont visionné une vidéo exigeant l'attention portant sur un patient de trauma simulé bénéficiant d'une laparotomie et ont enregistré (de manière indépendante/anonyme) les anomalies qu'ils et elles ont remarquées. La vidéo contenait quatre anomalies attendues/courantes (hypotension, tachycardie, hypoxie, hypothermie) et deux événements inattendus/rares bien en vue (mouvement de la tête du patient, fuite du cathéter veineux central). Nous avons analysé la capacité des participant·es à remarquer les événements attendus/inattendus (critère d'évaluation principal) et la proportion d'événements attendus/inattendus selon le groupe d'âge et l'exposition antérieure à l'enseignement par simulation (critères d'évaluation secondaires). RéSULTATS: Les anesthésiologistes de tous âges ont remarqué moins d'événements inattendus/rares que d'événements attendus/courants. Globalement, les anesthésiologistes plus jeunes ont manqué moins d'événements courants que leurs congénères plus âgé·es (P = 0,02). Il n'y avait pas d'association constante entre l'âge et la perception d'événements inattendus ou rares (P = 0,28), bien que la cohorte la plus jeune (< 30 ans) ait surpassé les autres groupes d'âge. La formation antérieure par simulation n'a pas eu d'incidence sur la proportion d'inobservation des événements inattendus ou rares, mais a été associée à moins de cécité d'inattention envers les événements attendus ou courants. Le repos perçu n'a pas eu d'impact sur la perception des événements. CONCLUSION: Les anesthésiologistes ont remarqué moins d'événements cliniques inattendus/rares que d'événements attendus/courants dans une vidéo exigeant l'attention portant sur la simulation d'un patient traumatisé, ce qui s'inscrit dans la cécité d'inattention. La formation préalable par simulation était associée à une meilleure capacité à remarquer les événements anticipés/attendus, mais ne réduisait pas la cécité d'inattention. Nos résultats peuvent avoir des implications pour la compréhension des accidents médicaux et les efforts visant à améliorer la conscience situationnelle, en particulier dans les contextes de soins périopératoires aigus et de soins intensifs.

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.

Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is an inflammatory premalignant disorder resulting from acquired genetic mutations in hematopoietic stem cells. This condition is common in aging populations and associated with cardiovascular morbidity and overall mortality, but its role in CKD is unknown. METHODS: We performed targeted sequencing to detect CHIP mutations in two independent cohorts of 87 and 85 adults with an eGFR<60 ml/min per 1.73m2. We also assessed kidney function, hematologic, and mineral bone disease parameters cross-sectionally at baseline, and collected creatinine measurements over the following 5-year period. RESULTS: At baseline, CHIP was detected in 18 of 87 (21%) and 25 of 85 (29%) cohort participants. Participants with CHIP were at higher risk of kidney failure, as predicted by the Kidney Failure Risk Equation (KFRE), compared with those without CHIP. Individuals with CHIP manifested a 2.2-fold increased risk of a 50% decline in eGFR or ESKD over 5 years of follow-up (hazard ratio 2.2; 95% confidence interval, 1.2 to 3.8) in a Cox proportional hazard model adjusted for age, sex, and baseline eGFR. The addition of CHIP to 2-year and 5-year calibrated KFRE risk models improved ESKD predictions. Those with CHIP also had lower hemoglobin, higher ferritin, and higher red blood cell mean corpuscular volume versus those without CHIP. CONCLUSIONS: In this exploratory analysis of individuals with preexisting CKD, CHIP was associated with higher baseline KFRE scores, greater progression of CKD, and anemia. Further research is needed to define the nature of the relationship between CHIP and kidney disease progression.

Is time really of the essence? Timeliness of narrative feedback in ophthalmology CBME assessments.

PURPOSE: Competency-based medical education relies on a strong program of assessment, and quality comments play a vital role in ensuring its success. The goal of this study is to determine the effect of the timeliness of assessment completion on the quality of the feedback. MATERIALS AND METHODS: Using the Quality of Assessment for Learning (QuAL) score 2478 assessments were evaluated. The assessments included those completed between July 2017 and December 2020 for 18 ophthalmology residents. Spearman correlation, Mann-Whitney U and Kruskal-Wallis tests were used to assess variations in QuAL scores based on the timeliness of assessment completion. RESULTS: The timeliness of assessment completion ranged from 0 to 299 d with the mean time for completion being 3 d. As the delay increased, the QuAL score decreased. Feedback provided 4, 5, and 14 d post-encounter demonstrated statistically significant differences in the QuAL score. Additionally, there was a significant difference in the timeliness of feedback when there is no written comment. CONCLUSIONS: This study demonstrates that the timeliness of assessment completion might have an effect on the quality of written feedback. Written feedback should be completed within 14 d of the encounter to optimize quantity and quality.

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.

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.

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.

Electrocardiographic predictors of atrial fibrillation in patients with cryptogenic stroke.

BACKGROUND: Empiric anticoagulation is not routinely indicated in patients with cryptogenic stroke without documentation of atrial fibrillation (AF). Therefore, identification of patients at increased risk of AF from this vulnerable group is vital. OBJECTIVES: To identify electrocardiographic (ECG) predictors of AF in patients with cryptogenic stroke or transient ischemic attack (TIA) undergoing insertion of an implantable cardiac monitor (ICM). METHODS: In this single-center study, 48 patients with cryptogenic stroke or TIA had an ICM implanted for detection of AF between January 2013 and September 2019. Patients with and without AF were compared in terms of p-wave duration and a novel index (MVP score). RESULTS: During a mean follow-up of 16 ± 14 months, AF was detected in seven patients (15%). Diagnosis of AF was made after a mean of 10 ± 14 months, with time to first AF detection ranging between 1 and 40 months. Patients with AF had a longer p-wave duration (136 ± 9 ms vs. 116 ± 10 ms; p = .0001) and a higher MVP score (4.5 ± 1.2 vs. 2.0 ± 0.9, p = .0001) than those without AF. Advanced interatrial block (IAB) was observed in 43% of patients with ICM evidence of AF and 0% of those without AF (p = .002). Age, LA size or LVEF were not predictors of AF. CONCLUSION: An increased p-wave duration, advanced IAB and high MVP score are associated with AF occurrence in patients with cryptogenic stroke. Identifying patients with these markers may be helpful as they may benefit from more exhaustive and prolonged monitoring.

A Canadian single institution real-world experience using the CROSS trial regimen in the treatment of oesophageal and gastroesophageal junction carcinoma.

BACKGROUND: Trimodality therapy using the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial protocol is an accepted standard of care for locally advanced oesophageal and gastroesophageal junction cancers. For medically inoperable patients, chemoradiotherapy (CRT) has been a therapeutic option. AIMS: This single institution review aimed to assess the real-world application of the CROSS trial protocol. METHODS: This is a retrospective review of 83 patients who underwent CRT with carboplatin and paclitaxel with trimodality or definitive intent between June 2012 and June 2018. Sixty-five patients underwent neoadjuvant CRT (NCRT); 40 had surgery, 18 had definitive CRT (DCRT). Patients' demographics, clinical, pathological, treatment and surgical characteristics were assessed. The data were analysed in exploratory analyses and Kaplan-Meier curves. RESULTS: For 83 patients, the following median values were seen: radiotherapy dose, 50.4 Gy; chemotherapy doses, 5; and time from CRT to surgery, 62 days. Twenty-three percent NCRT and 72% DCRT patients were aged ≥75 years, and 49% and 33% of these respectively had no interruptions to CRT. Patients aged ≥75 years were more likely to have DCRT (P = 0.001). Patients who underwent surgery were younger (P = 0.04). For NCRT and surgery, NCRT only and DCRT respectively, median overall survival was 35.5, 12.1 and 17.1 months (log rank P = 0.008); progression-free survival was 32.2, 10 and 9.6 months (log rank P = 0.001). CONCLUSIONS: Despite broadening of the CROSS trial eligibility criteria in our real-world data, there appears to be a survival benefit with trimodality therapy. The use of carboplatin and paclitaxel in DCRT may be of value and requires further study.

Are we choosing mobilization regimens for autologous stem cell transplantation in multiple myeloma wisely: A single center comparison of GCSF+/-plerixafor vs cyclophosphamide/GCSF+/-plerixafor.

BACKGROUND: Autologous stem cell transplantation (ASCT) is a standard consolidation treatment for eligible patients with multiple myeloma (MM). There is no standardized mobilization regimen for collection of CD34+ stem cells, which is crucial to the success of ASCT. Cyclophosphamide/GCSF is an effective regimen, although reported associated toxicities include risk of febrile neutropenia (FN). Since plerixafor was introduced in Canada, this mobilization agent has been increasingly used as needed with GCSF at Kingston Health Science Centre (KHSC), with elimination of cyclophosphamide. This single center, retrospective, quality improvement study evaluates mobilization and ASCT outcomes of MM patients who had undergone stem cell mobilization at KHSC with cyclophosphamide/GCSF+/-plerixafor without antibiotics, cyclophosphamide/GCSF+/-plerixafor with antibiotics, and GCSF+/-plerixafor without antibiotics. METHODS: A retrospective chart review was conducted evaluating 137 patients. The primary outcome measure was FN rates with mobilization. Balancing measures include CD34+ cell collected, plerixafor usage, days of apheresis and transplant outcomes. Chi-square, ANOVA, or Kruskal-Wallis methods were used to test statistical significance where appropriate. RESULTS: Our study noted a higher total and day one CD34+ count in the two groups utilizing cyclophosphamide in mobilization. All nine cases of FN occurred in these two groups (P < .05). Addition of antibiotics decreased, but did not eliminate risk of FN. There were no significant differences in the rate of plerixafor usage and number of apheresis days. Difference in transplant outcomes, including engraftment and transfusion support, were statistically but not clinically significant. A larger sample size may be needed to explore this fully. There was no significant difference in length of transplant hospital stay. CONCLUSION: The elimination of cyclophosphamide from mobilization regimens for MM appears to significantly reduce FN rates, without increasing balancing measures such as total number of apheresis days, plerixafor usage, duration of transplant hospitalization or mortality outcomes.

Retrospective Review of Time to Uterotonic Administration and Maternal Outcomes After Postpartum Hemorrhage.

OBJECTIVE: Despite advances in health care and ample resources, post-partum hemorrhage (PPH) rates are increasing in high income countries. Although guidelines recommend therapeutic uterotonics, timing of administration is open to judgement and most often based on (inherently inaccurate) visual estimates of blood loss. With severe hemorrhage, every minute of delay can have significant consequences. Our objective was to examine the timing of uterotonic administration and its impact upon maternal outcomes. We hypothesized that increased time to uterotonic administration following the identification of PPH would be associated with a greater decline in hemoglobin (Hb) and higher odds of hypotension and transfusion. METHODS: We reviewed all cases of PPH that occurred at an academic centre between June 2015 and September 2017. All cases of primary PPH (i.e., those declared within 24 h of delivery with estimated blood loss [EBL] >500 mL for vaginal and >1000 mL for cesarean deliveries) were analyzed. Patient records were excluded if they were missing information regarding time of PPH declaration, uterotonic administration, and/or Hb measures, or if a pre-existing medical condition could have contributed to PPH. RESULTS: Of 4397 births, there were 259 (5.9%) cases of primary PPH, of which 128 were included in this analysis. For these patients, each 5-minute delay in uterotonic treatment was associated with 26% higher odds of hypotension following delivery of any type. For vaginal deliveries (n = 86), each 5-minute delay was associated with 31% and 34% higher odds of hypotension and transfusion, respectively. CONCLUSION: In this study, delay in administration of therapeutic uterotonics was associated with a higher incidence of hypotension and transfusion in primary PPH patients.

Access to cancer medicines deemed essential by oncologists in 82 countries: an international, cross-sectional survey.

BACKGROUND: The WHO Essential Medicines List (EML) identifies priority medicines that are most important to public health. Over time, the EML has included an increasing number of cancer medicines. We aimed to investigate whether the cancer medicines in the EML are aligned with the priority medicines of frontline oncologists worldwide, and the extent to which these medicines are accessible in routine clinical practice. METHODS: This international, cross-sectional survey was developed by investigators from a range of clinical practice settings across low-income to high-income countries, including members of the WHO Essential Medicines Cancer Working Group. A 28-question electronic survey was developed and disseminated to a global network of oncologists in 89 countries and regions by use of a hierarchical snowball method; each primary contact distributed the survey through their national and regional oncology associations or personal networks. The survey was open from Oct 15 to Dec 7, 2020. Fully qualified physicians who prescribe systemic anticancer therapy to adults were eligible to participate in the survey. The primary question asked respondents to select the ten cancer medicines that would provide the greatest public health benefit to their country; subsequent questions explored availability and cost of cancer medicines. Descriptive statistics were used to compare access to medicines between low-income and lower-middle-income countries, upper-middle-income countries, and high-income countries. FINDINGS: 87 country-level contacts and two regional networks were invited to participate in the survey; 46 (52%) accepted the invitation and distributed the survey. 1697 respondents opened the survey link; 423 were excluded as they did not answer the primary study question and 326 were excluded because of ineligibility. 948 eligible oncologists from 82 countries completed the survey (165 [17%] in low-income and lower-middle-income countries, 165 [17%] in upper-middle-income countries, and 618 [65%] in high-income countries). The most commonly selected medicines were doxorubicin (by 499 [53%] of 948 respondents), cisplatin (by 470 [50%]), paclitaxel (by 423 [45%]), pembrolizumab (by 414 [44%]), trastuzumab (by 402 [42%]), carboplatin (by 390 [41%]), and 5-fluorouracil (by 386 [41%]). Of the 20 most frequently selected high-priority cancer medicines, 19 (95%) are currently on the WHO EML; 12 (60%) were cytotoxic agents and 13 (65%) were granted US Food and Drug Administration regulatory approval before 2000. The proportion of respondents indicating universal availability of each top 20 medication was 9-54% in low-income and lower-middle-income countries, 13-90% in upper-middle-income countries, and 68-94% in high-income countries. The risk of catastrophic expenditure (spending >40% of total consumption net of spending on food) was more common in low-income and lower-middle-income countries, with 13-68% of respondents indicating a substantial risk of catastrophic expenditures for each of the top 20 medications in lower-middle-income countries versus 2-41% of respondents in upper-middle-income countries and 0-9% in high-income countries. INTERPRETATION: These data demonstrate major barriers in access to core cancer medicines worldwide. These findings challenge the feasibility of adding additional expensive cancer medicines to the EML. There is an urgent need for global and country-level policy action to ensure patients with cancer globally have access to high priority medicines. FUNDING: None.

Genetic determinants of VWF clearance and FVIII binding modify FVIII pharmacokinetics in pediatric hemophilia A patients.

Factor VIII (FVIII) pharmacokinetic (PK) properties show high interpatient variability in hemophilia A patients. Although previous studies have determined that age, body mass index, von Willebrand factor antigen (VWF:Ag) levels, and ABO blood group status can influence FVIII PK, they do not account for all observed variability. In this study, we aim to describe the genetic determinants that modify the FVIII PK profile in a population of 43 pediatric hemophilia A patients. We observed that VWF:Ag and VWF propeptide (VWFpp)/VWF:Ag, but not VWFpp, were associated with FVIII half-life. VWFpp/VWF:Ag negatively correlated with FVIII half-life in patients with non-O blood type, but no correlation was observed for type O patients, suggesting that von Willebrand factor (VWF) half-life, as modified by the ABO blood group, is a strong regulator of FVIII PK. The FVIII-binding activity of VWF positively correlated with FVIII half-life, and the rare or low-frequency nonsynonymous VWF variants p.(Arg826Lys) and p.(Arg852Glu) were identified in patients with reduced VWF:FVIIIB but not VWF:Ag. Common variants at the VWF, CLEC4M, and STAB2 loci, which have been previously associated with plasma levels of VWF and FVIII, were associated with the FVIII PK profile. Together, these studies characterize the mechanistic basis by which VWF clearance and ABO glycosylation modify FVIII PK in a pediatric population. Moreover, this study is the first to identify non-VWF and non-ABO variants that modify FVIII PK in pediatric hemophilia A patients.

Secreted Phosphoprotein 24 is a Biomarker of Mineral Metabolism.

The 24 kD form of secreted phosphoprotein (SPP-24), a cytokine-binding bone matrix protein with various truncated C-terminal products, is primarily synthesized by the liver. SPP-24 shares homology with fetuin-A, a potent vascular and soft tissue calcification inhibitor and SPP-24 is one component of calciprotein particles (CPPs), a circulating fetuin-mineral complex. The limited molecular evidence to date suggests that SPP-24 may also function as an inhibitor of bone formation and ectopic vascular calcification, potentially through bone morphogenic protein 2 (BMP-2) and Wnt-signaling mediated actions. The C-terminal products of SPP-24 bind to BMP-2 and attenuate BMP-2-induced bone formation. The aim of this study was to assess circulating SPP-24 in relation to kidney function and in concert with markers of mineral metabolism in humans. SPP-24 was measured in the serum of total of 192 subjects using ELISA-based measurements. Subjects were participants of one of two cohorts: (1) mGFR Cohort (n = 80) was participants of a study of measured GFR (mGFR) using inulin urinary clearance, recruited mostly from a chronic kidney disease clinic with low-range kidney function (eGFR 38.7 ± 25.0 mL/min/1.73 m2) and (2) CaMOS Cohort (n = 112) was a subset of randomly selected, community-dwelling participants of year 10 of the Canadian Multicentre Osteoporosis Study with eGFR in the normal range of 75.0 ± 15.9 mL/min/1.73 m2. In the combined cohort, the mean SPP-24 was 167.7 ± 101.1 ng/mL (range 33.4-633.6 ng/mL). The mean age was 66.5 ± 11.3, 57.1% female and mean eGFR (CKD-EPI) was 59.9 ± 27.0 mL/min/1.73 m2 (range 8-122 mL/min/1.73 m2). There was a strong inverse correlation between SPP-24 and eGFR (R = - 0.58, p < 0.001) that remained after adjustment for age. Following adjustment for age, eGFR, and sex, SPP-24 was significantly associated with phosphate (R = - 0.199), PTH (R = 0.298), and the Wnt-signaling inhibitor Dickkopf-related protein 1 (R = - 0.156). The results of this study indicate that SPP-24 is significantly altered by kidney function and is the first human data linking levels of SPP-24 to other biomarkers involved in mineral metabolism. Whether there is a role for circulating SPP-24 in bone formation and ectopic mineralization requires further study.

Evaluating the effectiveness of let's talk period's high school educational outreach program: A pilot study.

INTRODUCTION: Menorrhagia impacts ~40% of adolescent females, with about half having an underlying bleeding disorder, most commonly von Willebrand Disease (VWD). VWD affects ~1 in 1000 individuals, though many are unaware of their condition. Let's Talk Period (LTP) is an online knowledge translation platform aimed at increasing awareness of bleeding disorders symptoms, with a validated self-administered bleeding assessment tool (Self-BAT). AIM: To evaluate the effectiveness of the LTP high school outreach program in Grade 9 girls' health classes quantitatively, using baseline, post-presentation, and follow-up quiz scores, and qualitatively, with student and teacher feedback forms. METHODS: The 75-minute in-class presentations, developed in alignment with the 2015 Ontario Curriculum for Grade 9 Health and Physical Activity, were led by a haemophilia nurse, clinical research assistant, and undergraduate student from the LTP team. Students completed baseline, post-presentation, and 4-6-week follow-up Kahoot quizzes featuring the same nine questions to evaluate change in knowledge levels and retention. Both student and teacher feedback were collected. RESULTS: There was a significant increase (p < 0.001) from baseline to post-presentation scores, with a significant gain in knowledge, for all questions (p < 0.01). Students found content related to the basics and management of menstruation to be most interesting. Many had constructive feedback on how the presentation method could be improved. On average, the presentations were rated an 8.6 of 10 by students and 8.75 of 10 by teachers. CONCLUSION: The LTP high school outreach program effectively increases student knowledge of menorrhagia and bleeding disorders. It was well-received by students and staff alike.

Adductor canal block with or without added magnesium sulfate following total knee arthroplasty: a multi-arm randomized controlled trial.

PURPOSE: Postoperative analgesia following total knee arthroplasty (TKA) often includes intrathecal opioids, periarticular injection (PAI) of local anesthetic, systemic multimodal analgesia, and/or peripheral nerve blockade. The adductor canal block (ACB) provides analgesia without muscle weakness and magnesium sulphate (MgSO4) may extend its duration. The purpose of this trial was to compare the duration and quality of early post-TKA analgesia in patients receiving postoperative ACB (± MgSO4) in addition to standard care. METHODS: Elective TKA patients were randomized to: 1) sham ACB, 2) ropivacaine ACB, or 3) ropivacaine ACB with added MgSO4. All received spinal anesthesia with intrathecal morphine, intraoperative PAI, and multimodal systemic analgesia. Patients and assessors remained blinded to allocation. Anesthesiologists knew whether patients had received sham or ACB but were blinded to MgSO4. The primary outcome was time to first analgesic (via patient-controlled analgesia [PCA] with iv morphine) following ACB. Secondary outcomes were morphine consumption, side effects, visual analogue scale pain scores, satisfaction until 24 hr postoperatively, and length of stay. RESULTS: Of 130 patients, 121 were included. Nine were excluded post randomization: four were protocol violations, three did not meet inclusion criteria, and two had severe pain requiring open label blockade. There were no differences in the median [interquartile range] time to first PCA request: sham, 310 min [165-550]; ropivacaine ACB, 298 min [120-776]; and ropivacaine ACB with MgSO4, 270 min [113-780] (P = 0.96). Similarly, we detected no differences in resting pain, opioid consumption, length of stay, or associated side effects until 24 hr postoperatively. CONCLUSION: We found no analgesic benefit of a postoperative ACB, with or without added MgSO4, in TKA patients undergoing spinal anesthesia and receiving intrathecal morphine, an intraoperative PAI, and multimodal systemic analgesia. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02581683); registered 21 October 2015.

RéSUMé: OBJECTIF: L'analgésie postopératoire suivant une arthroplastie totale du genou (ATG) inclut souvent des opioïdes intrathécaux, une injection périarticulaire (IPA) d'anesthésique local, une analgésie multimodale systémique, et/ou des blocs des nerfs périphériques. Le bloc du canal des adducteurs (BCA) permet une analgésie sans faiblesse musculaire et le sulfate de magnésium (MgSO4) pourrait prolonger sa durée. L'objectif de cette étude était de comparer la durée et la qualité de l'analgésie post-ATG précoce chez les patients recevant un BCA postopératoire (± MgSO4) en plus des soins standard. MéTHODE: Des patients devant subir une ATG non urgente ont été randomisés à recevoir : 1) un BCA placebo (groupe témoin), 2) un BCA avec ropivacaïne, ou 3) un BCA avec ropivacaïne et MgSO4. Tous ont reçu une rachianesthésie avec morphine intrathécale, une IPA peropératoire, et une analgésie multimodale systémique. L'allocation a été faite à l'insu des patients et des évaluateurs. Les anesthésiologistes savaient si les patients avaient reçu un placebo ou un BCA, mais n'étaient pas informés de l'ajout ou non de MgSO4. Le critère d'évaluation principal était le temps jusqu'à la première prise d'analgésique (via une analgésie contrôlée par le patient [ACP] avec de la morphine iv) après le BCA. Les critères secondaires comprenaient la consommation de morphine, les effets secondaires, les scores de douleur sur l'échelle visuelle analogue, la satisfaction jusqu'à 24 heures postopératoires, et la durée de séjour. RéSULTATS: Sur 130 patients, 121 ont été inclus. Neuf ont été exclus après la randomisation : quatre l'ont été en raison de violations du protocole, trois ne répondaient pas aux critères d'inclusion, et deux ont ressenti des douleurs graves nécessitant un bloc sans insu. Aucune différence n'a été observée dans le temps médian [écart interquartile] jusqu'à la première demande d'ACP : placebo, 310 min [165-550]; BCA ropivacaïne, 298 min [120-776]; et BCA ropivacaïne avec MgSO4, 270 min [113-780] (P = 0,96). De la même manière, nous n'avons détecté aucune différence dans la douleur au repos, la consommation d'opioïdes, la durée de séjour, ou les effets secondaires associés jusqu'à 24 heures postopératoires. CONCLUSION: Nous n'avons trouvé aucun avantage analgésique à un BCA postopératoire, avec ou sans ajout de MgSO4, chez les patients subissant une ATG sous rachianesthésie et recevant de la morphine intrathécale, une IPA peropératoire, et une analgésie multimodale systémique. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02581683); enregistrée le 21 octobre 2015.

Are patients truly informed? A retrospective chart review of the documentation of informed consent in laparoscopic cholecystectomy.

Background: Research on informed consent (IC) has traditionally focused on the documentation of the discussion with patients of potential complications. We sought to examine the completeness of documentation for all elements of IC for laparoscopic cholecystectomy (LC): potential complications, alternatives to LC and details of the procedure. Differences in the documentation of IC for elective and emergent LC were examined. Methods: A retrospective chart review of patients undergoing LC at our institution between 2015 and 2017 was performed. Completeness of documentation was defined as documentation of all 3 elements of IC in the clinic note, the operating room note or the consent form itself. Data were analyzed descriptively. We compared documention for emergent and elective cases as well as documentation by residents and attending physicians using t tests. Results: A total of 270 patients were included in the analysis. Only 5 (2%) had complete documentation of all elements of IC. Documentation of potential complications was noted in 232 cases (86%), of which 58 (25%) were elective and 174 (75%) were emergent. Details were noted in 28 (10%) cases, of which 21 (75%) were elective and 7 (25%) were emergent. Alternatives were documented the least frequently: they were documented in 23 cases (9%), of which 20 (87%) were elective and 3 (13%) were emergent. Residents performed better than attending physicians in documenting IC discussions in clinic notes and on consent forms, but not in operating room notes. Conclusion: Documentation of the elements of IC for LC was poor. Potential complications were the most frequently documented element of IC; alternatives and details were often omitted. Future studies comparing audiotaped IC conversations with the documentation of IC are warranted. The use of procedure-specific consent forms for LC may facilitate documentation.

Contexte: La recherche sur le consentement éclairé (CÉ) s'est longtemps intéressée surtout à la consignation du contenu des discussions avec les patients au sujet des complications potentielles. Nous avons voulu examiner l'exhaustivité de la consignation de tous les éléments du CÉ pour la cholécystectomie laparoscopique (CL) : complications potentielles, solutions de rechange à la CL et détails de l'intervention. Nous avons observé des différences dans la consignation des éléments du CÉ pour la CL urgente et non urgente. Méthodes: Nous avons procédé à un examen rétrospectif des dossiers de patients soumis à une CL dans notre établissement entre 2015 et 2017. La consignation au dossier était jugée complète lorsque les 3 éléments du CÉ étaient présents dans la note clinique, la note opératoire ou le formulaire de consentement lui-même. Nous avons effectué une analyse descriptive des données, et nous avons comparé la consignation des éléments pour les cas urgents et non urgents, effectuée par les résidents et les médecins traitants au moyen de tests t. Résultats: Au total, 270 patients ont été inclus dans l'analyse. Tous les éléments du CÉ étaient adéquatement consignés pour seulement 5 (2 %) d'entre eux. Les complications potentielles ont été consignées dans 232 cas (86 %), dont 58 (25 %) étaient non urgents et 174 (75 %) étaient urgents. Les détails de l'intervention ont été notés dans 28 cas (10 %), dont 21 (75 %) étaient non urgents et 7 (25 %) étaient urgents. Ce sont les solutions de rechange qui ont été le moins souvent consignées : elles ont été notées dans 23 cas (9 %), dont 20 (87 %) étaient non urgents et 3 (13 %) étaient urgents. Les résidents ont mieux fait que les médecins traitants pour ce qui est de consigner les discussions sur le CÉ dans les notes cliniques et les formulaires de CÉ, mais non dans les notes opératoires. Conclusion: La consignation des éléments du CÉ pour la CL a été faible. Les complications potentielles ont été l'élément du CÉ le plus souvent consigné au dossier; les solutions de rechange et les détails de l'intervention ont souvent été omis. Il faudra procéder à d'autres études pour comparer le contenu des discussions sur le CÉ enregistrées sur bande audio et sa consignation. L'utilisation de formulaires de CÉ spécifiques aux interventions pourrait faciliter la consignation de leurs éléments.

Cancellation of elective surgery: rates, reasons and effect on patient satisfaction.

Background: The cancellation of elective surgeries is a major problem that increases wait times, exacerbates costs and can negatively affect patients, both psychologically and physically. Our objectives were to investigate the reasons for cancellations across specialties at a single centre, to compare these reasons with previous data from the same centre between 2005 and 2009 and to examine how cancellations affected patients' lives and views of the medical system in cases when the cancellations were potentially preventable. Methods: Cancellation records of all elective surgeries scheduled between June 1, 2012, and Jan. 31, 2016, at a medium-sized, tertiary care, academic centre were retrospectively reviewed. We evaluated the rates and reasons for cancellation and interviewed a subset of patients whose surgery was cancelled for a potentially preventable reason (i.e., operating room running late, bed shortage, emergency case took place of scheduled surgery). Results: Across 11 surgical specialties, 2933 of 20 881 surgeries (14.0%) were cancelled and of these, 2448 (83.5%) were for administrative or structural reasons. Compared with the data collected previously for general, gynecological and urological procedures, cancellation rates increased from 8.1% to 11.8%. Although patients reported inconvenience, they were generally satisfied with the availability and the quality of the health care they received. Conclusion: Consistent with the previous study, our data suggest that most cancellations occur because of administrative or structural processes that are potentially preventable. Targeting these processes may help to reduce cancellations for elective surgeries and thereby improve economic efficiency and patient outcomes.

Contexte: L'annulation des chirurgies électives est un problème majeur qui allonge les temps d'attente, fait gonfler les coûts et peut affecter négativement les patients, tant psychologiquement que physiquement. Nos objectifs étaient de découvrir les raisons des annulations dans les diverses spécialités d'un seul centre, afin de comparer ces raisons à des données antérieures du même centre recueillies entre 2005 et 2009 et d'examiner en quoi les annulations affectent la vie des patients et leur perception du système médical dans les cas où les annulations auraient pu être évitées. Méthodes: Les dossiers d'annulation de toutes les chirurgies électives entre le 1er juin 2012 et le 31 janvier 2016 dans un centre hospitalier universitaire de soins tertiaires de taille moyenne ont été analysés de manière rétrospective. Nous avons évalué les taux d'annulation et les motifs, et interrogé un groupe de patients dont la chirurgie a été annulée pour des raisons potentiellement évitables (p. ex., retards au bloc opératoire, manque de lits, priorisation de cas plus urgents). Résultats: Entre les 11 spécialités chirurgicales, 2933 des 20 881 chirurgies (14,0 %) ont été annulées et parmi elles, 2448 (83,5 %) pour des raisons administratives ou structurelles. Comparativement aux données précédemment recueillies pour les interventions générales, gynécologiques et urologiques, les taux d'annulation ont augmenté de 8,1 % à 11,8 %. Même si les patients ont déploré des inconvénients, ils se sont généralement déclarés satisfaits de la qualité des soins reçus et de leur accessibilité. Conclusion: Comme lors de l'étude précédente, nos données suggèrent que les causes les plus fréquentes d'annulation sont liées à des marches à suivre administratives ou structurelles qui sont potentiellement évitables. Cibler ces marches à suivre pourrait contribuer à réduire le nombre d'annulations de chirurgies électives et améliorer de ce fait l'efficience économique et les résultats chez les patients.