Long COVID Definitions and Models of Care : A Scoping Review.

BACKGROUND: Definitions of long COVID are evolving, and optimal models of care are uncertain. PURPOSE: To perform a scoping review on definitions of long COVID and provide an overview of care models, including a proposed framework to describe and distinguish models. DATA SOURCES: English-language articles from Ovid MEDLINE, PsycINFO, the Cochrane Library, SocINDEX, Scopus, Embase, and CINAHL published between January 2021 and November 2023; gray literature; and discussions with 18 key informants. STUDY SELECTION: Publications describing long COVID definitions or models of care, supplemented by models described by key informants. DATA EXTRACTION: Data were extracted by one reviewer and verified for accuracy by another reviewer. DATA SYNTHESIS: Of 1960 screened citations, 38 were included. Five clinical definitions of long COVID varied with regard to timing since symptom onset and the minimum duration required for diagnosis; 1 additional definition was symptom score-based. Forty-nine long COVID care models were informed by 5 key principles: a core "lead" team, multidisciplinary expertise, comprehensive access to diagnostic and therapeutic services, a patient-centered approach, and providing capacity to meet demand. Seven characteristics provided a framework for distinguishing models: home department or clinical setting, clinical lead, collocation of other specialties, primary care role, population managed, use of teleservices, and whether the model was practice- or systems-based. Using this framework, 10 representative practice-based and 3 systems-based models of care were identified. LIMITATIONS: Published literature often lacked key model details, data were insufficient to assess model outcomes, and there was overlap between and variability within models. CONCLUSION: Definitions of long COVID and care models are evolving. Research is needed to optimize models and evaluate outcomes of different models. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (Protocol posted at https://effectivehealthcare.ahrq.gov/products/long-covid-models-care/protocol.).

Feasibility of Amulet occluder implantation after failed left atrial appendage occlusion attempt: Insights from the EMERGE LAA postapproval study.

BACKGROUND: Although expertise in left atrial appendage occlusion (LAAO) has grown, certain intricate anatomies may pose challenges, rendering them unsuitable for LAAO with the selected device. OBJECTIVE: This analysis aimed to characterize outcomes of patients with prior failed percutaneous LAAO procedures who underwent a subsequent attempt with an Amulet occluder in the EMERGE LAA postapproval study. METHODS: Patients enrolled in the National Cardiovascular Data Registry LAAO Registry who had an Amulet occluder implantation attempt between Food and Drug Administration approval (August 14, 2021) and June 30, 2023, were evaluated. A safety end point through 7 days or hospital discharge (whichever was later) and major adverse events through 45 days were reported. RESULTS: A total of 8591 patients underwent attempted Amulet occluder implantation, of whom 244 patients had prior failed LAAO. Implantation success was 88.9% and 96.2% in patients with prior failed LAAO and index LAAO, respectively (P < .001). The safety composite end point was low, occurring in 1.6% and 0.8% of patients with prior failed LAAO and index LAAO, respectively (P = .148). Any major adverse event through 45 days occurred in 7.4% and 6.3% of prior failed LAAO and index LAAO patient cohorts, respectively (P = .497); most adverse events were similar between the groups (P > .05). At 45 days, peridevice leak ≤3 mm was achieved in >90% of patients in either group. CONCLUSION: A high degree of implantation success with a low rate of adverse events can be achieved with the Amulet occluder. The findings imply that the dual occlusive mechanism Amulet occluder facilitates successful closure, even in challenging anatomic scenarios.

DNA methylation signatures of early-life adversity are exposure-dependent in wild baboons.

The early-life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute to these early-life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early-life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early-life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early-life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early-life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early-life effects on fitness-related traits.

Enteral Pentobarbital in the Difficult to Sedate Critically Ill Children.

OBJECTIVE: Difficult analgosedation is common and challenging in the pediatric intensive care unit (PICU). It is important to study alternative and supplemental sedatives for when the first-line agents become -insufficient. METHODS: In this retrospective chart-review study, we report our center's experience in using intermittent doses of enteral pentobarbital as an adjunct sedative in 13 difficult to sedate critically ill and mechanically ventilated children. We compare the average sedation score and cumulative doses of other -sedatives (opioids, benzodiazepines and alpha-2 agonists) in the 24 hours before and 24 hours after enteral -pentobarbital initiation. RESULTS: The addition of enteral pentobarbital was associated with lower State Behavioral State (SBS) scores in 8 out of the 13 patients and on average smaller doses of opioids (decreased by 11%), benzodiazepines (BZD) (decreased by 5%) and alpha-agonists (decreased by 20%). No adverse effects were noted attributable to pentobarbital administration. CONCLUSION: Enteral pentobarbital seems to be safe and effective agent in the difficult to sedate critically ill child.

3-Year Outcomes From the Amplatzer Amulet Left Atrial Appendage Occluder Randomized Controlled Trial (Amulet IDE).

BACKGROUND: The Amulet (Abbott) left atrial appendage occluder investigational device exemption trial is the largest randomized trial evaluating the safety and effectiveness of the Amulet left atrial appendage occluder compared with the Watchman 2.5 device (Boston Scientific) through 5 years. OBJECTIVES: This analysis evaluated the device effect on 3-year outcomes in the Amulet investigational device exemption trial. METHODS: The medication regimen and key clinical outcomes were reported through 3 years including: 1) the composite of ischemic stroke or systemic embolism (SE); 2) the composite of all strokes, SE, or cardiovascular (CV) death; 3) major bleeding; and 4) all-cause death and CV death. RESULTS: A total of 1,878 patients at 108 sites were randomized. A significantly higher percentage of patients were free of oral anticoagulation usage at 3 years with Amulet (96.2%) vs Watchman (92.5%) (P < 0.01). Clinical outcomes were comparable for the composite of ischemic stroke or SE (5.0% vs 4.6%; P = 0.69); the composite of all strokes, SE, or CV death (11.1% vs 12.7%; P = 0.31); major bleeding (16.1% vs 14.7%; P = 0.46); all-cause death (14.6% vs 17.9%; P = 0.08); and CV death (6.6% vs 8.5%; P = 0.14) for Amulet and Watchman, respectively. Through 3 years, device factors (device-related thrombus or peridevice leak ≥3 mm) preceded ischemic stroke events and CV deaths more frequently in Watchman compared with Amulet patients. CONCLUSIONS: The Amulet occluder demonstrated continued safety and effectiveness with over 96% free of oral anticoagulation usage through 3 years in a high-risk population compared to the Watchman device. (AMPLATZER Amulet LAA Occluder Trial [Amulet IDE]; NCT02879448).

Mechanisms, predictors, and evolution of severe peri-device leaks with two different left atrial appendage occluders.

AIMS: Incomplete left atrial appendage occlusion (LAAO) due to peri-device leak (PDL) is a limitation of the therapy. The Amulet IDE trial is the largest randomized head-to-head trial comparing the Amulet and Watchman 2.5 LAAO devices with fundamentally different designs. The predictors and mechanistic factors impacting differences in PDLs within the Amulet IDE trial are assessed in the current analysis. METHODS AND RESULTS: An independent core lab analysed all images for the presence or absence of severe PDL (>5 mm). The incidence, mechanistic factors, predictors using propensity score-matched controls, and evolution of severe PDLs through 18 months were assessed. Of the 1878 patients randomized in the trial, the Amulet occluder had significantly fewer severe PDLs than the Watchman device at 45 days (1.1 vs. 3.2%, P < 0.001) and 12 months (0.1 vs. 1.1%, P < 0.001). Off-axis deployment or missed lobes were leading mechanistic PDL factors in each device group. Larger left atrial appendage (LAA) dimensions including orifice diameter, landing zone diameter, and depth predicted severe PDL with the Watchman device, with no significant anatomical limitations noted with the Amulet occluder. Procedural and device implant predictors were found with the Amulet occluder attributed to the learning curve with the device. A majority of Watchman device severe PDLs did not resolve over time through 18 months. CONCLUSION: The dual-occlusive Amplatzer Amulet LAA occluder provided improved LAA closure compared with the Watchman 2.5 device. Predictors and temporal observations of severe PDLs were identified in the Amulet IDE trial. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov Unique identifier NCT02879448.

Saturday Pap Smear Clinic: addressing barriers to cervical cancer screening.

BACKGROUND: The incidence of cervical cancer has decreased by 70% since the 1950s. Preventative measures include vaccination against HPV strains and Papanicolaou tests. Early identification of cervical cancer through routine screening can significantly improve patient outcomes. MATERIALS AND METHODS: At our academic institution, Community Internal Medicine (CIM) Clinic, 63% of female patients aged 21-65 were compliant with cervical cancer screening. The opening of the 'Saturday Pap Smear Clinic' sought to address barriers by offering non-traditional appointment times on Saturday mornings with an all female staff. Our aim was to increase the cervical cancer screening rate by 1% within 12 weeks. Our team compared CIM (intervention) and family medicine (FM) (control) compliance rates from September 2021 to January 2022. Messages were sent to the patient indicating non-compliance and offering options to complete screening. RESULTS: At the start of this study, 5239 CIM patients were cervical cancer screening non-compliant. Postintervention, cervical screening rates among non-compliant women within CIM improved by 1.2%. The intervention cohort, CIM patients, had a significant improvement in compliance compared with the control group, FM patients. White women between the ages of 50 and 65 comprised the majority of patients who used the 'Saturday Pap Smear Clinic'. CONCLUSIONS: The availability of Saturday appointments for cervical cancer screening completion can enhance cervical cancer screening compliance among eligible women. Eliminating barriers for women can improve health outcomes.

DNA methylation signatures of early life adversity are exposure-dependent in wild baboons.

The early life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute to these early life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early life effects on fitness-related traits.

Public trust is earned: Historical discrimination, carceral violence, and the COVID-19 pandemic.

OBJECTIVE: To assess whether knowledge of Tuskegee, the U.S. Immigration and Customs Enforcement (ICE) agency's detainment of children, and satisfaction with the George Floyd death investigation were associated with trust in actors involved in the development and distribution of coronavirus vaccines. DATA SOURCES AND STUDY SETTING: National survey with a convenience sample of Black (n = 1019) and Hispanic (n = 994) adults between July 1 and 26, 2021. STUDY DESIGN: Observational study using stratified adjusted logistic regression models to measure the association between ratings of the trustworthiness of actors involved in the development and distribution of coronavirus vaccines. PRINCIPAL FINDINGS: Among Black respondents, lower satisfaction with the George Floyd death investigation was associated with lower trustworthiness ratings of pharmaceutical companies (ME: -0.09; CI: -0.15, 0.02), the FDA (ME: -0.07; CI: -0.14, -0.00), the Trump Administration (ME: -0.09; CI: -0.16, -0.02), the Biden Administration (ME: -0.07, CI: -0.10, 0.04), and elected officials (ME: -0.10, CI: -0.18, -0.03). Among Hispanic respondents, lower satisfaction was associated with lower trustworthiness ratings of the Trump Administration (ME: -0.14, CI: -0.22, -0.06) and elected officials (ME: -0.11; CI: -0.19, -0.02). Greater knowledge of ICE's detainment of children and families among Hispanic respondents was associated with lower trustworthiness ratings of state elected officials (ME: -0.09, CI: -0.16, 0.01). Greater knowledge of the US Public Health Service Study of Syphilis in Tuskegee was associated with higher trustworthiness ratings of their usual source of care (ME: 0.09; CI: 0.28, 0.15) among Black respondents (ME: 0.09; CI: 0.01, 0.16). CONCLUSIONS: Among Black respondents, lower satisfaction with the George Floyd death investigation was associated with lowered levels of trust in pharmaceutical companies, some government officials, and administrators; it was not associated with the erosion of trust in direct sources of health care delivery, information, or regulation. Among Hispanic respondents, greater knowledge of the ICE detainments was associated with lower trustworthiness ratings of elected state officials. Paradoxically, higher knowledge of the Study of Syphilis in Tuskegee was associated with higher trustworthiness ratings in usual sources of care.

Clinician-rated outcomes of patients with functional neurological disorders treated in an outpatient clinic.

BACKGROUND: Patients with functional neurological (conversion) disorder (FND) have historically been difficult to treat. Outcomes have been studied in research trials, documenting improvements; however, limited information is available from a community-treated FND cohort. OBJECTIVES: We aimed to examine clinical outcomes in outpatients with FND treated with the Neuro-Behavioral Therapy (NBT) approach. These uncontrolled setting treatment data could complement more structured clinical studies results. METHODS: We conducted a retrospective chart review of consecutive patients diagnosed with FND, ages 17 to 75, who were treated with the NBT workbook at the Rhode Island Hospital Behavioral Health clinic between 2014 and 2022. NBT consisted of 45-minute, individual, outpatient sessions, in clinic or via telehealth with one clinician. Global Assessment of Functioning (GAF), and Clinical Global Impression (CGI) -Severity, and -Improvement were scored for every appointment. RESULTS: Baseline characteristics are available for 107 patients. Mean age at FND symptom onset was 37 years. Patients had a mix of FND semiologies, which included Psychogenic Nonepileptic Seizures (71%), Functional Movement Disorder (24.3%), Functional Sensory Disorder (14%), Functional Weakness (6.5%), and Functional Speech Disorder (5.6%). Clinical evaluation scores revealed improvements over time. CONCLUSIONS: We describe a well-characterized sample of patients with various and mixed FND semiologies, who received manualized therapy, NBT, in an outpatient clinic. Patients had similar psychosocial profiles to those in clinical studies and displayed improvement in clinical measures. These results demonstrate the practicability of NBT for motor FND semiologies and for PNES, in a "real-world" outpatient practice, extending care beyond structured clinical trials.

Incidence, Predictors, and Clinical Outcomes of Device-Related Thrombus in the Amulet IDE Trial.

BACKGROUND: Device-related thrombus (DRT) following left atrial appendage occlusion (LAAO) can lead to adverse clinical outcomes. DRT rates and outcomes from randomized trials are limited. OBJECTIVES: This analysis investigated the incidence, predictors, and clinical outcomes of DRT following LAAO in the Amulet IDE (AMPLATZER Amulet LAA Occluder Trial) trial. METHODS: Successful implants occurred in 903 patients with an Amulet occluder (dual occlusive mechanism device) and 885 patients with a Watchman device (single occlusive mechanism device). These patients were then followed through 18 months and DRT was assessed by transesophageal echocardiography. RESULTS: The overall incidence of DRT was 3.9% (n = 70) with 3.4% (n = 30) in dual occlusive mechanism device patients and 4.8% (n = 40) in single occlusive mechanism device patients. Most DRTs (n = 19 of 31) were identified early (≤45 days) on the dual occlusive mechanism device, whereas most of the DRTs (n = 31 of 42) were identified late (>45 days) on the single occlusive mechanism device. Strong predictors of DRT included atrial fibrillation at time of procedure (HR: 2.44; 95% CI: 1.42-4.22; P < 0.01), female sex (HR: 1.65; 95% CI: 1.01-2.71; P = 0.04), and older age (HR: 1.04; 95% CI: 1.01-1.08; P = 0.02). There were no stroke events following DRT in the dual occlusive mechanism device group and 3 stroke events following DRT in the single occlusive mechanism device group. Patients with DRT were at a greater risk for cardiovascular mortality compared with non-DRT patients (8.7% vs 3.9%; HR: 2.33; 95% CI: 1.01-5.39; P = 0.04). CONCLUSIONS: Incidence of DRT following LAAO was low. Early DRTs are seen with the dual occlusive mechanism device and late DRTs are seen with the single occlusive mechanism device. Increased cardiovascular mortality risk in patients with DRT should be further investigated. (AMPLATZER Amulet LAA Occluder Trial; NCT02879448).

Outcomes of the roll-in cohort of the Amulet IDE trial of left atrial appendage occlusion.

Background: Left atrial appendage (LAA) occlusion is an alternative therapy to oral anticoagulants to reduce stroke risk in patients with nonvalvular atrial fibrillation (NVAF). The Amulet IDE trial compared the Amplatzer™ Amulet™ occluder (Abbott) with the Watchman™ 2.5 device (Boston Scientific) for LAA occlusion in patients with NVAF. Objective: The purpose of this study was to describe outcomes of the Amulet IDE trial roll-in cohort. Methods: At US sites up to 3 patients per implanter could be implanted with the Amulet occluder in the roll-in phase. The primary Endpoints in the Amulet IDE trial included safety (composite of procedure-related complications, all-cause death, or major bleeding at 12 months), effectiveness (composite of ischemic stroke or systemic embolism at 18 months), and rate of LAA occlusion at 45 days. Results: A total of 201 roll-in patients were enrolled. Device success occurred in 99% of patients, and device closure (residual jet ≤5 mm) was observed in 98.9% of patients at 45 days. The safety endpoint rate was numerically higher (worse) in the roll-in cohort compared to the randomized Amulet occluder cohort (18.4% vs 14.5%). Six patients (3.1%) experienced an ischemic stroke and 0 patients with a systemic embolism within 18 months, which was similar to the primary effectiveness endpoint rate in the randomized Amulet occluder cohort (2.8%). Conclusions: Despite lack of experience of the operators with the Amulet occluder in the roll-in phase, device implant success was high, a high rate of device closure was achieved, and low stroke rates were observed in patients with NVAF.

Peridevice Leak After Transcatheter Left Atrial Appendage Occlusion: An Analysis of the Amulet IDE Trial.

BACKGROUND: Peridevice leak (PDL) is a limitation of left atrial appendage occlusion. OBJECTIVES: The aim of this study was to assess the incidence of and outcomes associated with PDL in the Amulet IDE (AMPLATZER™ Amulet™ LAA Occluder Trial) randomized controlled trial. METHODS: Patients with atrial fibrillation at increased stroke risk were randomly assigned to undergo either Amulet (dual occlusive mechanism) or Watchman 2.5 (single occlusive mechanism) device implantation. Transesophageal echocardiography was performed at 45 days and 12 months postprocedure. Clinically significant PDL was defined as ≥3 mm. The primary endpoint was ischemic stroke or systemic embolism, and the secondary endpoint was stroke, systemic embolism, or cardiovascular death. The Kaplan-Meier method was used to estimate 18-month cumulative event rates landmarked at day 45 postprocedure. RESULTS: A total of 1,593 patients underwent successful left atrial appendage occlusion and had an evaluable transesophageal echocardiographic studies at 45 days. The dual-occlusive mechanism device provided superior closure (defined as leak <3 mm) compared with the single-occlusive mechanism device at 45 days (88.9% vs 74.1%; P < 0.01) and 12 months (90.5% vs. 78.3%; P < 0.01). Through 18 months, PDL was associated with a higher, but not statistically significant, risk for the primary endpoint (3.6% vs 1.8%; adjusted HR: 1.98; 95% CI: 0.93-4.19; P = 0.07) and a statistically significantly higher risk for the secondary endpoint (8.1% vs. 4.7%; adjusted HR: 1.66; 95% CI: 1.02-2.69; P = 0.04). CONCLUSIONS: The dual-occlusive mechanism device provided superior closure compared with the single-occlusive mechanism device at both 45 days and 1 year postprocedure. PDL ≥3 mm was associated with a significantly increased 18-month risk for the composite of stroke, systemic embolism, or cardiovascular death. Completeness of closure of the left atrial appendage has important implications for patient outcomes. (AMPLATZER™ Amulet™ LAA Occluder Trial [Amulet IDE]; NCT02879448).

Sex Differences in Safety and Effectiveness of LAAO: Insights From the Amulet IDE Trial.

BACKGROUND: Women have higher rates of acute complications after left atrial appendage occlusion (LAAO). However, data on long-term safety and effectiveness are limited. OBJECTIVES: The aim of this study was to examine sex-specific short- and long-term outcomes after LAAO in the Amulet IDE (Amplatzer™ Amulet™ LAA Occluder) trial. METHODS: The following outcomes were compared between men and women: in-hospital complications, device-related outcomes (peridevice leak at 45 days and device-related thrombus at 18 months), and long-term clinical outcomes (death, thromboembolism, and bleeding). Subanalyses for the interaction between sex and device type were performed. RESULTS: A total of 1,833 patients underwent attempted device implantation (917 with the Amulet and 916 with the Watchman), of whom 734 were women (40%). Device success was 97.4% in men and 97.1% in women (P = 0.60). Rates of major in-hospital adverse events were higher in women (4.4% vs 1.9%; P < 0.01), driven by major bleeding (3.7% vs 1.0%; P < 0.01) and pericardial effusion requiring intervention (2.0% vs 0.5%; P < 0.01). Peridevice leak and device-related thrombus were similar in men and women (18.3% vs 18.9% [P = 0.78] and 3.3% vs 5.0% [P = 0.10], respectively). There were no differences between men and women in rates of ischemic stroke or systemic embolism (2.6% vs 2.6%; P = 0.98), transient ischemic attack (1.3% vs 1.6%; P = 0.69), hemorrhagic stroke (0.5% vs 0.4%; P = 0.88), major bleeding (10.1% vs 10.9%; P = 0.49), cardiovascular death (4.3% vs 3.5%; P = 0.45), or all-cause death (8.9% vs 6.9%; P = 0.16). CONCLUSIONS: In the Amulet IDE trial, long-term clinical outcomes including effectiveness following LAAO were comparable in men and women despite the higher rates of in-hospital complications due to major bleeding and pericardial effusion in women. (Amplatzer™ Amulet™ LAA Occluder Trial [Amulet IDE]; NCT02879448).

Evaluation and Implementation of KIDs List Recommendations in a University Health System.

OBJECTIVE: The study aims to identify the rate of inappropriate prescribing per the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) List versus total prescribing in patients at University of Missouri Health Care hospitals. METHODS: This retrospective study evaluated orders for patients treated at University of Missouri Health Care inpatient units or emergency departments with a KIDs List medication between September 1, 2019, and September 1, 2020, or a reported adverse event to one of these medications between September 1, 2015, and September 1, 2020. Patients were excluded if the patient safety report was related to a medication error rather than an adverse event. Safety measures assessed included age and weight filtering, dose-range checking, clinical decision support, and override availability. RESULTS: There were 39 inappropriate orders and 4 possible adverse events identified. A total of 8 of 33 medications (24%) had age and weight filtering in place for at least 1 order sentence, 1 of 38 (2.6%) had dose-range checking, no medications had an active clinical decision support alert, and 33 of 38 (87%) had availability on automated dispensing cabinet override. CONCLUSIONS: Use of KIDs List medications is appropriately low, but low levels of safety measure implementation leave pediatric patients vulnerable.

Pre-hospital tracheal intubation in severe traumatic brain injury: a systematic review and meta-analysis.

BACKGROUND: Severe traumatic brain injury (TBI) continues to be a leading cause of death, particularly in young adults. Severe TBI contributes to significant socioeconomic burden secondary to the long-term disability, impacting the individual and their family, and wider society. The aim of this study was to determine whether establishing a pre-hospital definitive airway was beneficial to mortality and morbidity when compared with no pre-hospital airway. METHODS: A literature search for all relevant studies was performed in Medline, Embase, Cochrane, EBSCO, and Emcare databases, with studies comparing effects of pre-hospital tracheal intubation vs noninvasive airway management on mortality in non-paediatric patients with severe TBI. There were 1025 studies that had abstracts screened from this search. This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: We identified 19 studies that met inclusion criteria. The included studies identified no significant difference in mortality between pre-hospital and no pre-hospital tracheal intubation, with an odds ratio of 1.07 (95% CI, 0.72-1.57; P<0.001). The meta-analysis identified a trend favouring pre-hospital tracheal intubation with respect to long-term morbidity, with an odds ratio of 0.92 (95% CI, 0.51-1.67; P<0.001). CONCLUSIONS: Management of traumatic brain injuries is a constantly evolving field, with ever-changing target parameters regarding management. There is growing evidence, based on the RCTs and recent studies, that pre-hospital tracheal intubation in patients with severe TBI is beneficial if performed by well-trained, experienced practitioners in accordance with current TBI guidelines. PROSPERO REGISTRATION: CRD42021234439.

Selection against admixture and gene regulatory divergence in a long-term primate field study.

Genetic admixture is central to primate evolution. We combined 50 years of field observations of immigration and group demography with genomic data from ~9 generations of hybrid baboons to investigate the consequences of admixture in the wild. Despite no obvious fitness costs to hybrids, we found signatures of selection against admixture similar to those described for archaic hominins. These patterns were concentrated near genes where ancestry is strongly associated with gene expression. Our analyses also show that introgression is partially predictable across the genome. This study demonstrates the value of integrating genomic and field data for revealing how "genomic signatures of selection" (e.g., reduced introgression in low-recombination regions) manifest in nature; moreover, it underscores the importance of other primates as living models for human evolution.