Resident and teacher perceptions of the preceptor field note: a qualitative analysis.

Assessment of clinical teachers is a requirement by family medicine residency programs in Canada. This facilitates feedback to teachers and ensures the curriculum is delivered in an efficient and safe way. To protect resident confidentiality, preceptors often receive their teaching evaluations months to years later. Teachers have requested shorter feedback loops, greater numbers, and more frequent assessments to improve their skills. The preceptor field note (PFN) is a tool that allows learners to evaluate teachers during a single encounter providing more frequent and immediate feedback. This study documents teachers' and residents' initial impressions of the first iteration of the PFN.

L'évaluation des cliniciens enseignants est une exigence des programmes de résidence en médecine familiale au Canada. Elle procure une rétrtoaction aux enseignants et garantit que le programme d'études est dispensé de manière efficace et sûre. Pour protéger la confidentialité des résidents, les superviseurs reçoivent souvent les évaluations de leur enseignement des mois, voire des années plus tard. Les enseignants réclament des boucles de rétroaction plus courtes, et des évaluations plus nombreuses et plus fréquentes afin d'améliorer leurs compétences.La feuille de route du superviseur (FRS) est un outil qui permet aux apprenants d'évaluer les enseignants au cours d'une seule rencontre et de fournir une rétroaction plus fréquente et plus immédiate. Cette étude rend compte des premières impressions des enseignants et des résidents sur la première itération de la FRS.

Afraid and tired: A longitudinal study of the relationship between cancer-related fatigue and fear of cancer recurrence in long-term cancer survivors.

OBJECTIVE: Cancer-related fatigue (CRF) and fear of cancer recurrence (FCR) are two common concerns experienced by cancer survivors. However, the relationship between these two concerns is poorly understood, and whether CRF and FCR influence each other over time is unclear. METHODS: Data were from a national, prospective, longitudinal study, the American Cancer Society's Study of Cancer Survivors-I (SCS-I). Surveys were completed by 1395 survivors of 10 different cancer types at three time-points, including assessment 1.3 years (T1), 2.2 years (T2) and 8.8 years (T3) following their cancer diagnosis. CRF was assessed using the fatigue-inertia subscale of the Profile of Mood States, and FCR by the FCR subscale of the Cancer Problems in Living Scale. Multiple group random intercepts cross-lagged panel models investigated prospective associations between CRF and FCR. RESULTS: For younger participants (at or below median age of 55 years, n = 697), CRF at T1 and T2 marginally and significantly predicted FCR at T2 and T3, respectively, but no lagged effects of FCR on subsequent CRF were observed. Cross-lagged effects were not observed for survivors over 55 years of age. CONCLUSION: Both CRF and FCR are debilitating side effects of cancer and its treatments. Given that CRF may be predictive of FCR, it possible that early detection and intervention for CRF could contribute to lowering FCR severity.

A longitudinal analysis of COVID-19 prevention strategies implemented among US K-12 public schools during the 2021-2022 school year.

PURPOSE: Examine how school-based COVID-19 prevention strategy implementation varied over time, including by local characteristics. METHODS: School administrators (n = 335) from a nationally representative sample of K-12 public schools completed four surveys assessing COVID-19 prevention strategies at two-month intervals between October 2021 and June 2022. We calculated weighted prevalence estimates by survey wave. Generalized estimating equations (GEE) were used to model longitudinal changes in strategy implementation, accounting for school and county covariates. RESULTS: Opening doors/windows, daily cleaning, and diagnostic testing were reported by ≥ 50 % of schools at each survey wave. Several strategies were consistently implemented across the 2021-2022 school year (i.e., daily cleaning, opening doors and windows, diagnostic testing) while other strategies increased initially and then declined (i.e., contact tracing, screening testing, on-campus vaccination) or declined consistently throughout the school year (i.e., mask requirement, classroom distancing, quarantine). Although longitudinal changes in strategy implementation did not vary by school characteristics, strategy implementation varied by urban-rural classification and school level throughout the school year. CONCLUSIONS: Strategies that were consistently implemented throughout the school year were also reported by a majority of schools, speaking toward their feasibility for school-based infection control and prevention and potential utility in future public health emergencies.

Design, implementation and evaluation of a spiral module combining data science, digital health and evidence-based medicine in the undergraduate medical curriculum: A mixed methods study.

BACKGROUND: Digital health, data science and health informatics are increasingly important in health and healthcare, but largely ignored in undergraduate medical training. METHODS: In a large UK medical school, with staff and students, we co-designed a new, 'spiral' module (with iterative revisiting of content), covering data science, digital health and evidence-based medicine, implementing in September 2019 in all year groups with continuous evaluation and improvement until 2022. RESULTS: In 2018/19, a new module, 'Doctor as Data Scientist', was co-designed by academic staff (n = 14), students (n = 23), and doctors (n = 7). The module involves 22 staff, 120 h (43 sessions: 22 lectures, 15 group and six other) over a 5-year curriculum. Since September 2019, 5,200 students have been taught with good attendance. Module student satisfaction ratings were 92%, 84%, 84% and 81% in 2019, 2020, 2021 and 2022 respectively, compared to the overall course (81%). CONCLUSIONS: We designed, implemented and evaluated a new undergraduate medical curriculum that combined data science and digital health with high student satisfaction ratings.

Partial pressure of carbon dioxide/pH interaction and its association with mortality among patients mechanically ventilated in the emergency department.

OBJECTIVES: There is currently conflicting data as to the effects of hypercapnia on clinical outcomes among mechanically ventilated patients in the emergency department (ED). These conflicting results may be explained by the degree of acidosis. We sought to test the hypothesis that hypercapnia is associated with increased in-hospital mortality and decreased ventilator-free days at lower pH, but associated with decreased in-hospital mortality and increased ventilator-free days at higher pH, among patients requiring mechanical ventilation in the emergency department (ED). METHODS: Secondary analysis of patient level data from prior clinical trials and cohort studies that enrolled adult patients who required mechanical ventilation in the ED. Patients who had a documented blood gas while on mechanical ventilation in the ED were included in these analyses. The primary outcome was in-hospital mortality, and secondary outcome was ventilator-free days. Mixed-effects logistic, linear, and survival-time regression models were used to test if pH modified the association between partial pressure of carbon dioxide (pCO2) and outcome measures. RESULTS: Of the 2348 subjects included, the median [interquartile range (IQR)] pCO2 was 43 (35-54) and pH was 7.31 (7.22-7.39). Overall, in-hospital mortality was 27%. We found pH modified the association between pCO2 and outcomes, with higher pCO2 associated with increased probability of in-hospital mortality when pH is below 7.00, and decreased probability of in-hospital mortality when pH is above 7.10. These results remained consistent across multiple sensitivity and subgroup analyses. A similar relationship was found with ventilator-free days. CONCLUSIONS: Higher pCO2 is associated with decreased mortality and greater ventilator-free days when pH is >7.10; however, it is associated with increased mortality and fewer ventilator-free days when the pH is below 7.00. Targeting pCO2 based on pH in the ED may be a potential intervention target for future clinical trials to improve clinical outcomes.

Preoperative aerobic fitness and perioperative outcomes in patients undergoing cystectomy before and after implementation of a national lockdown.

Background: Lower fitness is a predictor of adverse outcomes after radical cystectomy. Lockdown measures during the COVID-19 pandemic affected daily physical activity. We hypothesised that lockdown during the pandemic was associated with a reduction in preoperative aerobic fitness and an increase in postoperative complications in patients undergoing radical cystectomy. Methods: We reviewed routine preoperative cardiopulmonary exercise testing (CPET) data collected prior to the pandemic (September 2018 to March 2020) and after lockdown (March 2020 to July 2021) in patients undergoing radical cystectomy. Differences in CPET variables, Postoperative Morbidity Survey (POMS) data, and length of hospital stay were compared. Results: We identified 267 patients (85 pre-lockdown and 83 during lockdown) who underwent CPET and radical cystectomy. Patients undergoing radical cystectomy throughout lockdown had lower ventilatory anaerobic threshold (9.0 [7.9-10.9] vs 10.3 [9.1-12.3] ml kg-1 min-1; P=0.0002), peak oxygen uptake (15.5 [12.9-19.1] vs 17.5 [14.4-21.0] ml kg-1 min-1; P=0.015), and higher ventilatory equivalents for carbon dioxide (34.7 [31.4-38.5] vs 33.4 [30.5-36.5]; P=0.030) compared with pre-lockdown. Changes were more pronounced in males and those aged >65 yr. Patients undergoing radical cystectomy throughout lockdown had a higher proportion of day 5 POMS-defined morbidity (89% vs 75%, odds ratio [OR] 2.698, 95% confidence interval [CI] 1.143-6.653; P=0.019), specifically related to pulmonary complications (30% vs 13%, OR 2.900, 95% CI 1.368-6.194; P=0.007) and pain (27% vs 9%, OR 3.471, 95% CI 1.427-7.960; P=0.004), compared with pre-lockdown on univariate analysis. Conclusions: Lockdown measures in response to the COVID-19 pandemic were associated with a reduction in fitness and an increase in postoperative morbidity among patients undergoing radical cystectomy.

Awareness with paralysis and symptoms of post-traumatic stress disorder among mechanically ventilated emergency department survivors (ED-AWARENESS-2 Trial): study protocol for a pragmatic, multicenter, stepped wedge cluster randomized trial.

BACKGROUND: Awareness with paralysis (AWP) is memory recall during neuromuscular blockade (NMB) and can cause significant psychological harm. Decades of effort and rigorous trials have been conducted to prevent AWP in the operating room, where prevalence is 0.1-0.2%. By contrast, AWP in mechanically ventilated emergency department (ED) patients is common, with estimated prevalence of 3.3-7.4% among survivors given NMB. Longer-acting NMB use is a critical risk for AWP, and we have shown an association between ED rocuronium use and increased AWP prevalence. As NMB are given to more than 90% of ED patients during tracheal intubation, this trial provides a platform to test an intervention aimed at reducing AWP. The overall objective is to test the hypothesis that limiting ED rocuronium exposure will significantly reduce the proportion of patients experiencing AWP. METHODS: This is a pragmatic, stepped wedge cluster randomized trial conducted in five academic EDs, and will enroll 3090 patients. Per the design, all sites begin in a control phase, under observational conditions. At 6-month intervals, sites sequentially enter a 2-month transition phase, during which we will implement the multifaceted intervention, which will rely on use of nudges and defaults to change clinician decisions regarding ED NMB use. During the intervention phase, succinylcholine will be the default NMB over rocuronium. The primary outcome is AWP, assessed with the modified Brice questionnaire, adjudicated by three independent, blinded experts. The secondary outcome is the proportion of patients developing clinically significant symptoms of post-traumatic stress disorder at 30 and 180 days after hospital discharge. We will also assess for symptoms of depression and anxiety, and health-related quality of life. A generalized linear model, adjusted for time and cluster interactions, will be used to compare AWP in control versus intervention phases, analyzed by intention-to-treat. DISCUSSION: The ED-AWARENESS-2 Trial will be the first ED-based trial aimed at preventing AWP, a critical threat to patient safety. Results could shape clinical use of NMB in the ED and prevent more than 10,000 annual cases of AWP related to ED care. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05534243 . Registered 06, September 2022.

Heart Rate Recovery Assessed by Cardiopulmonary Exercise Testing in Patients with Cardiovascular Disease: Relationship with Prognosis.

BACKGROUND: The use of exercise testing has expanded in recent decades and there is a wealth of information examining the prognostic significance of exercise variables, such as peak oxygen consumption or ventilatory measures whilst exercising. However, a paucity of research has investigated the use of recovery-derived parameters after exercise cessation. Heart rate recovery (HRR) has been considered a measure of the function of the autonomic nervous system and its dysfunction is associated with cardiovascular risk. OBJECTIVES: We aim to provide an overview of the literature surrounding HRR and its prognostic significance in patients with cardiovascular disease undertaking an exercise test. DATA SOURCES: In December 2020, searches of PubMed, Scopus, and ScienceDirect were performed using key search terms and Boolean operators. STUDY SELECTION: Articles were manually screened and selected as per the inclusion criteria. RESULTS: Nineteen articles met inclusion criteria and were reviewed. Disagreement exists in methodologies used for measuring and assessing HRR. However, HRR provides prognostic mortality information for use in clinical practice. CONCLUSIONS: HRR is a simple, non-invasive measure which independently predicts mortality in patients with heart failure and coronary artery disease; HRR should be routinely incorporated into clinical exercise testing.

Advancing Health Equity Knowledge, Attitudes, and Beliefs Within a National Health Nonprofit Organization.

OBJECTIVE: This study presents survey results assessing the impact of the American Cancer Society (ACS) health equity (HE) training on staff knowledge, attitudes, and beliefs about HE and social determinants of health (SDOH). DESIGN: This study is a quasi-experimental design examining survey responses over time and comparing responses from staff who participated in ACS HE training sessions and education opportunities and those who did not. SETTING: An electronic Web survey was distributed to all ACS and American Cancer Society Cancer Action Network (ACS CAN) staff in each of the 3 years that the training was held (2018-2020). PARTICIPANTS: ACS and ACS CAN staff who chose to take the survey were included in the study. INTERVENTION: Engagement with training hosted by the ACS HE team was examined. Training sessions were intended to introduce staff to HE and SDOH in the context of cancer outcomes and provide staff with the skills to become HE champions in the organization. MAIN OUTCOME MEASURES: This study examines whether participation in training sessions hosted by the HE team had an impact on knowledge of HE terms, attitudes, and beliefs about HE and engagement with HE. RESULTS: Trained respondents had a significantly higher HE knowledge summary score (98%) than those who were not trained (79%, SD = 0.26100, P < .001). Respondents who participated in training were more likely to believe that they could advance HE through their work at ACS and ACS CAN (88% compared with 66% of those who were not trained, SD = 0.47300, P < .001). Respondents who participated in training scored an average of 4.7 out of 6 on HE engagement compared with 3.8 among the untrained (SD = 1.425, P < .001). CONCLUSIONS: These findings demonstrate that participation in HE training is associated with higher levels of knowledge about HE and stronger personal attitudes and beliefs about the importance of addressing SDOH. This is a foundational step in staff taking action to integrate HE concepts into their day-to-day work toward reducing inequities in access to cancer treatment and health outcomes.

Longitudinal analysis of peer social support and quitting Smoking: Moderation by sex and implications for cessation interventions.

Social support predicts better health and lower mortality, but the benefits of peer social support for helping cigarette smokers quit are unclear. Moreover, sex as a moderating factor has not been investigated despite sex differences in social support processes. This study of smokers' perceived availability of peer social support in quitting cigarette smoking is a secondary analysis of 1,010 individuals enrolled in an RCT that provided quitting assistance using tailored emails scheduled around a quit date. Participants completed measures of peer support for quitting cigarettes at enrollment (baseline), and at 1-, 3-, and 6-month follow-ups. Peer support at follow-ups was categorized as never-present, always-present, or mixed. A Generalized Estimating Equation (GEE) examined the association between peer support and 7-day point prevalence abstinence at follow-ups, controlling for baseline peer support, experimental condition, stress, depression, and sociodemographic and smoking behavior-related variables. Interactions of peer support × time, and peer support × sex, were tested. Results indicated that among women, always-present or mixed peer support was associated with, respectively, odds of abstinence that were 4.36 (95 % CI, 2.54-7.49, p = 0.0001), and 2.21 (OR = 2.21, 95 % CI, 1.27-3.85, p = 0.005) greater than among women reporting never-present peer support. Among men, peer support did not predict abstinence. Women who smoke may be especially receptive to the benefits of peer support when attempting to quit. Investigation of the basis of their perceptions, how they might be increased, and whether interventions to change them would be effective, is warranted.

A lysine residue from an extracellular turret switches the ion preference in a Cav3 T-Type channel from calcium to sodium ions.

Cav3 T-type calcium channels from great pond snail Lymnaea stagnalis have a selectivity-filter ring of five acidic residues, EE(D)DD. Splice variants with exons 12b or 12a spanning the extracellular loop between the outer helix IIS5 and membrane-descending pore helix IIP1 (IIS5-P1) in Domain II of the pore module possess calcium selectivity or dominant sodium permeability, respectively. Here, we use AlphaFold2 neural network software to predict that a lysine residue in exon 12a is salt-bridged to the aspartate residue immediately C terminal to the second-domain glutamate in the selectivity filter. Exon 12b has a similar folding but with an alanine residue in place of lysine in exon 12a. We express LCav3 channels with mutated exons Ala-12b-Lys and Lys-12a-Ala and demonstrate that they switch the ion preference to high sodium permeability and calcium selectivity, respectively. We propose that in the calcium-selective variants, a calcium ion chelated between Domain II selectivity-filter glutamate and aspartate is knocked-out by the incoming calcium ion in the process of calcium permeation, whereas sodium ions are repelled. The aspartate is neutralized by the lysine residue in the sodium-permeant variants, allowing for sodium permeation through the selectivity-filter ring of four negatively charged residues akin to the prokaryotic sodium channels with four glutamates in the selectivity filter. The evolutionary adaptation in invertebrate LCav3 channels highlight the involvement of a key, ubiquitous aspartate, "a calcium beacon" of sorts in the outer pore of Domain II, as determinative for the calcium ion preference over sodium ions through eukaryotic Cav1, Cav2, and Cav3 channels.

Benzonatate Overdose Presenting as Cardiac Arrest with Rapidly Narrowing QRS Interval.

INTRODUCTION: Benzonatate is a local anesthetic-like sodium channel antagonist that is widely prescribed as an antitussive. While it may be reasonable to assume that patients would present with a prolonged QRS interval following benzonatate overdose, the published literature does not support this. We report a case of a patient presenting following a benzonatate overdose with a prolonged QRS on her initial electrocardiograph (ECG) rhythm strip with rapid normalization of QRS duration. CASE REPORT: A 14-year-old girl presented in cardiac arrest following a benzonatate overdose. The patient was found in cardiac arrest within minutes of last being known well. Bystanders immediately provided cardiopulmonary resuscitation (CPR), and she was in asystole on emergency medical services (EMS) arrival. Return of spontaneous circulation (ROSC) was obtained following administration of intraosseous epinephrine and naloxone. EMS obtained an ECG rhythm strip following ROSC demonstrating a sinus rhythm with a QRS duration of 160 ms. Over the ensuing 30 minutes, there was progressive narrowing of the QRS. A 12-lead ECG obtained on arrival in the emergency department (ED) 44 minutes later demonstrated a QRS duration of 94 ms. Initially, EMS ECG rhythm strips were unavailable and an isolated benzonatate ingestion was considered less likely as ECG intervals were normal. Benzonatate exposure was later confirmed with a urine benzonatate concentration, which was 8.5 mcg/mL. The patient made a full recovery. DISCUSSION: Cases of pediatric benzonatate overdose with rapid development of cardiac arrest and full recovery have been previously reported. In this case, evidence of cardiac sodium channel blockade was demonstrated with a prolonged QRS interval on initial ECG rhythm strip analysis. However, unlike previous cases, rapid resolution of QRS prolongation occurred in this case. While transient QRS prolongation may be observed, finding a normal QRS interval should not discount the possibility of benzonatate overdose.

A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study.

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over 6 months (March-August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of - 3 to - 5 or Riker Sedation-Agitation Scale of 1-3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. RESULTS: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65-7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19. CONCLUSIONS: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.

Does stereotactic body radiation improve outcomes compared to conventional radiation for liver cancer patients?

Introduction: Over the past decade, there has been a paradigm shift to higher doses per fraction of liver stereotactic body radiotherapy (SBRT). However, this shift may not be due to evidence alone, but rather result of convenience and remuneration. This prospective cohort study aims to compare outcomes of patients who received moderately hypofractionated and hypofractionated radiotherapy treatments for liver tumours. Methods: Patients treated for liver cancer with radiotherapy between 2004 and 2020 were prospectively entered in this study. Patients were stratified into two groups: hypofractionation group of patients receiving an average of 5 fractions, and moderate hypofractionation group of patients receiving an average of 17 fractions. Other components of precision radiotherapy such as image guidance were the same between groups. The primary outcome was 2-year overall survival. The secondary outcomes were (1) change in toxicity as assessed by the Radiation Therapy Oncology Group (RTOG) toxicity criteria from baseline to 3 months, and from baseline to 6 months; and (2) change in Child Pugh score from baseline to 3 months. Type I error was prespecified at 0.05. Results: 397 patients were included. A larger proportion of patients on hypofractionated regimens were alive at the 2-year time point, relative to those who received moderately hypofractionated regimens (42% vs 27% p = 0.010); no difference was noted at the 1-year time point. Mean toxicity change in RTOG symptoms from baseline to 3 and 6 months, and in Child Pugh score from baseline to 3 months, were not statistically different between the two groups. Conclusion: When compared to conventional radiation fractionation, liver SBRT tends to be associated with a significant overall survival benefit, justifying a randomized trial to confirm. The concern that the trend to higher dose per fraction may result in increased toxicity, specifically in the treatment of high-risk liver patients, appears to be unfounded. The hypofractionated component of SBRT may be the critical dosimetric factor impacting on survival.

The Feasibility of Implementing Targeted SEDation in Mechanically Ventilated Emergency Department Patients: The ED-SED Pilot Trial.

OBJECTIVES: Deep sedation in the emergency department (ED) is common, increases deep sedation in the ICU, and is negatively associated with outcome. Limiting ED deep sedation may, therefore, be a high-yield intervention to improve outcome. However, the feasibility of conducting an adequately powered ED-based clinical sedation trial is unknown. Our objectives were to assess trial feasibility in terms of: 1) recruitment, 2) protocol implementation and practice change, and 3) safety. Patient-centered clinical outcomes were assessed to better plan for a future large-scale clinical trial. DESIGN: Pragmatic, multicenter ( n = 3), prospective before-after pilot and feasibility trial. SETTING: The ED and ICUs at three medical centers. PATIENTS: Consecutive, adult mechanically ventilation ED patients. INTERVENTIONS: An educational initiative aimed at reliable ED sedation depth documentation and reducing the proportion of deeply sedated patients (primary outcome). MEASUREMENTS AND MAIN RESULTS: Sedation-related data in the ED and the first 48 ICU hours were recorded. Deep sedation was defined as a Richmond Agitation-Sedation Scale of -3 to -5 or a Sedation-Agitation Scale of 1-3. One thousand three hundred fifty-six patients were screened; 415 comprised the final population. Lighter ED sedation was achieved in the intervention group, and the proportion of deeply sedated patients was reduced from 60.2% to 38.8% ( p < 0.01). There were no concerning trends in adverse events (i.e., inadvertent extubation, device removal, and awareness with paralysis). Mortality was 10.0% in the intervention group and 20.4% in the preintervention group ( p < 0.01). Compared with preintervention, the intervention group experienced more ventilator-free days [22.0 (9.0) vs 19.9 (10.6)] and ICU-free days [20.8 (8.7) vs 18.1 (10.4)], p < 0.05 for both. CONCLUSIONS: This pilot trial confirmed the feasibility of targeting the ED in order to improve sedation practices and reduce deep sedation. These findings justify an appropriately powered clinical trial regarding ED-based sedation to improve clinical outcomes.

A Dual-Center Cohort Study on The Association Between Early Deep Sedation and Clinical Outcomes in Mechanically Ventilated Patients During the COVID-19 Pandemic: the COVID-SED Study.

Background : Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. Study Design and Methods : Dual-center, retrospective cohort study conducted over six months (March - August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 hours were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Riker Sedation-Agitation Scale of 1 - 3. To examine impact of early sedation depth on hospital mortality (primary outcome) we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. Results : 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation ( p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65 - 7.17; p <0.01). These results were stable in the subgroup of patients with COVID-19. Conclusions : The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach. Clinical Trial Registration : Not applicable.

Cancer health self-efficacy improvement in a randomized controlled trial.

BACKGROUND: eHealth interventions can help cancer survivors self-manage their health outside the clinic. Little is known about how best to engage and assist survivors across the age and cancer treatment spectra. METHODS: The American Cancer Society conducted a randomized controlled trial that assessed efficacy of, and engagement with, Springboard Beyond Cancer, an eHealth self-management program for cancer survivors. Intent-to treat analyses assessed effects of intervention engagement for treatment (on-treatment vs completed) overall (n = 176; 88 control, 88 intervention arm) and separately by age (<60 years vs older). Multiple imputation was used to account for participants who were lost to follow-up (n = 41) or missing self-efficacy data (n = 1) at 3 months follow-up. RESULTS: Self-efficacy for managing cancer, the primary outcome of this trial, increased significantly within the intervention arm and for those who had completed treatment (Cohen's d = 0.26, 0.31, respectively). Additionally, participants with moderate-to-high engagement in the text and/or web intervention (n = 30) had a significantly greater self-efficacy for managing cancer-related issues compared to the control group (n = 68), with a medium effect size (Cohen's d = 0.44). Self-efficacy did not differ between the intervention and control arm at 3 months post-baseline. CONCLUSIONS: Study results suggest that cancer survivors benefit variably from eHealth tools. To maximize effects of such tools, it is imperative to tailor information to a priori identified survivor subgroups and increase engagement efforts.

Construct Validity of the EuroQoL-5 Dimension and the Health Utilities Index in Head and Neck Cancer.

OBJECTIVE: The objective of this study was to evaluate the construct validity of 2 health utility instruments-the EuroQoL-5 Dimension (EQ-5D) and the Health Utilities Index-Mark 3 (HUI-3)-and to compare them with disease-specific measures in patients with head and neck cancer. STUDY DESIGN: Prospective cross-sectional analysis. SETTING: Princess Margaret Cancer Centre. METHODS: Patients were administered the EQ-5D, HUI-3, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its head and neck cancer module (EORTC QLQ-H&N35), and the University of Washington Quality of Life Questionnaire (UWQoL). Several a priori expected relations were examined. The correlative and discriminative properties of the various instruments were examined. RESULTS: A total of 209 patients completed the 4 questionnaires. A significant ceiling effect was observed among EQ-5D responses (23% reported a maximum score of 1). The EQ-5D (rho = 0.79) and HUI-3 (rho = 0.60) had a strong correlation with the social-emotional domain of the UWQoL. The EQ-5D had a moderate correlation with the physical domain of the UWQoL (rho = 0.42), whereas the HUI-3 had a weak correlation (rho = 0.29). The EQ-5D and HUI-3 were able to distinguish among levels of health severity measured on the EORTC QLQ-C30 though not the QLQ-H&N35. Comparatively, the UWQoL was able to distinguish levels of disease severity on the EORTC QLQ-C30 and QLQ-H&N35. CONCLUSION: The results of this study demonstrate that disease-specific domains from head and neck quality-of-life instruments are not strongly correlated with the EQ-5D and HUI-3. Consideration should be put toward development of a disease-specific preference-based measure for health economic evaluation. LEVEL OF EVIDENCE: 4.

Differential effects of inhibitors of PTZ-induced kindling on glutamate transporters and enzyme expression.

Epilepsy is a neurological disorder resulting from abnormal neuronal firing in the brain. Glutamate transporters and the glutamate-glutamine cycle play crucial roles in the development of seizures. In the present study, the correlation of epilepsy with glutamate transporters and enzymes was investigated. Herein, male Wistar rats were randomly allocated into four groups (six animals/group); 35 mg/kg pentylenetetrazole (PTZ) was used to induce a kindling model of epilepsy. Once the kindling model was established, animals were treated for 15 days with either valproic acid (VPA, 350 mg/kg) or ceftriaxone (CEF, 200 mg/kg) in addition to the control group receiving saline. After treatment, electrocorticography (ECoG) was performed to record the electrical activity of the cerebral cortex. The glutamate reuptake time (T80 ) was also determined in situ using an in vivo voltammetry. The expression levels of glutamate transporters and enzymes in the M1 and CA3 areas of the brain were determined using a real-time polymerase chain reaction (RT-PCR). ECoG measurements showed that the mean spike number of the PTZ + VPA and PTZ + CEF groups was significantly lower (p < 0.05) than that of the PTZ group. Compared with the PTZ group, VPA or CEF treatment decreased the glutamate reuptake time (T80 ). The expression levels of EAAC1, GLT-1, GLAST, glutamine synthetase (GS), and glutaminase were increased in the PTZ group. Treatment with VPA or CEF enhanced the expression levels of GLT-1, GLAST, EAAC1, and GS, whereas the glutaminase expression level was reduced. The current results suggest that VPA or CEF decreases seizure activity by increasing glutamate reuptake by upregulating GLT-1 and GLAST expression, implying a possible mechanism for treating epilepsy. Also, we have suggested a novel mechanism for the antiepileptic activity of VPA via decreasing glutaminase expression levels. To our knowledge, this is the first study to measure the glutamate reuptake time in situ during the seizure (i.e., real-time measurement).