Healthcare providers' perspectives on implementing a brief physical activity and diet intervention within a primary care smoking cessation program: a qualitative study.

BACKGROUND: Post-smoking-cessation weight gain can be a major barrier to quitting smoking; however, adding behavior change interventions for physical activity (PA) and diet may adversely affect smoking cessation outcomes. The "Picking up the PACE (Promoting and Accelerating Change through Empowerment)" study assessed change in PA, fruit/vegetable consumption, and smoking cessation by providing a clinical decision support system for healthcare providers to utilize at the intake appointment, and found no significant change in PA, fruits/vegetable consumption, or smoking cessation. The objective of this qualitative study was to explore the factors affecting the implementation of the intervention and contextualize the quantitative results. METHODS: Twenty-five semi-structured interviews were conducted with healthcare providers, using questions based on the National Implementation Research Network's Hexagon Tool. The data were analyzed using the framework's standard analysis approach. RESULTS: Most healthcare providers reported a need to address PA and fruit/vegetable consumption in patients trying to quit smoking, and several acknowledged that the intervention was a good fit since exercise and diet could improve smoking cessation outcomes. However, many healthcare providers mentioned the need to explain the fit to the patients. Social determinants of health (e.g., low income, food insecurity) were brought up as barriers to the implementation of the intervention by a majority of healthcare providers. Most healthcare providers recognized training as a facilitator to the implementation, but time was mentioned as a barrier by many of healthcare providers. Majority of healthcare providers mentioned allied health professionals (e.g., dieticians, physiotherapists) supported the implementation of the PACE intervention. However, most healthcare providers reported a need for individualized approach and adaptation of the intervention based on the patients' needs when implementing the intervention. The COVID-19 pandemic was found to impact the implementation of the PACE intervention based on the Hexagon Tool indicators. CONCLUSION: There appears to be a need to utilize a flexible approach when addressing PA and fruit/vegetable consumption within a smoking cessation program, based on the context of clinic, the patients' it is serving, and their life circumstances. Healthcare providers need support and external resources to implement this particular intervention. NAME OF THE REGISTRY: Clinicaltrials.gov. TRIAL REGISTRATION NUMBER: NCT04223336. DATE OF REGISTRATION: 7 January 2020 Retrospectively registered. URL OF TRIAL REGISTRY RECORD: https://classic. CLINICALTRIALS: gov/ct2/show/NCT04223336 .

A randomized sham-controlled trial of high-dosage accelerated intermittent theta burst rTMS in major depression: study protocol.

BACKGROUND: Intermittent theta burst stimulation (iTBS), a novel form of repetitive transcranial magnetic stimulation (rTMS), can be administered in 1/10th of the time of standard rTMS (~ 3 min vs. 37.5 min) yet achieves similar outcomes in depression. The brief nature of the iTBS protocol allows for the administration of multiple iTBS sessions per day, thus reducing the overall course length to days rather than weeks. This study aims to compare the efficacy and tolerability of active versus sham iTBS using an accelerated regimen in patients with treatment-resistant depression (TRD). As a secondary objective, we aim to assess the safety, tolerability, and treatment response to open-label low-frequency right-sided (1 Hz) stimulation using an accelerated regimen in those who do not respond to the initial week of treatment. METHODS: Over three years, approximately 230 outpatients at the Centre for Addiction and Mental Health and University of British Columbia Hospital, meeting diagnostic criteria for unipolar MDD, will be recruited and randomized to a triple blind sham-controlled trial. Patients will receive five consecutive days of active or sham iTBS, administered eight times daily at 1-hour intervals, with each session delivering 600 pulses of iTBS. Those who have not achieved response by the week four follow-up visit will be offered a second course of treatment, regardless of whether they initially received active or sham stimulation. DISCUSSION: Broader implementation of conventional iTBS is limited by the logistical demands of the current standard course consisting of 4-6 weeks of daily treatment. If our proposed accelerated iTBS protocol enables patients to achieve remission more rapidly, this would offer major benefits in terms of cost and capacity as well as the time required to achieve clinical response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04255784.

Xylitol for the prevention of acute otitis media episodes in children aged 1-5 years: a randomised controlled trial.

OBJECTIVE: To investigate the regular use of xylitol, compared with sorbitol, to prevent acute otitis media (AOM), upper respiratory tract infections (URTIs) and dental caries. DESIGN: Blinded randomised controlled trial with a 6-month study period. SETTING: Enrolment took place at 11 primary care practices in Ontario, Canada. PATIENTS: Children aged 1-5 years who did not use xylitol or sorbitol at enrolment. INTERVENTIONS: Children were randomly assigned to use a placebo syrup with sorbitol or xylitol syrup two times per day for 6 months. MAIN OUTCOME MEASURES: Primary outcome was the number of clinician-diagnosed AOM episodes over 6 months. Secondary outcomes were caregiver-reported URTIs and dental caries. RESULTS: Among the 250 randomised children, the mean (SD) age was 38±14 months and there were 124 girls (50%). There were three clinician-diagnosed AOM episodes in the 125 placebo group participants and six in the 125 xylitol group participants (OR 2.04; 95% CI 0.43, 12.92; p=0.50). There was no difference in number of caregiver-reported URTI episodes (rate ratio (RR) 0.88; 95% CI 0.70, 1.11) between the placebo (4.2 per participant over 6 months; 95% CI 3.6, 5.0) and xylitol (3.7; 95% CI 3.2, 4.4) groups. Dental caries were reported for four participants in the placebo group and two in the xylitol group (OR 0.42; 95% CI 0.04, 3.05; p=0.42). In a post-hoc analysis of URTIs during the COVID-19 pandemic, the rate among the 59 participants receiving placebo was 2.3 per participant over 6 months (95% CI 1.8, 3.0) and for the 55 receiving xylitol, 1.3 over 6 months (95% CI 0.92, 1.82; RR 0.56; 95% CI 0.36, 0.87). The most common adverse event was diarrhoea (28% with placebo; 34% with xylitol). CONCLUSIONS: Regular use of xylitol did not prevent AOM, URTIs or dental caries in a trial with limited statistical power. A post-hoc analysis indicated that URTIs were less common with xylitol exposure during the COVID-19 pandemic, but this finding could be spurious. TRIAL REGISTRATION NUMBER: NCT03055091.

Impact of the COVID-19 pandemic on Canadian emergency medical system management of out-of-hospital cardiac arrest: A retrospective cohort study.

AIM: We sought to describe the impact of the COVID-19 pandemic on the care provided by Canadian emergency medical system (EMS) clinicians to patients suffering out of hospital cardiac arrest (OHCA), and whether any observed changes persisted beyond the initial phase of the pandemic. METHODS: We analysed cases of adult, non-traumatic, OHCA from the Canadian Resuscitation Outcome Consortium (CanROC) registry who were treated between January 27th, 2018, and December 31st, 2021. We used adjusted regression models and interrupted time series analysis to examine the impact of the COVID-19 pandemic (January 27th, 2020 - December 31st, 2021)on the care provided to patients with OHCA by EMS clinicians. RESULTS: There were 12,947 cases of OHCA recorded in the CanROC registry in the pre-COVID-19 period and 17,488 during the COVID-19 period. We observed a reduction in the cumulative number of defibrillations provided by EMS (aRR 0.91, 95% CI 0.89 - 0.93, p < 0.01), a reduction in the odds of attempts at intubation (aOR 0.33, 95% CI 0.31 - 0.34, p < 0.01), higher rates of supraglottic airway use (aOR 1.23, 95% CI 1.16-1.30, p < 0.01), a reduction in vascular access (aOR for intravenous access 0.84, 95% CI 0.79 - 0.89, p < 0.01; aOR for intraosseous access 0.89, 95% CI 0.82 - 0.96, p < 0.01), a reduction in the odds of epinephrine administration (aOR 0.89, 95% CI 0.85 - 0.94, p < 0.01), and higher odds of resuscitation termination on scene (aOR 1.38, 95% CI 1.31 - 1.46, p < 0.01). Delays to initiation of chest compressions (2 min. vs. 3 min., p < 0.01), intubation (16 min. vs. 19 min., p = 0.01), and epinephrine administration (11 min. vs. 13 min., p < 0.01) were observed, whilst supraglottic airways were inserted earlier (11 min. vs. 10 min., p < 0.01). CONCLUSION: The COVID-19 pandemic was associated with substantial changes in EMS management of OHCA. EMS leaders should consider these findings to optimise current OHCA management and prepare for future pandemics.

Strengthening oropharyngeal muscles as an approach to treat post-stroke obstructive sleep apnea: A feasibility randomised controlled trial.

This study aimed to determine the feasibility of a randomised controlled trial (RCT) evaluating oropharyngeal exercise (OPE) intervention as an alternative therapy for obstructive sleep apnea (OSA) in patients with stroke or transient ischaemic attack (TIA). Despite the high prevalence of OSA in this population, the standard therapy, continuous positive airway pressure (CPAP), is often poorly tolerated. Thirty stroke/TIA patients with OSA unable to tolerate CPAP were randomly assigned to an oropharyngeal exercise or sham exercise protocol. They performed exercises for 6 weeks, 5 days per week, 30 minutes twice per day. Feasibility was ascertained by the proportion of enrolled patients who completed more than 80% of the OPE regimen. Isometric tongue pressures, apnea-hypopnea index (AHI), oxygen desaturation index (ODI), daytime sleepiness, and quality of life (QOL) outcomes were collected at baseline, post-training (6-week follow-up), and retention (10-week follow-up) to document preliminary efficacy. Adherence to study exercises was excellent, with 83% of participants completing more than 80% of the exercises. The isometric tongue pressures were observed to improve in the oropharyngeal exercise group (compared with the sham group), along with a decrease in OSA severity (measured by the AHI and ODI), reduced daytime sleepiness, and enhanced quality of life outcomes following the exercise programme. Only the effects on posterior isometric tongue pressure and daytime sleepiness remained significantly different between groups at the retention session. In conclusion, an RCT evaluating the efficacy of oropharyngeal exercises on post-stroke/TIA OSA is feasible and our preliminary results suggest a clinically meaningful effect.

Frequency of screening and SBT Technique Trial-North American Weaning Collaboration (FAST-NAWC): an update to the protocol and statistical analysis plan.

BACKGROUND: This update summarizes key changes made to the protocol for the Frequency of Screening and Spontaneous Breathing Trial (SBT) Technique Trial-North American Weaning Collaborative (FAST-NAWC) trial since the publication of the original protocol. This multicenter, factorial design randomized controlled trial with concealed allocation, will compare the effect of both screening frequency (once vs. at least twice daily) to identify candidates to undergo a SBT and SBT technique [pressure support + positive end-expiratory pressure vs. T-piece] on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American intensive care units. METHODS/DESIGN: Protocols for the pilot, factorial design trial and the full trial were previously published in J Clin Trials ( https://doi.org/10.4172/2167-0870.1000284 ) and Trials (https://doi: 10.1186/s13063-019-3641-8). As planned, participants enrolled in the FAST pilot trial will be included in the report of the full FAST-NAWC trial. In response to the onset of the coronavirus disease of 2019 (COVID-19) pandemic when approximately two thirds of enrollment was complete, we revised the protocol and consent form to include critically ill invasively ventilated patients with COVID-19. We also refined the statistical analysis plan (SAP) to reflect inclusion and reporting of participants with and without COVID-19. This update summarizes the changes made and their rationale and provides a refined SAP for the FAST-NAWC trial. These changes have been finalized before completion of trial follow-up and the commencement of data analysis. TRIAL REGISTRATION: Clinical Trials.gov NCT02399267.

Protocol for a pragmatic cluster randomised controlled trial to evaluate the effectiveness of digital health interventions in improving non-communicable disease management during the pandemic in rural Pakistan.

BACKGROUND: The COVID-19 pandemic has revealed gaps in global health systems, especially in the low- and middle-income countries (LMICs). Evidence shows that patients with non-communicable diseases (NCDs) are at higher risk of contracting COVID-19 and suffering direct and indirect health consequences. Considering the future challenges such as environmental disasters and pandemics to the LMICs health systems, digital health interventions (DHI) are well poised to strengthen health care resilience. This study aims to implement and evaluate a comprehensive package of DHIs of integrated COVID-NCD care to manage NCDs in primary care facilities in rural Pakistan. METHODS: The study is designed as a pragmatic, parallel two-arm, multi-centre, mix-methods cluster randomised controlled trial. We will randomise 30 primary care facilities in three districts of Punjab, where basic hypertension and diabetes diagnosis and treatment are provided, with a ratio of 1:1 between intervention and control. In each facility, we will recruit 50 patients who have uncontrolled hypertension. The intervention arm will receive training on an integrated COVID-NCD guideline, and will use a smartphone app-based telemedicine platform where patients can communicate with health providers and peer-supporters, along with a remote training and supervision system. Usual care will be provided in the control arm. Patients will be followed up for 10 months. Our primary indicator is systolic blood pressure measured at 10 months. A process evaluation guided by implementation science frameworks will be conducted to explore implementation questions. A cost-effectiveness evaluation will be conducted to inform future scale up in Pakistan and other LMICs. DISCUSSION: Our study is one of the first randomised controlled trials to evaluate the effectiveness of DHIs to manage NCDs to strengthen health system resilience in LMICs. We will also evaluate the implementation process and cost-effectiveness to inform future scale-up in similar resource constrained settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier-NCT05699369.

Predicting survival post-cardiac arrest: An observational cohort study.

Introduction: Over 400,000 out-of-hospital cardiac arrest (OHCA) occur each year in Canada and the United States with less than 10% survival to hospital discharge. Cardiac arrest is a heterogenous condition and patient outcomes are impacted by a multitude of factors. Prognostication is recommended at 72 hours after return of spontaneous circulation (ROSC), however there may be other factors that could predict patient outcome earlier in the post-arrest period. The objective of our study was to develop and internally validate a novel clinical prediction rule to risk stratify patients early in the post-cardiac arrest period. Methods: We performed a retrospective cohort study of adult (≥18 years) post-cardiac arrest patients between 2010 and 2015 from the Epistry Cardiac Arrest database in Toronto. Our primary analysis used ordinal logistic regression to examine neurologic outcome at discharge using the modified Rankin Scale (mRS). Our secondary analysis used logistic regression for neurologic outcome and survival to hospital discharge. Models were internally validated using bootstrap validation. Results: A total of 3432 patients met our inclusion criteria. Our clinical prediction model was able to predict neurologic outcome on an ordinal scale using our predefined variables with an AUC of 0.89 after internal validation. The predictive performance was maintained when examining neurologic outcome as a binary variable and survival to hospital discharge. Conclusion: We were able to develop a model to accurately risk stratify adult cardiac arrest patients early in the post-cardiac arrest period. Future steps are needed to externally validate this model in other healthcare settings.

Association between preoperative cardiac risk assessment and health care costs in major noncardiac surgery: a multicentre health economic analysis.

PURPOSE: Patients with impaired functional capacity who undergo major surgery are at increased risk of postoperative morbidity including complications and increased length of stay. These outcomes have been associated with increased hospital and health system costs. We aimed to assess whether common preoperative risk indices are associated with postoperative cost. METHODS: We conducted a health economic analysis focused on the subset of Measurement of Exercise Tolerance before Surgery (METS) study participants in Ontario, Canada. Participants were scheduled for major elective noncardiac surgery and underwent several preoperative assessments of cardiac risk, including physicians' subjective assessment, Duke Activity Status Index (DASI) questionnaire, peak oxygen consumption, and N-terminal pro-B-type natriuretic peptide concentration. Using linked health administrative data, postoperative costs were calculated for both one year and in-hospital. Using multiple regression models, we tested for association between the preoperative measures of cardiac risk and postoperative costs. RESULTS: Our study included 487 patients (mean [standard deviation] age 68 [11] yr and 47.0% female) who underwent noncardiac surgery between 13 June 2013 and 8 March 2016. Overall, the median [interquartile range] cost incurred within one year postoperatively was CAD 27,587 [13,902-32,590], of which CAD 12,928 [10,253-12,810] were incurred in-hospital and CAD 14,497 [10,917-15,017] were incurred by 30 days. None of the four preoperative measures of cardiac risk assessment were associated with costs incurred in hospital or at one year postoperatively. This lack of strong association persisted in sensitivity analyses considering type of surgical procedure, burden of preoperative cost, and when costs were categorized as quantiles. CONCLUSION: In patients undergoing major noncardiac surgery, common measures of functional capacity are not consistently associated with total postoperative cost. Until further data exist that differ from this analysis, clinicians and health care funders should not assume that preoperative measures of cardiac risk are associated with annual health care or hospital costs for such surgeries.

RéSUMé: OBJECTIF: La patientèle présentant une capacité fonctionnelle dégradée qui bénéficie d'une intervention chirurgicale majeure court un risque accru de morbidité postopératoire, y compris de complications et de prolongation de la durée de séjour. Ces issues ont été associées à une augmentation des coûts hospitaliers et du système de santé. Notre objectif était d'évaluer si des indices de risque préopératoires communs étaient associés aux coûts postopératoires. MéTHODE: Nous avons effectué une analyse de l'économie de la santé axée sur le sous-ensemble des participant·es à l'étude METS (Measurement of Exercise Tolerance before Surgery) en Ontario, au Canada. Les participant·es devaient bénéficier d'une chirurgie non cardiaque et non urgente majeure et ont complété plusieurs évaluations préopératoires du risque cardiaque, notamment l'évaluation subjective des médecins, le questionnaire DASI (Duke Activity Status Index), la consommation maximale d'oxygène et la concentration de prohormone N-terminale du peptide natriurétique de type B (cérébral) (NT-proBNP). À l'aide de données administratives couplées de santé, les coûts postopératoires ont été calculés à la fois pour une année et à l'hôpital. À l'aide de modèles de régression multiples, nous avons testé l'association entre les mesures préopératoires du risque cardiaque et les coûts postopératoires. RéSULTATS: Notre étude a inclus 487 personnes (âge moyen [écart type] 68 [11] ans et 47,0 % de femmes) ayant bénéficié d'une chirurgie non cardiaque entre le 13 juin 2013 et le 8 mars 2016. Dans l'ensemble, le coût médian [écart interquartile] engagé dans l'année qui a suivi l'opération était de 27 587 CAD [13 902­32 590], dont 12 928 CAD [10 253­12 810] ont été encourus à l'hôpital et 14 497 CAD [10 917­15 017] ont été encourus dans les premiers 30 jours. Aucune des quatre mesures préopératoires de l'évaluation du risque cardiaque n'était associée aux coûts engagés à l'hôpital ou un an après l'opération. Cette absence d'association forte persistait dans les analyses de sensibilité tenant compte du type d'intervention chirurgicale, du fardeau des coûts préopératoires et lorsque les coûts étaient classés en quantiles. CONCLUSION: Chez la patientèle bénéficiant d'une chirurgie non cardiaque majeure, les mesures courantes de la capacité fonctionnelle ne sont pas systématiquement associées au coût postopératoire total. Jusqu'à ce qu'il existe d'autres données qui diffèrent de cette analyse, les cliniciens et cliniciennes et les organismes finançant les soins de santé ne devraient pas présumer que les mesures préopératoires du risque cardiaque sont associées aux coûts annuels des soins de santé ou des hôpitaux pour de telles chirurgies.

Effect of Free Medicine Distribution on Health Care Costs in Canada Over 3 Years: A Secondary Analysis of the CLEAN Meds Randomized Clinical Trial.

Importance: Few interventions are proven to reduce total health care costs, and addressing cost-related nonadherence has the potential to do so. Objective: To determine the effect of eliminating out-of-pocket medication fees on total health care costs. Design, Setting, and Participants: This secondary analysis of a multicenter randomized clinical trial using a prespecified outcome took place across 9 primary care sites in Ontario, Canada (6 in Toronto and 3 in rural areas), where health care services are generally publicly funded. Adult patients (≥18 years old) reporting cost-related nonadherence to medicines in the past 12 months were recruited between June 1, 2016, and April 28, 2017, and followed up until April 28, 2020. Data analysis was completed in 2021. Interventions: Access to a comprehensive list of 128 medicines commonly prescribed in ambulatory care with no out-of-pocket costs for 3 years vs usual medicine access. Main Outcome and Measures: Total publicly funded health care costs over 3 years, including costs of hospitalizations. Health care costs were determined using administrative data from Ontario's single-payer health care system, and all costs are reported in Canadian dollars with adjustments for inflation. Results: A total of 747 participants from 9 primary care sites were included in the analysis (mean [SD] age, 51 [14] years; 421 [56.4%] female). Free medicine distribution was associated with a lower median total health care spending over 3 years of $1641 (95% CI, $454-$2792; P = .006). Mean total spending was $4465 (95% CI, -$944 to $9874) lower over the 3-year period. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, eliminating out-of-pocket medication expenses for patients with cost-related nonadherence in primary care was associated with lower health care spending over 3 years. These findings suggest that eliminating out-of-pocket medication costs for patients could reduce overall costs of health care. Trial Registration: ClinicalTrials.gov Identifier: NCT02744963.

Statins to prevent early cardiac dysfunction in cancer patients at increased cardiotoxicity risk receiving anthracyclines.

BACKGROUND AND AIMS: Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (LVEF) in anthracycline-treated patients at increased risk for CTRCD. METHODS: In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by >10% to <53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP). RESULTS: We randomized 112 patients (56.9 ± 13.6 years, 87 female, and 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13-27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (P = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (P = 0.20) or end-systolic volume (P = 0.12), CMR myocardial edema and/or fibrosis (P = 0.06-0.47), or peak hsTnI (P ≥ 0.99) and BNP (P = 0.23). CTRCD incidence was similar (4% versus 4%, P ≥ 0.99). There was no difference in adverse events. CONCLUSIONS: In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes. TRIAL REGISTRATION: NCT03186404.

Great expectations: patients' preferences for clinically significant results from genomic sequencing.

We aimed to describe patient preferences for a broad range of secondary findings (SF) from genomic sequencing (GS) and factors driving preferences. We assessed preference data within a trial of the Genomics ADvISER, (SF decision aid) among adult cancer patients. Participants could choose from five categories of SF: (1) medically actionable; (2) polygenic risks; (3) rare diseases; (4) early-onset neurological diseases; and (5) carrier status. We analyzed preferences using descriptive statistics and drivers of preferences using multivariable logistic regression models. The 133 participants were predominantly European (74%) or East Asian or mixed ancestry (13%), female (90%), and aged > 50 years old (60%). The majority chose to receive SF. 97% (129/133) chose actionable findings with 36% (48/133) choosing all 5 categories. Despite the lack of medical actionability, participants were interested in receiving SF of polygenic risks (74%), carrier status (75%), rare diseases (59%), and early-onset neurologic diseases (53%). Older participants were more likely to be interested in receiving results for early-onset neurological diseases, while those exhibiting lower decisional conflict were more likely to select all categories. Our results highlight a disconnect between cancer patient preferences and professional guidelines on SF, such as ACMG's recommendations to only return medically actionable secondary findings. In addition to clinical evidence, future guidelines should incorporate patient preferences.

Study protocol for a randomized controlled trial of Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: the PROMIZING study.

BACKGROUND: Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mechanical ventilation mode that delivers assistance to breathe in proportion to the patient's effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient's respiratory effort or workload within a normal range. Short-term and physiological benefits of this mode compared to pressure support ventilation (PSV) include better patient-ventilator synchrony and a more physiological response to changes in ventilatory demand. METHODS: The objective of this multi-centre randomized controlled trial (RCT) is to determine if, for patients with acute respiratory failure, ventilation with PAV+ will result in a shorter time to successful extubation than with PSV. This multi-centre open-label clinical trial plans to involve approximately 20 sites in several continents. Once eligibility is determined, patients must tolerate a short-term PSV trial and either (1) not meet general weaning criteria or (2) fail a 2-min Zero Continuous Positive Airway Pressure (CPAP) Trial using the rapid shallow breathing index, or (3) fail a spontaneous breathing trial (SBT), in this sequence. Then, participants in this study will be randomized to either PSV or PAV+ in a 1:1 ratio. PAV+ will be set according to a target of muscular pressure. The weaning process will be identical in the two arms. Time to liberation will be the primary outcome; ventilator-free days and other outcomes will be measured. DISCUSSION: Meta-analyses comparing PAV+ to PSV suggest PAV+ may benefit patients and decrease healthcare costs but no powered study to date has targeted the difficult to wean patient population most likely to benefit from the intervention, or used consistent timing for the implementation of PAV+. Our enrolment strategy, primary outcome measure, and liberation approaches may be useful for studying mechanical ventilation and weaning and can offer important results for patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02447692 . Prospectively registered on May 19, 2015.

How do members of the public expect to use variants of uncertain significance in their health care? A population-based survey.

PURPOSE: Genomic sequencing can generate complex results, including variants of uncertain significance (VUS). In general, VUS should not inform clinical decision-making. This study aimed to assess the public's expected management of VUS. METHODS: An online, hypothetical survey was conducted among members of the Canadian public preceded by an educational video. Participants were randomized to 1 of 2 arms, VUS or pathogenic variant in a colorectal cancer gene, and asked which types of health services they expected to use for this result. Expected health service use was compared between randomization arms, and associations between participants' sociodemographic characteristics, attitudes, and medical history were explored. RESULTS: Among 1003 respondents (completion rate 60%), more participants expected to use each type of health service for a pathogenic variant than for a VUS. However, a considerable proportion of participants expected to request monitoring (73.4%) and consult health care providers (60.9%) for a VUS. There was evidence to support associations between expectation to use health services for a VUS with family history of genetic disease, family history of cancer, education, and attitudes toward health care and technology. CONCLUSION: Many participants expected to use health services for a VUS in a colorectal cancer predisposition gene, suggesting a potential disconnect between patients' expectations for VUS management and guideline-recommended care.

Time Course of Early Hematoma Expansion in Acute Spot-Sign Positive Intracerebral Hemorrhage: Prespecified Analysis of the SPOTLIGHT Randomized Clinical Trial.

BACKGROUND: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 µg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. METHODS: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. RESULTS: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2-2.6). Median time from baseline CT to study drug was 62.5 (55-80) minutes, and from study drug to early post-dose CT was 19 (14.5-30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (-0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8-8.3) in the placebo arm (P=0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (-2.6 to 8.3) in the rFVIIa arm and 0.7 mL (-1.6 to 2.1) in the placebo arm (P=0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71-1.43]; P=0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994-1.003]; P=0.50; Table 3). CONCLUSIONS: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01359202.

School-based health care: improving academic outcomes for inner-city children-a prospective cohort quasi-experimental study.

BACKGROUND: We examined whether a school-based health center model improved academic achievement compared to usual care. METHODS: This was a quasi-experimental prospective cohort study. The primary outcome was an academic achievement. In addition, we analyzed sociodemographic characteristics and their relationship to academic achievement, and the wait time for a developmental assessment. RESULTS: The differences in change of grades over time (from 2016/2017 to 2018/2019) were small for reading (-0.83, 95% CI -3.48, 1.82, p = 0.51), writing (-1.11, 95% CI -3.25, 1.03, p = 0.28), and math (0.06, 95% CI -3.08, 2.94, p = 0.98). The experimental arm's average wait time for developmental assessment was 3.4 months. CONCLUSION: In this small, quasi-experimental prospective cohort study, we did not find evidence that our SBHC model improved academic achievement; however, the wait time at the SBHCs was considerably less than the provincial wait time for a developmental assessment. TRIAL REGISTRATION: NCT04540003. IMPACT: This study describes a unique and innovative school-based health center model. Our findings support the benefits of school-based health centers in diagnosing and treating children with developmental and mental health disorders for disadvantaged communities. This study did not find an improvement in academic achievement for school-based health center users. This study found that the wait time to developmental assessment was shorter for school-based health center users compared to the wait time reported in the community. Pandemic-associated school disruptions have highlighted the importance of accessible school-based health services for children requiring mental health and developmental assessments and care.

Survival and health care costs after inpatient elective surgery: comparison of patients with and without chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common among surgical patients, and patients with COPD have higher risk for complications and death within 30 days after surgery. We sought to describe the longer-term postoperative survival and costs of patients with COPD compared with those without COPD within 1 year after inpatient elective surgery. METHODS: In this retrospective population-based cohort study, we used linked health administrative databases to identify all patients undergoing inpatient elective surgery in Ontario, Canada, from 2005 to 2019. We ascertained COPD status using validated definitions. We followed participants for 1 year after surgery to evaluate survival and costs to the health system. We quantified the association of COPD with survival (Cox proportional hazards models) and costs (linear regression model with log-transformed costs) with partial adjustment (for sociodemographic factors and procedure type) and full adjustment (also adjusting for comorbidities). We assessed for effect modification by frailty, cancer and procedure type. RESULTS: We included 932 616 patients, of whom 170 482 (18%) had COPD. With respect to association with risk of death, COPD had a partially adjusted hazard ratio (HR) of 1.61 (95% confidence interval [CI] 1.58-1.64), and a fully adjusted HR of 1.26 (95% CI 1.24-1.29). With respect to impact on health system costs, COPD was associated with a partially adjusted relative increase of 13.1% (95% CI 12.7%-13.4%), and an increase of 4.6% (95% CI 4.3%-5.0%) with full adjustment. Frailty, cancer and procedure type (such as orthopedic and lower abdominal surgery) modified the association between COPD and outcomes. INTERPRETATION: Patients with COPD have decreased survival and increased costs in the year after surgery. Frailty, cancer and the type of surgical procedure modified associations between COPD and outcomes, and must be considered when risk-stratifying surgical patients with COPD.

A randomized controlled trial comparing femtosecond-enabled deep anterior lamellar keratoplasty and standard deep anterior lamellar keratoplasty (FEDS Study).

OBJECTIVES: To compare outcomes of femtosecond-enabled deep anterior lamellar keratoplasty (FE-DALK) and standard deep anterior lamellar keratoplasty (S-DALK). METHODS: An open label, randomized controlled trial (Kensington Eye Institute, Toronto, ON, Canada) including 100 eyes of 97 participants with either keratoconus or corneal scarring, randomized to either FE-DALK (n = 48) or S-DALK (n = 49). PRIMARY OUTCOMES: postoperative astigmatism and surgically induced corneal astigmatism (SIA) - both at 15 months. SECONDARY OUTCOMES: 6-, 12- and 15-month postoperative uncorrected- and best spectacle-corrected visual acuity, steep and flat keratometry, manifest sphere and astigmatism, rate of conversion to penetrating keratoplasty (PK), big-bubble success, central corneal thickness, endothelial cell count and complications. RESULTS: In intention-to-treat analysis, mean postoperative astigmatism in the FE-DALK (n = 30) and S-DALK (n = 30) groups at 15 months was 7.8 ± 4.4 D and 6.3 ± 5.0 D, respectively (p = 0.282) with an adjusted mean difference of 1.3 D (95% CI -1.08, +3.65). Mean SIA (arithmetic) was 9.2 ± 7.8 and 8.8 ± 5.4 D, respectively (p = 0.838) with a mean difference of 0.4 D (95% CI -3.13, +3.85). In an analysis of successful DALK cases only, mean postoperative astigmatism in the FE-DALK (n = 24) and S-DALK (n = 20) groups at 15 months (after excluding 4 eyes with AEs) was 7.3 ± 4.4 and 6.2 ± 4.9 D, respectively (p = 0.531) with an adjusted mean difference of 0.9 D (95% CI -1.94, +3.71). Mean SIA (arithmetic) was 9.1 ± 7.8 and 7.9 ± 4.6 D, respectively (p = 0.547) with a mean difference of 1.2 D (95% CI -2.70,+5.02). Comparison of secondary outcomes showed only weak statistical evidence. CONCLUSIONS: In this randomized controlled trial, FE-DALK and S-DALK showed comparable functional and anatomical outcomes.

Generating Items for a Novel Bedside Dysphagia Screening Tool Post Acute Pediatric Stroke.

Bedside dysphagia assessment protocols are not well developed in acute pediatric stroke unlike adults. The objective of this study was to identify items deemed relevant and feasible by expert consensus to inform the development of a bedside dysphagia screening tool for acute pediatric stroke. A two-phase study was conducted: (1) literature review and expert consultation generated a comprehensive list of dysphagia assessment items; (2) items were formatted in an online survey asking respondents opinion of relevance to acute pediatric stroke and feasibility for bedside administration by a trained health professional. The Dillman Tailored Design approach optimized response rate. Respondents were identified using the snowball method. Speech-language pathologists with > 2 years in pediatric dysphagia were invited to complete the survey. Demographic and practice variables were compared using univariate statistics. Item relevance and feasibility were made using binary or ordinal responses, combined to derive item-content validity indices (I-CVI) to guide item reduction. Items with I-CVI > 0.78 (excellent content validity) were moved forward to tool development. Of the 71 invited respondents, 57(80.3%) responded, of which 34(59.6%) were from North America. Sixty-one items were generated of which 4(6.6%) items were rated 'to keep'. These were face symmetry (I-CVI:0.89), salivary control (I-CVI:0.95), alertness (I-CVI:0.89) and choking (I-CVI:0.84). Of all respondents, 31(54.4%) endorsed swallowing trials, of which 25(80.6%) endorsed thin liquid by teaspoon (n = 17, 68%) or open cup (n = 20, 80%). We identified candidate items for bedside dysphagia screening with excellent content validity for acute pediatric stroke patients. Next steps include assessment of the psychometric value of each item in identifying dysphagia in children in the acute stage of recovery from stroke.

Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors have been demonstrated to promote reverse cardiac remodeling in people with diabetes or heart failure. Although it has been theorized that sodium-glucose cotransporter 2 inhibitors might afford similar benefits in people without diabetes or prevalent heart failure, this has not been evaluated. We sought to determine whether sodium-glucose cotransporter 2 inhibition with empagliflozin leads to a decrease in left ventricular (LV) mass in people without type 2 diabetes or significant heart failure. METHODS: Between April 2021 and January 2022, 169 individuals, 40 to 80 years of age, without diabetes but with risk factors for adverse cardiac remodeling were randomly assigned to empagliflozin (10 mg/d; n=85) or placebo (n=84) for 6 months. The primary outcome was the 6-month change in LV mass indexed (LVMi) to baseline body surface area as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and LV end-systolic volumes indexed to baseline body surface area and LV ejection fraction. RESULTS: Among the 169 participants (141 men [83%]; mean age, 59.3±10.5 years), baseline LVMi was 63.2±17.9 g/m2 and 63.8±14.0 g/m2 for the empagliflozin- and placebo-assigned groups, respectively. The difference (95% CI) in LVMi at 6 months in the empagliflozin group versus placebo group adjusted for baseline LVMi was -0.30 g/m2 (-2.1 to 1.5 g/m2; P=0.74). Median baseline (interquartile range) NT-proBNP (N-terminal-pro B-type natriuretic peptide) was 51 pg/mL (20-105 pg/mL) and 55 pg/mL (21-132 pg/mL) for the empagliflozin- and placebo-assigned groups, respectively. The 6-month treatment effect of empagliflozin versus placebo (95% CI) on blood pressure and NT-proBNP (adjusted for baseline values) were -1.3 mm Hg (-5.2 to 2.6 mm Hg; P=0.52), 0.69 mm Hg (-1.9 to 3.3 mm Hg; P=0.60), and -6.1 pg/mL (-37.0 to 24.8 pg/mL; P=0.70) for systolic blood pressure, diastolic blood pressure, and NT-proBNP, respectively. No clinically meaningful between-group differences in LV volumes (diastolic and systolic indexed to baseline body surface area) or ejection fraction were observed. No difference in adverse events was noted between the groups. CONCLUSIONS: Among people with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, sodium-glucose cotransporter 2 inhibition with empagliflozin did not result in a meaningful reduction in LVMi after 6 months. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04461041.