Low-Dose Colchicine for Secondary Prevention of Coronary Artery Disease: JACC Review Topic of the Week.

Among statin-treated patients, inflammation assessed by means of high-sensitivity C-reactive protein (hsCRP) is a more powerful determinant of cardiovascular death and all-cause mortality than low-density-lipoprotein cholesterol (LDL-C). Several therapies that target residual inflammatory risk significantly reduce vascular event rates. For coronary artery disease patients already taking guideline-directed medical care, including statins, low-dose colchicine (0.5 mg/d orally) has been shown to safely lower major adverse cardiovascular events by 31% among those with stable atherosclerosis and by 23% after recent myocardial infarction. These magnitudes of benefit are larger than those seen in contemporary secondary prevention trials of adjunctive lipid-lowering agents. Low-dose colchicine is contraindicated in patients with significant renal or liver dysfunction and should be temporarily discontinued when taking concomitant agents such as clarithromycin, ketoconazole, and cyclosporine that share metabolism pathways. Lipid lowering and inflammation inhibition are not in conflict but are synergistic. In the future, combined use of aggressive LDL-C-lowering and inflammation-inhibiting therapies may become standard of care for most atherosclerosis patients. In June 2023, the U.S. Food and Drug Administration approved the use of low-dose colchicine to reduce the risk of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease.

Trends in the Use of Procalcitonin at US Children's Hospital Emergency Departments.

OBJECTIVES: Procalcitonin (PCT) was approved by the Food and Drug Administration in 2016. We assessed changes in PCT utilization over time in emergency departments (EDs) at US Children's Hospitals and identified the most common conditions associated with PCT testing. METHODS: We performed a cross-sectional study of children <18 years of age presenting to 1 of 33 EDs contributing data to the Pediatric Health Information System between 2016 and 2020. We examined trends in PCT utilization during an ED encounter between institutions and over the study period. Using All Patients Refined Diagnosis Related Groups, we identified the most common conditions for which PCT was obtained (overall, and relative to the performance of a complete blood count). RESULTS: The overall rate of PCT testing increased from 0.2% of all ED visits in 2016 to 1.8% in 2020. Across hospitals, the proportion of ED encounters with PCT obtained ranged from 0.0005% to 4.3% with marked variability in overall use. Among children who had PCT testing performed, the most common diagnoses were fever (10.7%), infections of the upper respiratory tract (9.2%), and pneumonia (5.9%). Relative to the performance of a complete blood count, rates of PCT testing were highest among children with sepsis (28.7%), fever (21.4%), pulmonary edema/respiratory failure (17.3%), and bronchiolitis/respiratory syncytial virus pneumonia (15.6%). CONCLUSIONS: PCT utilization in the ED has increased over the past 5 years with variation between hospitals. PCT is most frequently obtained for children with respiratory infections and febrile illnesses.

Prognostic Value of Electrocardiographic QRS Diminution in Patients Hospitalized With COVID-19 or Influenza.

During the clinical care of hospitalized patients with COVID-19, diminished QRS amplitude on the surface electrocardiogram (ECG) was observed to precede clinical decompensation, culminating in death. This prompted investigation into the prognostic utility and specificity of low QRS complex amplitude (LoQRS) in COVID-19. We retrospectively analyzed consecutive adults admitted to a telemetry service with SARS-CoV-2 (n = 140) or influenza (n = 281) infection with a final disposition-death or discharge. LoQRS was defined as a composite of QRS amplitude <5 mm or <10 mm in the limb or precordial leads, respectively, or a ≥50% decrease in QRS amplitude on follow-up ECG during hospitalization. LoQRS was more prevalent in patients with COVID-19 than influenza (24.3% vs 11.7%, p = 0.001), and in patients who died than survived with either COVID-19 (48.1% vs 10.2%, p <0.001) or influenza (38.9% vs 9.9%, p <0.001). LoQRS was independently associated with mortality in patients with COVID-19 when adjusted for baseline clinical variables (odds ratio [OR] 11.5, 95% confidence interval [CI] 3.9 to 33.8, p <0.001), presenting and peak troponin, D-dimer, C-reactive protein, albumin, intubation, and vasopressor requirement (OR 13.8, 95% CI 1.3 to 145.5, p = 0.029). The median time to death in COVID-19 from the first ECG with LoQRS was 52 hours (interquartile range 18 to 130). Dynamic QRS amplitude diminution is a strong independent predictor of death over not only the course of COVID-19 infection, but also influenza infection. In conclusion, this finding may serve as a pragmatic prognostication tool reflecting evolving clinical changes during hospitalization, over a potentially actionable time interval for clinical reassessment.

Contamination Measurements from Simultaneous Activated Potassium Bromide Radiological Dispersal Devices with a Collimated Vehicular Sensor.

ABSTRACT: Surface contamination was quantified over a distributed source of activated potassium bromide from three detonations of Radiological Dispersal Devices (RDDs) at the Idaho National Laboratory Radiological Response Training Range, with a maximum sampled area of 19,900 m2, to provide a baseline comparison with other rapid, remote mapping methods. Measurements were obtained with a cerium bromide sensor collimated to a field of view of 3.14 m2, using lead shielding, and towed behind a ground vehicle. Sensor response correction factors for activated potassium bromide were calculated through simulation with SWORD to obtain activity per meter-squared. Continuous maps were produced by interpolating coverage from lawnmower raster scans. Radiological data was overlaid with aerial imagery from an automated unmanned aerial vehicle flight to provide contextual geological information relative to contamination levels. The contamination distribution measurements will be compared to unmanned aerial vehicle methods in future work.

Population dynamics and methodological assessments from a 15-year period of Amphibian monitoring in British Columbia's Southern Gulf Islands.

With amphibian populations facing a multitude of threats, including habitat loss, climate change, invasive species and infectious diseases, it is important to identify valuable amphibian habitat and the imminent pressures these environments face. Between 2004 and 2019, 6 years of amphibian surveys were conducted at Greenburn, Roe and McLean lakes in the Southern Gulf Islands of British Columbia, Canada. We assessed (1) species composition and trends of native amphibians, including at-risk northern red-legged frog (Rana aurora); (2) observations of invasive American bullfrog (Lithobates catesbeianus); and (3) the efficacy of visual encounter and trapping survey methods in determining multi-species amphibian occupancy. The shallow, semi-ephemeral McLean Lake hosted more amphibian species and more breeding activity than the larger, deeper waters of Greenburn and Roe lakes. Despite multiple observations, bullfrogs have thus far not established a detectable population within these lakes, with the presence of native and introduced predators as potential contributing factors. Declining trends in occupancy of native populations of R. aurora, Pacific chorus frog (Pseudacris regilla) and rough-skinned newt (Taricha granulosa) were observed at all three lakes. Results varied within years by species and survey method, highlighting the importance of effective replication and employing complementary survey methods to optimize studies of amphibian occupancy. These observations also emphasize the value of shallow, small- to medium-sized waterbodies to native amphibian populations in the Southern Gulf Islands. As these waterbodies become increasingly threatened by global climate change and habitat degradation, the potential impacts of declining freshwater ecosystem health on amphibian populations should be considered.

Provision of Guideline-Based Pediatric Asthma Care in US Emergency Departments.

OBJECTIVES: National guidelines for routine pediatric acute asthma care recommend providing corticosteroids, and discourage routinely obtaining chest radiographs (CXRs) and using antibiotics. We examined rates of adherence to all 3 of these aspects during emergency department (ED) visits and compared performance between pediatric and general EDs. METHODS: Using the National Hospital Ambulatory Medical Care Survey, we included all nontransfer ED visits for patients younger than 19 years with a diagnosis of asthma and treatment with albuterol from 2005 to 2015. Guideline-based care, defined as (1) corticosteroids, (2) no antibiotics, and (3) no CXR, was assessed for each visit. Hospitals were categorized as pediatric or general and compared according to rates of guideline-based care. Multivariable analyses were used to identify demographic and hospital-level characteristics associated with guideline-based care. RESULTS: More than 7 million ED visits met eligibility criteria. Antibiotic provision and CXR acquisition were significantly higher in general EDs (20% vs 11%, 40% vs 26%, respectively), while steroid provision was similar (63% vs 62%). Overall, 34% of visits involved guideline-based care, with a higher rate for pediatric EDs compared with general EDs (42% to 31%). Visit at a pediatric ED (odds ratio, 1.62 [confidence interval 1.17-2.25]) and black race (odds ratio, 1.48 [confidence interval 1.07-2.02]) were independently associated with guideline-based care in a multivariate analysis. CONCLUSIONS: Guideline-based care was more common in pediatric EDs, although only one-third of all pediatric-age visits met the definition of guideline-based care. Future policy and education efforts to reduce unnecessary antibiotic and CXR use for children with asthma are warranted.

Spatial Concentration and Spillover: Eviction Dynamics in Neighborhoods of Los Angeles, California, 2005-2015.

The lack of sufficient affordable housing in Los Angeles, California burdens many renter households with the threat of an eviction. Research has identified individual- and neighborhood-level sociodemographic correlates of eviction, but the uneven distribution of sociodemographic characteristics and housing conditions across neighborhoods likely produces broader patterns of spatial clustering in eviction prevalence across local areas. We use spatial autoregressive models to explain the spatial concentration and spillover effects for two types of formal eviction filings-court-based and no-fault Ellis Act petitions-within and across census tracts in Los Angeles. Court-based filings show greater and more persistent spatial concentration, particularly in neighborhoods with higher percentages of Black residents. We find evidence of spatial correlation for both types of eviction, however, suggesting that identifying the spatial distribution of eviction prevalence across local areas is important to understanding how location shapes eviction risk in metropolitan areas.

ß2-adrenoreceptor Signaling Increases Therapy Resistance in Prostate Cancer by Upregulating MCL1.

There is accumulating evidence that continuous activation of the sympathetic nervous system due to psychosocial stress increases resistance to therapy and accelerates tumor growth via ß2-adrenoreceptor signaling (ADRB2). However, the effector mechanisms appear to be specific to tumor type. Here we show that activation of ADRB2 by epinephrine, increased in response to immobilization stress, delays the loss of MCL1 apoptosis regulator (MCL1) protein expression induced by cytotoxic drugs in prostate cancer cells; and thus, increases resistance of prostate cancer xenografts to cytotoxic therapies. The effect of epinephrine on MCL1 protein depended on protein kinase A (PKA) activity, but was independent from androgen receptor expression. Furthermore, elevated blood epinephrine levels correlated positively with an increased MCL1 protein expression in human prostate biopsies. In summary, we demonstrate that stress triggers an androgen-independent antiapoptotic signaling via the ADRB2/PKA/MCL1 pathway in prostate cancer cells. IMPLICATIONS: Presented results justify clinical studies of ADRB2 blockers as therapeutics and of MCL1 protein expression as potential biomarker predicting efficacy of apoptosis-targeting drugs in prostate cancer.

Multiobjective and Interactive Genetic Algorithms for Weight Tuning of a Model Predictive Control-Based Motion Cueing Algorithm.

Driving simulators are effective tools for training, virtual prototyping, and safety assessment which can minimize the cost and maximize road safety. Despite the aim of a realistic motion generation for the impression of real-world driving, motion simulators are bound in a limited workspace. Motion cueing algorithms (MCAs) aim to plan an acceptable motion feeling for drivers, without infringing the simulated boundaries. Recently, model predictive control (MPC) has been widely used in MCAs; however, the tuning process for finding the best weights of the MPC optimization is still a challenge. As there are several objectives for the optimization without any standard weighting for solution evaluations, a nonbiased scalarization of solutions for the purpose of comparison is impossible. In this paper, a clear method for obtaining the best MPC weighting has been proposed. This method searches for the best tune of MPC cost function weights, reduces the user burden for weight tuning while receiving feedback from the user satisfaction. The MPC-based MCA weights are optimized using a multiobjective genetic algorithm (GA) considering objectives, such as minimization of motion inputs (linear acceleration and angular velocity), input rates, output displacements and the sensed motion errors. Any process based on trial-and-error has been omitted. The adjusted weights have to satisfy a set of predefined conditions related to maximum tolerated error and maximum displacement. The obtained Pareto-front is used for decision making via an interactive GA (IGA), aiming for maximization of the decision maker's satisfaction. A Web interface is developed to interact with the IGA and to influence the region of searching. Simulation results show the superiority of the proposed method compared with the previous empirical tuning method. The sensed motion error is minimized using the proposed method and with the same available workspace, a more realistic motion can be rendered to the driver.

Preseason Y Balance Test Scores are not Associated with Noncontact Time-Loss Lower Quadrant Injury in Male Collegiate Basketball Players.

The Y-Balance Test-Lower Quarter has shown promise as a screening tool for identifying athletes at risk of injury. Subsequent studies, utilizing heterogeneous populations or different operational definitions of injury, have presented equivocal findings. Therefore, studies evaluating the efficacy of the Y-Balance Test to discriminate injury risk in a homogeneous population is warranted. One-hundred sixty-nine male (mean age 19.9 ± 1.5 y) collegiate basketball players were recruited during 2 consecutive seasons (2016⁻2017/2017⁻2018). Athletes completed the Y-Balance testing protocol at the start of each preseason. Athletic trainers tracked noncontact time-loss lower quadrant injuries over the course of the season. Receiver operator characteristic curves failed to identify cutoff scores; therefore, previously reported cutoff scores were utilized when calculating relative risk. There was no association between preseason Y-Balance Test scores and noncontact time-loss lower back or lower extremity injury in a population of male collegiate basketball players. This study adds to a growing body of evidence that demonstrates no relationship between preseason Y-Balance Test scores and subsequent injury.

COMPARISON OF NON-CONTACT AND CONTACT TIME-LOSS LOWER QUADRANT INJURY RATES IN MALE COLLEGIATE BASKETBALL PLAYERS: A PRELIMINARY REPORT.

BACKGROUND: Male collegiate basketball (BB) players are at risk for musculoskeletal injury. The rate of time-loss injury in men's collegiate BB, for all levels of National Collegiate Athletic Association (NCAA) competition, ranges from 2.8 to 4.3 per 1000 athletic exposures (AE) during practices and 4.56 to 9.9 per 1000 AE during games. The aforementioned injury rates provide valuable information for sports medicine professionals and coaching staffs. However, many of the aforementioned studies do not provide injury rates based on injury mechanism, region of the body, or player demographics. HYPOTHESIS/ PURPOSE: The purpose of this study is two-fold. The first purpose of this study was to report lower quadrant (LQ = lower extremities and low back region) injury rates, per contact and non-contact mechanism of injury, for a cohort of male collegiate basketball (BB) players. The second purpose was to report injury risk based on prior history of injury, player position, and starter status. STUDY DESIGN: Prospective, descriptive, observational cohort. METHODS: A total of 95 male collegiate BB players (mean age 20.02 ± 1.68 years) from 7 teams (NCAA Division II = 14, NCAA Division III = 43, NAIA = 21, community college = 17) from the Portland, Oregon region were recruited during the 2016-2017 season to participate in this study. Each athlete was asked to complete an injury history questionnaire. The primary investigator collected the following information each week from each team's athletic trainer: athletic exposures (AE; 1 AE = game or practice) and injury updates. RESULTS: Thirty-three time-loss LQ injuries occurred during the study period. The overall time-loss injury rate was 3.4 per 1000 AE. Division III BB players had the highest rates of injury. There was no difference in injury rates between those with or without prior injury history. Guards had a significantly greater rate of non-contact time-loss injuries (p = 0.04). CONCLUSIONS: Guards experienced a greater rate of LQ injury than their forward/center counterparts. Starters and athletes with a prior history of injury were no more likely to experience a non-contact time-loss injury than nonstarters or those without a prior history of injury. These preliminary results are a novel presentation of injury rates and risk for this population and warrant continued investigation. LEVEL OF EVIDENCE: 2.

A method to identify pediatric high-risk diagnoses missed in the emergency department.

BACKGROUND: Diagnostic error can lead to increased morbidity, mortality, healthcare utilization and cost. The 2015 National Academy of Medicine report "Improving Diagnosis in Healthcare" called for improving diagnostic accuracy by developing innovative electronic approaches to reduce medical errors, including missed or delayed diagnosis. The objective of this article was to develop a process to detect potential diagnostic discrepancy between pediatric emergency and inpatient discharge diagnosis using a computer-based tool facilitating expert review. METHODS: Using a literature search and expert opinion, we identified 10 pediatric diagnoses with potential for serious consequences if missed or delayed. We then developed and applied a computerized tool to identify linked emergency department (ED) encounters and hospitalizations with these discharge diagnoses. The tool identified discordance between ED and hospital discharge diagnoses. Cases identified as discordant were manually reviewed by pediatric emergency medicine experts to confirm discordance. RESULTS: Our computerized tool identified 55,233 ED encounters for hospitalized children over a 5-year period, of which 2161 (3.9%) had one of the 10 selected high-risk diagnoses. After expert record review, we identified 67 (3.1%) cases with discordance between ED and hospital discharge diagnoses. The most common discordant diagnoses were Kawasaki disease and pancreatitis. CONCLUSIONS: We successfully developed and applied a semi-automated process to screen a large volume of hospital encounters to identify discordant diagnoses for selected pediatric medical conditions. This process may be valuable for informing and improving ED diagnostic accuracy.

Pediatric Review and Perioperative Considerations.

Perioperative management of pediatric patients demands knowledge of the relevant ways in which pediatric physiology and physiological regulation differs from the adult. This article will outline some of these most pertinent differences, and also present current recommendations for perioperative management.

The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation.

Interleukin 33 (IL-33) is among the earliest-released cytokines in response to allergens that orchestrate type 2 immunity. The prolyl cis-trans isomerase PIN1 is known to induce cytokines for eosinophil survival and activation by stabilizing cytokines mRNAs, but the function of PIN1 in upstream signaling pathways in asthma is unknown. Here we show that interleukin receptor associated kinase M (IRAK-M) is a PIN1 target critical for IL-33 signaling in allergic asthma. NMR analysis and docking simulations suggest that PIN1 might regulate IRAK-M conformation and function in IL-33 signaling. Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. Thus, the IL-33-PIN1-IRAK-M is an axis critical for dendritic cell activation, type 2 immunity and IL-33 induced airway inflammation.

Fluid Balance Is Associated with Clinical Outcomes and Extravascular Lung Water in Children with Acute Asthma Exacerbation.

RATIONALE: The effects of fluid administration during acute asthma exacerbation are likely unique in this patient population: highly negative inspiratory intrapleural pressure resulting from increased airway resistance may interact with excess fluid administration to favor the accumulation of extravascular lung water, leading to worse clinical outcomes. OBJECTIVES: Investigate how fluid balance influences clinical outcomes in children hospitalized for asthma exacerbation. METHODS: We analyzed the association between fluid overload and clinical outcomes in a retrospective cohort of children admitted to an urban children's hospital with acute asthma exacerbation. These findings were validated in two cohorts: a matched retrospective and a prospective observational cohort. Finally, ultrasound imaging was used to identify extravascular lung water and investigate the physiological basis for the inferential findings. MEASUREMENTS AND MAIN RESULTS: In the retrospective cohort, peak fluid overload [(fluid input - output)/weight] is associated with longer hospital length of stay, longer treatment duration, and increased risk of supplemental oxygen use (P values < 0.001). Similar results were obtained in the validation cohorts. There was a strong interaction between fluid balance and intrapleural pressure: the combination of positive fluid balance and highly negative inspiratory intrapleural pressures is associated with signs of increased extravascular lung water (P < 0.001), longer length of stay (P = 0.01), longer treatment duration (P = 0.03), and increased risk of supplemental oxygen use (P = 0.02). CONCLUSIONS: Excess volume administration leading to fluid overload in children with acute asthma exacerbation is associated with increased extravascular lung water and worse clinical outcomes.