Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor-Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis.

BACKGROUND: Increased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC). METHODS: We systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR). RESULTS: Among 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR. CONCLUSIONS: This review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization's recommendation to avoid using NNRTIs in countries where levels of PDR are high.

Epinephrine for Out-of-Hospital Cardiac Arrest: An Updated Systematic Review and Meta-Analysis.

OBJECTIVES: To perform an updated systematic review and meta-analysis of clinical trials evaluating epinephrine for adult out-of-hospital cardiac arrest resuscitation. DATA SOURCES: The search included MEDLINE, EMBASE, and Ovid Evidence-Based Medicine, clinical trial registries, and bibliographies. STUDY SELECTION: Randomized and quasi-randomized controlled trials that compared the current standard dose of epinephrine to placebo, high or low dose epinephrine, any other vasopressor alone or in combination were screened by three independent reviewers. DATA EXTRACTION: Randomized and quasi-randomized controlled trials that compared the current standard dose of epinephrine to placebo, high or low dose epinephrine, any other vasopressor alone or in combination were screened by three independent reviewers. DATA SYNTHESIS: A total of 17 trials (21,510 patients) were included; seven were judged to be at high risk of bias. Compared to placebo, pooled results from two trials showed that standard dose of epinephrine increased return of spontaneous circulation (risk ratio, 3.09; 95% CI, 2.82-3.89), survival to hospital admission (risk ratio, 2.50; 95% CI, 1.68-3.72), and survival to discharge (risk ratio, 1.44; 95% CI, 1.11-1.86). The largest placebo-controlled trial showed that standard dose of epinephrine also improved survival at 30 days and 3 months but not neurologic outcomes, standard dose of epinephrine decreased return of spontaneous circulation (risk ratio, 0.87; 95% CI, 0.77-0.98) and survival to admission (risk ratio, 0.88; 95% CI, 0.78-0.99) when compared with high dose epinephrine. There were no differences in outcomes between standard dose of epinephrine and vasopressin alone or in combination with epinephrine. CONCLUSIONS: Largely based on one randomized controlled trial, standard dose of epinephrine improved overall survival but not neurologic outcomes in out-of-hospital cardiac arrest patients compared with placebo. There is a paucity of trials with meaningful patient outcomes; future epinephrine trials should evaluate dose and method of delivery on long-term survival, neurologic function, and quality of life after cardiac arrest.

Antiretroviral resistance testing in HIV-positive people.

BACKGROUND: Resistance to antiretroviral therapy (ART) among people living with human immunodeficiency virus (HIV) compromises treatment effectiveness, often leading to virological failure and mortality. Antiretroviral drug resistance tests may be used at the time of initiation of therapy, or when treatment failure occurs, to inform the choice of ART regimen. Resistance tests (genotypic or phenotypic) are widely used in high-income countries, but not in resource-limited settings. This systematic review summarizes the relative merits of resistance testing in treatment-naive and treatment-exposed people living with HIV. OBJECTIVES: To evaluate the effectiveness of antiretroviral resistance testing (genotypic or phenotypic) in reducing mortality and morbidity in HIV-positive people. SEARCH METHODS: We attempted to identify all relevant studies, regardless of language or publication status, through searches of electronic databases and conference proceedings up to 26 January 2018. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov to 26 January 2018. We searched Latin American and Caribbean Health Sciences Literature (LILACS) and the Web of Science for publications from 1996 to 26 January 2018. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) and observational studies that compared resistance testing to no resistance testing in people with HIV irrespective of their exposure to ART.Primary outcomes of interest were mortality and virological failure. Secondary outcomes were change in mean CD4-T-lymphocyte count, clinical progression to AIDS, development of a second or new opportunistic infection, change in viral load, and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed each reference for prespecified inclusion criteria. Two review authors then independently extracted data from each included study using a standardized data extraction form. We analysed data on an intention-to-treat basis using a random-effects model. We performed subgroup analyses for the type of resistance test used (phenotypic or genotypic), use of expert advice to interpret resistance tests, and age (children and adolescents versus adults). We followed standard Cochrane methodological procedures. MAIN RESULTS: Eleven RCTs (published between 1999 and 2006), which included 2531 participants, met our inclusion criteria. All of these trials exclusively enrolled patients who had previous exposure to ART. We found no observational studies. Length of follow-up time, study settings, and types of resistance testing varied greatly. Follow-up ranged from 12 to 150 weeks. All studies were conducted in Europe, USA, or South America. Seven studies used genotypic testing, two used phenotypic testing, and two used both phenotypic and genotypic testing. Only one study was funded by a manufacturer of resistance tests.Resistance testing made little or no difference in mortality (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.36 to 2.22; 5 trials, 1140 participants; moderate-certainty evidence), and may have slightly reduced the number of people with virological failure (OR 0.70, 95% CI 0.56 to 0.87; 10 trials, 1728 participants; low-certainty evidence); and probably made little or no difference in change in CD4 cell count (mean difference (MD) -1.00 cells/mm³, 95% CI -12.49 to 10.50; 7 trials, 1349 participants; moderate-certainty evidence) or progression to AIDS (OR 0.64, 95% CI 0.31 to 1.29; 3 trials, 809 participants; moderate-certainty evidence). Resistance testing made little or no difference in adverse events (OR 0.89, 95% CI 0.51 to 1.55; 4 trials, 808 participants; low-certainty evidence) and probably reduced viral load (MD -0.23, 95% CI -0.35 to -0.11; 10 trials, 1837 participants; moderate-certainty evidence). No studies reported on development of new opportunistic infections or quality of life. We found no statistically significant heterogeneity for any outcomes, and the I² statistic value ranged from 0 to 25%. We found no subgroup effects for types of resistance testing (genotypic versus phenotypic), the addition of expert advice to interpretation of resistance tests, or age. Results for mortality were consistent when we compared studies at high or unclear risk of bias versus studies at low risk of bias. AUTHORS' CONCLUSIONS: Resistance testing probably improved virological outcomes in people who have had virological failure in trials conducted 12 or more years ago. We found no evidence in treatment-naive people. Resistance testing did not demonstrate important patient benefits in terms of risk of death or progression to AIDS. The trials included very few participants from low- and middle-income countries.

Considerations and guidance in designing equity-relevant clinical trials.

Health research has documented disparities in health and health outcomes within and between populations. When these disparities are unfair and avoidable they may be referred to as health inequities. Few trials attend to factors related to health inequities, and there is limited understanding about how to build consideration of health inequities into trials. Due consideration of health inequities is important to inform the design, conduct and reporting of trials so that research can build evidence to more effectively address health inequities and importantly, ensure that inequities are not aggravated. In this paper, we discuss approaches to integrating health equity-considerations in randomized trials by using the PROGRESS Plus framework (Place of residence, Race/ethnicity/culture/language, Occupation, Gender, Religion, Education, Socio-economic status, Social capital and "Plus" that includes other context specific factors) and cover: (i) formulation of research questions, (ii) two specific scenarios relevant to trials about health equity and (iii) describe how the PROGRESS Plus characteristics may influence trial design, conduct and analyses. This guidance is intended to support trialists designing equity-relevant trials and lead to better design, conduct, analyses and reporting, by addressing two main issues: how to avoid aggravating inequity among research participants and how to produce information that is useful to decision-makers who are concerned with health inequities.

Lack of difference in T wave variability between patients at risk of sudden cardiac death and healthy subjects.

BACKGROUND: T wave variability (Tvar) is a proposed method to predict sudden cardiac death (SCD). The purpose of this trial was to evaluate the reproducibility of Tvar measurements over time and demonstrate a difference in Tvar between patient populations at risk for ventricular arrhythmias and healthy subjects. METHODS: Sixty subjects were enrolled in into 3 groups: healthy subjects (Population I), patients at high risk of SCD (Population II), and patients with a recent ventricular tachyarrhythmia event (Population III). Recording and analysis of T wave amplitude variance (TAV) as a measure of Tvar was performed at baseline and 3 months. RESULTS: TAV could not be interpreted in 12 of 43 patients in Populations II and III due to PVCs or noise. No subject had a TAV value suggestive of high risk of SCD as per a previously defined cutoff of >59 µV. Median (range) values of TAV in µV at baseline for Populations I, II and III were 26 (15-39), 21 (13-43), and 24 (18-41), respectively (p = 0.39). TAV was reproducible within population's from baseline to 3 months (p = 0.27, 0.53, 0.17 for Populations I, II and III, respectively). There was no significant difference between TAV values of high risk patients and healthy subjects. CONCLUSION: Tvar was reproducible primarily in patients with left ventricular dysfunction. However, the role of Tvar as a risk stratifying tool remains inconclusive.

Development of a Canadian Guidance for Reporting Real-world Evidence for Regulatory and Health-Technology Assessment (HTA) Decision Making.

Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health (CADTH)), was established to develop a guidance for standardization of reporting of RWE for regulatory and HTA decision-making in Canada. In this article, we describe the methods to develop the Guidance for Reporting Real-World Evidence document and checklist for reporting RWE for regulatory and HTA decision-making in Canada. This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making.

Mexiletine as an adjunctive therapy to amiodarone reduces the frequency of ventricular tachyarrhythmia events in patients with an implantable defibrillator.

The most effective pharmacological management of frequent ventricular tachyarrhythmia events in patients with an implantable defibrillator who failed or did not tolerate amiodarone is unknown. The aim of this retrospective cohort study was to assess the efficacy and tolerability of mexiletine in such patients. The patients served as self-controls. The number of treated ventricular tachyarrhythmia episodes (primary outcome); mortality, shocks from the defibrillator, and electrical storm events (secondary outcomes) during mexiletine therapy was compared with a matched duration of observation just before initiating mexiletine in 29 patients who were treated with a median dose of 300 mg/d of mexiletine and were followed for a median of 12 months. None of the patients had to stop mexiletine due to side effect. There was a significant reduction in the incidence of ventricular tachycardia/fibrillation episodes (median 2 vs. 12 events, P = 0.001) and shocks (median 0 vs. 2 events, P = 0.003) in the first 3 months of treatment, but long-term efficacy was only observed among patients who continued amiodarone therapy. In conclusion, mexiletine, when added to amiodarone in case of amiodarone inefficacy, reduces ventricular tachycardia/fibrillation events and appropriate therapies in patients with an implantable cardioverter defibrillator. A randomized trial should validate the efficacy and safety of mexiletine as an adjunctive therapy to amiodarone.

Dronedarone and Captisol-enabled amiodarone in an experimental cardiac arrest.

OBJECTIVE: To compare the energy required for defibrillation and postshock outcomes after the administration of dronedarone, amiodarone, and placebo in a porcine model of cardiac arrest. METHODS: Forty-two pigs were randomized to amiodarone, dronedarone, or control treatments. After induction of ventricular fibrillation, compressions and ventilations were performed for 3 minutes and treatment was administered over 30 seconds. If defibrillation was unsuccessful, cardiopulmonary resuscitation continued and repeated shocks were administered every 2 minutes with continual hemodynamic monitoring for a total duration of 30 minutes. RESULTS: The cumulative energy required for defibrillation was 570 ± 422 J for dronedarone, 441 ± 365 J for amiodarone, and 347 ± 281 J for control (P = not significant). Survival at 30 minutes was 1 (7.1%) for dronedarone compared with 11 (78.6%) for control (P = 0.001). Mortality in the dronedarone group was because of refibrillation in 3 (21.4%) cases, atrioventricular block in 1 (7.1%) case, and hypotension not because of bradycardia in 9 (64.3%) cases. Two minutes after successful defibrillation, systolic aortic pressure was lower in dronedarone versus control (86.6 ± 26.9 vs. 110 ± 15.1 mm Hg; P = 0.035). CONCLUSIONS: The administration of dronedarone resulted in a significant reduction in survival and both systolic aortic and coronary perfusion pressure compared with control.

The ability of machine learning algorithms to predict defibrillation success during cardiac arrest: A systematic review.

OBJECTIVE: To evaluate the existing knowledge on the effectiveness of machine learning (ML) algorithms inpredicting defibrillation success during in- and out-of-hospital cardiac arrest. METHODS: MEDLINE, Embase, CINAHL and Scopus were searched from inception to August 30, 2022. Studies were included that utilized ML algorithms for prediction of successful defibrillation, observed as return of spontaneous circulation (ROSC), survival to hospital or discharge, or neurological status at discharge.Studies were excluded if involving a trauma, an unknown underlying rhythm, an implanted cardiac defibrillator or if focused on the prediction or onset of cardiac arrest. Risk of bias was assessed using the PROBAST tool. RESULTS: There were 2399 studies identified, of which 107 full text articles were reviewed and 15 observational studies (n = 5680) were included for final analysis. 29 ECG waveform features were fed into 15 different ML combinations. The best performing ML model had an accuracy of 98.6 (98.5 - 98.7)%, with 4 second ECG intervals. An algorithm incorporating end-tidal CO2 reported an accuracy of 83.3% (no CI reported). Meta-analysis was not performed due to heterogeneity in study design, ROSC definitions, and characteristics. CONCLUSION: Machine learning algorithms, specifically Neural Networks, have been shown to have potential to predict defibrillation success for cardiac arrest with high sensitivity and specificity.Due to heterogeneity, inconsistent reporting, and high risk of bias, it is difficult to conclude which, if any, algorithm is optimal. Further clinical studies with standardized reporting of patient characteristics, outcomes, and appropriate algorithm validation are still required to elucidate this. PROSPERO 2020 CRD42020148912.

Methods to teach schoolchildren how to perform and retain cardiopulmonary resuscitation (CPR) skills: A systematic review and meta-analysis.

Background: Worldwide, bystander CPR rates are low; one effective way to increase these rates is to train schoolchildren; however, the most effective way to train them is currently unknown. Methods: This systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies, evaluated whether CPR training for schoolchildren, using innovative teaching modalities (nonpractical, self, or peer-training) versus standard instructor-led training, resulted in higher quality CPR, self-confidence and short-term (≤3 months post-training) or long-term (>3 months post-training) retention of CPR skills. Results: From 9793 citations, 96 studies published between 1975 and 2022 (44 RCTs and 52 before/after studies) were included. There were 43,754 students, average age of 11.5 ±â€¯0.9 (range 5.9-17.6) and 49.2% male. Only 13 RCTs compared practical vs. nonpractical training (n = 5), self- vs. instructor-led training (n = 7) or peer- vs. instructor-led training (n = 5). The observed statistically significant differences in mean depth and rate of compressions between children with hands-on practical training and those without were not clinically relevant. Regardless of training modality, compression depth was consistently suboptimal. No differences were observed in CPR skills immediately or ≤ 3 months post-training, between children who were self- or peer-trained vs. instructor-led. Due to lack of data, we were unable to evaluate the impact of these novel training modalities on student self-confidence. Conclusion: Although innovative training modalities are equally effective to instructor-led training when teaching schoolchildren CPR, compression depth was frequently suboptimal. Recommendations on standardized training and evaluation methods are necessary to understand the best ways to train children.

Meta-analysis of Pragmatic and Explanatory Trials.

Pooling studies with different clinical and methodological features may lead to statistical heterogeneity, particularly if heterogeneity remains unexplained. One potential source of heterogeneity may be how much the included trials tend toward a pragmatic or explanatory design. Many tools have been developed to aid researchers in quantifying pragmatism in clinical trials, at both the design and appraisal stages.In this chapter we review these tools, illustrate examples of their use, and discuss methods of including pragmatism in meta-analysis as a way of exploring heterogeneity.We suggest a stepwise approach to incorporating evidence from pragmatic and explanatory trials which includes planning to assess pragmatism at the protocol stage, collecting data on pragmatism, extracting data on treatment effects, incorporating pragmatism in meta-analysis using subgroup analysis or meta-regression techniques, and interpreting and reporting the findings transparently.

Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The present study was undertaken to investigate the effectiveness and safety of dose reduction of tumor necrosis factor inhibitor (TNFi) therapy in the treatment of axial spondyloarthritis (SpA) compared to usual care. METHODS: We searched the Cochrane Central Register of Controlled Trials, Embase, Medline, and trial registries. We screened, extracted data, and assessed risk of bias in duplicate. Data were pooled using random-effects models; subgroup analyses were performed for type of TNFi, prior TNFi exposure, and follow-up duration. Outcomes of interest were Assessment of SpondyloArthritis international Society (ASAS) response and remission criteria, disease activity, relapse, and safety. RESULTS: We included 6 randomized trials with 747 participants (442 with ankylosing spondylitis and 305 with nonradiographic axial SpA). Compared to the standard dose, there were fewer events with the reduced dose for the ASAS criteria for 40% improvement (risk ratio [RR] 0.62 [95% confidence interval (95% CI) 0.49, 0.78]) and for ASAS partial remission (RR 0.17 [95% CI 0.06, 0.46]). There was a mean increase in the Bath Ankylosing Spondylitis Disease Activity Index score (mean difference [MD] 0.35 [95% CI 0.10, 0.60]) and no difference in C-reactive protein levels (MD 0.16 [95% CI -0.76, 1.07]) with the reduced dose. There were more disease flares/relapses (RR 1.73 [95% CI 1.32, 2.27]) with the reduced dose. There were no differences in infection rates (incidence rate ratio [IRR] 0.98 [95% CI 0.76, 1.25]) or injection/infusion reactions (IRR 0.71 [95% CI 0.42, 1.19]). CONCLUSION: Patients with axial SpA may experience little to no clinical benefit from reduction of TNFi therapy. Maintaining the standard dose probably improves the sustained effect on disease activity and helps to prevent disease flare.

Psychopathology in patients with ICDs over time: results of a prospective study.

INTRODUCTION: The effects of implantable cardioverter defibrillators (ICDs) and ICD shocks on psychological state have previously been studied. However, it is still unclear how health-related quality-of-life changes over time using standardized assessments. We sought to characterize the effects of ICDs and ICD shocks on psychological outcomes. METHODS: Three hundred-eight patients receiving ICDs were prospectively identified. Baseline QOL assessments including standardized psychological surveys [Hospital Anxiety and Depression Scale (HADS), Impact of Events Scale-Revised (IES-R), and Short Form 36 Health Survey (SF-36)] were obtained within 2 months of device implantation and at 6 and 12 months, respectively. Outcomes including ICD shocks were followed over the 12-month study period. RESULTS: The number of patients meeting criteria for anxiety or posttraumatic stress disorder (PTSD) at baseline (78/223, 35%) was higher than at 6 (34/223, 15%) or 12 (34/223, 15%) months (P < 0.01). There was a significant improvement over time in HADS (P < 0.001) and IES-R (PTSD) scores (P < 0.001). Amongst the 20 patients who received ICD shocks, no significant differences were observed in IES-R, SF-36, or HADS scores when compared with those who did not receive shocks at any time point. Patients who experienced electrical storms (N = 5) had significantly higher baseline PTSD scores (29.6 +/- 11.4 vs 14.6 +/- 11.6, P < 0.01). CONCLUSIONS: Patients receiving ICDs have significant rates of baseline psychopathology after implantation. However, psychological assessment scores tend to improve with time. ICD shocks do not appear to significantly impact psychological state. These results suggest the importance of close screening and referral for possible psychopathology in patients receiving ICDs, especially in the peri-implant period.

Common wearable devices demonstrate variable accuracy in measuring heart rate during supraventricular tachycardia.

BACKGROUND: Wearable devices are used as a noninvasive method of monitoring health. The accuracy of wearables for heart rate (HR) monitoring has been extensively studied in sinus rhythm, but evidence for tachyarrhythmias, particularly supraventricular tachycardia (SVT), is sparse. OBJECTIVE: The purpose of this study was to examine the accuracy of 4 common wearable devices-Apple Watch, Fitbit Charge HR, Garmin VivoSmart HR, and Polar A360-in measuring HR during paroxysmal SVT. METHODS: Data were gathered from 52 patients by placing 1 device on each wrist during an electrophysiological study at which SVT was induced. The device-measured HR was obtained by using the highest HR measured by the device during each SVT episode. This HR was compared with measurements from a 12-lead electrocardiogram (ECG), for which the rate during the last 5 seconds of SVT was averaged. RESULTS: For SVT episodes <15 seconds, the Apple, Fitbit, Garmin, and Polar devices registered an increase from baseline HR in 18.7%, 19.5%, 1.5%, and 37.7% of episodes, respectively. For episodes 15-60 seconds, the Apple, Fitbit, Garmin, and Polar devices registered an increase in 67.6%, 42.4%, 24.3%, and 65.5% of episodes, respectively. For episodes ≥60 seconds, the Apple and Polar devices had 23 of 23 and 19 of 21 episodes with at least 90% agreement between device-measured and ECG-measured HR, whereas the Fitbit and Garmin devices had 7 of 20 and 8 of 22 episodes with at least 90% agreement. CONCLUSION: All wearable devices are inaccurate for short-duration SVT. Some devices are accurate for longer duration SVT.

Health-Related Quality of Life in Patients With Atrial Fibrillation Treated With Catheter Ablation or Antiarrhythmic Drug Therapy: A Systematic Review and Meta-analysis.

BACKGROUND: Catheter ablation (CA) is performed in patients with atrial fibrillation (AF) to reduce symptoms and improve health-related quality of life (HRQL). METHODS: This systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated CA of any energy modality compared with antiarrhythmic drugs (AADs) using inverse-variance random-effects models. We searched for RCTs reporting HRQL and AF-related symptoms at 3, 6, 12, 24, 48, and 60 months after treatment as well as the number of repeat ablations. RESULTS: Of 15,878 records, we included 13 RCTs of CA vs AADs for the analyses of HRQL, 7 RCTs for the analyses of AF-related symptoms, and 13 RCTs for the number of repeat ablations. For the HRQL analyses at 3 months, there were significant increases in both the Physical Component Summary score (3 months' standardized mean difference = 0.58 [0.39-0.78]; P < 0.00001, I 2 = 6%, 3 trials, n = 443) and the Mental Component Summary score (3 months' standardized mean difference = 0.57 [0.37-0.77]; P < 0.00001, I 2 = 0%, 3 trials, n = 443), favouring CA over AADs. These differences were sustained at 12 months but not >24 months after randomization. Similar results were seen for AF-related symptoms. The number of repeat ablations and success rates after procedure varied considerably across trials. CONCLUSIONS: Evidence from few trials suggests that CA improves physical and mental health and AF-related symptoms in the short term, but these benefits decrease with time. More trials, reporting both HRQL and AF-related symptoms, at consistent time points are needed to assess the effectiveness of CA for the treatment of AF.

CONTEXTE: L'ablation par cathéter (AC) est réalisée chez les patients atteints de fibrillation auriculaire (FA) afin d'atténuer les symptômes et d'améliorer la qualité de vie liée à la santé (QVLS). MÉTHODOLOGIE: Cette revue systématique et méta-analyse d'essais contrôlés à répartition aléatoire (ECRA) a permis d'évaluer l'AC, toutes modalités énergétiques confondues, comparativement aux agents antiarythmiques (AA) à l'aide de modèles à effets aléatoires à variance inverse. Nous avons recherché les ECRA qui faisaient état de la QVLS et des symptômes liés à la FA à 3, 6, 12, 24, 48 et 60 mois après le traitement et qui précisaient le nombre d'ablations répétées. RÉSULTATS: À partir de 15 878 entrées, nous avons retenu 13 ECRA comparant l'AC à des AA pour l'analyse de la QVLS, 7 autres pour l'analyse des symptômes liés à la FA et 13 de plus aux fins de calcul du nombre d'ablations répétées. L'analyse de la QVLS à 3 mois indique une augmentation significative du score sommaire de la composante physique (différence moyenne normalisée à 3 mois = 0,58 [0,39-0,78]; p < 0,00001, I 2 = 6 %, 3 essais, n = 443) et du score sommaire de la composante mentale (différence moyenne normalisée à 3 mois = 0,57 [0,37-0,77]; p < 0,00001, I 2 = 0 %, 3 essais, n = 443), faisant pencher la balance en faveur de l'AC plutôt que des AA. Ces différences persistaient à 12 mois après la répartition aléatoire, mais pas aux moments d'évaluation ultérieurs (24, 48 et 60 mois). Des résultats similaires ont été observés au chapitre des symptômes liés à la FA. Le nombre d'ablations répétées et le taux de réussite postopératoire variaient considérablement d'un essai à l'autre. CONCLUSIONS: Les données probantes de quelques essais donnent à penser que l'AC améliore la santé physique et mentale ainsi que les symptômes liés à la FA à court terme, mais que ces bienfaits s'atténuent avec le temps. D'autres essais faisant état de la QVLS et des symptômes liés à la FA, à des moments d'évaluation constants, devront être réalisés pour évaluer l'efficacité réelle de l'AC dans le traitement de la FA.

First aid cooling techniques for heat stroke and exertional hyperthermia: A systematic review and meta-analysis.

BACKGROUND: Heat stroke is an emergent condition characterized by hyperthermia (>40 °C/>104 °F) and nervous system dysregulation. There are two primary etiologies: exertional which occurs during physical activity and non-exertional which occurs during extreme heat events without physical exertion. Left untreated, both may lead to significant morbidity, are considered a special circumstance for cardiac arrest, and cause of mortality. METHODS: We searched Medline, Embase, CINAHL and SPORTDiscus. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods and risk of bias assessments to determine the certainty and quality of evidence. We included randomized controlled trials, non-randomized trials, cohort studies and case series of five or more patients that evaluated adults and children with non-exertional or exertional heat stroke or exertional hyperthermia, and any cooling technique applicable to first aid and prehospital settings. Outcomes included: cooling rate, mortality, neurological dysfunction, adverse effects and hospital length of stay. RESULTS: We included 63 studies, of which 37 were controlled studies, two were cohort studies and 24 were case series of heat stroke patients. Water immersion of adults with exertional hyperthermia [cold water (14-17 °C/57.2-62.6 °F), colder water (8-12 °C/48.2-53.6 °F) and ice water (1-5 °C/33.8-41 °F)] resulted in faster cooling rates when compared to passive cooling. No single water temperature range was found to be associated with a quicker core temperature reduction than another (cold, colder or ice). CONCLUSION: Water immersion techniques (using 1-17 °C water) more effectively lowered core body temperatures when compared with passive cooling, in hyperthermic adults. The available evidence suggests water immersion can rapidly reduce core body temperature in settings where it is feasible.

2020 International Consensus on First Aid Science With Treatment Recommendations.

This is the summary publication of the International Liaison Committee on Resuscitation's 2020 International Consensus on First Aid Science With Treatment Recommendations. It addresses the most recent published evidence reviewed by the First Aid Task Force science experts. This summary addresses the topics of first aid methods of glucose administration for hypoglycemia; techniques for cooling of exertional hyperthermia and heatstroke; recognition of acute stroke; the use of supplementary oxygen in acute stroke; early or first aid use of aspirin for chest pain; control of life- threatening bleeding through the use of tourniquets, haemostatic dressings, direct pressure, or pressure devices; the use of a compression wrap for closed extremity joint injuries; and temporary storage of an avulsed tooth. Additional summaries of scoping reviews are presented for the use of a recovery position, recognition of a concussion, and 6 other first aid topics. The First Aid Task Force has assessed, discussed, and debated the certainty of evidence on the basis of Grading of Recommendations, Assessment, Development, and Evaluation criteria and present their consensus treatment recommendations with evidence-to-decision highlights and identified priority knowledge gaps for future research. The 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) Science With Treatment Recommendations (CoSTR) is the fourth in a series of annual summary publications from the International Liaison Committee on Resuscitation (ILCOR). This 2020 CoSTR for first aid includes new topics addressed by systematic reviews performed within the past 12 months. It also includes updates of the first aid treatment recommendations published from 2010 through 2019 that are based on additional evidence evaluations and updates. As a result, this 2020 CoSTR for first aid represents the most comprehensive update since 2010.

Rhythm and rate control of atrial fibrillation in the emergency department - A large community-based observational study.

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia presentation to the emergency department (ED) and frequently results in admission to the hospital. Although rarely life-threatening and not usually an emergent condition, AF places a large burden on our health-care system. The objective of this study was to describe the practices of ED physicians in the management of AF in a large urban Canadian city. METHODS: From January 1, 2010 to December 31, 2010, patients with a primary diagnosis of AF were identified across 10 EDs in Toronto, Canada (N=2,609). Fifty patients were selected at random from each hospital for a detailed chart review (n=500). RESULTS: Two hundred thirty-two patients (46%) received rate control, and 129 (26%) received rhythm control with the remainder (28%) receiving neither therapy. Sixty-seven percent of patients were discharged home. Most patients (79%) were symptomatic on arrival; however, only a minority of these (31%) received rhythm control. Factors that were associated with rhythm control included younger age, duration of palpitations ≤ 48 hours, a lower CHADS2 score, and the absence of left ventricular dysfunction. CONCLUSION: Our data suggest a wide range of practice amongst ED physicians treating patients presenting to the ED with a primary diagnosis of AF. A randomized trial is needed to better understand the optimal management strategy in this patient population and setting.

The role of pragmatism in explaining heterogeneity in meta-analyses of randomised trials: a protocol for a cross-sectional methodological review.

INTRODUCTION: There has been increasing interest in pragmatic trials methodology. As a result, tools such as the Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) are being used prospectively to help researchers design randomised controlled trials (RCTs) within the pragmatic-explanatory continuum. There may be value in applying the PRECIS-2 tool retrospectively in a systematic review setting as it could provide important information about how to pool data based on the degree of pragmatism. OBJECTIVES: To investigate the role of pragmatism as a source of heterogeneity in systematic reviews by (1) identifying systematic reviews with meta-analyses of RCTs that have moderate to high heterogeneity, (2) applying PRECIS-2 to RCTs of systematic reviews, (3) evaluating the inter-rater reliability of PRECIS-2, (4) determining how much of this heterogeneity may be explained by pragmatism. METHODS: A cross-sectional methodological review will be conducted on systematic reviews of RCTs published in the Cochrane Library from 1 January 2014 to 1 January 2017. Included systematic reviews will have a minimum of 10 RCTs in the meta-analysis of the primary outcome and moderate to substantial heterogeneity (I2≥50%). Of the eligible systematic reviews, a random selection of 10 will be included for quantitative evaluation. In each systematic review, RCTs will be scored using the PRECIS-2 tool, in duplicate. Agreement between raters will be measured using the intraclass correlation coefficient. Subgroup analyses and meta-regression will be used to evaluate how much variability in the primary outcome may be due to pragmatism. DISSEMINATION: This review will be among the first to evaluate the PRECIS-2 tool in a systematic review setting. Results from this research will provide inter-rater reliability information about PRECIS-2 and may be used to provide methodological guidance when dealing with pragmatism in systematic reviews and subgroup considerations. On completion, this review will be submitted to a peer-reviewed journal for publication.

Implantable Cardioverter Defibrillator Implantation Rates After Out of Hospital Cardiac Arrest: Are the Rates Guideline-Concordant?

BACKGROUND: Clinical practice guidelines recommend implantable cardioverter defibrillators (ICDs) for the secondary prevention of sudden death after a cardiac arrest not from a reversible cause, but "real world" implantation rates are not well described. METHODS: Adults with out of hospital cardiac arrest attended by Emergency Medical Services are captured in the Toronto Regional RescuNET database. We analyzed those who survived to hospital discharge and collected data on age, sex, initial rhythm, ST-elevation myocardial infarction (STEMI) on presenting electrocardiogram (ECG), in-hospital revascularization, neurologic status (Modified Rankin Scale [MRS]) at discharge, and admission hospital type. To estimate 'indicated' ICD implantation rates, "likely ICD-eligible" patients were defined as having an initial shockable rhythm, no STEMI on presenting ECG, no revascularization, and good neurologic status (MRS 0-3). "Not likely ICD-eligible" patients were defined as having a STEMI on presenting ECG, revascularization, or poor neurologic status (MRS 4-5). RESULTS: In the 1238 adults (2011-2014) analyzed, the overall ICD implantation rate was 23.9%. Two hundred fifty-six patients were "likely ICD-eligible," of whom 146 (57.0%) received an ICD. The implantation rate for "not likely ICD-eligible" patients was 16.7% (112 of 670). ICD eligibility could not be determined for 312 patients, of whom 38 (12.2%) received an ICD. Admission to a hospital with ICD implantation facilities was associated with a higher probability of ICD implantation (odds ratio, 2.85; 95% confidence interval, 1.40-5.82). CONCLUSIONS: Postcardiac arrest ICD implantation rates in eligible patients are lower than expected. Implementation strategies to monitor guideline adherence after out of hospital cardiac arrest are warranted.