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Summary: Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point. Introduction: Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome. Methods: VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry. Results: Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), −0.5 ± 1.1; p = 0.001) and at 3 months (−0.6 ± 1.1; p < 0.001), but not at 6 months (−0.3 ± 1.3; p = 0.066) or 12 months (−0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup ( N = 16; 25 %) had LS BMD Z-scores that were ≤−1.0 at 12 months. In these children, each additional 1,000 mg/m of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, −0.71 to −0.07; p = 0.017). Conclusions: The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤−1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort. [ABSTRACT FROM AUTHOR]

Background: Virtual care may improve access to healthcare and may be well suited to digitally connected youth, but experts caution that privacy and technology barriers could perpetuate access inequities. Success of virtual care will depend on its alignment with patient preferences. However, information on preferences for virtual and in-person healthcare is missing, especially for youth. We sought to quantify preferences for and barriers to virtual versus in-person mental and physical healthcare in youth and their parents, including in vulnerable segments of the population such as families with a parent with severe mental illness (SMI)., Methods: Participants were 219 youth and 326 parents from the Families Overcoming Risks and Building Opportunities for Wellbeing cohort from Canada, of which 61% of youth had at least one parent with SMI. Participants were interviewed about healthcare preferences and access to privacy/technology between October 2021 and December 2022., Results: Overall, youth reported a preference for in-person mental (66.6%) and physical healthcare (74.7%) versus virtual care or no preference, and to a somewhat lesser degree, so did their parents (48.0% and 53.9%). Half of participants reported privacy/technology barriers to virtual care, with privacy being the most common barrier. Preferences and barriers varied as a function of parent SMI status, socioeconomic status and rural residence., Conclusions: The majority of youth and parents in this study prefer in-person healthcare, and the preference is stronger in youth and in vulnerable segments of the population. Lack of privacy may be a greater barrier to virtual care than access to technology., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

End-of-life (EOL) care is a key aspect of critical care medicine (CCM) training. The goal of this study was to survey CCM residents and program directors (PDs) across Canada to describe current EOL care education. Using a literature review, we created a self-administered survey encompassing 10 CCM national objectives of training to address: (1) curricular content and evaluation methods, (2) residents' preparedness to meet these objectives, and (3) opportunities for educational improvement. We performed pilot testing and clinical sensibility testing, then distributed it to all residents and PDs across the 13 Canadian CCM programs. Our response rate was 84.3% overall (77 [81.1%] for residents and 13 [100%] for PDs). Residents rated direct observation, informal advice, and self-reflection as both the top 3 most utilized and perceived most effective teaching modalities. Residents most commonly reported comfort with skills related to pain and symptom management (n = 67, 94.3%; score > 3 on 5-point Likert scale), and least commonly reported comfort with donation after cardiac death skills (n = 26-38; 44.8%-65.5%). Base specialty and time in CCM training were independently associated with comfort ratings for some, but not all, EOL skills. With respect to family meetings, residents infrequently received feedback; however, most PDs believed feedback on 6 to 10 meetings is required for competence. When PD perceptions of teaching effectiveness were compared with resident comfort ratings, differences were most apparent for skills related to pain and symptom management, cultural awareness, and ethical principles. By the end of their first subspecialty training year, PDs expect residents to be competent at most, but not all, EOL skills. In summary, trainees and programs rely on clinical activities to develop competency in EOL care, resulting in some educational gaps. Transitioning to competency-based medical education presents an opportunity to address some of these gaps, while other gaps will require more specific curricular intervention.

Purpose: The 3 Wishes Project (3WP) promotes holistic end-of-life care in the intensive care unit (ICU) to honor dying patients, support families, and encourage clinician compassion. Organ donation is a wish that is sometimes made by, or on behalf of, critically ill patients. Our objective was to describe the interface between the 3WP and organ donation as experienced by families, clinicians, and organ donation coordinators., Methods: In a multicenter evaluation of the 3WP in 4 Canadian ICUs, we conducted a thematic analysis of transcripts from interviews and focus groups with clinicians, organ donation coordinators, and families of dying or died patients for whom donation was considered., Results: We analyzed transcripts from 26 interviews and 2 focus groups with 18 family members, 17 clinicians, and 6 organ donation coordinators. The central theme describes the mutual goals of the 3WP and organ donation-emphasizing personhood and agency across the temporal continuum of care. During family decision-making , conversations encouraged by the 3WP can facilitate preliminary discussions about donation. During preparation for donation , memory-making activities supported by the 3WP redirect focus toward personhood. During postmortem family care , the 3WP supports families, including when donation is unsuccessful, and highlights aspirational pursuits of donation while encouraging reflections on other fulfilled wishes., Conclusions: Organ donation and the 3WP provide complementary opportunities to engage in value-based conversations during the dying process. The shared values of these programs may help to incorporate organ donation and death into a person's life narrative and incorporate new life into a person's death narrative.

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT)., Materials and Methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy., Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05)., Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease.

On September 17, 2019, FDA granted accelerated approval to pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. The submission and review of this application was conducted through an FDA Oncology Center of Excellence initiative named Project Orbis whereby the FDA, the Australian Therapeutic Goods Administration, and Health Canada were able to simultaneously review and collaborate, rendering simultaneous approval decisions in all countries. Accelerated approval of the pembrolizumab plus lenvatinib combination was based on a single-arm trial of 94 patients, with previously treated metastatic endometrial cancer whose tumors were not MSI-H/dMMR. Efficacy was demonstrated on the basis of an objective response rate of 38.3% (95% confidence interval, 28.5%-48.9%) with 10 complete responses (10.6%) accompanied by supportive durations of response. Trials to confirm clinical benefit of this combination are ongoing. Here, we summarize the benefit-risk analysis supporting accelerated approval of the pembrolizumab plus lenvatinib combination and describe the methodology for the first Project Orbis review., (©2020 American Association for Cancer Research.)

Competing Interests: Competing interests: John Gordon Boyd reports receiving salary support from the Trillium Gift of Life Network, nonfinancial support from Caster Medical and a grant from Physician Services Incorporated, outside the submitted work. Maureen Meade reports receiving a knowledge translation grant from Canadian Blood Services, and salary support as a hospital donation physician for Trillium Gift of Life Network. Matthew J Weiss reports receiving ongoing funding from Transplant Québec for his work as medical director of organ donation. Karim Soliman reports receiving a stipend to support education in the province from the Trillium Gift of Life Network. Jeffrey Singh reports receiving a salary as the regional medical lead for donation at Trillium Gift of Life Network. Samantha Arora reports receiving a knowledge translation grant from Canadian Blood Services, and salary support for Hospital Donation Physician work with Trillium Gift of Life, outside the submitted work. Ian Ball reports receiving a consultant stipend from Trillium Gift of Life Network for work as a donation physician. Sam Shemie reports receiving salary support as a medical advisor for deceased organ donation, Canadian Blood Services. Laura Hornby reports receiving consulting fees from Canadian Blood Services. Prosanto Chaudhury reports receiving a salary as a medical director of Transplant Québec, and receiving honoraria from Novartis, Ipsen and Amgen for participation in advisory boards and for hosting invited speakers, outside the submitted work. Alissa Wright reports receiving a stipend for work as an Infectious Disease consultant for BC Transplant. Sean Keenan reports receiving ongoing funding for his work as Provincial Medical Director for BC Transplant. No other competing interests were declared.

Background: Practice variation is common for nephrotic syndrome (NS) treatment., Methods: A cross-sectional, web-based survey on NS treatment was administered to 58 Canadian pediatric nephrologists with the aim to document existing practice variation and compare practice with the recommendations of the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for NS., Results: Of the 58 nephrologists asked to participate in the survey, 40 (69 %) responded. Among these, 62 % prescribed initial daily glucocorticoid (GC) therapy for 6 weeks, 26 % for 4 weeks by 26 %, and 10 % prescribed 'other'. Alternate-day GC was continued for 6 weeks by 63 % of respondents and for >6 and <6 weeks by 32 and 6 %, respectively. For biopsy-confirmed minimal change disease, 65 and 46 % of respondents chose oral cyclophosphamide for frequently relapsing and steroid-dependent phenotypes, respectively; calcineurin inhibitors or mycophenolate were the second most popular choices. Kidney biopsy was 'always' performed by 16, 39, and 97 % of respondents for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Rituximab had been administered by 60 % of respondents; 22, 56, and 72 % reported that they would consider rituximab for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Most notable differences between practice and Guideline recommendations were first presentation GC duration, GC-sparing agent choices in frequently relapsing and steroid-dependent patients, and biopsy practices., Conclusions: There is substantial Canadian practice variation in NS treatment. Assessment of factors driving variation and strategies to implement Guideline recommendations are needed.

Purpose: To study the incidence of retinopathy of prematurity (ROP) in a neonatal intensive care unit and obtain information on risk factors associated with ROP., Methods: Four hundred twenty-three infants were screened for ROP between July 2006 and July 2010. Demographic information, clinical data, and risk factors were reviewed., Results: The incidence was 40.4% (171 infants) for ROP, 9.2% (39 infants) for severe ROP, and 5.67% (24 infants) for laser treatment. Mean gestational age and birth weight were significantly lower among infants with ROP versus those without ROP (26 ± 0.13 vs 28.55 ± 0.12 weeks, P < .0001 and 840.5 ±17.49 vs 1,190.24 ± 20.20 g, P < .0001, respectively). Birth weight (P < .001), gestational age (P < .001), mechanical ventilation therapy (P = .039), and necrotizing enterocolitis (P = .019) were independent risk factors for ROP., Conclusion: Gestational age and birth weight were the most significant risk factors for developing ROP. The study population had an elevated percentage of infants with birth weight less than 1,000 g (extremely low birth weight), yet there was no corresponding increase in severe ROP incidence and treatment when compared to other studies., (Copyright 2013, SLACK Incorporated.)

We assessed current water consumption during liquid fuel production, evaluating major steps of fuel lifecycle for five fuel pathways: bioethanol from corn, bioethanol from cellulosic feedstocks, gasoline from U.S. conventional crude obtained from onshore wells, gasoline from Saudi Arabian crude, and gasoline from Canadian oil sands. Our analysis revealed that the amount of irrigation water used to grow biofuel feedstocks varies significantly from one region to another and that water consumption for biofuel production varies with processing technology. In oil exploration and production, water consumption depends on the source and location of crude, the recovery technology, and the amount of produced water re-injected for oil recovery. Our results also indicate that crop irrigation is the most important factor determining water consumption in the production of corn ethanol. Nearly 70% of U.S. corn used for ethanol is produced in regions where 10-17 liters of water are consumed to produce one liter of ethanol. Ethanol production plants are less water intensive and there is a downward trend in water consumption. Water requirements for switchgrass ethanol production vary from 1.9 to 9.8 liters for each liter of ethanol produced. We found that water is consumed at a rate of 2.8-6.6 liters for each liter of gasoline produced for more than 90% of crude oil obtained from conventional onshore sources in the U.S. and more than half of crude oil imported from Saudi Arabia. For more than 55% of crude oil from Canadian oil sands, about 5.2 liters of water are consumed for each liter of gasoline produced. Our analysis highlighted the vital importance of water management during the feedstock production and conversion stage of the fuel lifecycle.