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Objective: The integration of robotic surgical training in a time-scarce residency program is a challenge for surgical educators. Simulation-based training is a tool that allows residents to acquire the necessary robotic skills without compromising patient safety. This study aimed to assess the learning curve of a robotic inanimate intestinal anastomosis drill., Design: Two trained graders performed a video-based assessment of each attempt of a side-to-side intestinal anastomosis drill using the Objective Structured Assessment of Technical Skill (OSATS) scale. Residents who achieved a passing score of 28 were included in the study. We assessed the number of attempts required to achieve a passing score and evaluated technical performance on different OSATS domains. Data were analyzed using independent t-test, 1-way ANOVA, and binary logistic regression., Setting: The University of Texas Southwestern PARTICIPANTS: 33 residents across 4 academic years RESULTS: Thirty-three residents performed 139 attempts with a mean of 4.2 ± 2 attempts per resident. On average, 3.3 attempts were required to achieve a passing score. Average OSATS score increased from 21.7 to 27.2 between the 1st and the 4th attempt, respectively (p < 0.001). Of the OSATS subcategories, time and motion showed the greatest score improvement of 1.5 on a 5-point Likert scale, 95% CI [0.82, 2.18] (p < 0.001). Despite varying baseline OSATS scores between residents on initial assessment, there was no significant difference in the final attempt score. On the initial attempt, a lower score and failure to finish were associated with greater odds of requiring 5 or more attempts to pass the drill., Conclusion: All OSATS metrics improved on an intestinal anastomosis drill after simulation training. A maximum of 6 attempts were required to achieve a passing score. Initial performance strongly predicts the number of attempts required to achieve a passing score. This feasible and effective drill provides trainees with robotic intestinal anastomosis training., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: There is limited evidence regarding body mass index (BMI) as an early marker of high-risk adenoma (HRA) at the time of screening colonoscopy. Because high-risk adenomas (HRA) can develop into colorectal cancer (CRC), BMI could serve as an important clinical predictor of future risk of CRC., Methods: We examined data from 1831 adults undergoing screening colonoscopy at the Forzani & MacPhail Colon Cancer Screening Center in Alberta, Canada. We fit multivariable logistic regression models to examine the association between BMI and HRA. Non-linear relationships for BMI on HRA were also evaluated using restricted cubic splines., Results: The mean BMI in patients with HRA was 28.2 kg/m 2 compared to 27.4 kg/m 2 in patients without adenomas (t test: p = 0.003). In the adjusted models, those with a BMI over 30 kg/m 2 had 1.45 (95% CI 1.05-2.00) times the odds of HRA detected during colonoscopy compared to those with a BMI below 25 kg/m 2 . Examining BMI as continuous, the odds of HRA were 1.20 (95% CI 1.04-1.37) times higher for every 5 kg/m 2 increase in BMI., Conclusion: The findings of this study suggest that excess body mass is associated with higher risk of HRA among a screening population and may be useful an early marker of future disease., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval Ethics approval for the data collection and recruitment was obtained from the University of Calgary Conjoint Health Research Ethics Board (CHREB) and was eventually transferred to the Health Research Ethics Board of Alberta Cancer Committee (ID HREBA.CC-16-2024). Consent to participate Written informed consent was obtained from all participants., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Stroke is a life-threatening medical condition that could lead to mortality or significant sensorimotor deficits. Various machine learning techniques have been successfully used to detect and predict stroke-related outcomes. Considering the diversity in the type of clinical modalities involved during management of patients with stroke, such as medical images, bio-signals, and clinical data, multimodal machine learning has become increasingly popular. Thus, we conducted a systematic literature review to understand the current status of state-of-the-art multimodal machine learning methods for stroke prognosis and diagnosis. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines during literature search and selection, our results show that the most dominant techniques are related to the fusion paradigm, specifically early, joint and late fusion. We discuss opportunities to leverage other multimodal learning paradigms, such as multimodal translation and alignment, which are generally less explored. We also discuss the scale of datasets and types of modalities used to develop existing models, highlighting opportunities for the creation of more diverse multimodal datasets. Finally, we present ongoing challenges and provide a set of recommendations to drive the next generation of multimodal learning methods for improved prognosis and diagnosis of patients with stroke.

This study investigates the feasibility of incorporating shredded polyethylene terephthalate (PET) post-consumer plastic waste as a partial replacement for coarse aggregates in unreinforced concrete such as masonry blocks. Standard concrete blocks were produced with varying PET content (0%, 5%, 25%, 35%, 50%) and tested for workability, air content, density, compressive strength, flexural strength, and thermal conductivity. Results indicated that replacing up to 25% of traditional aggregates with PET maintains adequate compressive strength for non-load-bearing applications and enhances thermal insulation by reducing the thermal conductivity from 0.7 W/m·°K to 0.27 W/m·°K at 25% replacement level, representing a significant improvement of approximately 61%. Higher PET content (35-50%) resulted in reduced structural integrity but improved insulation, suggesting its suitability for non-structural applications. This research highlights the potential of using PET plastic waste in unreinforced concrete, promoting sustainable construction practices by reducing plastic waste and conserving natural resources.

Background: Compared to open pancreaticoduodenectomies (OPD), the robotic (RPD) approach decreases the rate of complication and the length of stay (LOS). However, it remains unknown if these benefits persist in octogenarians, who are at higher risk for perioperative morbidity and mortality., Methods: A retrospective analysis of the ACS-NSQIP database was performed to identify patients aged 80 years or older who underwent PD for pancreatic adenocarcinoma between 2015-2021. Patients who underwent RPD or OPD were compared using inversed probability weighting of the propensity score. Outcomes assessed include operative time, LOS, non-home discharge, major complications, unplanned readmission, return to the operating room, mortality, and clinically relevant postoperative pancreatic fistula., Results: Of 30,751 patients, 1720 were octogenarians. One thousand six hundred twenty-five patients (94 %) underwent OPD, and 95 (6 %) underwent RPD. RPD was significantly associated with a reduced incidence of major complications (32.6 % vs. 45.6 %; p < 0.01) and a lower rate of non-home discharge (24.7 % vs. 34.3%; p < 0.05). However, RPD was associated with a longer operative time (438 min vs. 342 min; p < 0.0001). There was no difference in other assessed outcomes., Conclusion: RPD may reduce major postoperative complications and non-home discharges compared to the open approach for octogenarians., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

This work presents an exhaustive chemical characterization of the organic fraction of fine particulate matter (PM 2.5 ) collected at an urban site in the Greater Cairo Area, Egypt, one of the most polluted megacities in the world. An intensive 2-month sampling campaign was conducted at an urban site in Giza (Dokki), from November 26, 2019, to January 28, 2020. Daily (24-h integrated) PM 2.5 filter samples were then analyzed for their carbonaceous (OC, EC) and organic fractions including primary (n-alkanes, phthalates, fatty acids, polycyclic aromatic hydrocarbons, hopanes, sugars, and sugar alcohols) and secondary (isoprene and β-caryophyllene oxidation products, and dicarboxylic acids) compounds. Average organic (OC) and elemental carbon (EC) concentrations were 17.8 ± 6.6 μg/m 3 and 4.4 ± 1.5 μg/m 3 , respectively. Biomass burning was confirmed by high daily concentration levels of levoglucosan, mannosan, and galactosan (sum equals to 288 ng/m 3 ). Road traffic was also highlighted by the relative abundance of tetracosane and a carbon preference index close to unity as well as by the concentration ratios of PAHs and hopanes. Moreover, phthalates were identified for the first time in Cairo with high concentrations (654 ng/m 3 ) that might be attributable to open waste burning activities. Fatty acids and sugars were also investigated and assigned to cooking activities and primary biogenic sources, respectively. The average concentration of isoprene and β-caryophyllene oxidation products were 0.89 ± 0.83 ng/m 3 , and 0.01 ± 0.02 ng/m 3 , respectively. These low values are expected since no pine trees or even forests exist in Egypt. The macrotracer approach was employed alongside Monte Carlo simulation to identify sources of primary OC and evaluate the uncertainties associated with source attribution and OC reconstruction. The findings revealed a strong contribution from cooking (31% of observed OC) and biomass burning (18%), with median reconstructed OC levels showing significant uncertainty (64%) as expected., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Simulation and video-based assessment (VBA) offer residents the opportunity to develop operative skills while ensuring patient safety. This study aims to determine whether simulation training can predict residents' operative performance, focusing on the gastrojejunal (GJ) anastomosis during robotic pancreatoduodenectomy., Methods: Twenty-seven general surgery residents completed simulated robotic GJ drills and subsequently performed GJs in the operating room (OR). Both simulated and intraoperative performances were video recorded and retrospectively assessed by two blinded graders using the Objective Structural Assessment of Technical Skills (OSATS) scale, time to completion, and occurrence of errors. Intraoperative GJ OSATS scores were compared in cases with and without Clinically Relevant Delayed Gastric Emptying (CRDGE). Statistical analysis was performed using Spearman's rho, Chi-square, and Kruskal-Wallis tests., Results: For simulated GJs, the median OSATS score was 29 (IQR 27-33), time to completion was 30 min (IQR 27-35), and 11 cases had at least one error. Intraoperative GJs had a median OSATS of 30 (IQR 27-31), time to completion of 41 min (IQR 36-51), and errors occurred in nine cases. The OSATS score on the simulated GJs demonstrated a significant positive correlation to the OSATS score on the operative GJs (r = 0.74; p < 0.001) and less time to completion (r =  - 0.68; p < 0.001). A shorter simulated GJ completion time significantly correlated with a higher intraoperative OSATS score (r =  - 0.52; p < 0.01). Residents with at least one error in the simulated GJs had lower OSATS scores and higher times intraoperatively. Those cases with CRDGE had significantly lower intraoperative OSATS scores than those without CRDGE., Conclusion: Performance on a simulated robotic GJ environment is a robust predictor of OR GJ performance, demonstrating predictive validity. VBA of residents' operative GJ performance is associated with the presentation of CRDGE. Simulation-based training may be crucial to optimizing surgical outcomes before operating on patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the long-term functional outcomes of canalicular laceration repair using the Masterka® monocanalicular intubation system., Methods: this interventional case series included the data from 30 patients who underwent canalicular laceration repair with a 30-mm pushed monocanalicular stent (Masterka®) and suturing of the lacerated canaliculus with 8/0 Vicryl interrupted sutures. Operative details and complications were meticulously noted. Stent removal took place as early as 3 months post-surgery, with functional success defined as the absence of epiphora four years after surgery., Results: The average age of patients was 28.5±26.3 years, with 20 out of 30 patients (66.6%) being male. Lower canaliculus involvement was noted in 23 patients (76.6%), while the upper canaliculus was affected in 7 patients (23.4%). On average, patients presented for medical attention within approximately one day of sustaining with injuries, and all underwent successful repairs. Notably, functional success was observed in all 30 cases, constituting a 100% success rate. Stent-related complications were encountered in two patients (6.6%). One patient reported stent removal after an average follow-up period of one month, while the other developed a punctal granuloma one-month post-surgery, which regressed following one month of topical steroid treatment., Conclusion: Repairing canalicular lacerations using the self-retaining Masterka® monocanalicular intubation system demonstrated a notable achievement in long-term functional success while presenting minimal complications. To further substantiate these promising results, an interventional study that includes a comparison analysis with other types of intubation methods is warranted., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Purpose: The incidence of early-onset (<50 years of age) colorectal cancer (eoCRC) has been steadily increasing in high-income countries including Canada. Despite this increase in incidence, the etiology of eoCRC remains unclear and prospective cohort studies of potential risk factors are limited., Methods: We examined two prospective cohorts of healthy individuals (<50 years of age) who completed baseline questionnaires in the Ontario Health Study and Alberta's Tomorrow Project. We examined the associations between demographic characteristics, chronic health conditions, and lifestyle behaviours with the development of eoCRC using Cox proportional hazard models. Cohorts were analyzed separately and hazard ratios for each risk factor were pooled with random effects meta-analyses., Results: During an average follow-up of 6.63 years, 98 eoCRC cases occurred among study participants (n=127,852). A family history of CRC alone or with a history of other cancer types was associated with an increased risk of developing eoCRC (HR: 2.76, 95% CI: 1.43-5.32), but a family history of a non-CRC cancer only was not (HR: 1.18, 95% CI: 0.61-2.30). Heavy smokers (≥ 10 pack-years) at baseline had a higher risk of eoCRC compared to non-smokers (HR: 1.87, 95% CI: 1.00-3.52). Sex, socioeconomic factors, diabetes, alcohol consumption, among other factors were not significantly associated with the risk of eoCRC., Conclusion: Our findings indicate that specific CRC risk factors are also associated with developing eoCRC. The data in the study offers valuable insights that could be integrated in future meta-analyses. Additional prospective cohort studies are required to understand the etiology of eoCRC., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Randomized controlled trials (RCTs) are the gold standard for evaluating the comparative efficacy and safety of new cancer therapies. However, enrolling patients in control arms of clinical trials can be challenging for rare cancers, particularly in the context of precision oncology and targeted therapies. External Control Arms (ECAs) are a potential solution to address these challenges in clinical research design. We conducted a scoping review to explore the use of ECAs in oncology., Methods: We systematically searched four databases, namely MEDLINE, EMBASE, Web of Science, and Scopus. We screened titles, abstracts, and full texts for eligible articles focusing on patients undergoing therapy for cancer, employing ECAs, and reporting clinical outcomes., Results: Of the 629 articles screened, 23 were included in this review. The earliest included studies were published in 1996, while most studies were published in the past 5 years. 44% (10/23) of ECAs were employed in blood-related cancer studies. Geographically, 30% (7/23) of studies were conducted in the United States, 22% (5/23) in Japan, and 9% (2/23) in South Korea. The primary data sources used to construct the ECAs involved pooled data from previous trials (35%, 8/23), administrative health databases (17%, 4/23) and electronic medical records (17%, 4/23). While 52% (12/23) of the studies employed methods to align treatment and ECAs characteristics, 48% (11/23) lacked explicit strategies., Conclusion: ECAs offer a valuable approach in oncology research, particularly when alternative designs are not feasible. However, careful methodological planning and detailed reporting are essential for meaningful and reliable results., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Disparities in colorectal cancer (CRC) screening uptake by socioeconomic status have been observed in Canada. We used the OncoSim-Colorectal model to evaluate the health and economic outcomes associated with increasing the participation rates of CRC screening programs to 60% among Canadians in different income quintiles., Methods: Baseline CRC screening participation rates were obtained from the 2017 Canadian Community Health Survey. The survey participants were categorized into income quintiles using their reported household income and 2016 Canadian Census income quintile thresholds. Within each quintile, the participation rate was the proportion of respondents aged 50-74 who reported having had a fecal test in the past two years. Using the OncoSim-Colorectal model, we simulated an increase in CRC screening uptake to 60% across income quintiles to assess the effects on CRC incidence, mortality, and associated economic costs from 2024 to 2073., Results: Increasing CRC screening participation rates to 60% across all income quintiles would prevent 69,100 CRC cases and 36,600 CRC deaths over 50 years. The improvement of clinical outcomes would also translate to increased person-years and health-adjusted person-years. The largest impact was observed in the lowest income group, with 22,200 cases and 11,700 deaths prevented over 50 years. Increased participation could lead to higher screening costs ($121 million CAD more per year) and lower treatments costs ($95 million CAD less per year), averaged over the period 2024-2073., Conclusion: Increased screening participation will improve clinical outcomes across all income groups while alleviating associated treatment costs. The benefits of increased participation will be strongest among the lowest income quintile., (© 2024. The Author(s).)

Background: Internet-based health education is increasingly vital in patient care. However, the readability of online information often exceeds the average reading level of the US population, limiting accessibility and comprehension. This study investigates the use of chatbot artificial intelligence to improve the readability of cancer-related patient-facing content., Methods: We used ChatGPT 4.0 to rewrite content about breast, colon, lung, prostate, and pancreas cancer across 34 websites associated with NCCN Member Institutions. Readability was analyzed using Fry Readability Score, Flesch-Kincaid Grade Level, Gunning Fog Index, and Simple Measure of Gobbledygook. The primary outcome was the mean readability score for the original and artificial intelligence (AI)-generated content. As secondary outcomes, we assessed the accuracy, similarity, and quality using F1 scores, cosine similarity scores, and section 2 of the DISCERN instrument, respectively., Results: The mean readability level across the 34 websites was equivalent to a university freshman level (grade 13±1.5). However, after ChatGPT's intervention, the AI-generated outputs had a mean readability score equivalent to a high school freshman education level (grade 9±0.8). The overall F1 score for the rewritten content was 0.87, the precision score was 0.934, and the recall score was 0.814. Compared with their original counterparts, the AI-rewritten content had a cosine similarity score of 0.915 (95% CI, 0.908-0.922). The improved readability was attributed to simpler words and shorter sentences. The mean DISCERN score of the random sample of AI-generated content was equivalent to "good" (28.5±5), with no significant differences compared with their original counterparts., Conclusions: Our study demonstrates the potential of AI chatbots to improve the readability of patient-facing content while maintaining content quality. The decrease in requisite literacy after AI revision emphasizes the potential of this technology to reduce health care disparities caused by a mismatch between educational resources available to a patient and their health literacy.

Background: Laparoscopic hiatal hernia repair (LHHR) is a complex operation requiring advanced surgical training. Surgical simulation offers a potential solution for learning complex operations without the need for high surgical volume. Our goal is to develop a virtual reality (VR) simulator for LHHR; however, data supporting task-specific metrics for this procedure are lacking. The purpose of this study was to develop and assess validity and reliability evidence of task-specific metrics for the fundoplication phase of LHHR., Methods: In phase I, structured interviews with expert foregut surgeons were conducted to develop task-specific metrics (TSM). In phase II, participants with varying levels of surgical expertise performed a laparoscopic Nissen fundoplication procedure on a porcine stomach explant. Video recordings were independently assessed by two blinded graders using global and TSM. An intraclass correlation coefficient (ICC) was used to assess interrater reliability (IRR). Performance scores were compared using a Kruskal-Wallis test. Spearman's rank correlation was used to evaluate the association between global and TSM., Results: Phase I of the study consisted of 12 interviews with expert foregut surgeons. Phase II engaged 31 surgery residents, a fellow, and 6 attendings in the simulation. Phase II results showed high IRR for both global (ICC = 0.84, p < 0.001) and TSM (ICC = 0.75, p < 0.001). Significant between-group differences were detected for both global (χ 2  = 24.01, p < 0.001) and TSM (χ 2  = 18.4, p < 0.001). Post hoc analysis showed significant differences in performance between the three groups for both metrics (p < 0.05). There was a strong positive correlation between the global and TSM (rs = 0.86, p < 0.001)., Conclusion: We developed task-specific metrics for LHHR and using a fundoplication model, we documented significant reliability and validity evidence. We anticipate that these LHHR task-specific metrics will be useful in our planned VR simulator., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Within the past decade, minimally invasive pancreaticoduodenectomy has been increasingly adopted in high-volume cancer centers. Amid broader trends of a growing older population, the numbers of frail patients with cancer are expected to increase. In this study, we compared the postoperative outcomes of open pancreaticoduodenectomy and minimally invasive pancreaticoduodenectomy in frail patients with pancreatic ductal adenocarcinoma., Methods: Using the pancreatectomy-targeted American College of Surgeons-National Surgical Quality Improvement Program database (2014-2021), we identified pancreaticoduodenectomy cases for pancreatic ductal adenocarcinoma. Patients with a modified frailty index ≥2 were considered frail. We performed 2:1 (open pancreaticoduodenectomy to minimally invasive pancreaticoduodenectomy) optimal pair propensity score matching for both patient- and disease-specific characteristics. We evaluated baseline covariate balance for homogeneity and assessed 30-day postoperative outcomes: complications, discharge destination, major morbidity, and mortality., Results: We identified 3,143 frail patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. Of those, 275 (9%) underwent minimally invasive pancreaticoduodenectomy. Minimally invasive pancreaticoduodenectomy was associated with a lower rate of any complications compared with open pancreaticoduodenectomy (43% vs 54%; P < .001), major morbidity (29% vs 35%; P = .042), and nonhome discharge (12% vs 17%; P = .022). When comparing the 2 minimally invasive pancreaticoduodenectomy approaches, robotic surgery was associated with fewer complications compared with laparoscopy (39% vs 51%; P = .040) and a lower mortality rate (1% vs 4%; P = .041) CONCLUSION: In frail patients with pancreatic cancer, minimally invasive pancreaticoduodenectomy was associated with better postoperative outcomes than open pancreaticoduodenectomy. This study builds on growing literature reporting that, when properly implemented, minimally invasive pancreaticoduodenectomy is associated with more favorable postoperative outcomes. Given the particularly high risk of complication in frail patients, implementing a preoperative frailty assessment can provide valuable insights to inform patient counseling., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

This commentary provides a detailed overview of the extensive stakeholder engagement efforts critical to the development of the Future of Cancer Impact (FOCI) in Alberta report. The overarching aim of the FOCI report was to support informed and strategic discussions and actions that will help key stakeholders in the province prepare for a future with increasing cancer incidence and survival. Employing a comprehensive approach and a diverse range of engagement activities, insights from a wide spectrum of stakeholders were gathered and subsequently used to shape the content of the report. This inclusive process ensured broad representation of perspectives, contributing to a deeper understanding of the complexities in cancer care. The outcome is a robust, consensus-driven report with recommendations set to drive significant transformations within the healthcare system. These efforts highlight the critical role of extensive, inclusive, and collaborative engagement in shaping healthcare initiatives and advancing discussions crucial for the future of cancer care in Alberta.

Background: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan., Methods: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era., Results: Fifty-four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04)., Conclusions: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: We aimed to describe the association of patient-related factors such as race, socioeconomic status, and insurance on failure to rescue (FTR) after hepato-pancreato-biliary (HPB) surgeries., Methods: Using the National Inpatient Sample, we analyzed 98,788 elective HPB surgeries between 2004 and 2017. Major and minor complications were identified using ICD9/10 codes. We evaluated mortality rates and FTR (inpatient mortality after major complications). We used multivariate logistic regression analysis to assess racial, socioeconomic, and demographic factors on FTR, adjusting for covariates., Results: Overall, 43 % of patients (n = 42,256) had pancreatic operations, 36% (n = 35,526) had liver surgery, and 21% (n = 21,006) had biliary interventions. The overall major complication rate was 21% (n = 20,640), of which 8% (n = 1655) suffered FTR. Factors independently associated with increased risk for FTR were male sex, older age, higher Charlson Comorbidity Index, Hispanic ethnicity, Asian or other race, lower income quartile, Medicare insurance, and southern region hospitals., Conclusions: Medicare insurance, male gender, Hispanic ethnicity, and lower income quartile were associated with increased risk for FTR. Efforts should be made to improve the identification and subsequent treatment of complications for those at high risk of FTR., Competing Interests: Conflict of interest None to declare., (Published by Elsevier Ltd.)

Improved understanding of the biological heterogeneity of breast cancer (BC) has facilitated the development of more effective and personalized approaches to treatment. This study describes real-world evidence on treatment patterns and outcomes for a population-based cohort of patients with human epidermal growth factor receptor (HER2) IHC0 and -low BC with de novo or recurrent disease from Alberta, Canada. Patients 18+ years old diagnosed with HER2 IHC0/-low, de novo/recurrent BC from 2010 to 2019 were identified using Alberta's cancer registry. Analyses of these patients' existing electronic medical records and administrative claims data were conducted to examine patient characteristics, treatment patterns, and survival outcomes. A total of 3413 patients were included in the study, of which 72.10% initiated first line hormonal and non-hormonal systemic therapy. The 1-year overall survival (OS) was 81.09% [95% CI, 79.52-82.69]. Recurrent patients had a higher OS compared to de novo patients: 54.30 months [95% CI, 47.80-61.90] vs. 31.5 months [95% CI, 28.40-35.90], respectively. Median OS was 43.4 months [95% CI, 40.70-47.10] and 35.80 months [95% CI, 29.00-41.70] among patients with HER2-low and HER2 IHC0 cancer, respectively. The study results provide real-world evidence regarding the clinical outcomes of HER2 IHC0/-low and de novo/recurrent disease.

The association between red meat consumption and colorectal cancer has been rigorously examined. However, a more comprehensive understanding of how the intake of unprocessed red meat contributes to the development of early precancerous colorectal lesions, such as advanced colorectal adenomas (ACRAs), requires further investigation. We examined the associations between different types of red meat intake and ACRAs in a sample population of 1083 individuals aged ≥ 50 years undergoing an initial screening colonoscopy in Calgary, Alberta, Canada. Associations between grams per day of total, processed, and unprocessed red meat from diet history questionnaires and ACRAs were evaluated with multivariable logistic regression models. We also applied cubic spline models fitted with three knots (10th, 50th, and 90th percentiles) to identify potential nonlinear associations. We did not observe a meaningful association between unprocessed red meat intake and the presence of ACRAs. In contrast, for every 10 g/d increase in total and processed meat intake, we observed an increase in the odds of ACRAs at the screening colonoscopy (adjusted odds ratio (OR) = 1.05, 95% [CI = 1.01-1.09], p = 0.04) and (adjusted OR = 1.11, 95% [CI = 1.02-1.20], p = 0.02), respectively. This study highlights the importance of differentiating between types of red meat consumption in the context of dietary risks associated with ACRAs.

Background: We aimed to describe the financial implications of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in the USA., Materials and Methods: We conducted a retrospective cost analysis of 100 CRS/HIPEC procedures to examine the impact of patient and procedural factors on hospital costs and reimbursement. A comparison of surgeons' work relative value units (wRVUs) between CRS/HIPEC and a representative sample of complex surgical oncology procedures was made to assess the physicians' compensation rate. Univariable and multivariable backward logistic regression was used to analyze the association between perioperative variables and high direct cost (HDCs)., Results: The median direct cost per CRS/HIPEC procedure was US $44,770. The median hospital reimbursement was US $43,066, while professional reimbursement was US $8608, resulting in a positive contribution margin of US $7493/procedure. However, the contribution margin significantly varied with the payer mix. Privately insured patients had a positive median contribution margin of US $23,033, whereas Medicare-insured patients had a negative contribution margin of US $13,034. Length of stay (LOS) had the most significant association with HDC, and major complications had the most significant association with LOS. Finally, CRS/HIPEC procedures generated a median of 13 wRVU/h, which is significantly lower than the wRVU/h generated by open pancreatoduodenectomies, open gastrectomies, and hepatectomies. However, higher operation complexity and multiple visceral resections help compensate for the relatively low wRVU/h., Conclusions: CRS/HIPEC is an expensive operation, and prolonged LOS has the most significant impact on the total cost of the procedure. High-quality care is essential to improve patient outcomes and maintain the economic sustainability of the procedure., (© 2023. Society of Surgical Oncology.)

Background: The learning curve of robotic surgical skills is poorly understood. There is a lack of data on the transferability of skills from open and laparoscopic training to robotic surgery. In this retrospective cohort study, we investigated the impact of training acquired during intern year on the development of robotic skills in general surgery residents, prior to formal robotic training., Methods: Between 2019 and 2021, novice general surgery residents underwent robotic skill assessment using 3 validated inanimate drills before starting intern year. After completing basic open and laparoscopic proficiency-based curricula, they completed an identical robotic skill assessment at the end of intern year. Pre and post intern year robotic performances were recorded and analyzed by 2 blinded graders. Video-based assessment included completion time, errors, and the modified Objective Structured Assessment of Technical Skills (mOSATS) score., Results: The total time needed to complete all 3 robotic drills decreased from a mean of 26 to 17 minutes after intern year (p < 0.001). The number of errors decreased from a mean of 2.16 to 0.56 errors per subject (p < 0.001). The aggregated mOSATS score increased by an average of 41% (p < 0.001), with a greater increase in technical skill domains compared to the knowledge-based domain. The interrater intraclass correlation coefficient was 0.91., Conclusions: Baseline robotic surgical skills are limited without formal training. Our findings suggest that acquiring basic open and laparoscopic skills, such as knot tying, needle driving, and tissue handling results in improved performance on the robotic platform, prior to formal robotic training. Therefore, requiring trainees to complete fundamental open and laparoscopic training prior to robotic training may be an efficient and effective strategy within a surgical residency curriculum., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

The impact of cancer in Alberta is expected to grow considerably, largely driven by population growth and aging. The Future of Cancer Impact (FOCI) initiative offers an overview of the present state of cancer care in Alberta and highlights potential opportunities for research and innovation across the continuum. In this paper, we present a series of detailed projections and analyses regarding cancer epidemiological estimates in Alberta, Canada. Data on cancer incidence and mortality in Alberta (1998-2018) and limited-duration cancer prevalence in Alberta (2000-2019) were collected from the Alberta Cancer Registry. We used the Canproj package in the R software to project these epidemiological estimates up to the year 2040. To estimate the direct management costs, we ran a series of microsimulations using the OncoSim All Cancers Model. Our findings indicate that from 2020, the total number of annual new cancer cases and cancer-related deaths are projected to increase by 56% and 49% by 2040, respectively. From 2019, the five-year prevalence of all cancers in Alberta is projected to increase by 86% by 2040. In line with these trends, the overall direct cost of cancer management is estimated to increase by 53% in 2040. These estimates and projections are integral to future strategic planning and investment.

Background: Early warning score systems are widely used for identifying patients who are at the highest risk of deterioration to assist clinical decision-making. This could facilitate early intervention and consequently improve patient outcomes; for example, the National Early Warning Score (NEWS) system, which is recommended by the Royal College of Physicians in the United Kingdom, uses predefined alerting thresholds to assign scores to patients based on their vital signs. However, there is limited evidence of the reliability of such scores across patient cohorts in the United Arab Emirates., Objective: Our aim in this study was to propose a data-driven model that accurately predicts in-hospital deterioration in an inpatient cohort in the United Arab Emirates., Methods: We conducted a retrospective cohort study using a real-world data set that consisted of 16,901 unique patients associated with 26,073 inpatient emergency encounters and 951,591 observation sets collected between April 2015 and August 2021 at a large multispecialty hospital in Abu Dhabi, United Arab Emirates. The observation sets included routine measurements of heart rate, respiratory rate, systolic blood pressure, level of consciousness, temperature, and oxygen saturation, as well as whether the patient was receiving supplementary oxygen. We divided the data set of 16,901 unique patients into training, validation, and test sets consisting of 11,830 (70%; 18,319/26,073, 70.26% emergency encounters), 3397 (20.1%; 5206/26,073, 19.97% emergency encounters), and 1674 (9.9%; 2548/26,073, 9.77% emergency encounters) patients, respectively. We defined an adverse event as the occurrence of admission to the intensive care unit, mortality, or both if the patient was admitted to the intensive care unit first. On the basis of 7 routine vital signs measurements, we assessed the performance of the NEWS system in detecting deterioration within 24 hours using the area under the receiver operating characteristic curve (AUROC). We also developed and evaluated several machine learning models, including logistic regression, a gradient-boosting model, and a feed-forward neural network., Results: In a holdout test set of 2548 encounters with 95,755 observation sets, the NEWS system achieved an overall AUROC value of 0.682 (95% CI 0.673-0.690). In comparison, the best-performing machine learning models, which were the gradient-boosting model and the neural network, achieved AUROC values of 0.778 (95% CI 0.770-0.785) and 0.756 (95% CI 0.749-0.764), respectively. Our interpretability results highlight the importance of temperature and respiratory rate in predicting patient deterioration., Conclusions: Although traditional early warning score systems are the dominant form of deterioration prediction models in clinical practice today, we strongly recommend the development and use of cohort-specific machine learning models as an alternative. This is especially important in external patient cohorts that were unseen during model development., (©Hazem Lashen, Terrence Lee St John, Y Zaki Almallah, Madhu Sasidhar, Farah E Shamout. Originally published in JMIR AI (https://ai.jmir.org), 06.11.2023.)

Urine culture is often considered the gold standard for detecting the presence of bacteria in the urine. Since culture is expensive and often requires 24-48 hours, clinicians often rely on urine dipstick test, which is considerably cheaper than culture and provides instant results. Despite its ease of use, urine dipstick test may lack sensitivity and specificity. In this paper, we use a real-world dataset consisting of 17,572 outpatient encounters who underwent urine cultures, collected between 2015 and 2021 at a large multi-specialty hospital in Abu Dhabi, United Arab Emirates. We develop and evaluate a simple parsimonious prediction model for positive urine cultures based on a minimal input set of ten features selected from the patient's presenting vital signs, history, and dipstick results. In a test set of 5,339 encounters, the parsimonious model achieves an area under the receiver operating characteristic curve (AUROC) of 0.828 (95% CI: 0.810-0.844) for predicting a bacterial count ≥ 105 CFU/ml, outperforming a model that uses dipstick features only that achieves an AUROC of 0.786 (95% CI: 0.769-0.806). Our proposed model can be easily deployed at point-of-care, highlighting its value in improving the efficiency of clinical workflows, especially in low-resource settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ghosheh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Residency programs must prepare to train the next generation of surgeons on the robotic platform. The purpose of this study was to determine if baseline skills of residents on a virtual reality (VR) robotic simulator before intern year predicted future performance in a proficiency-based curriculum., Methods: Across two academic years, 21 general surgery PGY-1s underwent the robotic surgery boot camp at the University of Texas Southwestern. During boot camp, subjects completed five previously validated VR tasks, and their performance metrics (score, time, and economy of motion [EOM]) were extracted retrospectively from their Intuitive learning accounts. The same metrics were assessed during their residency until they reached previously validated proficiency benchmarks. Outcomes were defined as the score at proficiency, attempts to reach proficiency, and time to proficiency. Spearman's rho and Mann-Whitney U tests were used; median (IQR) was reported. Significance level was set at p < 0.05., Results: Twenty-one residents completed at least three out of the five boot camp tasks and achieved proficiency in the former during residency. The median average score at boot camp was 12.3 (IQR: 5.14-18.5). The median average EOM at boot camp was 599.58 cm (IQR: 529.64-676.60). The average score at boot camp significantly correlated with lower time to achieve proficiency (p < 0.05). EOM at boot camp showed a significant correlation with attempts to proficiency and time to proficiency (p < 0.01). Residents with an average baseline EOM below the median showed a significant difference in attempts to proficiency (p < 0.05) and time to proficiency (p < 0.05) compared to those with EOMs above or equal to the median., Conclusion: Residents with an innate ability to perform tasks with better EOM may acquire robotic surgery skills faster. Future investigators could explore how these innate differences impact performance throughout residency., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: The purpose of this retrospective, population-based, observational cohort analysis was to assess whether routine patient-reported outcomes (PRO) monitoring alone has an impact on real-world overall survival (OS) and hospitalizations among individuals diagnosed with lung, breast or colorectal cancer. The importance of follow-up care in post-PRO data collection was also discussed. Patients & methods: Administrative databases covering 17 cancer centers from Alberta, Canada were queried and individuals ≥18 years old and diagnosed with lung, breast or colorectal cancer from 1 January 2016 to 31 December 2019 were included and followed until 31 December 2020. Patients were stratified by whether they received routine PRO monitoring initiated within 120 days of diagnosis and matched 1:1 with use of propensity scores based on baseline characteristics. OS was assessed from the index date to death, and the respective Kaplan-Meier curves were estimated along with hazard ratios from Cox Proportional Hazard Models. Linear and logistic regression models were used to estimate mean differences and odds ratios (OR) respectively for healthcare resource utilization events including cancer physician visits, emergency department visits and outpatient ambulatory care encounters. Results: 4800 patients were included in each matched cohort. There was no statistically significant difference between PRO monitoring and non-monitoring cohorts in OS (HR = 1.01; 95% CI: 0.93-1.09; p = 0.836) and treatment discontinuation (OR = 0.98; 95% CI: 0.85-1.12; p = 0.75). Median OS was 51.5 months for unmonitored cohort (95% CI: 47.5-NA) versus 50.6 months for monitored cohort (95% CI: 47.6-55.7). Compared with PRO-monitored patients, unmonitored patients were associated with lower hospitalization risks (OR = 1.12; 95% CI: 1.03-1.22; p = 0.01). However, PRO-monitored patients experienced significantly fewer physician visits in comparison to unmonitored patients (MD = -1.036; 95% CI: -1.288 to -0.784, p < 0.001). Conclusion: Our results show that capturing patient-reported symptoms alone reduced the number of physician visits but neither reduced hospitalizations nor improved OS in this real-world cancer population. To drive more meaningful clinical impact, PRO monitoring programs must be met with rigorous follow-up response to the identified symptoms.

Historically, subject matter experts and healthcare professionals have played a pivotal role in driving oncology clinical trials. Although patients have been key participants, their deliberate and active contribution to the design and decision-making process has been limited. This scoping review aimed to examine the existing literature to scope the extent of active patient engagement in the design of oncology clinical trials and its corresponding influence on trial outcomes. We conducted a systematic search using two databases, namely MEDLINE (Ovid) and EMBASE, to identify relevant studies exploring patient engagement in cancer-related clinical research design. We identified seven studies that met the eligibility criteria. The studies highlighted the benefits of active patient involvement, such as improved recruitment strategies, and the attainment of more patient-centered trial outcomes. The influence of patient involvement varied from tangible developments like patient-friendly resources to indirect impacts like improved patient experiences and potentially higher adherence to trial intervention. The future of clinical trials should prioritize patients' values and perspectives, with regulatory bodies fostering these practices through clear guidelines. As the concept of patient centricity takes root in oncology research, the involvement of patients should evolve beyond mere participation.

Background: Based on findings from a single-arm, phase 2 basket trial (NCT02454972), lurbinectedin may be an effective treatment for individuals with small cell lung cancer (SCLC) who progressed on or after platinum-based chemotherapy., Objective: To estimate the comparative effectiveness of lurbinectedin versus the historical standard of care for relapsed SCLC in Canada., Methods: A synthetic control arm (SCA) analysis was conducted using real-world data. Population-level data were obtained from real-world databases in Alberta, Canada. Individuals diagnosed with SCLC who initiated post-platinum systemic therapy and met approximated eligibility criteria from the lurbinectedin trial were included in the SCA. Median overall survival (OS) in the SCA was estimated after adjusting for chemotherapy-free interval (CTFI; < 90 versus ≥ 90 days) and stage at initial diagnosis (extensive versus limited). The CTFI-adjusted hazard ratio was estimated using a Cox proportional hazards model., Results: One hundred seventy-four individuals were included in the SCA and 105 in the lurbinectedin trial. The adjusted median OS in the SCA was 6.1 months (95% CI 5.4-7.7 months; unadjusted: 6.7 months, 95% CI 6.0-7.7 months) versus 9.3 months (95% CI 6.3-11.8 months) in the lurbinectedin trial. The adjusted hazard ratio comparing lurbinectedin with the historical standard of care (referent group) was 0.61 (95% CI 0.45-0.82; unadjusted HR: 0.72; 95% CI 0.54-0.97). The hazard ratio was more pronounced among individuals with CTFI ≥ 90 days (HR: 0.49, 95% CI 0.33-0.73)., Conclusion: These findings suggest improved OS with lurbinectedin monotherapy versus the historical standard of care in Alberta, Canada., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Robotic colorectal surgery is becoming the preferred surgical approach for colorectal cancer (CRC). It offers several technical advantages over conventional laparoscopy that could improve patient outcomes. In this retrospective cohort study, we compared robotic and laparoscopic surgery for CRC using a national cohort of patients., Methods: Using the colectomy-targeted ACS-NSQIP database (2015-2020), colorectal procedures for malignant etiologies were identified by CPT codes for right colectomy (RC), left colectomy (LC), and low anterior resection (LAR). Optimal pair matching was performed. "Textbook outcome" was defined as the absence of 30-day complications, readmission, or mortality and a length of stay < 5 days., Results: We included 53,209 out of 139,759 patients screened for eligibility. Laparoscopic-to-robotic matching of 2:1 was performed for RC and LC, and 1:1 for LAR. The largest standardized mean difference was 0.048 after matching. Robotic surgery was associated with an increased rate of textbook outcomes compared to laparoscopy in RC and LC, but not in LAR (71% vs. 64% in RC, 75% vs. 68% in LC; p < 0.001). Robotic LAR was associated with increased major morbidity (7.1% vs. 5.8%; p = 0.012). For all three procedures, the mean conversion rate of robotic surgery was lower than laparoscopy (4.3% vs. 9.2%; p < 0.001), while the mean operative time was higher for robotic (225 min vs. 177 min; p < 0.001)., Conclusions: Robotic surgery for CRC offers an advantage over conventional laparoscopy by improving textbook outcomes in RC and LC. This advantage was not found in robotic LAR, which also showed an increased risk of serious complications. The associations highlighted in our study should be considered in the discussion of the surgical management of patients with colorectal cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused disruptions to cancer care by delaying diagnoses and treatment, presenting challenges and uncertainties for both patients and physicians. We conducted a nationwide online survey to investigate the effects of the pandemic and capture modifications, prompted by pandemic-related control measures, on cervical cancer screening-related activities from mid-March to mid-August 2020, across Canada., Methods: The survey consisted of 61 questions related to the continuum of care in cervical cancer screening and treatment: appointment scheduling, tests, colposcopy, follow-up, treatment of pre-cancerous lesions/cancer, and telemedicine. We piloted the survey with 21 Canadian experts in cervical cancer prevention and care. We partnered with the Society of Canadian Colposcopists, Society of Gynecologic Oncology of Canada, Canadian Association of Pathologists, and Society of Obstetricians and Gynecologists of Canada, which distributed the survey to their members via email. We reached out to family physicians and nurse practitioners via MDBriefCase. The survey was also posted on McGill Channels (Department of Family Medicine News and Events) and social media platforms. The data were analyzed descriptively., Results: Unique responses were collected from 510 participants (November 16, 2020, to February 28, 2021), representing 418 fully and 92 partially completed surveys. Responses were from Ontario (41.0%), British Columbia (21.0%), and Alberta (12.8%), and mostly comprised family physicians/general practitioners (43.7%), and gynecologist/obstetrician professionals (21.6%). Cancelled screening appointments were mainly reported by family physicians/general practitioners (28.3%), followed by gynecologist/obstetrician professionals (19.8%), and primarily occurred in private clinics (30.5%). Decreases in the number of screening Pap tests and colposcopy procedures were consistently observed across Canadian provinces. About 90% reported that their practice/institution adopted telemedicine to communicate with patients., Conclusions: The area most severely impacted by the pandemic was appointment scheduling, with an important level of cancellations reported. Survey results may inform resumptions of various fronts in cervical cancer screening and management., Funding: The present work was supported by the Canadian Institutes of Health Research (operating grant COVID-19 May 2020 Rapid Research Funding Opportunity VR5-172666 Rapid Research competition and foundation grant 143347 to Eduardo L Franco). Eliya Farah and Rami Ali each received an MSc stipend from the Department of Oncology, McGill University., Competing Interests: ME, EF, SB No competing interests declared, RA received an MSc. stipend from the Gerald Bronfman Department of Oncology, McGill University, EF Senior editor, eLife, (© 2023, El-Zein et al.)

Unrecognized deterioration of COVID-19 patients can lead to high morbidity and mortality. Most existing deterioration prediction models require a large number of clinical information, typically collected in hospital settings, such as medical images or comprehensive laboratory tests. This is infeasible for telehealth solutions and highlights a gap in deterioration prediction models based on minimal data, which can be recorded at a large scale in any clinic, nursing home, or even at the patient's home. In this study, we develop and compare two prognostic models that predict if a patient will experience deterioration in the forthcoming 3 to 24 h. The models sequentially process routine triadic vital signs: (a) oxygen saturation, (b) heart rate, and (c) temperature. These models are also provided with basic patient information, including sex, age, vaccination status, vaccination date, and status of obesity, hypertension, or diabetes. The difference between the two models is the way that the temporal dynamics of the vital signs are processed. Model #1 utilizes a temporally-dilated version of the Long-Short Term Memory model (LSTM) for temporal processes, and Model #2 utilizes a residual temporal convolutional network (TCN) for this purpose. We train and evaluate the models using data collected from 37,006 COVID-19 patients at NYU Langone Health in New York, USA. The convolution-based model outperforms the LSTM based model, achieving a high AUROC of 0.8844-0.9336 for 3 to 24 h deterioration prediction on a held-out test set. We also conduct occlusion experiments to evaluate the importance of each input feature, which reveals the significance of continuously monitoring the variation of the vital signs. Our results show the prospect for accurate deterioration forecast using a minimum feature set that can be relatively easily obtained using wearable devices and self-reported patient information., (© 2023. The Author(s).)

Background: The COVID-19 pandemic has disrupted cancer care, raising concerns regarding the impact of wait time, or 'lag time', on clinical outcomes. We aimed to contextualize pandemic-related lag times by mapping pre-pandemic evidence from systematic reviews and/or meta-analyses on the association between lag time to cancer diagnosis and treatment with mortality- and morbidity-related outcomes., Methods: We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library of Systematic Reviews for reviews published prior to the pandemic (1 January 2010-31 December 2019). We extracted data on methodological characteristics, lag time interval start and endpoints, qualitative findings from systematic reviews, and pooled risk estimates of mortality- (i.e., overall survival) and morbidity- (i.e., local regional control) related outcomes from meta-analyses. We categorized lag times according to milestones across the cancer care continuum and summarized outcomes by cancer site and lag time interval., Results: We identified 9032 records through database searches, of which 29 were eligible. We classified 33 unique types of lag time intervals across 10 cancer sites, of which breast, colorectal, head and neck, and ovarian cancers were investigated most. Two systematic reviews investigating lag time to diagnosis reported different findings regarding survival outcomes among paediatric patients with Ewing's sarcomas or central nervous system tumours. Comparable risk estimates of mortality were found for lag time intervals from surgery to adjuvant chemotherapy for breast, colorectal, and ovarian cancers. Risk estimates of pathologic complete response indicated an optimal time window of 7-8 weeks for neoadjuvant chemotherapy completion prior to surgery for rectal cancers. In comparing methods across meta-analyses on the same cancer sites, lag times, and outcomes, we identified critical variations in lag time research design., Conclusions: Our review highlighted measured associations between lag time and cancer-related outcomes and identified the need for a standardized methodological approach in areas such as lag time definitions and accounting for the waiting-time paradox. Prioritization of lag time research is integral for revised cancer care guidelines under pandemic contingency and assessing the pandemic's long-term effect on patients with cancer., Funding: The present work was supported by the Canadian Institutes of Health Research (CIHR-COVID-19 Rapid Research Funding opportunity, VR5-172666 grant to Eduardo L. Franco). Parker Tope, Eliya Farah, and Rami Ali each received an MSc. stipend from the Gerald Bronfman Department of Oncology, McGill University., Competing Interests: PT received MSc. stipends from the Gerald Bronfman Department of Oncology, McGill University, EF, RA received an MSc. stipend from the Gerald Bronfman Department of Oncology, McGill University, ME reports a patent related to the discovery “DNA methylation markers for early detection of cervical cancer”, registered at the Office of Innovation and Partnerships, McGill University, Montreal, Quebec, Canada, WM reports grants to his institution from Merck, Canadian Institutes of Health Research, Cancer Research Society, Terry Fox Research Institute, Samuel Waxman Cancer Research Foundation, and CCSRI; consultancy for Merck, BMS, Roche, GSK, Novartis, Amgen, Mylan, EMD Serono, and Sanofi; honoraria from McGill University, JGH, BMS, Merck, Roche, GSK, Novartis, Amgen, Mylan EMD Serono, and Sanofi; payments to his institution for participation in a clinical trial within the past 2 years BMS, Novartis, GSK, Roche, AstraZeneca, Methylgene, MedImmune, Bayer, Amgen, Merck, Incyte, Pfizer, Sanofi, Array, MiMic, Ocellaris Pharma, Astellas, Alkermes, Exelixis, VelosBio, and Genetech, EF reports support for the present manuscript in the form of a grant to his institution is his name from the Canadian Institutes of Health Research and the Cancer Research Society; consultancy for Merck; a patent related to the discovery “DNA methylation markers for early detection of cervical cancer”, registered at the Office of Innovation and Partnerships, McGill University, Montreal, Quebec, Canada; and financial interests with Elsevier and Elifesciences Ltd in the form of support fees to maintain the editorial office and work as Senior Editor, respectively, (© 2023, Tope et al.)

Prostate cancer (PCa) continues to threaten men's health, and treatment targeting the androgen receptor (AR) pathway is the major therapy for PCa patients. Several second-generation androgen receptor inhibitors (SG-ARIs), including enzalutamide (ENZ), apalutamide (APA) and darolutamide (DARO), have been developed to better block the activity of AR. Unavoidably, emergence of resistance to these novel drugs still persists. Herein, we identified glutathione S-transferase Mu 2 (GSTM2) as an important determinant in the acquisition of resistance to SG-ARIs. Elevated GSTM2 was detected in enzalutamide-resistant (ENZ-R) PCa, and overexpression of GSTM2 in naïve enzalutamide-sensitive (ENZ-S) cells effectively transformed them to ENZ-R PCa. Aryl hydrocarbon receptor (AhR), the upstream transcription factor, was implicated in the overexpression of GSTM2 in ENZ-R cells. Mechanistically, GSTM2 antagonized the effect of ENZ by rescuing cells from oxidative stress-associated damage and activation of p38 MAPK pathway. Surprisingly, high GSTM2 levels also associated with cross-resistance to APA and DARO. Taking together, these results provide new insight to ameliorate resistance to SG-ARIs and improve treatment outcome., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: A better understanding of the association between early physician follow-up after discharge and adverse outcomes among hospitalized patients may inform interventions aimed at reducing readmission for common chronic conditions., Objective: To assess whether hospitalized patients with early physician follow-up after discharge had lower rates of overall and condition-specific readmissions within 30 days and 90 days of discharge., Design, Setting, and Participants: This cohort study was conducted among Ontario, Canada, adults with first admission for acute myocardial infarction (AMI), congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD) during 2005 to 2019. The exposure was follow-up visit with a primary care physician or relevant specialist within 7 days of discharge. Cox proportional hazards models were used to compare patients with vs without early follow-up, adjusting for sociodemographic factors and comorbidities, weighting by propensity score-based overlap weights. Data were analyzed from January through July 2021., Main Outcomes and Measures: Primary outcomes were 30-day and 90-day readmissions, cardiac readmissions (readmission for AMI, CHF, or angina) for patients with cardiac conditions, and COPD-related readmissions for patients with COPD. Mortality at 30 days and 90 days was a secondary outcome. All percentages reported in Results are unweighted., Results: The study cohort comprised 450 746 patients, including 198 854 patients with AMI, 133 058 patients with CHF, and 118 834 patients with COPD; the median (IQR) age was 66 (56-77) years for AMI, 78 (68-85) years for CHF, and 73 (64-81) years for COPD, and there were 64 339 (32.35%) women, 62 575 (47.03%) women, and 59 179 (49.80%) women, respectively. There were 91 182 patients (45.85%), 56 491 patients (42.46%), and 40 159 patients (33.79%), respectively, who received an early follow-up visit. Overall, patients with early follow-up had higher rates of collaborative care (eg, CHF: 20 931 patients [37.85%] vs 11 101 of 76 567 patients [14.85%]) and visits to a specialist within 30 days (eg, CHF: 25 797 patients [45.67%] vs 20 548 patients [26.84%]). Those with early follow-up had lower 90-day readmission rates among patients with CHF (15 934 patients [28.21%] vs 23 121 patients [30.20%]; adjusted hazard ratio [aHR], 0.98; 95% CI, 0.96-0.99) and among those with COPD (8784 patients [21.87%] vs 18 097 of 78 675 patients [23.00%]; aHR, 0.95; 95% CI, 0.93-0.98). Among patients with COPD, those with early follow-up had lower 90-day COPD-related readmission rates (4015 patients [10.00%] vs 8449 patients [10.74%]; aHR, 0.93; 95% CI, 0.89-0.96), and among patients with CHF, those with early follow-up had lower 90-day mortality rates (4044 patients [7.16%] vs 6281 patients [8.20%]; aHR, 0.93; 95% CI, 0.90-0.97). There were no significant benefits at 30 days or for patients with AMI., Conclusions and Relevance: These findings suggest that early follow-up in conjunction with a comprehensive transitional care strategy for hospitalized patients with medically complex conditions coupled with ongoing effective chronic disease management may be associated with reduced 90-day readmissions.

Clinical time-series data retrieved from electronic medical records are widely used to build predictive models of adverse events to support resource management. Such data is often sparse and irregularly-sampled, which makes it challenging to use many common machine learning methods. Missing values may be interpolated by carrying the last value forward, or through linear regression. Gaussian process (GP) regression is also used for performing imputation, and often re-sampling of time-series at regular intervals. The use of GPs can require extensive, and likely adhoc, investigation to determine model structure, such as an appropriate covariance function. This can be challenging for multivariate real-world clinical data, in which time-series variables exhibit different dynamics to one another. In this work, we construct generative models to estimate missing values in clinical time-series data using a neural latent variable model, known as a Neural Process (NP). The NP model employs a conditional prior distribution in the latent space to learn global uncertainty in the data by modelling variations at a local level. In contrast to conventional generative modelling, this prior is not fixed and is itself learned during the training process. Thus, NP model provides the flexibility to adapt to the dynamics of the available clinical data. We propose a variant of the NP framework for efficient modelling of the mutual information between the latent and input spaces, ensuring meaningful learned priors. Experiments using the MIMIC III dataset demonstrate the effectiveness of the proposed approach as compared to conventional methods.

Background: Peer comparison audit and feedback has demonstrated effectiveness in improving antibiotic prescribing practices, but only a minority of prescribers view their reports. We rigorously tested 3 behavioral nudging techniques delivered by email to improve report opening., Methods: We conducted a pragmatic randomized controlled trial among Ontario long-term care prescribers enrolled in an ongoing peer comparison audit and feedback program which includes data on their antibiotic prescribing patterns. Physicians were randomized to 1 of 8 possible sequences of intervention/control allocation to 3 different behavioral email nudges: a social peer comparison nudge (January 2020), a maintenance of professional certification incentive nudge (October 2020), and a prior participation nudge (January 2021). The primary outcome was feedback report opening; the primary analysis pooled the effects of all 3 nudging interventions., Results: The trial included 421 physicians caring for >28 000 residents at 450 facilities. In the pooled analysis, physicians opened only 29.6% of intervention and 23.9% of control reports (odds ratio [OR], 1.51 [95% confidence interval {CI}, 1.10-2.07], P  = .011); this difference remained significant after accounting for physician characteristics and clustering (adjusted OR [aOR], 1.74 [95% CI, 1.24-2.45], P  = .0014). Of individual nudging techniques, the prior participation nudge was associated with a significant increase in report opening (OR, 1.62 [95% CI, 1.06-2.47], P  = .026; aOR, 2.16 [95% CI, 1.33-3.50], P  = .0018). In the pooled analysis, nudges were also associated with accessing more report pages (aOR, 1.28 [95% CI, 1.14-1.43], P  < .001)., Conclusions: Enhanced nudging strategies modestly improved report opening, but more work is needed to optimize physician engagement with audit and feedback., Clinical Trials Registration: NCT04187742., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

COVID-19 is caused by a novel coronavirus (2019-nCoV), which was declared as a pandemic after it emerged in China 2019. A vast international effort has been conducted to prevent and treat COVID-19 due to its high transmissibility and severe morbidity and mortality rates, particularly in individuals with chronic co-morbidities. In addition, polymorphic variants increased the need for proper vaccination to overcome the infectivity of new variants that are emerging across the globe. Many treatment options have been proposed and more than 25 vaccines are in various stages of development; however, the infection peaks are oscillating periodically, which raises a significant question about the effectiveness of the prevention measures and the persistence of this pandemic disease. In this review, we are exploring the most recent knowledge and advances in the treatment and vaccination options as well as the new emerging variants of 2019-nCoV and the possible mitigation of one of the most aggressive pandemics in the last centuries.

Prostate cancer is the second leading cause of cancer death among men in the United States. The androgen receptor (AR) antagonist enzalutamide is an FDA-approved drug for treatment of patients with late-stage prostate cancer and is currently under clinical study for early-stage prostate cancer treatment. After a short positive response period to enzalutamide, tumors will develop drug resistance. In this study, we uncovered that DNA methylation was deregulated in enzalutamide-resistant cells. DNMT activity and DNMT3B expression were upregulated in resistant cell lines. Enzalutamide induced the expression of DNMT3A and DNMT3B in prostate cancer cells with a potential role of p53 and pRB in this process. The overexpression of DNMT3B3, a DNMT3B variant, promoted an enzalutamide-resistant phenotype in C4-2B cell lines. Inhibition of DNA methylation and DNMT3B knockdown induced a resensitization to enzalutamide. Decitabine treatment in enzalutamide-resistant cells induced a decrease of the expression of AR-V7 and changes of genes for apoptosis, DNA repair, and mRNA splicing. Combination treatment of decitabine and enzalutamide induced a decrease of tumor weight, Ki-67 and AR-V7 expression and an increase of cleaved-caspase3 levels in 22Rv1 xenografts. The collective results suggest that DNA methylation pathway is deregulated after enzalutamide resistance onset and that targeting DNA methyltransferases restores the sensitivity to enzalutamide in prostate cancer cells., (©2021 American Association for Cancer Research.)

Clinical evidence suggests that some patients diagnosed with coronavirus disease 2019 (COVID-19) experience a variety of complications associated with significant morbidity, especially in severe cases during the initial spread of the pandemic. To support early interventions, we propose a machine learning system that predicts the risk of developing multiple complications. We processed data collected from 3,352 patient encounters admitted to 18 facilities between April 1 and April 30, 2020, in Abu Dhabi (AD), United Arab Emirates. Using data collected during the first 24 h of admission, we trained machine learning models to predict the risk of developing any of three complications after 24 h of admission. The complications include Secondary Bacterial Infection (SBI), Acute Kidney Injury (AKI), and Acute Respiratory Distress Syndrome (ARDS). The hospitals were grouped based on geographical proximity to assess the proposed system's learning generalizability, AD Middle region and AD Western & Eastern regions, A and B, respectively. The overall system includes a data filtering criterion, hyperparameter tuning, and model selection. In test set A, consisting of 587 patient encounters (mean age: 45.5), the system achieved a good area under the receiver operating curve (AUROC) for the prediction of SBI (0.902 AUROC), AKI (0.906 AUROC), and ARDS (0.854 AUROC). Similarly, in test set B, consisting of 225 patient encounters (mean age: 42.7), the system performed well for the prediction of SBI (0.859 AUROC), AKI (0.891 AUROC), and ARDS (0.827 AUROC). The performance results and feature importance analysis highlight the system's generalizability and interpretability. The findings illustrate how machine learning models can achieve a strong performance even when using a limited set of routine input variables. Since our proposed system is data-driven, we believe it can be easily repurposed for different outcomes considering the changes in COVID-19 variants over time., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Though consistently shown to detect mammographically occult cancers, breast ultrasound has been noted to have high false-positive rates. In this work, we present an AI system that achieves radiologist-level accuracy in identifying breast cancer in ultrasound images. Developed on 288,767 exams, consisting of 5,442,907 B-mode and Color Doppler images, the AI achieves an area under the receiver operating characteristic curve (AUROC) of 0.976 on a test set consisting of 44,755 exams. In a retrospective reader study, the AI achieves a higher AUROC than the average of ten board-certified breast radiologists (AUROC: 0.962 AI, 0.924 ± 0.02 radiologists). With the help of the AI, radiologists decrease their false positive rates by 37.3% and reduce requested biopsies by 27.8%, while maintaining the same level of sensitivity. This highlights the potential of AI in improving the accuracy, consistency, and efficiency of breast ultrasound diagnosis., (© 2021. The Author(s).)

Background: Antibiotic overprescribing in long-term care settings is driven by prescriber preferences and is associated with preventable harms for residents. We aimed to determine whether peer comparison audit and feedback reporting for physicians reduces antibiotic overprescribing among residents., Methods: We employed a province wide, difference-in-differences study of antibiotic prescribing audit and feedback, with an embedded pragmatic randomized controlled trial (RCT) across all long-term care facilities in Ontario, Canada, in 2019. The study year included 1238 physicians caring for 96 185 residents. In total, 895 (72%) physicians received no feedback; 343 (28%) were enrolled to receive audit and feedback and randomized 1:1 to static or dynamic reports. The primary outcomes were proportion of residents initiated on an antibiotic and proportion of antibiotics prolonged beyond 7 days per quarter., Results: Among all residents, between the first quarter of 2018 and last quarter of 2019, there were temporal declines in antibiotic initiation (28.4% to 21.3%) and prolonged duration (34.4% to 29.0%). Difference-in-differences analysis confirmed that feedback was associated with a greater decline in prolonged antibiotics (adjusted difference -2.65%, 95% confidence interval [CI]: -4.93 to -.28%, P = .026), but there was no significant difference in antibiotic initiation. The reduction in antibiotic durations was associated with 335 912 fewer days of treatment. The embedded RCT detected no differences in outcomes between the dynamic and static reports., Conclusions: Peer comparison audit and feedback is a pragmatic intervention that can generate small relative reductions in the use of antibiotics for prolonged durations that translate to large reductions in antibiotic days of treatment across populations. Clinical Trials Registration. NCT03807466., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

It is estimated that as many as 1 in 20 women worldwide are unable to successfully breastfeed or provide adequate nutrition for their infants through their breast milk alone. Compromised nutrition in the early stages of life places the infant at risk for insufficient growth as well as serious and potentially disabling or life-threatening complications. This review summarizes risk factors associated with impaired lactation that may result in either delayed lactogenesis or insufficient lactation. The risk factors for insufficient lactation are categorized into preglandular, glandular, and postglandular causes. Impaired lactation can occur despite maternal motivation, knowledge, support, and appropriate breastfeeding technique. Although there is no clear way to predict who will experience impaired lactation, knowledge about the risk factors can enable health care professionals to better identify at-risk mother-infant dyads. Early intervention may help prevent infant complications associated with inadequate nutritional intake., (© 2021 by the American College of Nurse-Midwives.)

Purpose: Lower eyelid management is challenging. The conchal cartilage is often considered a spacer of choice for treating lower eyelid retraction. However, dermis graft has also recently been shown to be a viable spacer. The aim of this study was to compare the efficacy of dermis graft to that of conchal cartilage graft in this indication., Methods: A retrospective comparative study was conducted in patients who underwent lower eyelid lengthening with autologous dermis graft (group 1) or autologous conchal cartilage graft (group 2). The main outcome measure was the reduction in inferior scleral show (ISS) assessed by three independent masked surgeons. Secondary outcome measures was the assessment of lagophthalmos and corneal keratitis. Complications were also recorded., Results: Twenty-five eyelids of 23 patients were included: 11 and 14 eyelids, respectively in group 1 (dermis graft) and group 2 (conchal cartilage graft). Patient mean follow-up was 12.3 (±12.5) and 7.1 (±7.7) months, respectively. No statistical differences in postoperative ISS reduction, lagophthalmos and exposure keratitis was observed ( p  = 0.540, p  = 0.946, p  = 0.934, respectively). Three patients experienced a grade I Clavien-Dindo complication in group 1 and one patient experienced a grade II complication in group 2 ( p  = 0.540)., Conclusion: Autologous dermis grafts and conchal cartilage grafts provide favorable outcomes without major complications.

Background: Case reports have described instances of peripheral and central nervous system toxicity during treatment with metronidazole; however, no large-scale studies have examined this association., Methods: We conducted a population-based nested case-control study of adults aged 66 years or older living in Ontario, Canada, between 1 April 2003 and 31 March 2017. Cases were individuals who attended hospital for any of cerebellar dysfunction, encephalopathy, or peripheral neuropathy within 100 days of a prescription for either metronidazole or clindamycin. We matched each case patient with up to 10 event-free control subjects who also received metronidazole or clindamycin. We used conditional logistic regression to test the association between metronidazole exposure and neurologic events, with clindamycin as the reference exposure., Results: We identified 1212 cases with recent use of either metronidazole or clindamycin and 12 098 controls. Neurologic adverse events were associated with an increased odds of metronidazole exposure compared to clindamycin (odds ratio [OR], 1.72 [95% confidence interval {CI}, 1.53-1.94]), which persisted after accounting for patient demographics, comorbidities, and other medication exposures (adjusted odds ratio [aOR], 1.43 [95% CI, 1.26-1.63]). We found a consistent association limited to either central (aOR, 1.46 [95% CI, 1.27-1.68]) or peripheral (aOR, 1.34 [95% CI, 1.02-1.76]) nervous system events. Among metronidazole recipients, the overall incidence of neurologic events at 100 days was approximately 0.25%., Conclusions: Metronidazole is associated with an increased risk of adverse peripheral and central nervous system events relative to clindamycin. Clinicians and patients should be aware of these rare but potentially serious adverse events., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To assess the level of cancer awareness and the relationship between the awareness of common cancer symptoms and risk factors and the sample's sociodemographic profile., Methods: A community-based cross-sectional study conducted in Tabuk city, a convenient sample of 675 participants completed a questionnaire about common factors causing cancer and symptoms related to cancer. Descriptive statistics and chi-squared analysis were used to measure sample characteristics and their association with knowledge of cancer risk factors and symptoms., Results: Level of education and family history were significantly related to awareness of cancer risk factors (P= 0.017) and (P= 0.048), respectively. Factors were significantly associated with awareness of cancer symptoms include Gender (P=0.000), nationality (P=0.013), and undergoing regular cancer screening tests (0.008). Internet was the primary source of information about cancer and related significantly to knowledge about cancer symptoms(P=0.000) and risk factors(P=0.00). More than half of the sample scored poorly for knowledge of both cancer risk factors (58.7%) and symptoms (66.2%) in terms of the overall level of cancer awareness. Smoking and heredity were the most identifiable cancer risk factors, and unexplained pain and weight loss were identified by the majority of study participants., Conclusion: The level of community knowledge requires further investigation, and more cancer awareness programs need to be conducted. People could be encouraged to use reliable sources of information to obtain accurate cancer information., .

Background: Macrolides are recommended as an adjunctive treatment for patients with moderate to severe chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. The objective of this study was to examine temporal trends in the provision of long-term macrolide therapy, specifically before and after publication of the landmark MACRO trial in August 2011 showing efficacy of macrolides for this indication., Methods: We performed an interrupted time series analysis using population-level health administrative data. The study cohort consisted of all Ontario residents who had COPD, were using at least 1 long-acting inhaler, and were aged 65 years and older between Apr. 1, 2004, and Mar. 31, 2018. We compared the baseline characteristics of eligible patients before and after publication of the MACRO trial. Our primary outcome was overall prevalence of long-term macrolide therapy; secondary outcomes were incidence of COPD-related hospitalizations, emergency department visits and outpatient exacerbations requiring high-dose steroids in each quarter. We performed an interrupted time series analysis to assess for changes in the incidence of macrolide prophylaxis by quarter-year over the study period., Results: The rate of long-term macrolide use increased from 0.8 per 1000 people in 2004 to 13.8 per 1000 people in 2018 (in the severe COPD group, the rate increased from 1.3 to 32.3 per 1000 people). The interrupted time series analysis showed that, before 2011, the prevalence of macrolide prophylaxis increased at a rate of 0.44 (95% confidence interval [CI] 0.39-0.50) per 1000 people per year; after 2011, the rate of increase grew by 1.18 (95% CI 1.07-1.29) per 1000 people to 1.63 (95% CI 1.56-1.69) per 1000 people per year. The seasonal pattern of COPD-related health care visits remained stable over the study period, and there was no detectable reduction in hospitalizations or emergency department visits at the population level., Interpretation: In the past decade, there has been a significant rise in the use of long-term macrolide therapy for patients with COPD. As this practice becomes increasingly common, it will be important to monitor its potential benefits on COPD exacerbations but also its potential effects on adverse events and antimicrobial resistance patterns., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

During the coronavirus disease 2019 (COVID-19) pandemic, rapid and accurate triage of patients at the emergency department is critical to inform decision-making. We propose a data-driven approach for automatic prediction of deterioration risk using a deep neural network that learns from chest X-ray images and a gradient boosting model that learns from routine clinical variables. Our AI prognosis system, trained using data from 3661 patients, achieves an area under the receiver operating characteristic curve (AUC) of 0.786 (95% CI: 0.745-0.830) when predicting deterioration within 96 hours. The deep neural network extracts informative areas of chest X-ray images to assist clinicians in interpreting the predictions and performs comparably to two radiologists in a reader study. In order to verify performance in a real clinical setting, we silently deployed a preliminary version of the deep neural network at New York University Langone Health during the first wave of the pandemic, which produced accurate predictions in real-time. In summary, our findings demonstrate the potential of the proposed system for assisting front-line physicians in the triage of COVID-19 patients.