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In young individuals with obesity, infertility, and endometrial cancer, significant, sustained weight loss through bariatric surgery may result in a durable oncologic and reproductive response. However, it is not known whether bariatric surgery is acceptable to this patient population. We performed a qualitative study to understand the acceptability of bariatric surgery in young individuals with obesity and endometrial cancer or atypical hyperplasia.All participants were of reproductive age with body mass index [BMI] ≥ 35 and grade 1 endometrial cancer or atypical hyperplasia. Semi-structured interviews were used to explore participant perception of their weight, fertility, and the possibility of bariatric surgery as part of the treatment strategy for their endometrial cancer/atypical hyperplasia. Thematic saturation was reached after 14 interviews.Fourteen participants with a median age of 34 years (range 27-38) and BMI of 42 (33-64) were interviewed. Participants were reluctant to accept bariatric surgery as a treatment option due to 1) lack of knowledge about the procedure, 2) stigma attached to bariatric surgery, and 3) fear of the risks associated with bariatric surgery. Their perception towards their weight, fertility, and cancer diagnosis was characterized by concepts of 'helplessness', 'isolation', 'frustration', and 'guilt'. We observed a significant gap in participant understanding of the complex interplay between their cancer, infertility, and obesity.More support and resources are required, with patient-oriented counseling focused on the implication of their weight on their cancer diagnosis and fertility, before presenting bariatric surgery as a treatment option.

To develop a machine learning (ML) algorithm to predict outcome of primary cytoreductive surgery (PCS) in patients with advanced ovarian cancer (AOC) METHODS: This retrospective cohort study included patients with AOC undergoing PCS between January 2017 and February 2021. Using radiologic criteria, patient factors (age, CA-125, performance status, BRCA) and surgical complexity scores, we trained a random forest model to predict the dichotomous outcome of optimal cytoreduction (1 cm) and no gross residual (RD = 0 mm) using JMP-Pro 15 (SAS). This model is available at https://ipm-ml.ccm.sickkids.ca.One hundred and fifty-one patients underwent PCS and randomly assigned to train (n = 92), validate (n = 30), or test (n = 29) the model. The median age was 58 (27-83). Patients with suboptimal cytoreduction were more likely to have an Eastern Cooperative Oncology Group 3-4 (11% vs. 0.75%, p = 0.004), lower albumin (38 vs. 41, p = 0.02), and higher CA125 (1126 vs. 388, p = 0.012) than patients with optimal cytoreduction (n = 133). There were no significant differences in age, histology, stage, or BRCA status between groups. The bootstrap random forest model had AUCs of 99.8% (training), 89.6%(validation), and 89.0% (test). The top five contributors were CA125, albumin, diaphragmatic disease, age, and ascites. For RD = 0 mm, the AUCs were 94.4%, 52%, and 84%, respectively.Our ML algorithm demonstrated high accuracy in predicting optimal cytoreduction in patients with AOC selected for PCS and may assist decision-making.

Contrast-associated AKI may result in higher morbidity and mortality. Intravenous fluid administration remains the mainstay for prevention. There is a lack of consensus on the optimal administration strategy. We studied the association of periprocedure fluid administration with contrast-associated AKI, defined as an increase in serum creatinine of at least 25% or 0.5 mg/dl from baseline at 3-5 days after angiography, and 90-day need for dialysis, death, or a 50% increase in serum creatinine.We conducted a secondary analysis of 4671 PRESERVE participants who underwent angiographic procedures. Although fluid type was randomized, strategy of administration was at the discretion of the clinician. We divided the study cohort into quartiles by total fluid volume. We performed multivariable logistic regression, adjusting for clinically important covariates. We tested for the interaction between fluid volume and duration of fluid administration, categorized as6 or ≥6 hours.The mean (SD) age was 70 (8) years, 94% of participants were male, and median (interquartile range) eGFR was 60 (41-60) ml/min per 1.73 mWe found that administration of a total volume of 1000 ml, starting at least 1 hour before contrast injection and continuing postcontrast for a total of 6 hours, is associated with a similar risk of adverse outcomes as larger volumes of intravenous fluids administered for periods6 hours. Mean fluid volumes964 ml may be associated with a higher risk for the primary outcome, although residual confounding cannot be excluded.

Poorly fitting prosthetic sockets contribute to decreased quality of life, health, and well-being for persons with amputations. Therefore, improved socket fit is a high clinical priority.In this study, we describe the design and testing of a novel sensor system that can be incorporated into a prosthetic socket to measure distal end weight bearing in the socket and can alert a prosthesis user if poor socket fit is suspected. We present the results of testing this device with three Veterans who were new prosthesis users and three Veterans who were experienced prosthesis users.We collected sensor data during walking trials while participants wore varying numbers of sock plies and qualitative feedback on the design of the socket fit sensor system. For analysis, peak sensor measurements during walking cycles were identified and combined with socket fit data (i.e., a clinician-determined level of "good," "too tight," or "too loose" and the number of sock ply worn each trial). We found consistent relationships between peak sensor measurements and socket fit in our sample. Also, all users expressed an interest in the device, highlighting its potential benefits during early prosthesis training.Implications for RehabilitationEnsuring socket fit is challenging for many prosthesis users.A novel wearable sensor system can be used to identify socket fit issues for some prosthesis users.This type of system could be most helpful for new prosthesis users and those with sensory and cognitive challenges.

To assess the effects of the implementation of a standardized voiding protocol in patients undergoing minimally invasive hysterectomy at a single cancer center in terms of the urinary tract infection (UTI) rate, time to first void, and overnight stays secondary to urinary retention.We enrolled 102 consecutive patients undergoing minimally invasive hysterectomy at a single cancer center during a 12-month period. A pre-intervention cohort of 100 consecutive patients was identified for comparison. A multidisciplinary team developed and implemented a standardized voiding protocol using quality improvement methodology. We compared the demographics, time to first void, rate of urinary retention, and UTI rates between the pre- and post-intervention cohorts.Our intervention led to a significant reduction in the time to first void (289 min vs. 566 min; P 0.001), rate of urinary retention (2% vs. 10%; P = 0.015), and postoperative UTI (4% vs. 8%; P = 0.249). There was a similar rate of patients going home with a Foley catheter (9% vs. 11%; P = 0.850).Implementation of a standardized voiding protocol was associated with a reduction in rate of UTI, time to first void, and overnight stays secondary to urinary retention.

In processing the impact of the pandemic amidst other global crises, we found rereading Brandt and Clinton's “The Limits of the Local” article, published 20 years ago next year, to offer much, both theoretically and practically. Written within its own tumultuous time, according to its editors, it argues for transcontextualizing accounts of literacy and employing thingness as a means to subvert local/global dichotomies in literacy studies. In this essay, we reflect on this work 20 years later, and propose an extension of Brandt and Clinton's transcontextualizing perspective through an affirmative ontology of éclosion. We hope this actualization will provide an orientation for furthering transcontextual literacy studies that meet the urgency of our own tumultuous times.

Timely treatment of epithelial ovarian cancer (EOC) by gynecologic oncologists (GOs) with a combination of surgery and/or chemotherapy has been advocated. Nonetheless, some patients are not assessed by GOs prior to starting their treatment or have surgery by non-GOs. This study aims to determine trends over time in non-mucinous EOC care and to evaluate the impact of care on survival.Using province-wide administrative data, patients diagnosed with non-mucinous EOC between 2007 and 2018 were identified. Multivariate Cox proportional hazards regression models were used to evaluate the impact of GO assessment prior to initiating treatment or having surgery done by a non-GO on mortality.A total of 10,086 EOC patients were included between 2007 and 2018. During the study period, there was an 8% increase in GO assessment (79% in 2007 to 87% in 2018-19, p ≤ 0.001) and a 19% increase in surgeries performed by GOs (69% in 2007 to 88% in 2018-19, p ≤ 0.001). On multivariate analysis, there was an increased hazard of all-cause mortality for patients not assessed by GOs before first treatment (Hazard ratio (HR): 1.61; 95% CI 1.46-1.79). There was an increased hazard of all-cause mortality if ovarian cancer surgery was performed by non-GOs (HR 2.03; 95% CI 1.80-2.30).Assessment by GO before starting initial treatment is associated with improved survival in women with non-mucinous EOC as the type of surgeon performing primary ovarian cancer surgery. Assessment by GO for all patients with new or suspected ovarian cancer diagnosis before initiation of primary treatment should be advocated.

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Next-generation genomic sequencing has identified multiple novel molecular alterations in cancer. Since the identification of DNA methylation and histone modification, it has become evident that genes encoding epigenetic modifiers that locally and globally regulate gene expression play a crucial role in normal development and cancer progression. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is the enzymatic catalytic subunit of the polycomb-repressive complex 2 (PRC2) that can alter gene expression by trimethylating lysine 27 on histone 3 (H3K27). EZH2 is involved in global transcriptional repression, mainly targeting tumor-suppressor genes. EZH2 is commonly overexpressed in cancer and shows activating mutations in subtypes of lymphoma. Extensive studies have uncovered an important role for EZH2 in cancer progression and have suggested that it may be a useful therapeutic target. In addition, tumors harboring mutations in other epigenetic genes such as ARID1A, KDM6, and BAP1 are highly sensitive to EZH2 inhibition, thus increasing its potential as a therapeutic target. Recent studies also suggest that inhibition of EZH2 enhances the response to tumor immunotherapy. Many small-molecule inhibitors have been developed to target EZH2 or the PRC2 complex, with some of these inhibitors now in early clinical trials reporting clinical responses with acceptable tolerability. In this review, we highlight the recent advances in targeting EZH2, its successes, and potential limitations, and we discuss the future directions of this therapeutic subclass.

Background Multisite practical clinical trials evaluate treatments in real-world practice. A multisite randomized Veterans Health Administration (VHA) cooperative study (CSP#555) published in 2011 compared the first long-acting injectable (LAI) second-generation antipsychotic (SGA), Risperidone Consta®, in veterans with a diagnosis of schizophrenia or schizoaffective disorder, to oral antipsychotics, with unexpected null results for effectiveness and cost-effectiveness. Whether null results of this type could change VHA practice has not been studied. Methods A longitudinal observational analysis was used to evaluate the impact of the trial findings on VHA clinical practices. National administrative data compared new starts on LAI risperidone during the 4 years before the publication of CSP#555 in 2011 to new starts on LAI risperidone during the 4 years after. Results Among 119,565 Veterans with the indicated diagnoses treated with antipsychotics from 2007 to 2015, the number and proportion of new starts on LAI risperidone declined significantly following the study publication, as did the total number of annual users and drug expenditures. However, data from 2007 to 2010 showed the decline in new starts actually preceded the publication of CSP#555. This change was likely explained by the increase in new starts, total use, and expenditures on a newer medicine, LAI paliperidone, a 4-week LAI treatment, in the 2 years prior to the publication of CSP#555. Conclusions The declining use of LAI risperidone likely primarily reflects the substitution of a longer-acting LAI SGA, paliperidone, that came to market 2 years before the study publication, a substitution that may have been reinforced by null CSP#555 study results for LAI risperidone.

While the stock image of the anarchist as a masked bomber or brick thrower prevails in the public eye, a more representative figure should be a printer at a printing press. In Letterpress Revolution, Kathy E. Ferguson explores the importance of printers, whose materials galvanized anarchist movements across the United States and Great Britain from the late nineteenth century to the 1940s. Ferguson shows how printers—whether working at presses in homes, offices, or community centers—arranged text, ink, images, graphic markers, and blank space within the architecture of the page. Printers' extensive correspondence with fellow anarchists and the radical ideas they published created dynamic and entangled networks that brought the decentralized anarchist movements together. Printers and presses did more than report on the movement; they were constitutive of it, and their vitality in anarchist communities helps explain anarchism’s remarkable persistence in the face of continuous harassment, arrest, assault, deportation, and exile. By inquiring into the political, material, and aesthetic practices of anarchist print culture, Ferguson points to possible methods for cultivating contemporary political resistance.

Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.A total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P0.001).In this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).

Reflex genetic testing of tumor tissue is being completed to direct cancer treatment; however, the patient impact of this genetic testing model is unknown. This survey study evaluates psychological outcomes following tumor and germline genetic testing in individuals with a new diagnosis of high-grade serous ovarian cancer (HGSOC). Individuals were recruited from two hospitals in Toronto, Canada. Participants completed surveys 1 week after receiving tumor results and 1 week after receiving germline results (which included genetic counseling). Outcomes included cancer-related distress (Impact of Events Scale: IES), genetic testing-related distress (Multidimensional Impact of Cancer Risk Assessment: MICRA), and patient satisfaction. Paired t-tests were used to evaluate differences in outcomes following each genetic test result; Cohen's d was used to evaluate effect size. Subgroup analyses were undertaken according to age at diagnosis (60 years vs. ≥60 years) and test results (any positive vs. both negative). McNemar's test assessed differences in satisfaction. Fifty-two individuals were included in the analyses. Mean IES scores were similar following disclosure of tumor and germline results (27.39 vs. 26.14; p = 0.481; d = 0.101). Compared to following tumor result disclosure, MICRA scores were significantly lower following receipt of germline results with genetic counseling (27.23 vs. 22.69; p = 0.007; d = 0.435). Decreases in MICRA scores from tumor to germline result disclosure were greater for those diagnosed60 years or those who received only negative test results. Most individuals were satisfied/highly satisfied following tumor (85.7%) and germline (89.8%) results disclosure (p = 0.774). Reflex tumor, and subsequent germline, genetic testing is a new model of care for cancer patients. In our cohort, genetic testing-related distress decreased significantly following receipt of germline results with genetic counseling, especially for individuals diagnosed under 60 years and those receiving only negative results. Most individuals were satisfied with this model of care.

Malignant bowel obstruction (MBO) in patients with advanced gynecologic cancer (GyCa) can negatively impact clinical outcomes and quality of life. Oncology nurses can support these patients with adequate tools/processes.Patients with GyCa with/at risk of MBO endure frequent emergency or hospital admissions, impacting patient care.Optimizing oncology nurses' role to improve care for patients with GyCa with/at risk of MBO, the gynecology oncology interprofessional team collaborated to develop a proactive outpatient nurse-led MBO model of care (MOC).The MBO MOC involves a risk-based algorithm engaging interdisciplinary care, utilizing standardized tools, risk-based assessment, management, and education for patients and nurses. The MOC has improved patient-reported confidence level of bowel self-management and decreased hospitalization. Following education, nurses demonstrated increased knowledge in MBO management.An outpatient nurse-led MBO MOC can improve patient care and may be extended to other cancer centers, fostering collaboration and best practice.

National policies have targeted widespread exclusionary discipline in schools which is associated with negative academic outcomes. Principals play an important role in making disciplinary decisions, yet little is understood about how their mindsets might impact disciplinary decisions. We hypothesized that principals' mindsets regarding the purpose of discipline (exclusion versus prevention) would predict their responses to misbehavior. In a random nation-wide sample (N=234), principals responded to misbehavior by a hypothetical Black or White student. Exclusion beliefs predicted more severe discipline, while prevention beliefs predicted greater endorsement of referring the student to a school counselor. Principal prevention mindsets also predicted less exclusionary discipline in real-world contexts.

Background With the advent of COVID-19, many healthcare workers (HWs) in Australia requested access to powered air purifying respirators (PAPR) for improved respiratory protection, comfort and visibility. The urgency of the response at our hospital required rapid deployment of innovative training to ensure the safe use of PAPRs, in particular, a video-feedback training option to prepare HWs for PAPR competency. Aim To explore the feasibility, acceptability, and utility of video-feedback in PAPR training and competency assessment. Methods Semi-structured interviews were conducted with 12 HWs, including clinicians from Intensive Care, Anaesthetics and Respiratory Medicine, at a large teaching hospital in Australia. Findings Participants believed that the use of video-feedback in PAPR training was feasible, acceptable and useful. They described a variety of benefits to learning and retention, from a variety of ways in which they engaged with the personal video-feedback. Participants also described the impact of reviewing personalised practice footage, compared to generic footage of an ideal performance. Conclusion By conceptualising video-feedback using a pedagogical approach, this study contributes to knowledge around optimising methods for training HWs in PPE use, particularly when introducing a new and complex PPE device during an infectious disease outbreak.

Background: First-line treatment of epithelial ovarian cancer (EOC) consists of a combination of cytoreductive surgery and platinum-based chemotherapy. Recently, targeted therapies such as bevacizumab have been shown to improve oncologic outcomes in a subset of a high-risk population. The objective of this study is to evaluate the patterns of practice and outcomes of first-line systemic treatment of advanced EOC, focusing on the adoption of bevacizumab. Methods: A population cohort study was conducted using administrative data in Ontario, Canada. Patients diagnosed with advanced stage non-mucinous EOC between 2014 and 2018 were identified. Datasets were linked to obtaining information on first-line treatment including surgery, systemic therapy, providers of care, systemic therapy facilities, and acute care utilization (emergency department (ED) visits and hospitalizations) during systemic treatment. Multivariate logistic regression was used to determine factors associated with systemic therapy utilization. Results: Among 3726 patients with advanced EOC, 2838 (76%) received chemotherapy: 1316 (47%) received neoadjuvant chemotherapy, 1060 (37%) underwent primary cytoreductive surgery followed by chemotherapy, and 462 (16%) received chemotherapy only. The median age was 67 (range: 20–100). Most chemotherapies were prescribed by gynecologic oncologists (60%) and in level 1 academic cancer centres (58%). Only 54 patients (3.1%) received bevacizumab in the first-line setting after its approval in Ontario in 2016. Bevacizumab was more likely to be administered by medical oncologists compared to gynecologic oncologists (OR 3.95, 95% CI 2.11–7.14). In total, 1561 (55%) and 1594 (56%) patients had at least one ED visit and/or hospitalization during systemic treatment, respectively. The most common reasons for ED visits were fever and bowel obstruction. Conclusion: Patterns of care for EOC in Ontario differed between care providers. The uptake of bevacizumab for first-line treatment of EOC was low. Acute care utilization related to EOC was high.

Introduction The COVID-19 pandemic has had significant impact on clinical care and traditional clinical trial operations, but it is unclear whether these impacts persist in pragmatic trials with a centralized study design. The Diuretic Comparison Project (DCP) is a Point-of Care pragmatic trial testing the hypothesis that chlorthalidone is superior to hydrochlorothiazide at the prevention of major cardiovascular (CV) events and non-cancer death. DCP relies on telephone consent, data collection from the electronic health record and Medicare, forgoes study visits, and limits provider time beyond usual care. DCP paused recruitment on VA directive in response to COVID-19 from 3/17/2020 until 7/1/2020. We assessed the impact of the COVID-19 pandemic on the centralized recruitment, patient follow-up, data collection, and outcome ascertainment performed in the DCP. Methods To assess clinical activity level and trial metrics, we compared data from two 8-month time periods: Pre-Pandemic (July 2019 – February 2020) and Mid-Pandemic (July 2020 – February 2021). Consent and randomization rates, study medication adherence, blood pressure (BP) and electrolyte follow-up rates, VA records of CV events, all-cause hospitalization, and death rates were compared for these two periods. Results Providers agreed to participate at a lower rate mid-pandemic (71%) than pre-pandemic (65%), but more patients were contacted (5,363 vs. 7,622) and consented (3,048 vs. 3,718) mid-pandemic. Patients refilled medications and remained on their randomized diuretic at the same frequency (90%) in both periods. Overall, rates of BP, electrolyte measurements, and hospitalizations decreased mid-pandemic while deaths increased. Conclusions While recruitment, enrollment, and adherence did not suffer during the pandemic, documented blood pressure checks and laboratory evaluations decreased, likely due to fewer in-person visits during the pandemic. All-cause VA hospitalizations decreased, despite a considerable number of COVID-related hospitalizations. While this suggests some changes in clinical care during the pandemic, the overall impact on DCP’s ability to operate mostly unimpacted during a global pandemic is another important strength of Point of Care clinical trials. Clinical Trial Registration NCT02185417 Registered 9 July 9 2014 https://clinicaltrials.gov/ct2/show/NCT02185417