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Background: SODIUM-HF was a large clinical trial testing dietary sodium restriction compared to usual care in patients with heart failure that showed no reduction in clinical events. It has been suggested that diuretic doses in response to dietary sodium modification may have influenced the trial results., Objective: We assessed the effects of baseline diuretic dose and diuretic dose changes on clinical outcomes in the SODIUM-HF trial., Methods: Diuretics were converted to furosemide-equivalent diuretic total daily doses. Furosemide dose was treated as a continuous variable and also stratified into 0 mg, 1-39 mg, 40 mg, 41-80 mg, and >80 mg daily. The baseline diuretic dose and change in diuretic dose were assessed and correlated with dietary sodium restriction and changes in dietary sodium intake. We then examined the relationship between diuretic dosing and the primary outcomes of SODIUM-HF (cardiovascular-related emergency department visit, cardiovascular-related hospitalization, and all-cause mortality)., Results: Of the 806 patients enrolled in the SODIUM-HF trial, 784 had known diuretic status at baseline: 209 patients (26.7%) with 0 mg, 134 patients (17%) with 1-39 mg, 205 patients (26.1%) with 40 mg, 118 patients (15.1%) with 41-80 mg, and 118 patients (15.1%) with >80 mg. No correlation was found between dietary sodium intake and diuretic dose, either at baseline or change throughout the study (P>0.05). For the primary outcomes, the 2-year risk of primary outcomes was strongly correlated with diuretic dose at baseline across the overall SODIUM-HF population (P<0.001). No significant association was found between the treatment arm and the risk of primary outcomes, within each baseline diuretic dose range or with change in diuretic dose (both P>0.05)., Conclusions: Although a higher baseline diuretic dose was associated with worse clinical outcomes, no association was found between dietary sodium restriction, baseline or change in diuretic dose and the primary outcomes., Competing Interests: Declaration of competing interest JAE is supported by the Alberta Health Services \(AHS) Chair in Cardiac Sciences; reports research support for trial leadership from Bayer, Merck & Co, Novo Nordisk, Cytokinetics, Applied Therapeutics, American Regent; reports honoraria for consultancy from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Otsuka, Bayer, Novartis; and serves as an advisor to US2.ai. All other authors report no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Context: Social support is an important consideration during athletes' rehabilitation following a concussion. Yet, its influence during the return-to-sport (RTS) strategy has been underexplored., Design: Concussed athletes' experiences with social support during RTS were explored prospectively using an explanatory sequential mixed methods design., Methods: University rugby, basketball, and track and field athletes (N = 8) from a single Canadian institution, 19-23 years of age (mean = 20.63, SD = 1.51), completed concentric circles maps, the Perceived Available Support in Sport Questionnaire, and 2 semistructured interviews during their RTS. We analyzed concentric circles maps and questionnaire data descriptively and interview data using codebook thematic analysis., Results: Athletes identified 16 different social support agents. The 5 most important agents during RTS were athletic therapists, student therapists, head coaches, significant others, and teammates/friends. Significant others provided the most emotional (mean = 2.82, SD = 1.85) and esteem (mean = 2.63, SD = 1.85) support, and the athletic therapist (mean = 1.82, SD = 1.35) and head coaches (mean = 0.93, SD = 1.19) provided the most informational and tangible support. We generated 4 themes from athletes' interviews: social support behaviors, contextual factors, concussion and RTS factors, and psychological readiness factors., Conclusions: The number of social support agents present, frequency of support types, and demonstration of support behaviors decreased across the concussion RTS strategy. Contextual (ie, toughness), concussion (ie, visibility), and RTS (ie, prognosis uncertainty) factors influenced athletes' perceptions of social support agents' support behaviors. Results add to our limited understanding of athletes' social support during RTS following a concussion and suggest exploring the integration of behavior-specific (eg, checking in, providing reassurance, and demonstrating compassion) social support strategies to promote concussion rehabilitation and readiness to RTS.

Background: In VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), participants with heart failure (HF) and reduced ejection fraction, vericiguat decreased the primary composite outcome (time to first HF hospitalization [HFH] or cardiovascular death [CVD]) (897 events) compared with placebo (972 events) (hazard ratio, 0.90; 95% confidence interval [CI], 0.82-0.98; P = .02). In this prespecified secondary analysis, we applied the weighted composite end point (WCE) and the win ratio (WR) methods to provide complementary assessments of treatment effect., Methods and Results: The WCE method estimated the mean HFH-adjusted survival based on prespecified weights from a Delphi panel of the VICTORIA executive committee and national leaders: mild (weight per event, 0.39), moderate (0.5), or severe (0.67) HFH, and CVD (1.0). The unmatched WR was estimated for the descending hierarchy of CVD, then recurrent HFH. The WCE used all 3412 primary clinical events: 875 severe HFH (vericiguat, 416/ placebo, 459), 1614 moderate HFH (767/847), 68 mild HFH (38/30), and 855 CVD (414/441). Improved HFH-adjusted survival occurred with vericiguat (mean 78.2% vs 75.6%, difference 2.4%, 95% CI, 1.7%-3.2%, P < .0001). Based on a comparison of 6,375,624 pairs, the WR of 1.13 (95% CI 1.03-1.24, P = .01) also indicated improved clinical outcomes with vericiguat., Conclusions: The results of the WCE and WR methods were consistent with the primary analysis of the time to first HFH or CVD. Although both WCE and WR assessed recurrent events, the WCE allowed inclusion of all recurrent events, insights on the severity of HFH events, and an absolute measure of the participant-treatment experience. This approach complements conventional assessment, better informing consumers of new therapeutics and future trial designs., Competing Interests: Disclosures of Interest Dr. Westerhout has received consulting fees from Bayer Canada. Dr. Anstrom reports research support from the National Institutes of Health and Patient-Centered Outcomes Research Institute and research support from Bayer and Merck outside the submitted work. Dr. Hernandez reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squib, Merck, Novartis, and Verily, as well as consulting from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Myokardia, and Novartis. Dr. Ponikowski reports personal fees from Boehringer Ingelheim, AstraZeneca, Servier, Bristol Myers Squibb, Amgen, Novartis, Merck, Pfizer, and Berlin Chemie, as well as grants and personal fees from Vifor Pharma. Dr. Ezekowitz has received research grants from Bayer, Merck, Servier, Amgen Sanofi, Novartis, Cytokinetics, American Regent, and Applied Therapeutics; and consulting fees from Bayer, Merck, Servier, Amgen, Sanofi, Novartis, Cytokinetics, American Regent, and Applied Therapeutics. Dr. Voors received research grants from Boehringer Ingelheim and Roche Diagnostics; and consulting fees from Merck, Bayer, Amgen, AstraZeneca, Boehringer Ingelheim, Cytokinetics, Myokardia, Novartis, Servier, and Roche Diagnostics. Dr. Felker has received research grants from NHLBI, American Heart Association, Amgen, Bayer, BMS, Merck, Cytokinetics, and CSL-Behring; he has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Medtronic, Cardionomic, Boehringer-Ingelheim, American Regent, Abbott, Astra-Zeneca, Reprieve, Myovant, Sequana, Windtree Therapuetics, and Whiteswell; and has served on clinical end point committees and data safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, LivaNova, Siemens, and Rocket Pharma. Dr. Blaustein is an employee of Merck Sharp & Dohme, LLC, a subsidiary of Merck & Co Inc., Rahway, NJ. Dr. Nkulikiyinka is an employee of Bayer AG, Wuppertal, Germany. Dr. O'Connor has received research funding from Merck; and consulting fees from Bayer, Dey LP, and Bristol Myers Squibb Foundation. Dr. Armstrong reports institutional and personal grants from Merck, Bayer, CLS Limited, Eli Lilly, and Boehringer Ingelheim and personal fees from Merck, Boehringer Ingelheim, Bayer, and Novo Nordisk. All other authors report no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

While a low degree of energy compensation is typically reported over the 24 h following a session of exercise, the prolonged impact of a bout of exercise on energy intake remains unclear. To overcome the challenge associated with accurately measuring energy intake in a free-living environment, this study employed the use of a meal replacement beverage to assess the 3 day impact of an exercise session on energy intake. In a randomized, crossover study, 14 participants (8 male, 6 female) completed two trials: (1) EX: 75 min exercise on a motorized treadmill (75% VO 2peak ); and (2) SED: 75 min sedentary control session. Each condition was followed by 3 days of exclusive ad libitum consumption of a meal replacement beverage. Appetite-regulating hormones, subjective appetite, energy intake, and energy expenditure were assessed. Exercise transiently suppressed the orexigenic hormone acyl-ghrelin (p < 0.05) and elevated the appetite-supressing hepatokine GDF-15 (p < 0.05). Despite these acute changes, overall perceived appetite was elevated over the 3 day assessment period with exercise (p < 0.05). No increase in energy intake or change in postexercise physical activity patterns were observed. One acute session of moderate to vigorous exercise is unlikely to affect short-term, three-day energy balance in healthy individuals., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objectives: Prognostic tools with evidence for external validity in routine clinical practice are needed to align care with patients' preferences and deliver timely supportive services. Current models have limited, if any, evidence for external validity and none have been implemented and evaluated in clinical practice on a large scale. This study sought to provide evidence for external validity in a real life setting of the Cohen prognostic model that integrates actuarial factors with the 'Surprise Question' to assess 6-month, 12-month and 18-month survival of prevalent haemodialysis patients., Methods: Cross-sectional study of 1372 patients in a Canadian university-based programme between 2010 and 2019. Survival probabilities were compared with observed survival. Discrimination and calibration were assessed through predicted risk-stratified observed survival, cumulative AUC, Somer's Dxy and a calibration slope estimate., Results: Discrimination performance was moderate with a C statistic of 0.71-0.72 for all three time points. The model overpredicted mortality risk with the best predictive accuracy for 6- month survival. The differences between observed and mean predicted survival at 6 months, 12 months and 18 months were 3.2%, 8.8% and 12.9%, respectively. Kaplan-Meier curves stratified by Cox-based risk group showed good discrimination between high-risk and low-risk patients with HR estimates (95% CI): C2 vs C1 3.07 (1.57-5.99), C3 vs C1 5.85 (3.06-11.17), C4 vs C1 13.24 (6.91-25.34))., Conclusions: The Cohen prognostic model can be incorporated easily into routine dialysis care to identify patients at high risk for death over 6 months, 12 months and 18 months and help target vulnerable patients for timely supportive care interventions., 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.)

The effectiveness of newborn screening (NBS) for congenital hypothyroidism (CH) relies on timely screening, confirmation of diagnosis, and initiation and ongoing monitoring of treatment. The objective of this study was to ascertain the extent to which infants with CH have received timely and appropriate management within the first 3 years of life, following diagnosis through NBS in Alberta, Canada. Deidentified laboratory data were extracted between 1 April 2014 and 31 March 2019 from Alberta Health administrative databases for infants born in this time frame. Time to lab collection was anchored from date of birth. Timeliness was assessed as the frequency of monitoring of Thyroid Stimulating Hormone (TSH) and appropriateness as the frequency of children maintaining biochemical euthyroidism. Among 160 term infants, 95% had confirmation of diagnosis by 16 days of age. The cohort had a median of 2 (range 0-5) TSH measurements performed in the time interval from 0 to 1 month, 4 (0-12) from 1 to 6 months, 2 (0-10) from 6 to 12 months, and 7 (0-21) from 12 to 36 months. Approximately half were still biochemically hypothyroid (TSH > 7 mU/L) at 1 month of age. After becoming euthyroid, at least some period of hypo- (60%) or hyperthyroidism (TSH < 0.2 mU/L) (39%) was experienced. More work needs to be performed to discern factors contributing to prolonged periods of hypothyroidism or infrequent lab monitoring.

Background: In heart failure (HF) trials, there has been an emphasis on utilizing more patient-centered outcomes, including quality of life (QoL) and days alive and out of hospital. We aimed to explore the impact of QoL adjusted days alive and out of hospital as an outcome in 2 HF clinical trials., Methods: Using data from 2 trials in HF (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT] and Study of Dietary Intervention under 100 mmol in Heart Failure [SODIUM-HF]), we determined treatment differences using percentage days alive and out of hospital (%DAOH) adjusted for QoL at 18 months as the primary outcome. For each participant, %DAOH was calculated as a ratio between days alive and out of hospital/total follow-up. Using a regression model, %DAOH was subsequently adjusted for QoL measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score., Results: In the GUIDE-IT trial, 847 participants had a median baseline Kansas City Cardiomyopathy Questionnaire Overall Summary Score of 59.0 (interquartile range, 40.8-74.3), which did not change over 18 months. %DAOH was 90.76%±22.09% in the biomarker-guided arm and 88.56%±25.27% in the usual care arm. No significant difference in QoL adjusted %DAOH was observed (1.09% [95% CI, -1.57% to 3.97%]). In the SODIUM-HF trial, 796 participants had a median baseline Kansas City Cardiomyopathy Questionnaire Overall Summary Score of 69.8 (interquartile range, 49.3-84.3), which did not change over 18 months. %DAOH was 95.69%±16.31% in the low-sodium arm and 95.95%±14.76% in the usual care arm. No significant difference was observed (1.91% [95% CI, -0.85% to 4.77%])., Conclusions: In 2 large HF clinical trials, adjusting %DAOH for QoL was feasible and may provide complementary information on treatment effects in clinical trials., Competing Interests: Disclosures Dr Felker reported receiving grant support from Merck and personal fees from Medtronic, Bristol Myers Squibb, Trevena, GlaxoSmithKline, Myokardia, and Stealth BioTherapeutics. Dr Macdonald reports research grants from the National Health and Medical Research Committee, the New South Wales Department of Health, and the St Vincent’s Clinic Foundation; consulting fees from AstraZeneca, Boehringer Ingelheim, and Novartis; honoraria payments from the Japanese Circulation Society; support for attending meetings or travel from Astellas; and stock or stock options in Infensa Biologics. R.W. Troughton reports research grants from the Health Research Council of New Zealand, consulting fees from Merck and Roche Diagnostics, and honoraria payments from Roche Diagnostics. Dr O’Connor reported receiving grant support from Roche Diagnostics and the National Institutes of Health. J.A. Ezekowitz reports research support for trial leadership or grants from American Regent, Applied Therapeutics, AstraZeneca, Bayer, Cytokinetics, Merck & Co, Novo Nordisk, and Otsuka; honoraria for consultancy from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, and Otsuka; and serves as an advisor to US2.ai. The other authors report no conflicts.

Background: The association between frailty and health status in patients with heart failure with preserved ejection fraction (HFpEF) is not well known., Objectives: The authors examined the association between: 1) patient-reported frailty, measured by the Fried frailty phenotype, Kansas City Cardiomyopathy Questionnaire Physical Limitation Score (KCCQ-PLS), 6-minute walking distance (6MWD), and other baseline characteristics; 2) baseline frailty compared with KCCQ-PLS and 24-week 6MWD; 3) frailty and changes in KCCQ-PLS and 6MWD; and 4) vericiguat and frailty at 24 weeks., Methods: In a post hoc analysis, patients in the VITALITY-HFpEF (Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF) trial were categorized as not frail (0 symptoms), prefrail (1-2 symptoms), and frail (≥3 symptoms) according to patient-reported number of frailty symptoms. Correlations and linear regression models were used to examine the association between frailty and other measures, and between frailty and KCCQ-PLS at baseline with 24-week 6MWD., Results: Among 739 patients, 27.3% were not frail, 37.6% were prefrail, and 35.0% were frail at baseline. Frail patients were older, more likely to be women, and less likely to be from Asia. Baseline KCCQ-PLS and 6MWD (mean ± SD) among not frail, prefrail, and frail patients was 68.2 ± 23.2, 61.7 ± 22.6, and 48.4 ± 23.8 and 328.5 ± 117.1 m, 310.8 ± 98.9 m, and 250.7 ± 104.3 m (P < 0.01 for both). After accounting for baseline 6MWD, frailty status at baseline, but not KCCQ-PLS, was significantly associated with 6MWD at 24 weeks. By 24 weeks, 47.5% of patients had no change in frailty, 45.5% had become less frail, and 7.0% had become more frail. Treatment with vericiguat did not alter frailty status at 24 weeks., Conclusions: Patient-reported frailty is modestly correlated with both the KCCQ-PLS and 6MWD but offers prognostic insight into 6MWD at 24 weeks. (Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF [VITALITY-HFpEF]; NCT03547583)., Competing Interests: Funding Support and Author Disclosures The VITALITY-HFpEF trial was funded by Bayer and Merck Sharp and Dohme Corp, a subsidiary of Merck and Co, Inc. Dr Lam has received research grant support from Bayer, the National Medical Research Council of Singapore, Boston Scientific, Roche Diagnostics, Medtronic, Vifor Pharma, and AstraZeneca; has received consulting fees from Merck, Bayer, Boston Scientific, Roche Diagnostics, Vifor Pharma, AstraZeneca, Novartis, Amgen, Janssen Research and Development LLC, Menarini, Boehringer Ingelheim, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, Novo Nordisk, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, Cytokinetics, WebMD Global LLC, Radcliffe Group Ltd, and Corpus; has patent PCT/SG2016/050217 pending and patent 16/216929 pending; and is co-founder and nonexecutive director of eKo.ai. Dr Westerhout has received consulting fees from Bayer Canada. Dr Spertus has received research grant support from the National Institutes of Health, Abbott Vascular, and American College of Cardiology Foundation; has received consulting fees from Janssen, Novartis, Amgen, Myokardia/Bristol Myers Squibb, AstraZeneca, Bayer, and Merck and Co, Inc; has served on the scientific advisory board for United Healthcare; has served on the board of directors for Blue Cross Blue Shield of Kansas City; and owns the copyright to the Kansas City Cardiomyopathy Questionnaire, Seattle Angina Questionnaire, and Peripheral Artery Questionnaire. Dr Anstrom has received research grant support from Merck and Co, Inc, and the National Institutes of Health. Dr Blaustein is an employee of Merck and Co, Inc. Dr Ezekowitz has received research grant support and consulting fees from Bayer, Merck, Servier, Amgen, Sanofi, Novartis, Cytokinetics, American Regent, Otsuka, and Applied Therapeutics. Dr Pieske has received research grant support from Merck Sharp & Dohme, Bayer, and Servier; consulting fees from Merck Sharp & Dohme, Bayer, Servier, Bristol-Myers Squibb, MedScape, Daiichi Sankyo, and Novartis; and nonfinancial support from Merck Sharp & Dohme, Bayer, and Novartis. Dr Roessig is an employee of Bayer AG. Dr Butler has received consulting fees from Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Roche, and Vifor. Dr Armstrong has received research grant support from Merck, Bayer, Boehringer Ingelheim, Boehringer Ingelheim/Eli Lilly, and CSL Limited; and consulting fees from Merck, Bayer, and Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Puberty suppression is a standard of care for gender-affirming therapy in gender-diverse youth. Leuprolide acetate is a gonadotropin-releasing hormone agonist (GnRHa) commonly used for pubertal suppression. There are concerns that GnRHa agents prolong the rate-corrected QT interval (QTc) when used as androgen deprivation therapy in management of prostate cancer; however, there is a paucity of literature regarding the effect of leuprolide acetate on QTc intervals in gender-diverse youth., Aim: To determine the proportion of gender-diverse youth with QTc prolongation on leuprolide acetate therapy., Methods: A retrospective chart review of gender-diverse youth initiated on leuprolide acetate between July 1, 2018 and December 31, 2019 was conducted at a tertiary care pediatric hospital in Alberta, Canada. Youth aged 9-18 years were included if a 12-lead electrocardiogram was completed after initiating leuprolide acetate. The proportion of adolescents with clinically significant QTc prolongation was assessed, defined as QTc >460 milliseconds (ms)., Results: Thirty-three pubertal youth were included. The cohort had a mean age of 13.7 years (standard deviation [SD] 2.1) and 69.7% identified as male (assigned female at birth). The mean post-leuprolide acetate QTc was 415 ms (SD 27, range 372-455). Twenty-two (66.7%) of youth were prescribed concomitant medications, including QTc-prolonging medications in 15.2%. None of the 33 youth on leuprolide acetate had QTc prolongation. Only 24.2% patients had a borderline QTc (QTc 440-460 ms)., Conclusion: No gender-diverse youth on leuprolide acetate demonstrated clinically significant QTc prolongation., Competing Interests: No competing financial interests exist., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Background: Composite endpoints for estimating treatment efficacy are routinely used in several therapeutic areas and have become complex in the number and types of component outcomes included. It is assumed that its components are of similar asperity and chronology between both treatment arms as well as uniform in magnitude of the treatment effect. However, these assumptions are rarely satisfied. Understanding this heterogeneity is important in developing a meaningful assessment of the treatment effect., Methods: We developed the Weighted Composite Endpoint (WCE) method which uses weights derived from stakeholder values for each event type in the composite endpoint. The derivation for the product limit estimator and the variance of the estimate are presented. The method was then tested using data simulated from parameters based on a large cardiovascular trial. Variances from the estimated and traditional approach are compared through increasing sample size., Results: The WCE method used all of the events through follow-up and generated a multiple recurrent event survival. The treatment effect was measured as the difference in mean survivals between two treatment arms and corresponding 95% confidence interval, providing a less conservative estimate of survival and variance, giving a higher survival with a narrower confidence interval compared to the traditional time-to-first-event analysis., Conclusions: The WCE method embraces the clinical texture of events types by incorporating stakeholder values as well as all events during follow-up. While the effective number of events is lower in the WCE analysis, the reduction in variance enhances the ability to detect a treatment effect in clinical trials., (© 2023. Crown.)

Background: Sodium restriction is a nonpharmacologic treatment suggested by practice guidelines for the management of patients with heart failure (HF). In this study, we synthesized the data from randomized controlled trials (RCTs) evaluating the effects of sodium restriction on clinical outcomes in patients with HF., Methods: In this aggregate data meta-analysis, Cochrane Central, MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase Ovid, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus databases were searched up to April 2, 2022. RCTs were included if they investigated the effects of sodium/salt restriction as compared to no restriction on clinical outcomes in patients with HF. Outcomes of interest included mortality, hospitalization, change in New York Heart Association functional class, and quality of life (QoL)., Results: Seventeen RCTs were identified (834 and 871 patients in intervention and control groups, respectively). Sodium restriction did not reduce the risk of all-cause death (odds ratio, 0.95 [95% CI, 0.58-1.58]), hospitalization (odds ratio, 0.84 [95% CI, 0.62-1.13]), or the composite of death/hospitalization (odds ratio, 0.88 [95% CI, 0.63-1.23]). The results were similar in different subgroups, except for the numerically lower risk of death with reduced sodium intake reported in RCTs with dietary sodium at the 2000 to 3000 mg/d range as opposed to <2000 mg/d (and in RCTs with versus without fluid restriction as a co-intervention). Among RCTs reporting New York Heart Association change, 2 RCTs (which accounted for two-thirds of the data) showed improvement in New York Heart Association class with sodium restriction. Substantial heterogeneity existed for QoL: 6 RCTs showed improvement of QoL and 4 RCTs showed no improvement of sodium restriction on QoL., Conclusions: In a meta-analysis of RCTs, sodium restriction was not associated with fewer deaths or hospitalizations in patients with HF. Dietary sodium restriction may be associated with improvements in symptoms and QoL.

The introduction of next generation sequencing (NGS) technologies has revolutionized the practice of Medical Genetics, and despite initial reticence in its application to prenatal genetics (PG), it is becoming gradually routine, subject to availability. Guidance for the clinical implementation of NGS in PG, in particular whole exome sequencing (ES), has been provided by several professional societies with multiple clinical studies quoting a wide range of testing yields. ES was introduced in our tertiary care center in 2017; however, its use in relation to prenatally assessed cases has been limited to the postnatal period. In this study, we review our approach to prenatal testing including the use of microarray (CMA), and NGS technology (gene panels, ES) over a period of three years. The overall diagnostic yield was 30.4%, with 43.2% of those diagnoses being obtained through CMA, and the majority by using NGS technology (42% through gene panels and 16.6% by ES testing, respectively). Of these, 43.4% of the diagnoses were obtained during ongoing pregnancies. Seventy percent of the abnormal pregnancies tested went undiagnosed. We are providing a contemporary, one tertiary care center retrospective view of a real-life PG practice in the context of an evolving use of NGS within a Canadian public health care system that may apply to many similar jurisdictions around the world.

Introduction: Heart failure (HF), and especially HF with preserved ejection fraction (HFpEF), remains a challenging condition to define. The heterogenous nature of this population may be related to a variety of underlying etiologies interacting myocardial dysfunction., Method: Alberta HEART study was a prospective, observational cohort that enrolled participants along the spectrum of heart failure including: healthy controls, people at risk of HF, and patients with HF and preserved (HFpEF) or reduced ejection fraction (HFrEF). We aimed to explore phenotypes of patients with HF and at-risk of developing HF. Utilising 27 detailed clinical, echocardiographic and biomarker variables, latent class analysis with and without multiple imputation was undertaken to identify distinct clinical phenotypes., Results: Of 621 participants, 191 (30.8%) and 169 (27.2%) were adjudicated by cardiologists to have HFpEF and HFrEF respectively. In the overall cohort, latent class analysis identified four distinct phenotypes. Phenotype A (n=152, 24.5%) was a healthy and low risk group. Phenotype B (n=129, 20.8%) demonstrated increased left ventricular mass and end-diastolic volumes, with elevated natriuretic peptides and clinical features of congestion. Phenotype C (n=128, 20.6%) was primarily characterised by obesity (80%) and normal indexed cardiac chamber sizes, low natriuretic peptide levels and minimal features of congestion.  Phenotype D (n=212, 34.1%) consisted of elderly patients with clinical features of congestions. Phenotypes B and D demonstrated the highest risk of mortality and hospitalization over a median follow-up of 3.7 years., Conclusion: Phenotypes with congestive features demonstrated increased risk profiles. Heart failure is a heterogenous classification which requires further work to appropriately categorise patients based on the underlying etiology or mechanism of impairment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Playing the piano at expert levels typically involves significant levels of trial-and-error learning since the majority of practice occurs in isolation. To better optimize musical outcomes, pianists might be well served by emulating some of the practices found in sports, where motor learning strategies are grounded in biomechanics and ergonomics in order to improve performance and reduce risk of performance-related injuries. The purpose of the current study is to examine trunk-hand coordination and preparatory movement strategization in piano performance, while considering the influence of anthropometry, skill level of the performer, and musical context. Using a ten-camera motion capture system, movement of C7 and right-hand distal phalanges was tracked at three different playing speeds during performance of an excerpt from Beethoven's "Appassionata" Sonata. There were three participants: two males and one female of differing anthropometric characteristics and skill levels. Motor strategization was examined. Expertise influenced starting trunk position: Initiation intervals and trunk range of motion (ROM) both suggested anthropometry to be a performance factor. For the shortest performer, trunk movement appeared to be used as an efficiency measure to compensate for a shorter arm reach. Skill level was revealed by examining right-hand velocity at the fastest tempo. The current study hypothesizes that an examination of proximal-to-distal preparatory strategies in terms of anthropometry and skill level can help to optimize motor learning for pianists. To realize piano performance as a whole-body skill and encourage healthy practice, pedagogy needs to educate learners regarding fundamental biomechanical and ergonomic principles, movement optimization, and movement strategization in the service of artful performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Turner, Visentin, Oye, Rathwell and Shan.)

Background: We describe variables and outcomes associated with peri-operative mechanical circulatory support (MCS) utilization among patients enrolled in the Levosimendan in patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial., Methods: In the LEVO-CTS trial, MCS utilization (defined as intra-aortic balloon pump, extracorporeal membrane oxygenation, or surgical ventricular assist device) within 5 days of surgery was examined. The association between MCS use and outcomes including 90-day mortality, 30-day renal-replacement therapy, and hospital and critical stay length of stay were determined., Results: Among the 849 patients from 70 centers randomized to levosimendan or placebo, 85 (10.0%) patients were treated with MCS (71 intra-aortic balloon pump, 7 extracorporeal membrane oxygenation, 7 ventricular assist device); with 89.4% started on post-operative day 0. Inter-institutional use ranged from 0% to 100%. Variables independently associated with MCS utilization included combined coronary artery bypass grafting and valve surgery (adjusted odds ratio [OR] 2.73, 95% confidence interval [CI] 1.70-4.37, P < .001), history of lung disease (OR 1.70, 95% CI 1.06-2.70, P = .029), and history of heart failure (OR 2.44, 95% CI 1.10-5.45, P = .027). Adjusted 90-day mortality (22.4% vs 4.1%, hazard ratio 6.11, 95% CI 3.95-9.44, P < .001) was higher, and median critical care length of stay (8.0 vs 4.0 days, P < .001) was longer in patients managed with MCS., Conclusions: In a randomized controlled trial of high-risk cardiac surgical patients in North America, we observed patient, and surgical variables associated with MCS utilization. MCS use was associated with a higher risk of post-operative mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To examine characteristics of children referred for obesity management based on referral frequency, child- and referrer-related variables associated with re-referral, and determine whether re-referral increased treatment initiation., Study Design: This population-level, retrospective analysis included all 2- to 17-year-olds referred for obesity management to 1 of 3 multidisciplinary clinics in Alberta, Canada between April 2013 and December 2017. Children were dichotomized based on referral frequency, specifically once only or more than once (re-referred). Data were retrieved from standardized referral forms and patient registries. Analyses included logistic regression and generalized estimating equations models., Result: We analyzed data from 2745 children (47.2% female; mean age: 11.4 years; mean body mass index z score: 3.03) and 2705 physicians (60.2% female; 65.6% pediatricians). Overall, 300 (10.2%) children were re-referred with most (n = 276; 92.0%) being referred twice. Children were less likely to be re-referred if they were referred by a family physician (vs pediatrician) (aOR 0.62; 95% CI 0.46-0.84; P = .0018) or scheduled a clinic appointment following their index referral (aOR: 0.29; 95% CI 0.21-0.4; P < .001). Treatment initiation was higher in children who were referred once only (42.1%) vs their re-referred peers (18.0%; P < .0001); however, for children who were re-referred, they were more likely to initiate treatment following their second referral (aOR 2.3; 95% CI 1.22-4.31; P = .01). This improvement was not sustained on subsequent referrals (aOR 0.44; 95% CI 0.17-1.12; P = .08)., Conclusions: Few children were re-referred for pediatric obesity management; however, for those children who were re-referred, being re-referred once only increased the likelihood of treatment initiation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: N-terminal pro-b-type natriuretic peptide (NT-proBNP) values may be influenced by patient factors beyond the severity of illness, including atrial fibrillation (AF), renal dysfunction, or increased body mass index (BMI). We hypothesized that these factors may influence the achievement of NT-proBNP targets and clinical outcomes., Methods: A total of 894 patients with heart failure with reduced ejection fraction were enrolled in The Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment trial. NT-proBNP was analysed every 3 months., Results: Forty per cent of patients had AF, the median estimated glomerular filtration rate (eGFR) was 59 mL/min/1.73 m 2 [interquartile range (IQR) 43-76], and median BMI was 29 kg/m 2 (IQR 25-34). Patients with AF, eGFR < 60 mL/min/1.73 m 2 , or a BMI < 29 kg/m 2 had a higher level of NT-proBNP at randomization and over all study visits (all P values < 0.001). Over 18 months, the rate of change of NT-proBNP was less for patients with AF (compared with those without AF, P = 0.037) and patients with an eGFR < 60 mL/min/1.73 m 2 (compared with eGFR > 60 mL/min/1.73 m 2 , P < 0.001). The rate of change of NT-proBNP was similar for patients with a BMI above or below the median value. Using the 90 day NT-proBNP, patients with AF, lower eGFR, or lower BMI were less likely to achieve the target NT-proBNP < 1000 pg/mL than patients without AF, higher eGFR, or higher BMI, respectively. None of these differed between the Usual Care or Guided Care arm for AF, eGFR, or BMI (P interactions all NS)., Conclusions: Patients with AF, a lower BMI, or worse renal function are less likely to achieve a lower or target NT-proBNP. Clinicians should be aware of these factors both when interpreting NT-proBNP levels and making therapeutic decisions about heart failure therapies., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: It is recommended that primary care-based physicians refer children with overweight and obesity to multidisciplinary paediatric obesity management, which can help to improve weight and health., Objective: To determine predictors of referral to multidisciplinary paediatric obesity management., Methods: This retrospective, population-level study included physicians who could refer 2-17 years old with a body mass index ≥85th percentile to one of three multidisciplinary paediatric obesity management clinics in Alberta, Canada. Physician demographic and procedural data were obtained from Practitioner Claims and Provider Registry maintained by Alberta Health from January 2014 to December 2017. Physician characteristics were compared based on whether they did or did not refer children for obesity management. Univariable and multivariable logistic regression models analysed associations between physician characteristics and referral making., Results: Of the 3863 physicians (3468 family physicians, 395 paediatricians; 56% male; 49.3 ± 12.2 years old; 22.3 ± 12.6 years since graduation) practicing during the study period, 1358 (35.2%) referred at least one child for multidisciplinary paediatric obesity management. Multivariable regression revealed that female physicians (versus males) [odds ratio (OR): 1.68, 95% confidence interval (CI): 1.46-1.93; P < 0.0001], paediatricians (versus family physicians) (OR: 4.89, 95% CI: 3.85-6.21; P < 0.0001) and urban-based physicians (versus non-urban-based physicians) (OR: 2.17, 95% CI: 1.79-2.65; P < 0.0001) were more likely to refer children for multidisciplinary paediatric obesity management., Conclusions: Approximately one-third of family physicians and paediatricians referred children for multidisciplinary paediatric obesity management. Strategies are needed to improve referral practices for managing paediatric obesity, especially among male physicians, family physicians and non-urban-based physicians as they were less likely to refer children., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Renal dysfunction is a strong predictor of outcomes in patients with acute heart failure (AHF). However, less is known about how sex may influence the prognostic import of renal function in AHF., Methods and Results: In a post hoc analysis of the ASCEND-HF trial including 5377 patients with AHF (33% female), patients were categorized into 3 groups based on the changes in renal function during their hospital stay. Worsening, stable, and improving renal functions were defined as a ≥20% decrease, a <20% change, and a ≥20% increase in the estimated glomerular filtration rate, respectively. The primary outcome was the composite of 30-day all-cause mortality or HF rehospitalization. The median baseline and discharge estimated glomerular filtration rate were 58.4 and 56.9 mL/min/1.73 m 2 , respectively. Worsening, stable, and improving renal function was observed in 31.9%, 63.2, and 4.9% of patients, respectively. Worsening renal function was associated with adverse outcomes at 30 days (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.22-1.76). This association existed in both males and females (aHR 1.42 and aHR 1.56, respectively, both P < .01). There was an interaction between renal function changes and sex (P = .025), because improving renal function was associated with better outcomes in men (aHR 0.29, 95% CI 0.13-0.66) as compared with women (aHR 1.18, 95% CI 0.59-2.35). There was no interaction between the ejection fraction and renal function in association with subsequent outcomes., Conclusions: Irrespective of sex, worsening renal function was associated with poorer outcomes at 30 days in patients with AHF. More studies are warranted to further delineate the possible sex differences in this setting., Competing Interests: Disclosures The authors report no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death., Methods: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data., Results: Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety., Interpretation: There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered., Trial Registration: ClinicalTrials.gov, no. NCT04329611., Competing Interests: Competing interests: Aravind Ganesh reports payments to his institution from the Canadian Institutes of Health Research (CIHR), the Canadian Cardiovascular Society, Alberta Innovates and Campus Alberta Neuroscience; consulting fees from MD Analytics, My Medical Panel, Atheneum, DeepBench and Research on Mind; meetings or travel support from American Academy of Neurology, Association of Indian Neurologists in America, American Heart Association and University of Calgary; and a provisional patent application for a system for patient monitoring and delivery of remote ischemic conditioning or other cuff-based therapies. He is a member of the editorial boards of Neurology: Clinical Practice, Neurology and Stroke. He has stock in SnapDx (patient monitoring and decision support technology), American Health Analytics (AHA Health Ltd.; patient monitoring) and TheRounds.com (physician social network). Bijoy Menon reports grants or contracts from CIHR, the Heart and Stroke Foundation of Canada and Alberta Innovates Health Solutions and patents from the United States Patent and Trademark Office on systems of triage in acute stroke. He is a member of and has stock in Circle NVI. Michael Hill reports that Apotex Pharma provided the drug and placebo for the current trial as an in-kind contribution to the study. He was the main contact with Apotex Pharma and has no other relationship with the company; there were no obligations attached to this donation of drug and placebo., (© 2021 CMA Joule Inc. or its licensors.)

Piano performance motor learning research requires more "artful" methodologies if it is to meaningfully address music performance as a corporeal art. To date, research has been sparse and it has typically constrained multiple performance variables in order to isolate specific phenomena. This approach has denied the fundamental ethos of music performance which, for elite performers, is an act of interpretation, not mere reproduction. Piano performances are intentionally manipulated for artistic expression. We documented motor movements in the complex task of performance of the first six measures of Chopin's "Revolutionary" Etude by two anthropometrically different elite pianists. We then discussed their motor strategy selections as influenced by anthropometry and the composer's musical directives. To quantify the joint angles of the trunk, shoulders, elbows, and wrists, we used a VICON 3 D motion capture system and biomechanical modeling. A Kistler force plate (1 N, Swiss) quantified center of gravity (COG) shifts. Changes in COG and trunk angles had considerable influence on the distal segments of the upper limbs. The shorter pianist used an anticipatory strategy, employing larger shifts in COG and trunk angles to produce dynamic stability as compensation for a smaller stature. Both pianists took advantage of low inertial left shoulder internal rotation and adduction to accommodate large leaps in the music. For the right arm, motor strategizing was confounded by rests in the music. These two cases illustrated, in principle, that expert pianists' individualized motor behaviors can be explained as compensatory efforts to accommodate both musical goals and anthropometric constraints. Motor learning among piano students can benefit from systematic attention to motor strategies that consider both of these factors.

Background: Despite a temporal increase in respiratory failure in patients hospitalized with acute heart failure (HF), clinical trials have largely not reported the incidence or associated clinical outcomes for patients requiring mechanical ventilation., Methods and Results: After pooling 5 acute HF clinical trials, we used multivariable logistic regression adjusted for demographics, comorbidities, examinations, and laboratory findings to assess associations between mechanical ventilation and clinical outcomes. Among the 8296 patients, 210 (2.5%) required mechanical ventilation. Age, sex, smoking history, baseline ejection fraction, HF etiology, and the proportion of patients randomized to treatment or placebo in the original clinical trial were similar between groups (all, P > 0.05). Baseline diabetes mellitus was more common in the mechanical ventilation group (P = 0.02), but other comorbidities, including chronic lung disease, were otherwise similar (all P > 0.05). HF rehospitalization at 30 days (12.7% vs 6.6%, P < 0.001) and all-cause 60-day mortality (33.3% vs 6.1%, P < 0.001) was higher among patients requiring mechanical ventilation. After multivariable adjustment, mechanical ventilation use was associated with an increased 30-day HF rehospitalization (odds ratio 2.03; 95% confidence interval, 1.29-3.21, P = 0.002), 30-day mortality (odds ratio 10.40; 95% confidence interval, 7.22-14.98, P < 0.001), and 60-day mortality (odds ratio 7.68; 95% confidence interval, 5.50-10.74, P < 0.001). The influence of mechanical ventilation did not differ by HF etiology or baseline ejection fraction (both, interaction P > 0.20)., Conclusions: Respiratory failure during an index hospitalization for acute HF was associated with increased rehospitalization and all-cause mortality. The development of respiratory failure during an acute HF admission identifies a particularly vulnerable population, which should be identified for closer monitoring., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Chronic pain is a common and distressing symptom reported by patients with chronic kidney disease (CKD). Clinical practice and research in this area do not appear to be advancing sufficiently to address the issue of chronic pain management in patients with CKD., Objectives: To determine the prevalence and severity of chronic pain in patients with CKD., Design: Systematic review and meta-analysis., Setting: Interventional and observational studies presenting data from 2000 or later. Exclusion criteria included acute kidney injury or studies that limited the study population to a specific cause, symptom, and/or comorbidity., Patients: Adults with glomerular filtration rate (GFR) category 3 to 5 CKD including dialysis patients and those managed conservatively without dialysis., Measurements: Data extracted included title, first author, design, country, year of data collection, publication year, mean age, stage of CKD, prevalence of pain, and severity of pain., Methods: Databases searched included MEDLINE, CINAHL, EMBASE, and Cochrane Library, last searched on February 3, 2020. Two reviewers independently screened all titles and abstracts, assessed potentially relevant articles, and extracted data. We estimated pooled prevalence of overall chronic pain, musculoskeletal pain, bone/joint pain, muscle pain/soreness, and neuropathic pain and the I 2 statistic was computed to measure heterogeneity. Random effects models were used to account for variations in study design and sample populations and a double arcsine transformation was used in the model calculations to account for potential overweighting of studies reporting either very high or very low prevalence measurements. Pain severity scores were calibrated to a score out of 10, to compare across studies. Weighted mean severity scores and 95% confidence intervals were reported., Results: Sixty-eight studies representing 16 558 patients from 26 countries were included. The mean prevalence of chronic pain in hemodialysis patients was 60.5%, and the mean prevalence of moderate or severe pain was 43.6%. Although limited, pain prevalence data for peritoneal dialysis patients (35.9%), those managed conservatively without dialysis (59.8%), those following withdrawal of dialysis (39.2%), and patients with earlier GFR category of CKD (61.2%) suggest similarly high prevalence rates., Limitations: Studies lacked a consistent approach to defining the chronicity and nature of pain. There was also variability in the measures used to determine pain severity, limiting the ability to compare findings across populations. Furthermore, most studies reported mean severity scores for the entire cohort, rather than reporting the prevalence (numerator and denominator) for each of the pain severity categories (mild, moderate, and severe). Mean severity scores for a population do not allow for "responder analyses" nor allow for an understanding of clinically relevant pain., Conclusions: Chronic pain is common and often severe across diverse CKD populations providing a strong imperative to establish chronic pain management as a clinical and research priority. Future research needs to move toward a better understanding of the determinants of chronic pain and to evaluating the effectiveness of pain management strategies with particular attention to the patient outcomes such as overall symptom burden, physical function, and quality of life. The current variability in the outcome measures used to assess pain limits the ability to pool data or make comparisons among studies, which will hinder future evaluations of the efficacy and effectiveness of treatments. Recommendations for measuring and reporting pain in future CKD studies are provided., Trial Registration: PROSPERO Registration number CRD42020166965., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Adult sportspersons (Masters athletes, aged 35 years and older) have unique coaching preferences. No existing resources provide coaches with feedback on their craft with Masters athletes. Three studies evaluated an Adult-Oriented Coaching Survey. Study 1 vetted the face validity of 50 survey items with 12 Masters coaches. Results supported the validity of 48 items. In Study 2, 383 Masters coaches completed the survey of 50 items. Confirmatory factor analysis and exploratory structural equation modeling indicated issues with model fit. Post hoc modifications improved fit, resulting in a 22-item, five-factor model. In Study 3, 467 Masters athletes responded to these 22 items reflecting perceptions of their coaches. Confirmatory factor analysis (comparative fit index = .951, standardized root mean square residual = .036, and root mean square error of approximation = .049) and exploratory structural equation modeling (comparative fit index = .977, standardized root mean square residual = .019, and root mean square error of approximation = .041) confirmed the model. The resultant Adult-Oriented Sport Coaching Survey provides a reliable and factorially valid instrument for measuring adult-oriented coaching practices.

Background: Pain is common in patients with chronic kidney disease (CKD). Analgesics may be appropriate for some CKD patients., Objectives: To determine the prevalence of overall analgesic use and the use of different types of analgesics including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), adjuvants, and opioids in patients with CKD., Design: Systematic review and meta-analysis., Setting: Interventional and observational studies presenting data from 2000 or later. Exclusion criteria included acute kidney injury or studies that limited the study population to a specific cause, symptom, and/or comorbidity., Patients: Adults with stage 3-5 CKD including dialysis patients and those managed conservatively without dialysis., Measurements: Data extracted included title, first author, design, country, year of data collection, publication year, mean age, stage of CKD, prevalence of analgesic use, and the types of analgesics prescribed., Methods: Databases searched included MEDLINE, CINAHL, EMBASE, and Cochrane Library. Two reviewers independently screened all titles and abstracts, assessed potentially relevant articles, and extracted data. We estimated pooled prevalence of analgesic use and the I 2 statistic was computed to measure heterogeneity. Random-effects models were used to account for variations in study design and sample populations, and a double arcsine transformation of the prevalence variables was used to accommodate potential overweighting of studies with very large or very small prevalence measurements. Sensitivity analyses were performed to determine the magnitude of publication bias and assess possible sources of heterogeneity., Results: Forty studies were included in the analysis. The prevalence of overall analgesic use in the random-effects model was 50.8%. The prevalence of acetaminophen, NSAIDs, and adjuvant use was 27.5%, 17.2%, and 23.4%, respectively, while the prevalence of opioid use was 23.8%. Due to the possibility of publication bias, the actual prevalence of acetaminophen use in patients with advanced CKD may be substantially lower than this meta-analysis indicates. A trim-and-fill analysis decreased the pooled prevalence estimate of acetaminophen use to 5.4%. The prevalence rate for opioid use was highly influenced by 2 large US studies. When these were removed, the estimated prevalence decreased to 17.3%., Limitations: There was a lack of detailed information regarding the analgesic regimen (such as specific analgesics used within each class and inconsistent accounting for patients on multiple drugs and the use of over-the-counter analgesics such as acetaminophen and NSAIDs), patient characteristics, type of pain being treated, and the outcomes of treatment. Data on adjuvant use were very limited. These results, therefore, must be interpreted with caution., Conclusions: There was tremendous variability in the prescribing patterns of both nonopioid and opioid analgesics within and between countries suggesting widespread uncertainty about the optimal pharmacological approach to treating pain. Further research that incorporates robust reporting of analgesic regimens and links prescribing patterns to clinical outcomes is needed to guide optimal clinical practice., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Although experts have noted that adolescent athletes should be educated about concussions to improve their safety, there is no agreement on the most effective strategy to disseminate concussion education. The purpose of this study was to develop, implement and assess a concussion education programme. More precisely, four interactive oral presentations were delivered to high school student-athletes (N = 35, M age  = 15.94, SD = 0.34) in a large urban centre. Participants completed a questionnaire at three time-points during the season to measure changes in their knowledge (CK) and attitudes (CA) of concussions, and focus group interviews were conducted following the concussion education programme. Questionnaire data revealed participants' post-intervention CK scores were higher than their pre-intervention scores. During the focus groups, the student-athletes said they acquired CK about the role of protective equipment and symptom variability, and in terms of CA, they intended to avoid dangerous in-game collisions in the future. Our study was the first to create and deliver a concussion education intervention across multiple time-points, and to use mixed-methods in its assessment. These findings may be of interest to researchers, practitioners and stakeholders in sport who are invested in making the sport environment safer through concussion education and awareness.