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The Cochrane Database of Systematic... Jan 2022Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with... (Review)
Review
BACKGROUND
Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. Treatment options for MMN are few. People with MMN do not usually respond to steroids or plasma exchange. Uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin (IVIg). This is an update of a Cochrane Review first published in 2005, with an amendment in 2007. We updated the review to incorporate new evidence.
OBJECTIVES
To assess the efficacy and safety of intravenous and subcutaneous immunoglobulin in people with MMN.
SEARCH METHODS
We searched the following databases on 20 April 2021: the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP for randomised controlled trials (RCTs) and quasi-RCTs, and checked the reference lists of included studies.
SELECTION CRITERIA
We considered RCTs and quasi-RCTs examining the effects of any dose of IVIg and subcutaneous immunoglobulin (SCIg) in people with definite or probable MMN for inclusion in the review. Eligible studies had to have measured at least one of the following outcomes: disability, muscle strength, or electrophysiological conduction block. We used studies that reported the frequency of adverse effects to assess safety.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the literature searches to identify potentially relevant trials, assessed risk of bias of included studies, and extracted data. We followed standard Cochrane methodology.
MAIN RESULTS
Six cross-over RCTs including a total of 90 participants were suitable for inclusion in the review. Five RCTs compared IVIg to placebo, and one compared IVIg to SCIg. Four of the trials comparing IVIg versus placebo involved IVIg-naive participants (induction treatment). In the other two trials, participants were known IVIg responders receiving maintencance IVIg at baseline and were then randomised to maintenance treatment with IVIg or placebo in one trial, and IVIg or SCIg in the other. Risk of bias was variable in the included studies, with three studies at high risk of bias in at least one risk of bias domain. IVIg versus placebo (induction treatment): three RCTs including IVIg-naive participants reported a disability measure. Disability improved in seven out of 18 (39%) participants after IVIg treatment and in two out of 18 (11%) participants after placebo (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.89 to 10.12; 3 RCTs, 18 participants; low-certainty evidence). The proportion of participants with an improvement in disability at 12 months was not reported. Strength improved in 21 out of 27 (78%) IVIg-naive participants treated with IVIg and one out of 27 (4%) participants who received placebo (RR 11.00, 95% CI 2.86 to 42.25; 3 RCTs, 27 participants; low-certainty evidence). IVIg treatment may increase the proportion of people with resolution of at least one conduction block; however, the results were also consistent with no effect (RR 7.00, 95% CI 0.95 to 51.70; 4 RCTs, 28 participants; low-certainty evidence). IVIg versus placebo (maintenance treatment): a trial that included participants on maintenance IVIg treatment reported an increase in disability in 17 out of 42 (40%) people switching to placebo and seven out of 42 (17%) remaining on IVIg (RR 2.43, 95% CI 1.13 to 5.24; 1 RCT, 42 participants; moderate-certainty evidence) and a decrease in grip strength in 20 out of 42 (48%) participants after a switch to placebo treatment compared to four out of 42 (10%) remaining on IVIg (RR 0.20, 95% CI 0.07 to 0.54; 1 RCT, 42 participants; moderate-certainty evidence). Adverse events, IVIg versus placebo (induction or maintenance): four trials comparing IVIg and placebo reported adverse events, of which data from two studies could be meta-analysed. Transient side effects were reported in 71% of IVIg-treated participants versus 4.8% of placebo-treated participants in these studies. The pooled RR for the development of side effects was 10.33 (95% CI 2.15 to 49.77; 2 RCTs, 21 participants; very low-certainty evidence). There was only one serious side effect (pulmonary embolism) during IVIg treatment. IVIg versus SCIg (maintenance treatment): the trial that compared continuation of IVIg maintenance versus SCIg maintenance did not measure disability. The evidence was very uncertain for muscle strength (standardised mean difference 0.08, 95% CI -0.84 to 1.00; 1 RCT, 9 participants; very low-certainty evidence). The evidence was very uncertain for the number of people with side effects attributable to treatment (RR 0.50, 95% CI 0.18 to 1.40; 1 RCT, 9 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Low-certainty evidence from three small RCTs shows that IVIg may improve muscle strength in people with MMN, and low-certainty evidence indicates that it may improve disability; the estimate of the magnitude of improvement of disability has wide CIs and needs further studies to secure its significance. Based on moderate-certainty evidence, it is probable that most IVIg responders deteriorate in disability and muscle strength after IVIg withdrawal. SCIg might be an alternative treatment to IVIg, but the evidence is very uncertain. More research is needed to identify people in whom IVIg withdrawal is possible and to confirm efficacy of SCIg as an alternative maintenance treatment.
Topics: Humans; Immunoglobulins, Intravenous; Plasma Exchange; Polyneuropathies; Randomized Controlled Trials as Topic
PubMed: 35015296
DOI: 10.1002/14651858.CD004429.pub3 -
Alimentary Pharmacology & Therapeutics Aug 2023We conducted a systematic review to assess medical therapy for the treatment and prevention of pouchitis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
We conducted a systematic review to assess medical therapy for the treatment and prevention of pouchitis.
METHODS
Randomised controlled trials (RCTs) of medical therapy in adults with or without pouchitis were searched to March 2022. Primary outcomes included clinical remission/response, maintenance of remission and prevention of pouchitis.
RESULTS
Twenty RCTs (N = 830) were included. Acute pouchitis: One study compared ciprofloxacin with metronidazole. At 2 weeks, 100% (7/7) of ciprofloxacin participants achieved remission, compared with 67% (6/9) of metronidazole participants (RR: 1.44, 95% CI: 0.88-2.35, very low certainty evidence). One study compared budesonide enemas with oral metronidazole. Fifty percent (6/12) of budesonide participants achieved remission compared with 43% (6/14) of metronidazole participants (RR: 1.17, 95% CI: 0.51-2.67, low certainty evidence). Chronic pouchitis: Two studies (n = 76) assessed De Simone Formulation. Eighty-five percent (34/40) of De Simone Formulation participants maintained remission at 9-12 months compared with 3% (1/36) placebo participants (RR: 18.50, 95% CI: 3.86-88.56, moderate certainty evidence). One study assessed vedolizumab. Thirty-one percent (16/51) of vedolizumab participants achieved clinical remission at 14 weeks compared with 10% (5/51) of placebo participants (RR: 3.20, 95% CI: 1.27-8.08, moderate certainty evidence).
PROPHYLAXIS
Two studies assessed De Simone Formulation. Ninety percent (18/20) of De Simone Formulation participants did not develop pouchitis compared with 60% (12/20) of placebo participants (RR: 1.50, 95% CI: 1.02-2.21, moderate certainty evidence).
CONCLUSIONS
Apart from vedolizumab and the De Simone formulation, the effects of other medical interventions for pouchitis are uncertain.
Topics: Adult; Humans; Metronidazole; Remission Induction; Pouchitis; Ciprofloxacin; Budesonide; Randomized Controlled Trials as Topic
PubMed: 37246609
DOI: 10.1111/apt.17568 -
Future Oncology (London, England) Sep 2022To review safety and efficacy outcomes in studies of first-line maintenance therapies for advanced ovarian cancer. A systematic literature review was performed (27... (Review)
Review
To review safety and efficacy outcomes in studies of first-line maintenance therapies for advanced ovarian cancer. A systematic literature review was performed (27 February 2020) to identify clinical outcomes including progression-free survival (PFS), overall survival (OS) and Grade ≥3 adverse events. Overall 50 references met prespecified criteria; 18 studies evaluated 10 different agents, including PARP inhibitors. PFS was an end point in 16 trials and OS in 12 trials. PARP inhibitors reported better PFS hazard ratios (HRs: 0.59-0.68) compared with other classes; no mature OS data were identified. Safety reporting was inconsistent. Reported PFS HRs were better for PARP inhibitors than for other ovarian cancer maintenance therapies; overall survival data remain immature.
Topics: Humans; Female; Poly(ADP-ribose) Polymerase Inhibitors; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Progression-Free Survival
PubMed: 36102225
DOI: 10.2217/fon-2022-0578 -
Nordic Journal of Psychiatry Aug 2022To perform a systematic review on the use of maintenance treatment to prevent relapse and recurrence in patients with psychotic unipolar or bipolar depression. (Meta-Analysis)
Meta-Analysis
PURPOSE
To perform a systematic review on the use of maintenance treatment to prevent relapse and recurrence in patients with psychotic unipolar or bipolar depression.
METHODS
We conducted an electronic search in December 2019 (and an updated search in July 2021) of four databases (PubMed, Embase, PsycINFO, and Cochrane) to identify controlled studies comparing the relapse rates of patients receiving maintenance treatment for psychotic unipolar depression and psychotic bipolar depression. A meta-analysis was made that included three studies comparing antidepressant (AD) and antipsychotic (AP) combination therapy with AD monotherapy. We used the GRADE tool to assess the quality of evidence.
RESULTS
We included five randomized controlled trials fulfilling the inclusion criteria, making three comparisons: (a) AD + AP versus AD monotherapy; (b) AD + AP versus AP monotherapy; (c) AD + electroconvulsive therapy versus AD monotherapy. The included studies only examined patients with psychotic unipolar depression. The largest included study reported a statistically significant advantage of AD + AP compared with AD monotherapy. We made a meta-analysis of the three studies comparing AD + AP combination therapy with AD monotherapy, which included 195 patients and 56 events. The meta-analysis did not show a statistically significant difference between these treatments.
CONCLUSIONS
Contrary to the finding of the largest study, we did not find a statistically significant difference between AD + AP combination therapy and AD monotherapy in the meta-analysis. There is insufficient evidence to support the superiority of any treatment modality as maintenance treatment for psychotic depression. Further studies are required.
Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Depression; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Recurrence
PubMed: 34665684
DOI: 10.1080/08039488.2021.1990997 -
Journal of Gastroenterology and... Apr 2023Patients with ulcerative proctitis have favorable long-term outcomes but are typically excluded from ulcerative colitis clinical trials. Refractory proctitis presents a... (Review)
Review
Patients with ulcerative proctitis have favorable long-term outcomes but are typically excluded from ulcerative colitis clinical trials. Refractory proctitis presents a management conundrum for gastroenterologists, and there remains a lack of clarity as to the best therapeutic strategy. This study aimed to undertake a systematic review of studies assessing the clinical efficacy and safety of therapies for refractory proctitis. PubMed, Embase, Cochrane Library, and MEDLINE databases were searched without restriction from inception to October 27, 2022. Both interventional and noninterventional studies examining efficacy of therapeutic modalities for the induction and/or maintenance of remission in refractory proctitis were included. Included studies were grouped by therapeutic modalities as follows: (i) immunomodulators, (ii) monoclonal antibodies, (iii) topical calcineurin inhibitors, (iv) other topical therapies, and (v) appendicectomy. The search strategy identified 3301 studies, of which 13 met eligibility criteria for inclusion. Clinical remission rates for systemic therapies ranged from 20-26% for azathioprine to 50-69% for tumor necrosis factor-α inhibitor therapies. The use of systemic therapies for proctitis raised safety concerns, with 22-37% of patients discontinuing therapies due to adverse effects across four retrospective cohort studies. Prospective clinical trials of topically applied tacrolimus demonstrated clinical remission rates of 42-46%, with a favorable safety profile. Substantial heterogeneity in study design precluded meta-analysis. Refractory ulcerative proctitis remains a neglected entity, with a dearth of prospective clinical trials to guide therapeutic decision-making. Current evidence supports a role for topically administered tacrolimus.
Topics: Humans; Colitis, Ulcerative; Tacrolimus; Prospective Studies; Retrospective Studies; Proctitis; Remission Induction
PubMed: 36644922
DOI: 10.1111/jgh.16111 -
Hematology (Amsterdam, Netherlands) Dec 2022Despite conspicuous advances in innovating novel drugs and combination regimens in multiple myeloma (MM) in recent decades, the most appropriate maintenance regimens... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite conspicuous advances in innovating novel drugs and combination regimens in multiple myeloma (MM) in recent decades, the most appropriate maintenance regimens after inductive therapy are still controversial and opaque.
OBJECTIVE
We aimed to identify the most effective maintenance treatment for newly diagnosed multiple myeloma (NDMM) patients via network meta-analysis.
METHOD
We searched PubMed, Embase, Cochrane Library, Scopus, and Google Scholars from inception to April, 2022. Odds ratios (ORs) were generated for dichotomous variants. The primary endpoint was overall survival (OS).
RESULTS
Eventually a total of 19 trials, including 11 treatments and 8337 patients, were included in this analysis. For OS, lenalidomide (OR ranged from 1.61 to 1.99) and daratumumab (OR ranged from 1.83 to 2.41) showed significant efficacy over placebo. Maintenance therapy comprising lenalidomide-carfilzomib (OR ranged from 3.19 to 6.95), lenalidomide-prednisone (OR ranged from 2.62 to 4.44), bortezomib-thalidomide (OR ranged from 2.48 to 3.64), daratumumab (OR ranged from 2.0 to 2.98), lenalidomide (OR ranged from 1.4 to 3.19), ixazomib (OR ranged from 1.36 to 2.05), thalidomide (OR ranged from 1.5 to 1.86) demonstrated significant effects in prolongin PFS compared with placebo; Among the efficient therapies, lenalidomide-carfilzomib was significantly superior to lenalidomide (OR ranged from 2.18 to 2.20), daratumumab (OR ranged from 1.49 to 2.66) and ixazomib (OR ranged from 2.75 to 3.57).
CONCLUSION
Considering OS and PFS, lenalidomide-carfilzomib should be recommended as the best therapy. In clinical practice, this must be weighed against the increased risk of adverse events and financial burden. However, more head-to-head studies are needed to confirm these findings.
Topics: Antineoplastic Combined Chemotherapy Protocols; Boron Compounds; Bortezomib; Glycine; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Prednisone; Thalidomide
PubMed: 36125238
DOI: 10.1080/16078454.2022.2121900 -
Herbal medicines for insomnia through regulating 5-hydroxytryptamine receptors: a systematic review.Chinese Journal of Natural Medicines Jul 2023Insomnia is a common sleep disorder without effective therapy and can affect a person's life. The mechanism of the disease is not completely understood. Hence, there is... (Review)
Review
Insomnia is a common sleep disorder without effective therapy and can affect a person's life. The mechanism of the disease is not completely understood. Hence, there is a need to understand the targets related to insomnia, in order to develop innovative therapies and new compounds. Recently, increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia. Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain. In this review, the role of 5-hydroxytryptamine (5-HT) in insomnia development is summarized, while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes, in order to provide reference for subsequent research.
Topics: Sleep Initiation and Maintenance Disorders; Plants, Medicinal; Receptors, Serotonin; Serotonin; Sleep; Humans; Animals
PubMed: 37517817
DOI: 10.1016/S1875-5364(23)60405-4 -
European Journal of Preventive... Oct 2023To provide a quantitative analysis of eHealth-supported interventions on health outcomes in cardiovascular rehabilitation (CR) maintenance (phase III) in patients with... (Meta-Analysis)
Meta-Analysis
AIMS
To provide a quantitative analysis of eHealth-supported interventions on health outcomes in cardiovascular rehabilitation (CR) maintenance (phase III) in patients with coronary artery disease (CAD) and to identify effective behavioural change techniques (BCTs).
METHODS AND RESULTS
A systematic review was conducted (PubMed, CINAHL, MEDLINE, and Web of Science) to summarize and synthesize the effects of eHealth in phase III maintenance on health outcomes including physical activity (PA) and exercise capacity, quality of life (QoL), mental health, self-efficacy, clinical variables, and events/rehospitalization. A meta-analysis following the Cochrane Collaboration guidelines using Review Manager (RevMan5.4) was performed. Analyses were conducted differentiating between short-term (≤6 months) and medium/long-term effects (>6 months). Effective behavioural change techniques were defined based on the described intervention and coded according to the BCT handbook. Fourteen eligible studies (1497 patients) were included. eHealth significantly promoted PA (SMD = 0.35; 95%CI 0.02-0.70; P = 0.04) and exercise capacity after 6 months (SMD = 0.29; 95%CI 0.05-0.52; P = 0.02) compared with usual care. Quality of life was higher with eHealth compared with care as usual (SMD = 0.17; 95%CI 0.02-0.32; P = 0.02). Systolic blood pressure decreased after 6 months with eHealth compared with care as usual (SMD = -0.20; 95%CI -0.40-0.00; P = 0.046). There was substantial heterogeneity in the adapted BCTs and type of intervention. Mapping of BCTs revealed that self-monitoring of behaviour and/or goal setting as well as feedback on behaviour were most frequently included.
CONCLUSION
eHealth in phase III CR is effective in stimulating PA and improving exercise capacity in patients with CAD while increasing QoL and decreasing systolic blood pressure. Currently, data of eHealth effects on morbidity, mortality, and clinical outcomes are scarce and should be investigated in future studies.
REGISTRATION
PROSPERO: CRD42020203578.
Topics: Humans; Cardiac Rehabilitation; Quality of Life; Exercise; Coronary Artery Disease; Telemedicine
PubMed: 37154363
DOI: 10.1093/eurjpc/zwad145 -
The Cochrane Database of Systematic... Jul 2023Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease.
OBJECTIVES
To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 30 November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years. Vedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence). Vedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.
Topics: Humans; Adult; Crohn Disease; Antibodies, Monoclonal, Humanized; Colitis, Ulcerative; Inflammatory Bowel Diseases; Remission Induction
PubMed: 37458279
DOI: 10.1002/14651858.CD013611.pub2 -
Resuscitation Oct 2023To perform an updated systematic review and meta-analysis on temperature control in adult patients with cardiac arrest. (Meta-Analysis)
Meta-Analysis Review
AIM
To perform an updated systematic review and meta-analysis on temperature control in adult patients with cardiac arrest.
METHODS
The review is an update of a previous systematic review published in 2021. An updated search including PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed on May 31, 2023. Controlled trials in humans were included. The population included adult patients with cardiac arrest. The review included all aspects of temperature control including timing, temperature, duration, method of induction and maintenance, and rewarming. Two investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Data were pooled using random-effects models. Certainty of evidence was evaluated using GRADE.
RESULTS
The updated systematic search identified six new trials. Risk of bias in the trials was assessed as intermediate for most of the outcomes. For temperature control with a target of 32-34 °C vs. normothermia or 36 °C, two new trials were identified, with seven trials included in an updated meta-analysis. Temperature control with a target of 32-34 °C did not result in an improvement in survival (risk ratio: 1.06 [95%CI: 0.91, 1.23]) or favorable neurological outcome (risk ratio: 1.27 [95%CI: 0.89, 1.81]) at 90-180 days after the cardiac arrest (low certainty evidence). Subgroup analysis according to location of cardiac arrest (in-hospital vs. out-of-hospital) found similar results. A sensitivity analysis of nine trials comparing temperature control at 32-34 °C to normothermia or 36 °C for favorable neurological outcome at any time point also did not show an improvement in outcomes (risk ratio: 1.14 [95%CI 0.98, 1.34]). New individual trials comparing a target of 31-34 °C, temperature control for 12-24 hours to 36 hours, a rewarming rate of 0.25-0.5 °C/hour, and the effect of temperature control with fever prevention found no differences in outcomes.
CONCLUSIONS
This updated systematic review showed no benefit of temperature control at 32-34 °C compared to normothermia or 36 °C, although the 95% confidence intervals cannot rule out a potential beneficial effect. Important knowledge gaps exist for topics such as hypothermic temperature targets, rewarming rate, and fever control.
Topics: Humans; Adult; Temperature; Body Temperature; Hypothermia, Induced; Heart Arrest; Hypothermia; Out-of-Hospital Cardiac Arrest
PubMed: 37558083
DOI: 10.1016/j.resuscitation.2023.109928