Composite Safety Outcome Research Articles

Rhythm control for atrial fibrillation in patients with end-stage or chronic kidney disease

Abstract Background Although early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF), its use in patients with chronic kidney disease (CKD) remains challenging. Purpose This study aimed to investigate the benefits and risks of ERC in CKD. Methods This population-based cohort study included 5,224 patients with AF (65% male, median age 63 years) with CKD stage III–IV (n=3564) and end-stage renal disease (ESRD, n=1660), who underwent ERC or rate control between 2005 and 2015. The primary outcome consisted of cardiovascular death, ischemic stroke, heart failure-related hospitalization, and acute myocardial infarction. Results During a median follow-up of 3.5 years, ERC, compared to rate control, was associated with a reduced risk of the primary outcome (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.74–0.98) without increasing the composite safety outcome in CKD stage III–IV (HR 0.99, 95% CI 0.86–1.13). Among patients with ESRD, the primary outcome did not differ between ERC and rate control (HR 0.97, 95% CI 0.81–1.17) but ERC was associated with an increased risk of composite safety outcome (HR 1.29, 95% CI 1.11–1.50), compared to rate control. However, considering the non-adherence to ERC, its comparative effectiveness on the primary outcome was observed in ESRD (HR 0.81, 95% CI 0.68–0.98). Additionally, ablation procedures did not increase the risk of composite safety outcome (HR 0.63, 95% CI 0.32–1.24). Conclusion ERC demonstrated a modest risk-benefit profile in ESRD compared to CKD stage III–IV. Randomized clinical trials should validate the efficacy of ERC, including ablation procedures, particularly in patients with ESRD.

Safety of an Accelerated Ferric Gluconate Inpatient Infusion Regimen.

Inpatient use of intravenous iron has been increasing. Ferric gluconate is traditionally given once daily. Twice-daily dosing provides faster iron repletion, but there are limited data to support the safety of twice-daily dosing. The aim of this study was to investigate the safety of twice-daily dosing for ferric gluconate compared with daily dosing. This was an institutional review board-approved retrospective observational study of hospitalized adult patients who received intravenous ferric gluconate 250 mg daily or twice daily between January 1 and April 3, 2022. The primary composite safety outcome included hypotension, infusion reaction, rapid response alert, or escalation in level of care. Secondary outcomes included total amount of iron received, hospital length of stay, and changes in laboratory values. A total of 126 patients were included in this study, with 63 patients in each group. The primary outcome occurred in 29 patients (46%) in the twice-daily group compared with 36 patients (57.1%) in the daily group (relative risk = 0.81; 95% CI, 0.57-1.13; P = 0.212). Changes in iron, hemoglobin, and transferrin saturation were similar between the 2 groups. Median length of stay was statistically shorter in the twice-daily group (7.79 days) compared with the daily group (12.9 days; p = 0.006). In this retrospective single-center study of hospitalized adult patients, those who received intravenous ferric gluconate twice daily did not experience an increased rate of a composite safety outcome of hypotension, infusion reactions, or escalation in level of care compared with those with daily dosing.

Evaluation of the feasibility and efficacy of point-of-care antibody tests for biomarker guided management of COVID-19.

Biomarker guided therapy could improve management of COVID-19 inpatients. Although some results indicate that antibody tests are prognostic, little is known about patient management using point-of-care (POC) antibody tests. COVID-19 inpatients were recruited to evaluate 2 POC tests: LumiraDX and RightSign. Ease of use data was collected. Blood was also collected for centralized testing using established antibody assays (GenScript cPass). A nested case-control study assessed if POC tests conducted on stored specimens were predictive of time to sustained recovery, mortality, and a composite safety outcome. While both POC tests exhibited moderate agreement with the GenScript assay (both agreeing with 89% of antibody determinations), they were significantly different from the GenScript assay. Treating the GenScript assay as the gold standard, the LumiraDX assay had 99.5% sensitivity and 58.1% specificity while the RightSign assay had 89.5% sensitivity and 84.0% specificity. The LumiraDX assay frequently gave indeterminant results. Both tests were significantly associated with clinical outcomes. Although both POC tests deviated moderately from the GenScript assay, they predicted outcomes of interest. The RightSign test was easier to use and was more likely to detect those lacking antibody compared to the LumiraDX test treating GenScript as the gold standard.

Safety of acute internal carotid artery stenting during endovascular thrombectomy in patients with acute ischemic stroke: a retrospective analysis of the OPTIMISE registry

BackgroundThe optimal management of tandem carotid lesions during endovascular thrombectomy (EVT) remains uncertain. The safety and efficacy of acute carotid artery stenting (aCAS) are debated, including safety concerns such as...

Revision of an Adult Burn Center's Resuscitation Guideline Leads to Lower Resuscitation Requirements.

In 2018, the institutional burn resuscitation guideline was updated to remove the use of high-dose ascorbic acid (HDAA) therapy, to lower 24-hour resuscitation fluid estimations from 4 to 2 mL/kg/TBSA, and to optimize guidance around appropriate colloid resuscitation. This retrospective study compared the incidence of a composite safety outcome (acute kidney injury, or intra-abdominal hypertension requiring intervention) between the pre-guideline update to post-guideline update. Secondarily, 24-hour resuscitation volumes, hourly urine output, vasopressor use, and mechanical ventilation duration were compared as well. The composite safety outcome was similar between the 2 groups (40% vs 29%; P = .27), but the post-group showed significantly lower 24-hour resuscitation volumes (3.74 vs 2.94 mL/kg/TBSA; P < .01), as well as lower urine output (1.26 vs 0.75 mL/kg/h; P < .01). There was no difference between the groups with respect to vasopressor use, mechanical ventilation duration, or mortality. This study suggests that a simplified resuscitation protocol without HDAA, combined with a lower starting fluid rate, led to significantly lower 24-hour resuscitation volumes without an increase in adverse safety events.

Cryoballoon pulmonary vein isolation as first-line treatment of typical atrial flutter: long-term outcomes of the CRAFT trial

BackgroundCRAFT was an international, multicentre, randomised controlled trial across 11 sites in the United UK and Switzerland. Given the evidence that pulmonary vein triggers may be responsible for atrial flutter (AFL) as well as atrial fibrillation (AF), we hypothesised that cryoballoon pulmonary vein isolation (PVI) would provide greater symptomatic arrhythmia reduction than cavotricuspid isthmus (CTI) ablation, whilst also reducing the subsequent burden of AF. Twelve-month outcomes were previously reported. In this study, we report the extended outcomes of the CRAFT study to 36 months.MethodsPatients with typical AFL and no evidence of AF were randomised 1:1 to cryoballoon PVI or radiofrequency CTI. All patients received an implantable loop recorder (ILR) for continuous cardiac rhythm monitoring. The primary outcome was time-to-symptomatic arrhythmia recurrence > 30 s. Secondary outcomes included time-to-first-AF episode ≥ 2 min. The composite safety outcome included death, stroke and procedural complications.ResultsA total of 113 patients were randomised to cryoballoon PVI (n = 54) or radiofrequency CTI ablation (n = 59). Ninety-one patients reconsented for extended follow-up beyond 12 months. There was no difference in the primary outcome between arms, with the primary outcome occurring in 12 PVI vs 11 CTI patients (HR 0.97; 95% CI 0.43–2.20; p = 0.994). AF ≥ 2 min was significantly less frequent in the PVI arm, affecting 26 PVI vs 36 CTI patients (HR 0.48; 95% CI 0.29–0.79; p = 0.004). The composite safety outcome occurred in 5 PVI and 6 CTI patients (p = 0.755).ConclusionCryoballoon PVI shows similar efficacy to radiofrequency CTI ablation in reducing symptomatic arrhythmia recurrence in patients presenting with isolated typical AFL but significantly reduces the occurrence of subsequent AF.Graphical

Cardiogenic Shock Intravascular Cooling Trial (CHILL-SHOCK)

Cardiogenic shock (CS) is complicated by high mortality rates. Targeted temperature control (TTC) has been proposed as an adjunct therapy in CS. This study aims to examine the safety of TTC in patients presenting with CS. In this open-label, randomized controlled pilot trial, 20 patients with hemodynamic criteria for CS were assigned to standard of care plus TTC vs standard of care alone. The primary outcome was a composite safety outcome, including well-described complications of TTC. Secondary outcomes included mortality at 90 days, invasive hemodynamic and echocardiographic parameters, electrocardiographic measurements, and inotrope dosing. There were no significant differences in the composite analysis of prespecified safety outcomes (3 events in the TTC group vs 0 events in the control group; P = 0.24). Patients randomized to TTC demonstrated a statistically significant increase in cardiac index and cardiac power index compared to the control group at 48-96 hours after randomization (3.6 [3.1, 3.9] L/min/m2 vs 2.6 [2.5, 3.15] L/min/m2; P = 0.029 and 0.61 [0.55, 0.7] W/m2 vs 0.53 [0.435, 0.565] W/m2; P = 0.029, respectively). TTC may be a safe adjunct therapy for patients presenting with CS and may yield improvement in specific hemodynamic parameters.

Maternal outcomes following postpartum autotransfusion of blood lost during vaginal obstetric hemorrhage.

Autotransfusion following vaginal delivery has not been as widely adopted and existing data on this topic are limited to small case series. This is a single-center retrospective matched cohort study. Deliveries exposed to autotransfusion during obstetric hemorrhage were matched to unexposed controls with obstetric hemorrhage who did not receive autotransfusion. The primary outcome was allogeneic transfusion of packed red blood cells. Planned secondary analyses included change in hemoglobin following delivery, composite maternal safety outcomes, and unplanned postpartum health care utilization. Thirty-six deliveries exposed to autotransfusion were matched to 144 unexposed controls. There was no significant difference in allogenic transfusion of packed red blood cells in the patients exposed to autotransfusion red with unexposed controls (adjusted OR 1.1; 95% CI 0.5-2.4). Deliveries that received autotransfusion had a less severe pre- to post-delivery decline in hemoglobin compared with unexposed controls across all values of QBL (p = .003). There were no significant differences in maternal morbidity outcomes evaluated in exposed versus unexposed deliveries. Autotransfusion in cases of vaginal obstetric hemorrhage did not attenuate rates of allogenic packed red blood cell transfusion but did result in a less severe pre- to postdelivery decline in hemoglobin at discharge. Autotransfusion cases did not have any markers of increased maternal morbidity when compared with a control group. These findings support emerging evidence indicating that autotransfusion of blood lost during vaginal obstetric hemorrhage is a safe and potentially effective tool for use in the management of obstetric hemorrhage.

Antibiotic Therapy for Pneumonia in the Neonatal Intensive Care Unit: Is 5 Days Enough?

Abstract Background Antibiotic therapy provided to infants in the NICU is associated with both short-and-long-term adverse consequences. In 2019, the Neonatal Antimicrobial Stewardship Program (NEO-ASP) at Nationwide Children’s Hospital (NCH), Columbus, OH, recommended a five-day antibiotic course with a time-out for treatment of pneumonia in the seven NCH network NICUs. Objective To determine the duration of antibiotic therapy for pneumonia after implementation of a 5-day antibiotic treatment course and describe its safety among infants in the NICU. Methods Prospective surveillance of antibiotic therapy provided to infants in 7 NCH NICUs (1, level 4; 5, Level 3; 1, level 2) who were diagnosed with pneumonia by the attending neonatologist based on clinical and radiographic abnormalities from 8/2020 to 4/2022. Pertinent clinical, laboratory, and microbiologic data were obtained from electronic health records. Infants were excluded if they had positive bacterial cultures of blood, urine, or cerebrospinal fluid. The length of therapy (LOT) was defined as any calendar day that the infant received ≥1 antibiotic while definitive treatment course was the duration of appropriate antibiotic therapy. Safety was defined a priori by re-initiation of antibiotic therapy within 14 days after discontinuation of the initial treatment and/or mortality (overall/sepsis-related). Results From 8/2020 to 4/2022, NICU infants (66% male) were diagnosed with 136 episodes of pneumonia at a median (IQR) age of 2 (1-20) days. 61 (45%) of episodes were late onset at ≥3 days of age. All infants had sterile cultures of blood, urine, and cerebrospinal fluid, if performed. Their median (IQR) birth weight and gestational age were 2780 (1090-3450) g and 36 (28-38) wk, respectively. At the time of pneumonia diagnosis, 44% of infants were receiving CPAP while 55% were on mechanical ventilation (11% high frequency oscillatory ventilation). The median (IQR) LOT was 6 (5-6) days and length of definitive treatment was 5 (5-5) days. Overall mortality was 5% (7/128) with 2% of deaths being sepsis-related (n=3; Table 1). The majority of pneumonia episodes (88%; n=120) were treated with 5 days of definitive antibiotic therapy and 22 (16%) episodes had antibiotics restarted within 14 days (Table 1). There was no significant difference in the composite safety outcome between ≤5 vs. 6-20 days of definitive antibiotic therapy (p=0.29). Table 1. Safety assessments of definitive antibiotic treatment for 136 pneumonia episodes in 128 infants Table 2. Underlying conditions, antibiotic duration, and cause of death among 7 infants in the NICU Conclusion(s) There was excellent adherence (88%) to the NEO-ASP recommendation of a 5-day definitive treatment course for pneumonia and in addition, the intervention seemed safe.

Five-Year Outcomes after Paclitaxel Drug-Coated Balloon Treatment of Femoropopliteal Lesions in Diabetic and Chronic Limb-Threatening Ischemia Cohorts: IN.PACT Global Study Post Hoc Analysis

PurposeTo summarize the 5-year outcomes of drug-coated balloon (DCB) for the treatment of femoropopliteal lesions in patients with diabetes mellitus (DM) or chronic limb-threatening ischemia (CLTI) compared to non-DM and intermittent claudication (IC).MethodsThe IN.PACT Global study was a real-world prospective, multicenter, international, single-arm study that enrolled 1535 participants. Post hoc analyses were conducted for participants with DM (n = 560) versus non-DM (n = 842) and CLTI (n = 156) versus IC (n = 1246). Assessments included freedom from clinically driven target lesion revascularization (CD-TLR) through 60 months, a composite safety outcome (freedom from device- and procedure-related death through 30 days, and freedom from major target limb amputation and freedom from CD-target vessel revascularization within 60 months), and major adverse events (MAEs).ResultsKaplan–Meier estimates of 60-month freedom from CD-TLR were 67.7% and 70.5% (p = 0.25) in the DM and non-DM cohorts; and 60.7% and 70.5% (p = 0.006) in the CLTI and IC cohorts. The Kaplan–Meier 60-month composite safety outcomes were 65.1% DM versus 68.9% non-DM (p = 0.12); 53.2% CLTI versus 69.1% IC (p < 0.001). Between DM and non-DM, MAE rates were not significantly different through 60 months except for all-cause mortality which was higher in DM (23.8% versus 16.6%; p < 0.001). Participants with CLTI had a higher cumulative incidence of major target limb amputation (6.8% versus 1.1%; p < 0.001) and all-cause mortality (37.4% versus 17.4%; p < 0.001) through 60 months compared to IC.ConclusionsIn this real-world study, 5-year reintervention rates following DCB angioplasty were similar between DM and non-DM, but mortality rates were expectedly higher in patients with DM. Reintervention, mortality, and amputation rates were all higher in CLTI patients compared to IC, which is consistent with the known frailty of this patient population.Level of EvidenceLevel 3, Non-randomized controlled cohort/follow-up study

Efficacy and Safety of Ticagrelor versus Clopidogrel in Dialysis Patients with Coronary Syndromes: A Systematic Review and Meta-Analysis.

(1) Background: The optimal antiplatelet therapy for end-stage kidney disease (ESKD) patients on chronic dialysis presenting with acute or chronic coronary syndromes (ACS or CCS) remains uncertain. This meta-analysis aimed to compare the efficacy and safety endpoints of ticagrelor and clopidogrel in ESKD patients requiring dialysis and presenting with ACS or CCS. (2) Methods: Studies were included comparing ticagrelor and clopidogrel in ESKD patients on chronic dialysis with ACS or CCS. The primary composite efficacy outcome was a combination of all-cause and cardiovascular mortality, recurrent myocardial infarction or coronary revascularization, and ischemic or hemorrhagic stroke. The primary safety outcome was major and non-major bleeding events. (3) Results: Five observational studies met the eligibility criteria. The pooled analysis showed no significant difference in the primary composite efficacy outcome between ticagrelor and clopidogrel (p = 0.40). Similarly, the 2 groups had no significant differences in all-cause mortality (p = 0.82) or cardiovascular mortality (p = 0.79). Ticagrelor did not show a significantly different risk of coronary revascularization (p = 0.35) or recurrent myocardial infarction (p = 0.41) compared to clopidogrel. Also, the risk of stroke was similar (p = 0.21). The 2 groups had no significant difference in the primary composite safety outcome (p = 0.22) or major bleeding events (p = 0.27). (4) Conclusions: In ESKD patients on chronic dialysis with ACS or CCS, there was no significant difference in efficacy or safety outcomes between ticagrelor and clopidogrel. Further randomized controlled trials are needed to establish the optimal antiplatelet therapy in this population.

Endovascular Treatment and Microsurgical Clipping for the Management of Paraclinoid Intracranial Aneurysms: A Systematic Review and Meta-Analysis

We aimed to compare the efficacy and safety of microsurgical clipping versus endovascular treatment (EVT) for paraclinoid aneurysms. A systematic search for studies including patients with paraclinoid aneurysms treated with a microsurgical or endovascular technique was conducted in 6 databases from inception to February 2022. Efficacy outcomes included complete angiographic occlusion at last follow-up, favorable functional outcome, and recurrence of the aneurysm. For safety, we assessed a composite of intraoperative and postoperative complications. Data were pooled using a random-effects model. A total of 95 studies including 6711 patients, 3029 in the surgical group and 3682 in the EVT group were found. Pooled rates of complete occlusion were 94% (95% CI 91%-96%; I2=0%) in the surgical group and 69% (95% CI 63%-74%; I2=79%) in the EVT group, respectively. The favorable functional outcome rate was 86% (95% CI 76%-92%; I2=72%) with surgical treatment and 95% (95% CI 92%-97%; I2=61%) with EVT. The rate of aneurysm recurrence with surgical treatment was 1% (95% CI 0%-4%; I2=0%) and 12% (95% CI 9%-16%; I2=57%) with EVT. The composite safety outcome rate in the surgical group was 24% (95% CI 18%-30%; I2=90%) and 10% (95% CI 8%-13%; I2=71%) in the EVT group. Our findings suggest that microsurgical clipping seems to have a higher efficacy than EVT in terms of angiographic occlusion and aneurysm recurrence; however, EVT seems to be safer in terms of intraoperative and postoperative complications. Considering the heterogeneity and low-level evidence of the data available, further prospective randomized studies are warranted to confirm our findings.

Minithoracotomy vs Conventional Sternotomy for Mitral Valve Repair

The safety and effectiveness of mitral valve repair via thoracoscopically-guided minithoracotomy (minithoracotomy) compared with median sternotomy (sternotomy) in patients with degenerative mitral valve regurgitation is uncertain. To compare the safety and effectiveness of minithoracotomy vs sternotomy mitral valve repair in a randomized trial. A pragmatic, multicenter, superiority, randomized clinical trial in 10 tertiary care institutions in the UK. Participants were adults with degenerative mitral regurgitation undergoing mitral valve repair surgery. Participants were randomized 1:1 with concealed allocation to receive either minithoracotomy or sternotomy mitral valve repair performed by an expert surgeon. The primary outcome was physical functioning and associated return to usual activities measured by change from baseline in the 36-Item Short Form Health Survey (SF-36) version 2 physical functioning scale 12 weeks after the index surgery, assessed by an independent researcher masked to the intervention. Secondary outcomes included recurrent mitral regurgitation grade, physical activity, and quality of life. The prespecified safety outcomes included death, repeat mitral valve surgery, or heart failure hospitalization up to 1 year. Between November 2016 and January 2021, 330 participants were randomized (mean age, 67 years, 100 female [30%]); 166 were allocated to minithoracotomy and 164 allocated to sternotomy, of whom 309 underwent surgery and 294 reported the primary outcome. At 12 weeks, the mean between-group difference in the change in the SF-36 physical function T score was 0.68 (95% CI, -1.89 to 3.26). Valve repair rates (≈ 96%) were similar in both groups. Echocardiography demonstrated mitral regurgitation severity as none or mild for 92% of participants at 1 year with no difference between groups. The composite safety outcome occurred in 5.4% (9 of 166) of patients undergoing minithoracotomy and 6.1% (10 of 163) undergoing sternotomy at 1 year. Minithoracotomy is not superior to sternotomy in recovery of physical function at 12 weeks. Minithoracotomy achieves high rates and quality of valve repair and has similar safety outcomes at 1 year to sternotomy. The results provide evidence to inform shared decision-making and treatment guidelines. isrctn.org Identifier: ISRCTN13930454.

Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study

IntroductionThe BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study.MethodsThe BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up.ResultsBaseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age.ConclusionWe describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up.Trial registrationBATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832.PRECISE: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.

708 Clinical Impact of a Revised Burn Resuscitation Guideline at an Adult Burn Center

Abstract Introduction The American Burn Association recommends volume resuscitation at 2-4ml/kg/TBSA; however, in practice, fluid resuscitation often exceeds these goals. Additional strategies used for burn resuscitation include the use of colloid rescue and high dose ascorbic acid (HDAA). In 2018, our institution moved from a fluid resuscitation strategy which included calculating fluid requirements using 4ml/kg/TBSA and HDAA infusion for burns &amp;gt; 30% TBSA to a strategy that calculated fluids using a 2ml/kg/TBSA with the removal of HDAA. Additionally, the guidance for colloid rescue was updated to provide specific time points for evaluation of the need for initiation of this intervention. The primary objective of this study was to compare outcomes of the new institutional resuscitation strategy to the previous one. Methods This was a retrospective cohort study evaluating outcomes for acute burn resuscitation between the previous institutional resuscitation guideline with the updated guideline. This study included adult patients admitted for burn injury with &amp;gt;20% TBSA between August 1, 2016, to September 30, 2021. The primary outcome was a composite safety endpoint which included incidence of acute kidney injury and intra-abdominal hypertension requiring intervention. Acute kidney injury was defined as a serum creatinine increase 1.5 times baseline. Statistical analyses utilized the Mann-Whitney U test for non-normally distributed continuous data and the chi-squared and Fischer’s exact test for categorical data. A p-value of &amp;lt; 0.05 was considered statistically significant. Results The final analysis included 43 in the pre-group and 52 in the post-group update. Baseline characteristics between the groups were similar. The primary composite safety outcome was non-statistically significantly lower in the post-guideline update group (39.5% vs. 28.8%, p= 0.273). Total fluid volume administered (3.74 ml/kg/TBSA vs. 2.97 mL/kg/TBSA, p=0.007) and hourly urine output within the first 24 hours (1.26 mL/kg/hour vs. 0.75 mL/kg/hour, p=0.007) were significantly lower in the post-group. No differences were observed in vasopressor use (32.6% vs 36.5%, p=0.63), vasopressor duration (70.3 hours vs. 50.4 hours p=0.24), or duration of mechanical ventilation (5.1 days vs 10.4 days, p=0.113). Conclusions The burn resuscitation guideline update resulted in significantly lower 24 hour- fluid volumes, without negative hemodynamic consequences. Applicability of Research to Practice The comparison of two resuscitation protocols provides evidence for other institutions to help optimize their resuscitation practice

Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal

BackgroundAlthough clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach — the Eat, Sleep, Console care approach — is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown.MethodsIn this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks’ gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death.ResultsA total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups.ConclusionsAs compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.)

Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.

A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden. We identified 109 739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11 625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA2DS2-VASc score ≥4); (2) ERC and lower comorbidity burden (CHA2DS2-VASc score 2-3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA2DS2-VASc score 0-1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC. In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72-0.95]; P=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; P=0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54-1.57]; P=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; P=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- P=0.027) but not in OptumLabs (interaction-P=0.720). ERC was not associated with an increased risk for the primary safety outcome. ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA2DS2-VASc score ≥4).

Direct oral anticoagulants for atrial fibrillation in early postoperative valve repair or bioprosthetic replacement

ObjectiveDespite increased use of direct oral anticoagulants (DOACs), limited evidence guides their use in the early postoperative period after bioprosthetic valve implantation in patients with atrial fibrillation. Our objective was to describe the efficacy and safety of DOACs and warfarin in the first 3 months after surgical bioprosthetic valve replacement or repair in patients with atrial fibrillation. MethodsThis was a retrospective, registry-informed cohort study of surgical patients who underwent bioprosthetic valve replacement or repair, had concomitant atrial fibrillation and received oral anticoagulation at discharge. The primary efficacy outcome was a composite of death, ischemic stroke, transient ischemic attack, and systemic embolism; the primary safety outcome was a composite of major bleeding. Key secondary outcomes were comparative analyses of primary outcomes, temporal anticoagulation prescribing patterns, and 30-day readmission rates. ResultsA total of 1743 patients were included. Of the 570 patients in the DOAC group, 17 (2%) met the composite efficacy outcome and 55 (10%) met the composite safety outcome. Of the 1173 patients receiving warfarin, 41 (3%) and 114 (10%) met the composite efficacy and safety outcomes, respectively. Comparative secondary analysis was not statistically significant for either the efficacy (adjusted odds ratio, 0.85; 95% confidence interval, 0.46-1.55, P = .59) or safety (adjusted odds ratio, 0.94; 95% confidence interval, 0.66-1.34, P = .76) outcomes. The 30-day readmission rates were similar between both groups. ConclusionsOur results suggest DOACs may be safe and effective alternatives to warfarin in the early postoperative period after valve repair or surgical bioprosthetic replacement. Confirmation awaits adequately powered prospective studies.

Prophylactic epinephrine attenuates severe bleeding in lung transplantation patients undergoing transbronchial lung biopsy: Results of the PROPHET randomized trial

Severe hemorrhage is an uncommon yet potentially life-threatening complication of transbronchial lung biopsy. Lung transplantation recipients undergo multiple bronchoscopies with biopsy and are considered to be at an increased risk for bleeding from transbronchial biopsy, independent of traditional risk factors. We aimed to evaluate the efficacy and safety of endobronchial administration of prophylactic topical epinephrine in attenuating transbronchial biopsy-related hemorrhage in lung transplant recipients. The Prophylactic Epinephrine for the Prevention of Transbronchial Lung Biopsy-related Bleeding in Lung Transplant Recipients study was a 2-center, randomized, double blind, placebo-controlled clinical trial. Participants undergoing transbronchial lung biopsy were randomized to receive 1:10,000-diluted topical epinephrine vs saline placebo administered prophylactically into the target segmental airway. Bleeding was graded based on a clinical severity scale. The primary efficacy outcome was incidence of severe or very severe hemorrhage. The primary safety outcome was a composite of 3-hours all-cause mortality and an acute cardiovascular event. A total of 66 lung transplantation recipients underwent 100 bronchoscopies during the study period. The primary outcome of severe or very severe hemorrhage occurred in 4 cases (8%) in the prophylactic epinephrine group and in 13 cases (24%) in the control group (p=0.04). The composite primary safety outcome did not occur in any of the study groups. In lung transplantation recipients undergoing transbronchial lung biopsy, prophylactic administration of 1:10,000-diluted topical epinephrine into the target segmental airway before biopsy attenuates the incidence of significant endobronchial hemorrhage without conveying a significant cardiovascular risk. (ClinicalTrials.gov identifier: NCT03126968).

Efficacy and safety of low dose aspirin plus clopidogrel in the treatment of elderly patients with symptomatic intracranial artery stenosis.

As one of the most common causes of stroke, symptomatic intracranial artery stenosis (sICAS) is a great threat to public health, and its financial burden is substantial, with annual direct high medical costs particularly in China. Currently, the long-term use of conventional dual antiplatelet therapy (DAPT) as the primary modality of treatment for sICAS decreases the risk of stroke recurrence but increases the risk of bleeding. We aimed to evaluate the efficacy and safety of low dose aspirin plus clopidogrel for the treatment of sICAS in the elderly population. This randomized, controlled study included 181 older patients with transient ischemic attack (TIA) or ischemic stroke (IS) attributed to sICAS, who were recruited between April 2015 and November 2020. The 90 patients assigned to the low dose therapy group included aspirin, 75 mg, plus clopidogrel, 50 mg, daily for 90 and 91 patients assigned to the conventional group included aspirin, 100 mg, plus clopidogrel, 75 mg, daily for 90 days (aspirin or clopidogrel alone daily thereafter) were included in this intention-to-treat analysis. Efficacy and safety analyses were done in this trial. One hundred eighty-one eligible elderly patients with sICAS were enrolled in this trial. The median age was 70 years ranged 60-83 years. Seventy-five participants were with TIA and 106 with IS. The median time of follow-up was 30 months ranged 1-36 months. Ninety patients were assigned randomly to the low dose group and 91 patients to the conventional group. The rate of primary, secondary and composite efficacy were not significantly different between the low dose and conventional group (P > 0.05). The rate of composite safety outcome was 7.8% (7/90) in the low dose group, which was lower than 17.6% (16/91) in the conventional group (χ2 = 3.921, P = 0.048). At the time of last follow-up, 17 (9.4%) of 181 patients developed GI injuries, which occurred in four (4.4%) of 90 patients in the low dose group and in 13 (14.3%) of 91 patients in the conventional group (χ2 = 4.058, P = 0.044). The primary efficacy outcome occurred in six (18.2%) of 33 patients with severe sICAS and in 22 (38.6%) of 57 patients with moderate sICAS (χ2 = 4.064, P = 0.044) in the low dose group. In this study, the safety of low dose aspirin combined with clopidogrel proved to be equally efficient and significantly safer than those of conventional dose within 24 months in elderly patients with sICAS. However, the small size of this study limits the validity of the results. Further larger longitudinal and randomized controlled trials are necessary to evaluate the role of low dose DAPT in the patients with sICAS.