Trends in survival from out-of-hospital cardiac arrest with a shockable rhythm and its association with bystander resuscitation: a retrospective study.

OBJECTIVE: Over 300 000 cases of out-of-hospital cardiac arrests (OHCAs) occur each year in the USA and Europe. Despite decades of investment and research, survival remains disappointingly low. We report the trends in survival after a ventricular fibrillation/pulseless ventricular tachycardia OHCA, over a 13-year period, in a French urban region, and describe the simultaneous evolution of the rescue system. METHODS: We investigated four 18-month periods between 2005 and 2018. The first period was considered baseline and included patients from the randomised controlled trial 'DEFI 2005'. The three following periods were based on the Paris Sudden Death Expertise Center Registry (France). Inclusion criteria were non-traumatic cardiac arrests treated with at least one external electric shock with an automated external defibrillator from the basic life support team and resuscitated by a physician-staffed ALS team. Primary outcome was survival at hospital discharge with a good neurological outcome. RESULTS: Of 21 781 patients under consideration, 3476 (16%) met the inclusion criteria. Over all study periods, survival at hospital discharge increased from 12% in 2005 to 25% in 2018 (p<0.001), and return of spontaneous circulation at hospital admission increased from 43% to 58% (p=0.004).Lay-rescuer cardiopulmonary resuscitation (CPR) and telephone CPR (T-CPR) rates increased significantly, but public defibrillator use remained limited. CONCLUSION: In a two-tiered rescue system, survival from OHCA at hospital discharge doubled over a 13-year study period. Concomitantly, the system implemented an OHCA patient registry and increased T-CPR frequency, despite a consistently low rate of public defibrillator use.

Family presence during resuscitation.

BACKGROUND: Patients and their relatives often expect to be actively involved in decisions of treatment. Even during resuscitation and acute medical care, patients may want to have their relatives nearby, and relatives may want to be present if offered the possibility. The principle of family presence during resuscitation (FPDR) is a triangular relationship where the intervention of family presence affects the healthcare professionals, the relatives present, and the care of the patient involved. All needs and well-being must be balanced in the context of FPDR as the actions involving all three groups can impact the others. OBJECTIVES: The primary aim of this review was to investigate how offering relatives the option to be present during resuscitation of patients affects the occurrence of post-traumatic stress disorder (PTSD)-related symptoms in the relatives. The secondary aim was to investigate how offering relatives the option to be present during resuscitation of patients affects the occurrence of other psychological outcomes in the relatives and what effect family presence compared to no family presence during resuscitation of patients has on patient morbidity and mortality. We also wanted to investigate the effect of FPDR on medical treatment and care during resuscitation. Furthermore, we wanted to investigate and report the personal stress seen in healthcare professionals and if possible describe their attitudes toward the FPDR initiative. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL from inception to 22 March 2022 without any language limits. We also checked references and citations of eligible studies using Scopus, and searched for relevant systematic reviews using Epistomonikos. Furthermore, we searched ClinicalTrials.gov, WHO ICTRP, and ISRCTN registry for ongoing trials; OpenGrey for grey literature; and Google Scholar for additional trials (all on 22 March 2022). SELECTION CRITERIA: We included randomized controlled trials of adults who have witnessed a resuscitation attempt of a patient (who was their relative) at the emergency department or in the pre-hospital emergency medical service.  The participants of this review included relatives, patients, and healthcare professionals during resuscitation.  We included relatives aged 18 years or older who have witnessed a resuscitation attempt of a patient (who is their relative) in the emergency department or pre-hospital. We defined relatives as siblings, parents, spouses, children, or close friends of the patient, or any other descriptions used by the study authors. There were no limitations on adult age or gender. We defined patient as a patient with cardiac arrest in need of cardiopulmonary resuscitation (CPR), a patient with a critical medical or traumatic life-threatening condition, an unconscious patient, or a patient in any other way at risk of sudden death. We included all types of healthcare professionals as described in the included studies. There were no limitations on age or gender. DATA COLLECTION AND ANALYSIS: We checked titles and abstracts of studies identified by the search, and obtained the full reports of those studies deemed potentially relevant. Two review authors independently extracted data. As it was not possible to conduct meta-analyses, we synthesized data narratively. MAIN RESULTS: The electronic searches yielded a total of 7292 records after deduplication. We included 2 trials (3 papers) involving a total of 595 participants: a cluster-randomized trial from 2013 involving pre-hospital emergency medical services units in France, comparing systematic offer for a relative to witness CPR with the traditional practice, and its 1-year assessment; and a small pilot study from 1998 of FPDR in an emergency department in the UK. Participants were 19 to 78 years old, and between 56% and 64% were women. PTSD was measured with the Impact of Event Scale, and the median score ranged from 0 to 21 (range 0 to 75; higher scores correspond to more severe disease). In the trial that accounted for most of the included participants (570/595), the frequency of PTSD-related symptoms was significantly higher in the control group after 3 and 12 months, and in the per-protocol analyses a significant statistical difference was found in favor of FPDR when looking at PTSD, anxiety and depression, and complicated grief after 1 year.  One of the included studies also measured duration of patient resuscitation and personal stress in healthcare professionals during FPDR and found no difference between groups. Both studies had high risk of bias, and the evidence for all outcomes except one was assessed as very low certainty. AUTHORS' CONCLUSIONS: There was insufficient evidence to draw any firm conclusions on the effects of FPDR on relatives' psychological outcomes.   Sufficiently powered and well-designed randomized controlled trials may change the conclusions of the review in future.

Association between basic life support and survival in sports-related sudden cardiac arrest: a meta-analysis.

AIMS: To evaluate the association of basic life support with survival after sports-related sudden cardiac arrest (SR-SCA). METHODS AND RESULTS: In this systematic review and meta-analysis, a search of several databases from each database inception to 31 July 2021 without language restrictions was conducted. Studies were considered eligible if they evaluated one of three scenarios in patients with SR-SCA: (i) bystander presence, (ii) bystander cardiopulmonary resuscitation (CPR), or (iii) bystander automated external defibrillator (AED) use and provided information on survival. Risk of bias was evaluated using Risk of Bias in Non-randomized Studies of Interventions. The primary outcome was survival at the longest follow up. The meta-analysis was conducted using the random-effects model. The Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach was used to rate certainty in the evidence. In total, 28 non-randomized studies were included. The meta-analysis showed significant benefit on survival in all three groups: bystander presence [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.48-4.37; I2 = 25%; 9 studies-988 patients], bystander CPR (OR 3.84, 95% CI 2.36-6.25; I2 = 54%; 23 studies-2523 patients), and bystander AED use (OR 5.25, 95% CI 3.58-7.70; I2 = 16%; 19 studies-1227 patients). The GRADE certainty of evidence was judged to be moderate. CONCLUSION: In patients with SR-SCA, bystander presence, bystander CPR, and bystander AED use were significantly associated with survival. These results highlight the importance of witness intervention and encourage countries to develop their first aid training policy and AED installation in sport settings.

Ultrasensitive Troponin I and Incident Cardiovascular Disease.

BACKGROUND: To examine the association of ultrasensitive cTnI (cardiac troponin I) with incident cardiovascular disease events (CVDs) in the primary prevention setting. METHODS: cTnI was analyzed in the baseline plasma (2008-2012) of CVD-free volunteers from the Paris Prospective Study III using a novel ultrasensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection of 0.013 pg/mL. Incident CVD hospitalizations (coronary heart disease, stroke, cardiac arrhythmias, deep venous thrombosis or pulmonary embolism, heart failure, or arterial aneurysm) were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed SD increase of cTnI in Cox models using age as the time scale. RESULTS: The study population includes 9503 participants (40% women) aged 59.6 (6.3) years. cTnI was detected in 99.6% of the participants (median value=0.63 pg/mL, interquartile range, 0.39-1.09). After a median follow-up of 8.34 years (interquartile range, 8.0-10.07), 516 participants suffered 612 events. In fully adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (hazard ratio, 1.18 [1.08-1.30]). Among all single risk factors, cTnI had the highest discrimination capacity for incident CVD events (C index=0.6349). Adding log cTnI to the SCORE 2 (Systematic Coronary Risk Evaluation) risk improved moderately discriminatory capacity (C index 0.698 versus 0.685; bootstrapped C index difference: 0.0135 [95% CI, 0.0131-0.0138]), and reclassification of the participants (categorical net reclassification index, 0.0628 [95% CI, 0.023-0.102]). Findings were consistent using the US pooled cohort risk equation. CONCLUSIONS: Ultrasensitive cTnI is an independent marker of CVD events in the primary prevention setting.

Does age influence out-of-hospital cardiac arrest incidence and outcomes among women? Insights from the Paris SDEC.

AIMS: Age and sex disparities in out-of-hospital cardiac arrest (OHCA) have been described. Reproductive age may have a protected effect on females vs. males, although results are conflicting. We aimed to clarify this using the Paris Sudden Death Expertise Centre (SDEC) registry. METHODS AND RESULTS: The Paris SDEC registry collects OHCAs occurring in the Greater Paris Area. We included all OHCAs of presumed cardiac causes occurring between 2013 and 2018. Patients were divided into age groups: 1-13, 13-50, 50-75, and >75 years. Sex and age disparities in OHCA incidence and outcomes were analysed using multivariable negative binomial and logistic regression models. There were 19 782 OHCAs meeting inclusion criteria: 0.37% aged 1-13 years, 12.4% aged 13-50 years, 40.4% aged 50-75 years, and 46.9% aged >75 years. Adjusted incidence rate ratios (IRRs) in females vs. males were for the youngest to the older age groups: 1.29 [95% confidence interval (CI) 0.78-2.13], 0.54 [0.49-0.59], 0.60 [0.56-0.64], and 0.75 [0.67-0.84]. At reproductive age, females were more likely than males to have a return of spontaneous circulation [adjusted odds ratio (OR) 1.60 (1.27-2.02)], to be alive at hospital admission [OR: 1.49 (1.18-1.89)]. In both sexes, patients aged 13-50 years were more likely to survive at hospital discharge than those aged 50-75 years [males: OR 1.81 (1.49-2.20), females: 2.24 (1.54-3.25)]. However, at reproductive age, no sex disparity was observed in survival at hospital discharge [OR: 1.16 (0.75-1.80)]. CONCLUSION: Incidence rate ratios were similar between pre- and post-menopausal aged patients. At reproductive age, no sex disparity in survival at hospital discharge was observed, suggesting that menopausal status may not influence OHCA occurrence and prognosis.

Evolution of Incidence, Management, and Outcomes Over Time in Sports-Related Sudden Cardiac Arrest.

BACKGROUND: Major efforts have been made to reduce the burden of sports-related sudden cardiac arrest (SrSCA). The extent to which the incidence, management, and outcomes changed over time has not been investigated. OBJECTIVES: The purpose of this study was to assess temporal trends in SrSCA incidence, management, and survival. METHODS: Using data from the French National Institute of Health and Medical Research, we evaluated the evolution of incidence, prehospital management, and survival at hospital discharge of SrSCA among subjects aged 18 to 75 years, over 6 successive 2-year periods between 2005 and 2018. RESULTS: Among the 377 SrSCA, 20 occurred in young competitive athletes (5.3%), whereas 94.7% occurred in middle-aged recreational sports participants. Comparing the last 2-year to the first 2-year period, SrSCA incidence remained stable (6.24 vs 7.00 per million inhabitants/y; P = 0.51), with no significant differences in patients' mean age (46.6 ± 13.8 years vs 51.0 ± 16.4 years; P = 0.42), sex (men 94.7% vs 95.2%; P = 0.99), and history of heart disease (12.5% vs 15.9%; P = 0.85). However, frequency of bystander cardiopulmonary resuscitation and public automated external defibrillator use increased significantly (34.9% vs 94.7%; P < 0.001 and 1.6% vs 28.8%; P = 0.006, respectively). Survival to hospital discharge improved steadily, reaching 66.7% in the last study period compared with 23.8% in the first (P < 0.001). CONCLUSIONS: Incidence of SrSCA remained relatively stable over time, suggesting a need for improvement in screening strategies. However, major improvements in on-field resuscitation led to a 3-fold increase in survival, underlining the value of public education in basic life support that should serve as an example for SCA in general.

Incidence and factors associated with out-of-hospital peri-intubation cardiac arrest: a secondary analysis of the CURASMUR trial.

The Incidence of peri-intubation cardiac arrest (PICA) has been rarely assessed in the out-of-hospital setting. The objectives of this study were to assess the incidence and factors associated with PICA (cardiac arrest occurring within 15 min of intubation) in an out-of-hospital emergency setting, wherein emergency physicians perform standardized airway management using a rapid sequence intubation technique in adult patients. This was a secondary analysis of the "Succinylcholine versus Rocuronium for out-of-hospital emergency intubation" (CURASMUR) trial, which compared the first attempt intubation success rate between succinylcholine and rocuronium in adult patients requiring emergency tracheal intubation for any vital distress except cardiac arrest. Enrollment occurred from January 2014 to August 2016 in 17 French out-of-hospital emergency medical units. All operators were emergency physicians. The PICA incidence was recorded and multivariable logistic regression analysis was used to identify the factors associated with its occurrence. A total of 1226 patients were included with a mean age of 55.9 ± 19 years. PICA was recorded in 35 (2.8%) patients. Multivariable analysis indicated that the occurrence of PICA was independently associated with a body mass index (BMI) > 30 kg m2 [adjusted odds ratio (aOR) 4.85; 95% confidence interval (CI) 1.82-12.90, p = 0.02], oxygen saturation (SpO2) before intubation < 90% (aOR 3.4; 95% CI 1.50-7.60, p = 0.003), difficult intubation (defined by an Intubation Difficulty Score [IDS] > 5, [aOR 3.59; 95% CI 1.82-8.08, p = 0.02], the use of rocuronium instead of succinylcholine (aOR 2.47; 95% CI 1.08-5.64, p = 0.03), post intubation hypoxaemia (aOR 2.70; 95% CI 1.05-6.95, p = 0.04), post-intubation hypotension (aOR 4.07; 95% CI 1.62-10.22, p = 0.003), and pulmonary aspiration(aOR 4.78; 95% CI 1.48-15.36, p = 0.009). Early PICA occurred in approximately 3% of cases in the out-of-hospital setting. We identified several independent risk factors for PICA, including obesity, hypoxaemia before intubation and difficult intubation.

Incidence, Complications, and Factors Associated with Out-of-Hospital First Attempt Intubation Failure in Adult Patients: A Secondary Analysis of the CURASMUR Trial Data.

Objectives: The objectives of this study were to evaluate first attempt intubation failure rate, its associated factors, and its related complications in out-of-hospital emergency setting, when emergency physicians perform standardized airway management using rapid sequence intubation in adult patients. Material and methods: The present study was a substudy of the Succinylcholine versus Rocuronium for out-of-hospital Emergency Intubation (CURASMUR) Trial, which compared Succinylcholine and Rocuronium used for Rapid sequence intubation. First attempt Intubation failure rate and early intubation related complications were recorded. We used multivariable logistic regression analysis to determine first intubation failure associated factors. Results: A total of 1230 patients were included with mean age of 55.9 +/- 19 years. First attempt intubation failure was recorded in 285 (23.2%) patients. The occurrence of a first attempt intubation failure was independently associated with history of ear, nose, and throat neoplasia (OR 2.20, CI 95% 1.06-4.60). Early intubation related complications were more frequent in case of first attempt intubation failure: 80 of 285 (28.4%) in patients with first attempt intubation failure and 185 of 945 (19.6%) in patients with successful first attempt intubation [OR 1.44; CI 95%, 1.11-1.87]. Conclusion: Based on a large multicenter study on out-of-hospital tracheal intubation of adult patients, we found that first attempt intubation failure rate was high and that history of ear, nose, and throat (ENT) neoplasia was an independent associated factor. Failure in first intubation attempt was associated with significantly more intubation related complications.

Temporal Trends of Out-of-Hospital Cardiac Arrests Without Resuscitation Attempt by Emergency Medical Services.

BACKGROUND: Significant improvements in survival from out-of-hospital cardiac arrest (OHCA) have been reported; however, these are based only on data from OHCA in whom resuscitation is initiated by emergency medical services (EMS). We aimed to assess the characteristics and temporal trends of OHCA without resuscitation attempt by EMS. METHODS: Prospective population-based study between 2011 and 2016 in the Greater Paris area (6.7 million inhabitants). All cases of OHCA were included in collaboration with EMS units, 48 different hospitals, and forensic units. RESULTS: Among 15 207 OHCA (mean age 70.7±16.9 years, 61.6% male), 5486 (36.1%) had no resuscitation attempt by EMS. Factors that were independently associated with increase in likelihood of no resuscitation attempt included: age of patients (odds ratio, 1.06 per year [95% CI, 1.05-1.06], P<0.001), female sex (odds ratio, 1.21 [95% CI, 1.10-1.32], P=0.002), OHCA at home location (odds ratio, 3.38 [95%CI, 2.86-4.01], P<0.001), and absence of bystander (odds ratio, 1.94 [95% CI, 1.74-2.16], P<0.001). Overall, the annual number of OHCA increased by 9.1% (from 2923 to 3189, P=0.028). This increase was related to an increase of the annual number of OHCA without resuscitation attempt by EMS by 26.3% (from 993 to 1253, P=0.012), while the annual number of OHCA with resuscitation attempt by EMS did not significantly change (from 1930 to 1936, P=0.416). Considering only cases with resuscitation attempt, survival rate at hospital discharge increased (from 7.3% to 9.5%, P=0.02). However, when considering all OHCA, survival improvement did not reach statistical significance (from 4.8% to 5.7%, P=0.17). CONCLUSIONS: We demonstrated an increase of the total number of OHCA related to an increase of the number of OHCA without resuscitation attempt by EMS. This increasing proportion of OHCA without resuscitation attempt attenuates improvement in survival rates achieved in EMS-treated patients.

COVID-19-related medical research: a meta-research and critical appraisal.

BACKGROUND: Since the start of the COVID-19 outbreak, a large number of COVID-19-related papers have been published. However, concerns about the risk of expedited science have been raised. We aimed at reviewing and categorizing COVID-19-related medical research and to critically appraise peer-reviewed original articles. METHODS: The data sources were Pubmed, Cochrane COVID-19 register study, arXiv, medRxiv and bioRxiv, from 01/11/2019 to 01/05/2020. Peer-reviewed and preprints publications related to COVID-19 were included, written in English or Chinese. No limitations were placed on study design. Reviewers screened and categorized studies according to i) publication type, ii) country of publication, and iii) topics covered. Original articles were critically appraised using validated quality assessment tools. RESULTS: Among the 11,452 publications identified, 10,516 met the inclusion criteria, among which 7468 (71.0%) were peer-reviewed articles. Among these, 4190 publications (56.1%) did not include any data or analytics (comprising expert opinion pieces). Overall, the most represented topics were infectious disease (n = 2326, 22.1%), epidemiology (n = 1802, 17.1%), and global health (n = 1602, 15.2%). The top five publishing countries were China (25.8%), United States (22.3%), United Kingdom (8.8%), Italy (8.1%) and India (3.4%). The dynamic of publication showed that the exponential growth of COVID-19 peer-reviewed articles was mainly driven by publications without original data (mean 261.5 articles ± 51.1 per week) as compared with original articles (mean of 69.3 ± 22.3 articles per week). Original articles including patient data accounted for 713 (9.5%) of peer-reviewed studies. A total of 576 original articles (80.8%) showed intermediate to high risk of bias. Last, except for simulation studies that mainly used large-scale open data, the median number of patients enrolled was of 102 (IQR = 37-337). CONCLUSIONS: Since the beginning of the COVID-19 pandemic, the majority of research is composed by publications without original data. Peer-reviewed original articles with data showed a high risk of bias and included a limited number of patients. Together, these findings underscore the urgent need to strike a balance between the velocity and quality of research, and to cautiously consider medical information and clinical applicability in a pressing, pandemic context. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/5zjyx/.

Effect of Rocuronium vs Succinylcholine on Endotracheal Intubation Success Rate Among Patients Undergoing Out-of-Hospital Rapid Sequence Intubation: A Randomized Clinical Trial.

Importance: Rocuronium and succinylcholine are often used for rapid sequence intubation, although the comparative efficacy of these paralytic agents for achieving successful intubation in an emergency setting has not been evaluated in clinical trials. Succinylcholine use has been associated with several adverse events not reported with rocuronium. Objective: To assess the noninferiority of rocuronium vs succinylcholine for tracheal intubation in out-of-hospital emergency situations. Design, Setting and Participants: Multicenter, single-blind, noninferiority randomized clinical trial comparing rocuronium (1.2 mg/kg) with succinylcholine (1 mg/kg) for rapid sequence intubation in 1248 adult patients needing out-of-hospital tracheal intubation. Enrollment occurred from January 2014 to August 2016 in 17 French out-of-hospital emergency medical units. The date of final follow-up was August 31, 2016. Interventions: Patients were randomly assigned to undergo tracheal intubation facilitated by rocuronium (n = 624) or succinylcholine (n = 624). Main Outcomes and Measures: The primary outcome was the intubation success rate on first attempt. A noninferiority margin of 7% was chosen. A per-protocol analysis was prespecified as the primary analysis. Results: Among 1248 patients who were randomized (mean age, 56 years; 501 [40.1%] women), 1230 (98.6%) completed the trial and 1226 (98.2%) were included in the per-protocol analysis. The number of patients with successful first-attempt intubation was 455 of 610 (74.6%) in the rocuronium group vs 489 of 616 (79.4%) in the succinylcholine group, with a between-group difference of -4.8% (1-sided 97.5% CI, -9% to ∞), which did not meet criteria for noninferiority. The most common intubation-related adverse events were hypoxemia (55 of 610 patients [9.0%]) and hypotension (39 of 610 patients [6.4%]) in the rocuronium group and hypoxemia (61 of 616 [9.9%]) and hypotension (62 of 616 patients [10.1%]) in the succinylcholine group. Conclusions and Relevance: Among patients undergoing endotracheal intubation in an out-of-hospital emergency setting, rocuronium, compared with succinylcholine, failed to demonstrate noninferiority with regard to first-attempt intubation success rate. Trial Registration: ClinicalTrials.gov Identifier: NCT02000674.

Correction: Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1002572.].

Interventions for necrotizing soft tissue infections in adults.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are severe and rapidly spreading soft tissue infections of the subcutaneous tissue, fascia, or muscle, which are mostly caused by bacteria. Associated rates of mortality and morbidity are high, with the former estimated at around 23%, and disability, sequelae, and limb loss occurring in 15% of patients. Standard management includes intravenous empiric antimicrobial therapy, early surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies such as intravenous immunoglobulin (IVIG). OBJECTIVES: To assess the effects of medical and surgical treatments for necrotizing soft tissue infections (NSTIs) in adults in hospital settings. SEARCH METHODS: We searched the following databases up to April 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers, pharmaceutical company trial results databases, and the US Food and Drug Administration and the European Medicines Agency websites. We checked the reference lists of included studies and reviews for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs conducted in hospital settings, that evaluated any medical or surgical treatment for adults with NSTI were eligible for inclusion. Eligible medical treatments included 1) comparisons between different antimicrobials or with placebo; 2) adjuvant therapies such as intravenous immunoglobulin (IGIV) therapy compared with placebo; no treatment; or other adjuvant therapies. Eligible surgical treatments included surgical debridement compared with amputation, immediate versus delayed intervention, or comparisons of number of interventions.RCTs of hyperbaric oxygen (HBO) therapy for NSTI were ineligible because HBO is the focus of another Cochrane Review. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome measures were 1) mortality within 30 days, and 2) proportion of participants who experience a serious adverse event. Secondary outcomes were 1) survival time, and 2) assessment of long-term morbidity. We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: We included three trials randomising 197 participants (62% men) who had a mean age of 55 years. One trial compared two antibiotic treatments, and two trials compared adjuvant therapies with placebo. In all trials, participants concomitantly received standard interventions, such as intravenous empiric antimicrobial therapy, surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies. All trials were at risk of attrition bias and one trial was not blinded.Moxifloxacin versus amoxicillin-clavulanate One trial included 54 participants who had a NSTI; it compared a third-generation quinolone, moxifloxacin, at a dose of 400 mg given once daily, against a penicillin, amoxicillin-clavulanate, at a dose of 3 g given three times daily for at least three days, followed by 1.5 g three times daily. Duration of treatment varied from 7 to 21 days. We are uncertain of the effects of these treatments on mortality within 30 days (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.39 to 23.07) and serious adverse events at 28 days (RR 0.63, 95% CI 0.30 to 1.31) because the quality of the evidence is very low.AB103 versus placebo One trial of 43 randomised participants compared two doses, 0.5 mg/kg and 0.25 mg/kg, of an adjuvant drug, a CD28 antagonist receptor (AB103), with placebo. Treatment was given via infusion pump for 10 minutes before, after, or during surgery within six hours after the diagnosis of NSTI. We are uncertain of the effects of AB103 on mortality rate within 30 days (RR of 0.34, 95% CI 0.05 to 2.16) and serious adverse events measured at 28 days (RR 1.49, 95% CI 0.52 to 4.27) because the quality of the evidence is very low.Intravenous immunoglobulin (IVIG) versus placebo One trial of 100 randomised participants assessed IVIG as an adjuvant drug, given at a dose of 25 g/day, compared with placebo, given for three consecutive days. There may be no clear difference between IVIG and placebo in terms of mortality within 30 days (RR 1.17, 95% CI 0.42 to 3.23) (low-certainty evidence), nor serious adverse events experienced in the intensive care unit (ICU) (RR 0.73 CI 95% 0.32 to 1.65) (low-certainty evidence).Serious adverse events were only described in one RCT (the IVIG versus placebo trial) and included acute kidney injury, allergic reactions, aseptic meningitis syndrome, haemolytic anaemia, thrombi, and transmissible agents.Only one trial reported assessment of long-term morbidity, but the outcome was not defined in the way we prespecified in our protocol. The trial used the Short Form Health Survey (SF36). Data on survival time were provided upon request for the trials comparing amoxicillin-clavulanate versus moxifloxacin and IVIG versus placebo. However, even with data provided, it was not possible to perform survival analysis. AUTHORS' CONCLUSIONS: We found very little evidence on the effects of medical and surgical treatments for NSTI. We cannot draw conclusions regarding the relative effects of any of the interventions on 30-day mortality or serious adverse events due to the very low quality of the evidence.The quality of the evidence is limited by the very small number of trials, the small sample sizes, and the risks of bias in the included trials. It is important for future trials to clearly define their inclusion criteria, which will help with the applicability of future trial results to a real-life population.Management of NSTI participants (critically-ill participants) is complex, involving multiple interventions; thus, observational studies and prospective registries might be a better foundation for future research, which should assess empiric antimicrobial therapy, as well as surgical debridement, along with the placebo-controlled comparison of adjuvant therapy. Key outcomes to assess include mortality (in the acute phase of the condition) and long-term functional outcomes, e.g. quality of life (in the chronic phase).

Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis.

BACKGROUND: Anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are recognized as a major barrier to patients' access to organ transplantation and the major cause of graft failure. The capacity of circulating anti-HLA DSAs to activate complement has been suggested as a potential biomarker for optimizing graft allocation and improving the rate of successful transplantations. METHODS AND FINDINGS: To address the clinical relevance of complement-activating anti-HLA DSAs across all solid organ transplant patients, we performed a meta-analysis of their association with transplant outcome through a systematic review, from inception to January 31, 2018. The primary outcome was allograft loss, and the secondary outcome was allograft rejection. A comprehensive search strategy was conducted through several databases (Medline, Embase, Cochrane, and Scopus). A total of 5,861 eligible citations were identified. A total of 37 studies were included in the meta-analysis. Studies reported on 7,936 patients, including kidney (n = 5,991), liver (n = 1,459), heart (n = 370), and lung recipients (n = 116). Solid organ transplant recipients with circulating complement-activating anti-HLA DSAs experienced an increased risk of allograft loss (pooled HR 3.09; 95% CI 2.55-3.74, P = 0.001; I2 = 29.3%), and allograft rejection (pooled HR 3.75; 95% CI: 2.05-6.87, P = 0.001; I2 = 69.8%) compared to patients without complement-activating anti-HLA DSAs. The association between circulating complement-activating anti-HLA DSAs and allograft failure was consistent across all subgroups and sensitivity analyses. Limitations of the study are the observational and retrospective design of almost all included studies, the higher proportion of kidney recipients compared to other solid organ transplant recipients, and the inclusion of fewer studies investigating allograft rejection. CONCLUSIONS: In this study, we found that circulating complement-activating anti-HLA DSAs had a significant deleterious impact on solid organ transplant survival and risk of rejection. The detection of complement-activating anti-HLA DSAs may add value at an individual patient level for noninvasive biomarker-guided risk stratification. TRIAL REGISTRATION: National Clinical Trial protocol ID: NCT03438058.

Effect of Bag-Mask Ventilation vs Endotracheal Intubation During Cardiopulmonary Resuscitation on Neurological Outcome After Out-of-Hospital Cardiorespiratory Arrest: A Randomized Clinical Trial.

Importance: Bag-mask ventilation (BMV) is a less complex technique than endotracheal intubation (ETI) for airway management during the advanced cardiac life support phase of cardiopulmonary resuscitation of patients with out-of-hospital cardiorespiratory arrest. It has been reported as superior in terms of survival. Objectives: To assess noninferiority of BMV vs ETI for advanced airway management with regard to survival with favorable neurological function at day 28. Design, Settings, and Participants: Multicenter randomized clinical trial comparing BMV with ETI in 2043 patients with out-of-hospital cardiorespiratory arrest in France and Belgium. Enrollment occurred from March 9, 2015, to January 2, 2017, and follow-up ended January 26, 2017. Intervention: Participants were randomized to initial airway management with BMV (n = 1020) or ETI (n = 1023). Main Outcomes and Measures: The primary outcome was favorable neurological outcome at 28 days defined as cerebral performance category 1 or 2. A noninferiority margin of 1% was chosen. Secondary end points included rate of survival to hospital admission, rate of survival at day 28, rate of return of spontaneous circulation, and ETI and BMV difficulty or failure. Results: Among 2043 patients who were randomized (mean age, 64.7 years; 665 women [32%]), 2040 (99.8%) completed the trial. In the intention-to-treat population, favorable functional survival at day 28 was 44 of 1018 patients (4.3%) in the BMV group and 43 of 1022 patients (4.2%) in the ETI group (difference, 0.11% [1-sided 97.5% CI, -1.64% to infinity]; P for noninferiority = .11). Survival to hospital admission (294/1018 [28.9%] in the BMV group vs 333/1022 [32.6%] in the ETI group; difference, -3.7% [95% CI, -7.7% to 0.3%]) and global survival at day 28 (55/1018 [5.4%] in the BMV group vs 54/1022 [5.3%] in the ETI group; difference, 0.1% [95% CI, -1.8% to 2.1%]) were not significantly different. Complications included difficult airway management (186/1027 [18.1%] in the BMV group vs 134/996 [13.4%] in the ETI group; difference, 4.7% [95% CI, 1.5% to 7.9%]; P = .004), failure (69/1028 [6.7%] in the BMV group vs 21/996 [2.1%] in the ETI group; difference, 4.6% [95% CI, 2.8% to 6.4%]; P < .001), and regurgitation of gastric content (156/1027 [15.2%] in the BMV group vs 75/999 [7.5%] in the ETI group; difference, 7.7% [95% CI, 4.9% to 10.4%]; P < .001). Conclusions and Relevance: Among patients with out-of-hospital cardiorespiratory arrest, the use of BMV compared with ETI failed to demonstrate noninferiority or inferiority for survival with favorable 28-day neurological function, an inconclusive result. A determination of equivalence or superiority between these techniques requires further research. Trial Registration: clinicaltrials.gov Identifier: NCT02327026.

Impact of neighbourhood socio-economic status on bystander cardiopulmonary resuscitation in Paris.

BACKGROUND: No European data currently describe the relation between neighbourhood socio-economic status (SES) and rates of out-of-hospital cardiac arrest (OHCA) bystander cardiopulmonary resuscitation (CPR). This study aims to analyse this effect with a robust deprivation index. METHODS: Data about all OHCA in Paris were collected prospectively between 2000 and 2010. A geographical neighbourhood unit was assigned to each case. Median household income, and rates of blue-collar workers, unemployment, and adults without high school diplomas were selected as SES characteristics and used to classify neighbourhoods as low SES or higher SES. We analysed the relationship between neighbourhood SES characteristics and the probability of receiving bystander CPR. RESULTS: Of the 4009 OHCA with mappable addresses recorded, 777 (19.4%) received bystander CPR. Compared to OHCA who did not receive bystander CPR, those receiving CPR were significantly more likely to have occurred in public locations, have had a witness to their OHCA, and not to have collapsed in a low SES neighbourhood, or in a neighbourhood with a median household income in the lowest quartile and with rates of no high school diplomas and blue-collar workers in the highest quartile. In the multilevel analyses, bystander CPR provision was significantly less frequent in low than in higher SES neighbourhoods (OR 0.85; 95% confidence interval [CI] 0.72-0.99). CONCLUSION: In the city of Paris, OHCA victims were less likely to receive bystander CPR in low SES neighbourhoods. These first European data are consistent with observations in North America and Asia.

Optimization of automated external defibrillator deployment outdoors: An evidence-based approach.

BACKGROUND: The benefits of available automatic external defibrillators (AEDs) for out-of-hospital cardiac arrests (OHCAs) are well known, but strategies for their deployment outdoors remain somewhat arbitrary. Our study sought to assess different strategies for AED deployment. METHODS: All OHCAs in Paris between 2000 and 2010 were prospectively recorded and geocoded. A guidelines-based strategy of placing an AED in locations where more than one OHCA had occurred within the past five years was compared to two novel strategies: a grid-based strategy with a regular distance between AEDs and a landmark-based strategy. The expected number of AEDs necessary and their median (IQR) distance to the nearest OHCA were assessed for each strategy. RESULTS: Of 4176 OHCAs, 1372 (33%) occurred in public settings. The first strategy would result in the placement of 170 AEDs, with a distance to OHCA of 416 (180-614) m and a continuous increase in the number of AEDS. In the second strategy, the number of AEDs and their distance to the closest OHCA would change with the grid size, with a number of AEDs between 200 and 400 seeming optimal. In the third strategy, median distances between OHCAs and AEDs would be 324m if placed at post offices (n=195), 239 at subway stations (n=302), 137 at bike-sharing stations (n=957), and 142 at pharmacies (n=1466). CONCLUSION: This study presents an original evidence-based approach to strategies of AED deployment to optimize their number and location. This rational approach can estimate the optimal number of AEDs for any city.