SpO2 /FIO2 on Presentation as a Predictor for Early Hemodynamic Deterioration in Intermediate Risk Acute Pulmonary Embolism.

BACKGROUND: Patients with intermediate-risk acute pulmonary embolism are at risk of hemodynamic deterioration, and identification of risk factors for decompensation could guide the administration of thrombolytics. We aimed to assess whether SpO2 /FIO2 on presentation is associated with early hemodynamic deterioration in this population. METHODS: A retrospective chart review of subjects admitted between 2006 and 2018 with intermediate-risk pulmonary embolism (hemodynamically stable with right ventricle to left ventricle ratio > 0.9 or tricuspid annular plane systolic excursion < 18 mm). Early hemodynamic deterioration was defined as requirements for vasopressors or rescue thrombolytics within 48 h. Results are presented as median (interquartile range). RESULTS: A total of 178 subjects were included. Early hemodynamic deterioration occurred in 13% of the subjects and was associated with a median (interquartile range) lower SpO2 /FIO2 on presentation in univariate analysis (243 [123-275] versus 438 [335-457], P < .001) and in a multivariate analysis, including heart rate and right ventricle to left ventricle ratio as covariates (odds ratio 0.992, 95% CI 0.987-0.996; P < .001). The initial SpO2 /FIO2 predicted hemodynamic deterioration with an area under the receiver operating characteristic curve of 0.81 and a threshold of 260 was associated with a sensitivity of 74% and specificity of 88%. Sensitivity analyses restricted to subjects with hypoxemia on presentation and subjects with an elevated troponin level led to similar results. CONCLUSIONS: In intermediate-risk pulmonary embolism, SpO2 /FIO2 on presentation can help predict the risk of early hemodynamic deterioration.

Lower Cutoffs for LC-MS/MS Urine Drug Testing Indicates Better Patient Compliance.

BACKGROUND: Urine drug testing is used by health care providers to determine a patient's compliance to their prescribed regimen and to detect non-prescribed medications and illicit drugs. However, the cutoff levels used by clinical labs are often arbitrarily set and may not reflect the urine drug concentrations of compliant patients. OBJECTIVES: Our aim was to test the hypothesis that commonly used cutoffs for many prescribed and illicit drugs were set too high, and methods using these cutoffs may yield a considerable number of false-negative results. The goals of this study were to outline the way to analyze patient results and estimate a more appropriate cutoff, develop and validate a high sensitivity analytical method capable of quantitating drugs and metabolites at lower than the commonly used cutoffs, and determine the number of true positive results that would have been missed when using the common cutoffs. STUDY DESIGN: This was a retrospective study of urine specimens submitted for urine drug testing as part of the monitoring of prescription drug compliance described in chronic opioid therapy treatment guidelines. SETTING: The study was set in a clinical toxicology laboratory, using specimens submitted for routine analysis by health care providers in the normal course of business. METHODS: Lognormal distributions of test results were generated and fitted with a trendline to estimate the required cutoff level necessary to capture the normal distributions of each drug for the patient population study. A validated laboratory derived liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis capable of achieving the required cutoff levels was developed for each drug and/or metabolite. RESULTS: The study shows that a lognormal distribution of patient urine test results fitted with a trendline is appropriate for estimating the required cutoff levels needed to assess medication adherence. The study showed a wide variation in the false-negative rate, ranging from 1.5% to 94.3% across a range of prescribed and illicit drugs. LIMITATIONS: The patient specimens were largely sourced from patients in either a long-term pain management program or in treatment for substance use disorder in the US. These specimens may not be representative of patients in other types of treatment or in countries with different approaches to these issues. CONCLUSIONS: The high-sensitivity method reduces false-negative results which could negatively impact patient care. Clinicians using less sensitive methods for detecting and quantifying drugs and metabolites in urine should exercise caution in assessing patient adherence using and changing the treatment plan based on those results. KEY WORDS: Urine drug testing, patient adherence, clinical toxicology, immunoassay, LC-MS, definitive drug testing, REMS, negative test results, false negative.

Top 10 Lessons Learned from Project Healthy Schools.

Childhood obesity is increasing in the United States; obese children are more likely to become obese adults with obesity-associated health issues. Effective programs designed to reduce the prevalence of childhood overweight and obesity are needed. We sought to review one such program, Project Healthy Schools (PHS), for key findings. Project Healthy Schools is a health curriculum that includes educational lessons, school environment changes, and health measurement. Data have shown improvement in numerous metrics after the program, including positive changes in physiologic measures and healthier lifestyle behaviors. The school's socioeconomic status has been shown to correlate with baseline and follow-up measures, and gender differences exist. Additionally, school environmental changes support improved health behaviors. The collaborative effort and support of various stakeholders have led to the success of this health education program, resulting in numerous physiologic and behavioral benefits in middle school students throughout Michigan, and providing a replicable, real-world approach to combating childhood obesity.

Using Milestones as Evaluation Metrics During an Emergency Medicine Clerkship.

BACKGROUND: The Accreditation Council for Graduate Medical Education's (ACGME) Milestones presumes graduating medical students will enter residency proficient at Milestone level 1 for 23 skills. The Next Accreditation System now includes Milestones for each postgraduate specialty, and it is unlikely that schools will document every emergency medicine (EM) applicant's EM-specific skills in their performance evaluation. OBJECTIVES: The goals of this research were to determine if assessment of the Milestones was feasible during a medical student clerkship and examine the proportion of medical students performing at Milestone level 1. METHODS: This study was conducted at a center with Liaison Committee on Medical Education-approved medical training and a 4-year EM residency. Using traditional clerkship, we studied the feasibility of an ACGME EM Milestones-based clerkship assessment. Data led to redesign of the clerkship and its evaluation process, including all level 1 anchor(s) to add "occasionally" (>60%), "usually" (>80%), and "always" (100%) on a Likert scale to on-shift assessment forms. RESULTS: During the feasibility phase (2013-14), 75 students rotated though the clerkship; 55 evaluations were issued and 50 contained the Milestone summary. Eight deficiencies were noted in Milestone 12 and three in Milestone 14. After changes, 49 students rotated under the new evaluation rubric. Of 575 completed on-shift evaluations, 16 Milestone deficiencies were noted. Of 41 institutional evaluations issued, only one student had deficiencies noted, all of which pertained to patient care. All evaluations in this second cohort contained each student's Milestone proficiency. CONCLUSIONS: Assessment of the Milestones is feasible. Communication of ACGME EM Milestone proficiency may identify students who require early observation or remediation. The majority of students meet the anchors for the Milestones, suggesting that clerkship assessment with the ACGME EM Milestones does not adequately differentiate students.

An automated method to assay locomotor activity in third instar Drosophila melanogaster larvae.

INTRODUCTION: The purpose of these studies was to describe a novel application of an automated data acquisition/data reduction system, DanioVision™ by Noldus. DanioVision™ has the ability to detect changes in locomotor activity in third instar Drosophila melanogaster larvae. The noncompetitive GABAA receptor antagonist picrotoxin (PTX), was used as a pharmacologic agent to decrease locomotor activity. METHODS: Two strains of Drosophila were used in these studies; wild-type flies and flies with a mutation in the Rdl gene (Rdl(MD-RR)). Rdl(MD-RR)Drosophila are naturally occurring mutants that express an aberrant form of the GABAA receptor, which has a lower affinity for PTX, but not GABA itself. Larvae, extracted from food in 20% sucrose, were randomly placed into vials containing vehicle or PTX (0.03-3mM). After incubation of 2-24h, individual larvae were put in each well of a 6-well culture plate previously coated with 2% agar, the plate was then placed in the DanioVision™ apparatus. The activity of individual larva was recorded for 5 min, digitized and analyzed using Ethovision® XT software. RESULTS: Incubation of third instar wild-type larvae in 1mM PTX for 4 or 24h decreased activity; whereas, a 2h incubation in PTX was without effect. PTX caused a concentration-dependent decrease in activity as demonstrated by consistently reduced locomotor activity with 1.0 and 3.0mM: 0.3mM resulted in variable decreases in locomotor activity and 0.03 mM yielded no effect. By contrast, PTX did not affect activity in Rdl(MD-RR) larvae even at the highest concentration, 3.0mM. DISCUSSION: Using an automated data acquisition system, it was found that PTX decreases activity in third instar Drosophila larvae due to a selective blockade of the GABAA receptor. The method will reduce the likelihood of human error and bias, as well as increase the speed and ease of data collection and analysis.

The role of INDY in metabolism, health and longevity.

Indy (I'm Not Dead Yet) encodes the fly homolog of a mammalian SLC13A5 plasma membrane transporter. INDY is expressed in metabolically active tissues functioning as a transporter of Krebs cycle intermediates with the highest affinity for citrate. Decreased expression of the Indy gene extends longevity in Drosophila and C. elegans. Reduction of INDY or its respective homologs in C. elegans and mice induces metabolic and physiological changes similar to those observed in calorie restriction. It is thought that these physiological changes are due to altered levels of cytoplasmic citrate, which directly impacts Krebs cycle energy production as a result of shifts in substrate availability. Citrate cleavage is a key event during lipid and glucose metabolism; thus, reduction of citrate due to Indy reduction alters these processes. With regards to mammals, mice with reduced Indy (mIndy(-/-)) also exhibit changes in glucose metabolism, mitochondrial biogenesis and are protected from the negative effects of a high calorie diet. Together, these data support a role for Indy as a metabolic regulator, which suggests INDY as a therapeutic target for treatment of diet and age-related disorders such as Type II Diabetes and obesity.

Increased mitochondrial biogenesis preserves intestinal stem cell homeostasis and contributes to longevity in Indy mutant flies.

The Drosophila Indy (I'm Not Dead Yet) gene encodes a plasma membrane transporter of Krebs cycle intermediates, with robust expression in tissues associated with metabolism. Reduced INDY alters metabolism and extends longevity in a manner similar to caloric restriction (CR); however, little is known about the tissue specific physiological effects of INDY reduction. Here we focused on the effects of INDY reduction in the Drosophila midgut due to the importance of intestinal tissue homeostasis in healthy aging and longevity. The expression of Indy mRNA in the midgut changes in response to aging and nutrition. Genetic reduction of Indy expression increases midgut expression of the mitochondrial regulator spargel/dPGC-1, which is accompanied by increased mitochondrial biogenesis and reduced reactive oxygen species (ROS). These physiological changes in the Indy mutant midgut preserve intestinal stem cell (ISC) homeostasis and are associated with healthy aging. Genetic studies confirm that dPGC-1 mediates the regulatory effects of INDY, as illustrated by lack of longevity extension and ISC homeostasis in flies with mutations in both Indy and dPGC1. Our data suggest INDY may be a physiological regulator that modulates intermediary metabolism in response to changes in nutrient availability and organismal needs by modulating dPGC-1.

Surgical treatment of hyperpronation using an extraosseous talotarsal stabilization device: radiographic outcomes in 70 adult patients.

The purpose of this study was to determine radiographic correction achieved in adult patients treated with an extraosseous talotarsal stabilization (EOTTS) procedure. Patients diagnosed with flexible/reducible talotarsal joint dislocation (partial) underwent surgical correction with the HyProCure(®) EOTTS device. Preoperative and postoperative weightbearing radiographs taken in the anteroposterior (AP) and lateral views for a total 95 feet (in 70 patients) were analyzed to determine standardized radiographic angles, and to quantify the correction obtained after the EOTTS procedure. Postoperative radiographs were taken at an average follow-up of 17 days from the surgery date. The mean preoperative and postoperative talar second metatarsal angles (measured from the AP radiographs) were 24.8° ± 1.0° and 5.8° ± 0.9°, respectively, that is, mean decrease by 19°. The mean preoperative and postoperative talar declination angles (measured from the lateral radiographs) were 25.1° ± 0.7° and 19.4° ± 0.5°, respectively, that is, mean decrease by 5.7°. The mean preoperative and postoperative calcaneal inclination angles (measured from the lateral radiographs) were 21° ± 0.7° and 21.8° ± 0.7°, respectively, that is, mean increase by 0.8°. Postoperatively, the talar second metatarsal and talar declination angles were reduced to average values reported in the literature for normal feet. This study shows the efficacy of a minimally invasive EOTTS procedure in restoring the normal angular relationships between hindfoot and forefoot osseous structures on weightbearing, in both the transverse and sagittal planes. This indicates stabilization of the talotarsal joint complex and elimination of hyperpronation, which may lead to reduced pain, improved foot functional abilities, and patient satisfaction.

Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke.

Exercise preconditioning has been shown to reduce neuronal damage in ischemic/reperfusion (I/R) injury. ERK1/2 signaling in injury has been thought to modulate neuroprotection. In this study, we investigated the effects of ERK1/2 activation on the expression and activity of MMP-9 and downstream neuronal apoptosis. Adult male Sprague-Dawley rats were subjected to 30min of exercise on a treadmill for 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament. Apoptotic protein caspase-3 and neuronal apoptosis in cortex and striatum was determined by Western blot at 24h reperfusion and TUNEL staining at 48h reperfusion in 5 I/R injury groups: no treatment, MMP-9 inhibitor (doxycycline), pre-ischemic exercise, exercised animals undergone ERK1/2 inhibition (U0126), and dual inhibition of ERK1/2 and MMP-9 in exercised ischemic rats. Cerebral MMP-9 expression in ischemic rats with different treatment was determined at 6, 12 and 24h reperfusion by real-time PCR for mRNA, Western blot for protein and zymography for enzyme activity. Exercise preconditioning significantly (p<0.05) reduced apoptosis determined by caspase-3 and TUNEL. In non-exercised rats, doxycycline treatment had significant (p<0.05) reductions in apoptosis after I/R injury. The dual ERK1/2-MMP-9 inhibited exercised animals had significantly (p<0.05) reduced neuronal apoptosis that was similar to that seen in exercised ischemic rats. MMP-9 expression in I/R injury was significantly (p<0.05) reduced in the exercised animals as compared to non-exercised controls. When ERK1/2 was inhibited, the reduced MMP-9 expression was reversed to the level seen in the non-exercised controls. This study has suggested that exercise-induced neuroprotection in I/R injury may be mediated by MMP-9 and ERK1/2 expression, leading to a reduction in neuronal apoptosis.

Aquatic plant-derived changes in oil sands naphthenic acid signatures determined by low-, high- and ultrahigh-resolution mass spectrometry.

Mass spectrometry is a common tool for studying the fate of complex organic compound mixtures in oil sands processed water (OSPW), but a comparison of low-, high- ( approximately 10 000), and ultrahigh-resolution ( approximately 400 000) instrumentation for this purpose has not previously been made. High-resolution quadrupole time-of-flight mass spectrometry (QTOF MS) and ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), with negative-ion electrospray ionization, provided evidence for the selective dissipation of components in OSPW. Dissipation of oil sands naphthenic acids (NAs with general formula C(n)H(2n+z)O(2) where n is the number of carbon atoms, and Z is zero or a negative even number describing the number of rings) was masked (by components such as fatty acids, O(3), O(5), O(6), O(7), SO(2), SO(3), SO(4), SO(5), SO(6), and NO(4) species) at low resolution (1000) when using a triple quadrupole mass spectrometer. Changes observed in the relative composition of components in OSPW appear to be due primarily to the presence of plants, specifically cattails (Typha latifolia) and their associated microorganisms. The observed dissipation included a range of heteratomic species containing O(2), O(3), O(4), and O(5), present in Athabasca oil sands acid extracts. For the heteratomic O(2) species, namely naphthenic acids, an interesting structural relationship suggests that low and high carbon number NAs are dissipated by the plants preferentially, with a minimum around C(14)/C(15). Other heteratomic species containing O(6), O(7), SO(2), SO(3), SO(4), SO(5), SO(6), and NO(4) appear to be relatively recalcitrant to the cattails and were not dissipated to the same extent in planted systems.

Four weeks of optimal load ballistic resistance training at the end of season attenuates declining jump performance of women volleyball players.

Anecdotal and research evidence is that vertical jump performance declines over the competitive volleyball season. The purpose of this study was to evaluate whether a short period of ballistic resistance training would attenuate this loss. Fourteen collegiate women volleyball players were trained for 11 weeks with periodized traditional and ballistic resistance training. There was a 5.4% decrease (p < 0.05) in approach jump and reach height during the traditional training period (start of season to midseason), and a 5.3% increase (p < 0.05) during the ballistic training period (midseason to end of season), but values were not different from start to end of season. These changes in overall jump performance were reflective of changes in underlying neuromuscular performance variables: in particular, power output and peak velocity during loaded jump squats, countermovement jumps, and drop jumps. During the first 7 weeks of traditional heavy resistance training, it appears that the neuromuscular system is depressed, perhaps by the combination of training, game play, and skills practice precluding adequate recovery. Introduction of a novel training stimulus in the form of ballistic jump squats and reduction of heavy resistance training of the leg extensors stimulated a rebound in performance, in some cases to exceed the athlete's ability at the start of the season. Periodization of in-season training programs similar to that used in this study may provide volleyball players with good vertical jump performance for the crucial end-of-season games.

Evaluation of a lower-body compression garment.

The aims of this study were to determine how custom-fit compression shorts affect athletic performance and to examine the mechanical properties of the shorts. Ten male and 10 female track athletes on a university's nationally competitive track team, specializing in sprint or jump events, participated in the study. Testing utilized the compression shorts with loose-fitting gym shorts as the control garment. Several significant effects were revealed for the custom-fit compressive garment. Although 60 m sprint time was not affected, hip flexion angle was reduced. Skin temperature increased more and at a faster rate during a warm-up protocol. Muscle oscillation was decreased during vertical jump landing. Countermovement vertical jump height increased when the participants were wearing the custom-fit compression garment. In materials testing, the elasticity of the compressive garment provides increased flexion and extension torque at the end range of extension and flexion, respectively, and may assist the hamstrings in controlling the leg at the end of the swing phase in sprinting. The compressive garment significantly reduced impact force by 27% compared with American football pants alone. Through various mechanisms, these findings may translate into an effect on athletic performance and a reduction in injuries.