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Background Adherence to evidence-based care processes and patient outcomes in intensive care units (ICUs) can be influenced by staffing and resource availability. We aimed to evaluate if there is a weekend effect on adherence to evidence-based care processes, and hospitalization outcomes and whether a checklist implementation could mitigate potential differences. Methods Post hoc analysis of the Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) study dataset collected before and after checklist implementation in 34 ICUs across 15 countries (2013-2017). Admission days were classified as ‘weekend/holidays’ or ‘weekdays’ according to local work schedules and public holidays. The primary outcome was the omission of 10 evidence-based care processes addressed in the checklist. Mortality and length of stay differences between weekend/holiday and weekday admissions were evaluated as secondary outcomes. Results 4256 patients contributed 1141 weekend versus 3501 weekday observation days pre-intervention, and 2014 versus 6507 post-intervention. Pre-intervention, peptic ulcer prophylaxis was omitted more frequently on weekends/holidays than weekdays (adjusted rate ratio [aRR], 0.58 [95%–confidence interval [CI] 0.38-0.88), whereas head-of-bed elevation was omitted more often on weekdays than on weekends/holidays (aRR, 3.17 [1.14-8.86]). Post-intervention, peptic ulcer prophylaxis omission rates became similar (aRR, 1.03 [0.68-1.56], but head-of-bed elevation became omitted more often on weekends than on weekdays (aRR, 0.63 [0.45-0.88]). Post-intervention, oral care was omitted more frequently on weekends/holidays than in weekdays (aRR, 0.63 [0.45-0.9]), and central catheter removal was more frequent on weekdays than in weekends/holidays (aRR, 1.11 [1.02-1.21]). No significant differences in mortality or length of stay were found. Conclusion A weekend effect influenced adherence to some care processes. While checklist implementation improved overall adherence, some disparities diminished, while new ones emerged. Organizational, cultural, and temporal factors should be further studied to optimize care delivery across all times and settings. Clinical Trial Registration Number NCT01973829

Importance Assisted ventilation during delayed cord clamping (DCC) may improve the physiologic transition of extremely preterm infants immediately after birth. Objective To determine whether assisted ventilation during 120 seconds of DCC was associated with reduced higher-level resuscitative interventions (intubation, chest compressions, or epinephrine administration) compared with DCC for 30 to 60 seconds followed by resuscitation. Design, Setting, and Participants This was a secondary analysis of the VentFirst randomized clinical trial that was conducted from September 2, 2016, through February 21, 2023, at 12 centers in the US and Canada. Infants born at 23 weeks 0 days’ to 28 weeks 6 days’ gestational age (GA) were included. Intervention Infants randomized to the intervention received either positive-pressure ventilation or continuous positive airway pressure from 30 to 120 seconds after birth, followed by umbilical cord clamping. Those randomized to control received 30 to 60 seconds of DCC followed by assisted ventilation. Main Outcomes and Measures The main outcome was the odds of higher-level resuscitative interventions in the delivery room (DR). Intention-to-treat analyses within 2 a priori cohorts (infants breathing well and not breathing well 30 seconds after birth) used the Cochran-Mantel-Haenszel method to estimate the odds ratios (ORs) of intervention vs control. Results All 570 infants enrolled in the trial were included. Infants had a median (IQR) GA of 26.6 (25.2-27.9) weeks and 273 (47.9%) were female. A total of 271 infants (47.5%) were assessed as not breathing well 30 seconds after birth (150 intervention and 121 control), and 299 (52.5%) were assessed as breathing well 30 seconds after birth (128 intervention and 171 control). In the not-breathing-well cohort, 146 infants (53.9%) were intubated in the DR, 4 received chest compressions (2 intervention and 2 control), and 1 received epinephrine (control). Intubation was less frequent in the intervention group (71 infants [47.3%] vs 75 infants [62.0%]; OR, 0.52; 95% CI, 0.30-0.89). When adjusted by GA strata at randomization, infants in the 26 to 28 weeks’ GA stratum who were in the intervention group were less likely to be intubated in the DR (18 of 79 infants [22.8%] vs 29 of 60 infants [48.3%]; OR, 0.32; 95% CI, 0.15-0.65). However, there was no difference in intubation rates for infants in the 23 to 25 weeks’ GA stratum (53 of 71 infants [74.7%] vs 46 of 61 infants [75.4%]; OR, 0.96; 95% CI, 0.44-2.12). Among infants breathing well at 30 seconds, 74 (24.7%) were intubated in the DR, and none received compressions or epinephrine. Intubation rates were similar between intervention and control in the breathing-well cohort. Conclusions and Relevance While the VentFirst trial did not find a difference in death or intraventricular hemorrhage, this secondary analysis found that assisted ventilation during DCC was associated with less intubation in the DR, primarily among infants born at 26 to 28 weeks’ gestation who were not breathing well 30 seconds after birth. Additional studies are needed before implementing assisted ventilation during DCC in clinical practice. Trial Registration ClinicalTrials.gov Identifier: NCT02742454

Ventricular arrhythmias after electrical cardioversion for AF are rare. Most of these arrhythmias are related to QT prolongation, resulting from marked and sudden slowing of heart rates, treatment with Class III antiarrhythmic drugs or other QT-prolonging medications, and the ventricular repolarisation remodelling effect of electrical cardioversion. A case of polymorphic ventricular tachycardia post-cardioversion of rapid AF in a patient with tachycardia-induced cardiomyopathy and the use of amiodarone is reported.

Abstract The advent of high-throughput sequencing has led to an exponential increase in genomic data, highlighting the need for efficient and accurate models to analyze and interpret this information. In this study, we introduce a novel, exomic foundational model that leverages a combination of the human reference genome and multispecies data to improve variant detection and interpretation. Our model utilizes a short-range transformer architecture and is trained on a large dataset of human exomic sequences derived from the Tapestry study. Through a series of ablation studies and scaling experiments, we demonstrate the effectiveness of our model in predicting next token accuracy and identifying clinically pathogenic variants. We also show that our model outperforms existing models in a range of downstream tasks, including variant effect prediction and disease state identification. In fact, our largest sequence transformer for range adaptive nucleotide decoding variant (1B parameters) surpassed previous benchmarks, demonstrating a mean accuracy of 0.880 [an 8.2% improvement over the original nucleotide transformer (NT) and a 7% improvement over NT-v2]. Furthermore, we construct a unique exomic ClinVar dataset to evaluate the model’s performance on pathogenicity and disease states. Our results highlight the potential of this model to improve our understanding of the human exome and its role in disease. The model and its applications have significant implications for genomics-based diagnosis and personalized medicine, including tailored therapeutic development.

Background: Piperacillin-Tazobactam (PTZ) is often used to treat community-acquired intra-abdominal infections (CA-IAIs) despite common causative pathogens being susceptible to more narrow-spectrum agents. However, susceptibility to PTZ among these predominant pathogens has been declining. Antibiotic de-escalation to non-antipseudomonal beta-lactams whenever possible is an important strategy to prevent the development of resistance to PTZ. Objective: The purpose of this study is to assess PTZ length of therapy in patients with CA-IAI, by comparing patients who received a pharmacist-led intervention involving the de-escalation of PTZ to narrow-spectrum regimens with those who did not receive the intervention. Methods: A retrospective analysis was conducted among patients >18 years old and admitted with CA-IAI empirically placed on PTZ between January 1, 2022, through June 30, 2022 (pre-intervention group), and January 1, 2024, through June 30, 2024 (post-intervention group). A total of 246 patients were included in the pre-intervention group and 129 patients in the post-intervention group. The utilization of PTZ, hospital length of stay (LOS), and treatment-associated complications were assessed using linear and logistic regression model, respectively. Results: Compared with patients in the pre-intervention group, those in the post-intervention group had a mean 1.2-day reduction in PTZ length of therapy (2.3 vs 1.2 days, P < 0.001). There was no difference in LOS, (β = 0.001, 98% confidence interval [CI] −1.29 to 1.29; P = 0.477), hospital readmission within 30 days due to IAI (odds ratio [OR] = 0.85, 98% CI = 0.51 to 1.44; P = 0.56), treatment-associated complications during current hospitalization (OR = 0.77, 98% CI = 0.45 to 1.32; P = 0.35), development of Clostridium difficile -associated diarrhea (OR = 3.29, 98% CI = 0.77 to 22.4; P = 0.14), or medication toxicity (OR = 2.07, 98% CI = 0.79 to 6.08; P = 0.15). Conclusion and relevance: The use of narrow-spectrum antibiotics for the empiric treatment of CA-IAI-reduced PTZ length of therapy and did not result in adverse clinical outcomes.

Context.— Treatments are available for common forms of systemic amyloidosis that show promise for extending and improving the quality of life for patients. Early diagnosis and accurate identification of amyloid fibril type are crucial for successful treatment, but the diagnosis and workup of amyloidosis is inconsistent among pathologists and laboratories. Thus, the goal of this guideline is to offer recommendations for proper testing and workup for amyloidosis to optimize patient care. Objective.— To establish evidence-based recommendations for appropriate laboratory testing to detect amyloidosis and identify the specific amyloidogenic protein. Design.— The College of American Pathologists convened a panel of experts to develop recommendations following the standards established by the National Academy of Medicine for developing trustworthy clinical practice guidelines. The panel conducted a systematic literature review addressing 6 key questions. Using the Grading of Recommendations Assessment, Development and Evaluation framework, recommendations were created based on the available evidence, certainty of that evidence, and key judgments as defined in the framework. Results.— Four conditional recommendations and 3 good practice statements were established to provide guidance for proper testing and workup of amyloidosis. Conclusions.— This guideline summarizes the available evidence on the diagnosis and workup of systemic amyloidosis in tissue samples, including the challenges and limitations of common approaches and techniques. Recommendations for pathologists and laboratories receiving these samples are provided.

Background Recent studies suggest that general surgery (GS) residents perform more operations related to their future specialty compared with their peers. In this multi-institutional study, we examined the process of early specialization among GS residents pursuing a career in vascular surgery (VS). Methods Data from the US Resident OPerative Experience (ROPE) Consortium, comprising 20 Accreditation Council for Graduate Medical Education (ACGME)-accredited GS residency programs across the United States, were queried. Case volume and type were compared between GS residents pursuing vs fellowship and all other residents. Effect size was evaluated using Cohen’s d statistic. Effect size was considered large if d > 0.8, moderate if 0.5 ≤ d < 0.8, small if 0.2 ≤ d < 0.5, and inconsequential if d < 0.2. Results A total of 1343 GS residents graduated from 2010-2020 across all programs participating in ROPE, of which 135 (10.1%) pursued vs fellowship. Total major vascular case volume was significantly greater among residents pursuing vs fellowship (138 [100-207] vs 100 [80-139], P < 0.0001) with a large effect size (d = 1.81). Vascular cases reported in a surgeon chief role (27 [9-53] vs 10 [2-29], P < 0.0001, d = 0.76, moderate effect) and surgeon junior role (107 [79-154] vs 88 [62-118], P < 0.0001, d = 1.00, large effect) were also greater among GS residents pursing a vs specialty. Nearly all vascular operative categories demonstrated similar trends ( P < 0.01 each). Conclusions GS residents pursuing a vs fellowship perform more vascular cases compared with their peers. Given the differences in both surgeon chief and surgeon junior roles, career focus may begin as early as the junior resident years.