Metabolomic profiling of metoprolol hypertension treatment reveals altered gut microbiota-derived urinary metabolites.

INTRODUCTION: Metoprolol succinate is a long-acting beta-blocker prescribed for the management of hypertension (HTN) and other cardiovascular diseases. Metabolomics, the study of end-stage metabolites of upstream biologic processes, yield insight into mechanisms of drug effectiveness and safety. Our aim was to determine metabolomic profiles associated with metoprolol effectiveness for the treatment of hypertension. METHODS: We performed a prospective pragmatic trial (NCT02293096) that enrolled patients between 30 and 80 years with uncontrolled HTN. Patients were started on metoprolol succinate at a dose based upon systolic blood pressure (SBP). Urine and blood pressure measurements were collected weekly. Individuals with a 10% decline in SBP or heart rate (HR) were considered responsive. Genotype for the CYP2D6 enzyme, the primary metabolic pathway for metoprolol, was evaluated for each subject. Unbiased metabolomic analyses were performed on urine samples using UPLC-QTOF mass spectrometry. RESULTS: Urinary metoprolol metabolite ratios are indicative of patient CYP2D6 genotypes. Patients taking metoprolol had significantly higher urinary levels of many gut microbiota-dependent metabolites including hydroxyhippuric acid, hippuric acid, and methyluric acid. Urinary metoprolol metabolite profiles of normal metabolizer (NM) patients more closely correlate to ultra-rapid metabolizer (UM) patients than NM patients. Metabolites did not predict either 10% SBP or HR decline. CONCLUSION: In summary, urinary metabolites predict CYP2D6 genotype in hypertensive patients taking metoprolol. Metoprolol succinate therapy affects the microbiome-derived metabolites.

Genomic markers associated with successful treatment of hypertension with lisinopril: A pilot study.

OBJECTIVE: To identify single nucleotide variants (SNVs) associated with lisinopril effectiveness. MATERIALS AND METHODS: This was an observational study using a candidate gene approach to examine SNVs associated with lisinopril effectiveness. Drug effectiveness was defined as 10% decrease in systolic blood pressure at 1 week follow-up. We used the Illumina GWAS MEGA chip to examine variants in the renin/angiotensin pathway that may be associated with drug effectiveness. RESULTS: 61 subjects were enrolled, and 33 (54.1%) were responsive to lisinopril therapy. SNVs in AGT (p = 0.0141), REN (p = 0.0192), and ACE2 (p = 0.0002) were found to be associated with successful treatment on lisinopril. Conclusion and relevance: SNVs in the renin and angiotensin pathway are associated with lisinopril effectiveness in a pilot cohort of patients with uncontrolled hypertension.

Public Perceptions on Why Women Receive Less Bystander Cardiopulmonary Resuscitation Than Men in Out-of-Hospital Cardiac Arrest.

BACKGROUND: Women who suffer an out-of-hospital cardiac arrest receive bystander cardiopulmonary resuscitation (CPR) less often than men. Understanding public perceptions of why this occurs is a necessary first step toward equitable application of this potentially life-saving intervention. METHODS: We conducted a national survey of members of the public using Mechanical Turk, Amazon's crowdsourcing platform, to determine reasons why women might receive bystander CPR less often than men. Eligible participants were adults (≥18 years) located in the United States. Responses were excluded if the participant was not able to define CPR correctly. Participants were asked to answer the following free-text question: "Do you have any ideas on why women may be less likely to receive CPR than men when they collapse in public?" Descriptive statistics were used to define the cohort. The free-text response was coded using open coding, and major themes were identified via classical content analysis. RESULTS: In total, 548 subjects were surveyed. Mean age was 38.8 years, and 49.8% were female. Participants were geographically distributed as follows: 18.5% West, 9.2% Southwest, 22.0% Midwest, 27.5% Southeast, and 22.9% Northeast. After analysis, 3 major themes were detected for why the public perceives that women receive less bystander CPR. They include the following: (1) sexualization of women's bodies; (2) women are weak and frail and therefore prone to injury; and (3) misperceptions about women in acute medical distress. Overall, 41.9% (227) were trained in CPR while 4.4% reported having provided CPR in a medical emergency. CONCLUSIONS: Members of the general public perceive fears about inappropriate touching, accusations of sexual assault, and fear of causing injury as inhibiting bystander CPR for women. Educational and policy efforts to address these perceptions may reduce the sex differences in the application of bystander CPR.

Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study.

Background: Little is known about the relative harms of edible and inhalable cannabis products. Objective: To describe and compare adult emergency department (ED) visits related to edible and inhaled cannabis exposure. Design: Chart review of ED visits between 1 January 2012 and 31 December 2016. Setting: A large urban academic hospital in Colorado. Participants: Adults with ED visits with a cannabis-related International Classification of Diseases, Ninth or 10th Revision, Clinical Modification (ICD-9-CM or ICD-10-CM), code. Measurements: Patient demographic characteristics, route of exposure, dose, symptoms, length of stay, disposition, discharge diagnoses, and attribution of visit to cannabis. Results: There were 9973 visits with an ICD-9-CM or ICD-10-CM code for cannabis use. Of these, 2567 (25.7%) visits were at least partially attributable to cannabis, and 238 of those (9.3%) were related to edible cannabis. Visits attributable to inhaled cannabis were more likely to be for cannabinoid hyperemesis syndrome (18.0% vs. 8.4%), and visits attributable to edible cannabis were more likely to be due to acute psychiatric symptoms (18.0% vs. 10.9%), intoxication (48% vs. 28%), and cardiovascular symptoms (8.0% vs. 3.1%). Edible products accounted for 10.7% of cannabis-attributable visits between 2014 and 2016 but represented only 0.32% of total cannabis sales in Colorado (in kilograms of tetrahydrocannabinol) during that period. Limitation: Retrospective study design, single academic center, self-reported exposure data, and limited availability of dose data. Conclusion: Visits attributable to inhaled cannabis are more frequent than those attributable to edible cannabis, although the latter is associated with more acute psychiatric visits and more ED visits than expected. Primary Funding Source: Colorado Department of Public Health and Environment.

Predicting response to lisinopril in treating hypertension: a pilot study.

INTRODUCTION: Only ~ 50% of hypertensive patients will respond to treatment. OBJECTIVE: This pilot study aims to identify clinical and metabolite markers that predict response to lisinopril. METHODS: Hypertensive patients (n = 45) received lisinopril (10 mg) at their baseline visit. Blood pressures were reevaluated one week later. Responders to lisinopril (n = 19) were defined by a 10% decline in systolic blood pressure. Plasma metabolites were evaluated with mass spectrometry. RESULTS: BMI (p = 0.009), GFR (p = 0.015) and 2-oxoglutarate were included in a logistic regression model to predict response to lisinopril. CONCLUSIONS: Further validation cohorts are needed to confirm the predictive values of these clinical and metabolic markers.

Examining the Impact of Layperson Rescuer Gender on the Receipt of Bystander CPR for Women in Cardiac Arrest.

BACKGROUND: Women who suffer a witnessed out-of-hospital cardiac arrest receive bystander cardiopulmonary resuscitation (CPR) less often than men. To understand this phenomenon, we queried whether there are differences in deterrents to providing CPR based on the rescuer's gender. METHODS: Participants were surveyed using a national crowdsourcing platform. Participants ranked the following 5 previously identified themes as reasons: rescuers are afraid to injure or hurt women; rescuers might have a misconception that women do not suffer cardiac arrest; rescuers are afraid to be accused of sexual assault or sexual harassment; rescuers have a fear of touching women or that their touch might be inappropriate; and rescuers think that women are faking it or being overdramatic. Participants were adult US residents able to correctly define CPR. Participants ranked the themes if the rescuer was gender unidentified, a man, and a woman, in variable order. RESULTS: In November 2018, 520 surveys were completed. The respondents identified as 42.3% women, 74.2% White, 10.4% Black, and 6.7% Hispanic. Approximately half (48.1%) of the cohort knew how to perform CPR, but only 7.9% had ever performed CPR. When the rescuer was identified as a man, survey participants ranked fear of sexual assault or sexual harassment and fear of touching women or that the touch might be inappropriate as the top reasons (36.2% and 34.0% of responses, respectively). Conversely, when the rescuer was identified as a woman, survey respondents reported fear of hurting or injuring as the top reason (41.2%). CONCLUSIONS: Public perceptions as to why women receive less bystander CPR than men were different based on the gender of the rescuer. Participants reported that men rescuers would potentially be hindered by fears of accusations of sexual assault/harassment or inappropriate touch, while women rescuers would be deterred due to fears of causing physical injury.

Evaluation of Quantitative Pupillometry in Acute Postinjury Pediatric Concussion.

BACKGROUND: Although millions of children sustain concussions each year, a rapid and objective test for concussion has remained elusive. The aim of this study was to investigate quantitative pupillometry in pediatric patients in the acute, postinjury setting. METHODS: This was a prospective case-control study of concussed patients presenting to the emergency department within 72 hours of injury. Pupillary measurements were gathered using NeurOptics' PLR 3000; evaluation included a symptom checklist and neurocognitive assessment. Data were analyzed using descriptive statistics and regression models. RESULTS: A total of 126 participants were enrolled. One significant difference in pupillometry between concussed and control participants was found: left minimum pupil diameter in 12- to 18 year-olds (P = 0.02). Models demonstrating odds of a concussion revealed significant associations for time to 75% recovery (T75) of the left pupil in five- to 11-year-olds and average dilation velocity of the left pupil in 12- to 18-year-olds (P = 0.03 and 0.02 respectively). Models predicting symptom improvement showed one significant association: percent change of the right pupil in five-to-11-year-olds (P = 0.02). Models predicting neurocognitive improvement in 12- to 18-year-olds demonstrated significant association in T75 in the left pupil for visual memory, visual motor processing speed, and reaction time (P = 0.002, P = 0.04, P = 0.04). CONCLUSIONS: The limited statistically significant associations found in this study suggest that pupillometry may not be useful in pediatrics in the acute postinjury setting for either the diagnosis of concussion or to stratify risk for prolonged recovery.

Caregiver Satisfaction with Emergency Department Care for Pediatric Patients with Neurodevelopmental Disorders.

OBJECTIVE: Children with neurodevelopmental disorders (NDDs) often encounter increased adversity when navigating the health care system. In this study, we explored the pediatric emergency department (PED) experience for patients with NDDs and their caregivers compared with that of patients without NDDs. METHODS: Data for this study were obtained from National Research Corporation patient experience survey questionnaires and electronic medical record (EMR) data for patients presenting to a PED between May 2018 and September 2019. ED satisfaction was determined by the top-box approach; ED ratings of 9/10 or 10/10 were considered to reflect high ED satisfaction. Demographics, Emergency Severity Index, ED length of stay, time from arrival to triage, time to provider assessment, and diagnoses were extracted from the EMR. Patients with NDDs were identified based on International Classification of Diseases, Tenth Revision codes; patients with intellectual disabilities, pervasive and specific developmental disorders, or attention-deficit/hyperactivity disorders were included in the NDD cohort. One-to-one propensity score matching between patients with and without NDDs was performed, and a multivariable logistic regression model was built on the matched cohort. RESULTS: Patients with NDDs represented over 7% of survey respondents. Matching was successful for 1162 patients with NDDs (99.5%), resulting in a matched cohort sample size of 2324. Caregivers of patients with NDDs had 25% lower odds of reporting high ED satisfaction (95% confidence interval [CI], 0.62-0.91, p = 0.004). CONCLUSION: Caregivers of patients with NDDs make up a significant proportion of survey respondents and are more likely to rate the ED poorly than caregivers of patients without NDDs. This suggests an opportunity for targeted interventions in this population to improve patient care and experience.

9-1-1 Activations from Ambulatory Care Centers: A Sicker Pediatric Population.

BACKGROUND: Pediatric patients transferred by Emergency Medical Services (EMS) from urgent care (UC) and office-based physician practices to the emergency department (ED) following activation of the 9-1-1 EMS system are an under-studied population with scarce literature regarding outcomes for these children. The objectives of this study were to describe this population, explore EMS level-of-care transport decisions, and examine ED outcomes. METHODS: This was a retrospective review of patients zero to <15 years of age transported by EMS from UC and office-based physician practices to the ED of two pediatric receiving centers from January 2017 through December 2019. Variables included reason for transfer, level of transport, EMS interventions and medications, ED medications/labs/imaging ordered in the first hour, ED procedures, ED disposition, and demographics. Data were analyzed with descriptive statistics, X test, point biserial correlation, two-sample z test, Mann-Whitney U test, and 2-way ANOVA. RESULTS: A total of 450 EMS transports were included in this study: 382 Advanced Life Support (ALS) runs and 68 Basic Life Support (BLS) runs. The median patient age was 2.66 years, 60.9% were male, and 60.7% had private insurance. Overall, 48.9% of patients were transported from an office-based physician practice and 25.1% were transported from UC. Almost one-half (48.7%) of ALS patients received an EMS intervention or medication, as did 4.41% of BLS patients. Respiratory distress was the most common reason for transport (46.9%). Supplemental oxygen was the most common EMS intervention and albuterol was the most administered EMS medication. There was no significant association between level of transport and ED disposition (P = .23). The in-patient admission rate for transported patients was significantly higher than the general ED admission rate (P <.001). CONCLUSION: This study demonstrates that pediatric patients transferred via EMS after activation of the 9-1-1 system from UC and medical offices are more acutely ill than the general pediatric ED population and are likely sicker than the general pediatric EMS population. Paramedics appear to be making appropriate level-of-care transport decisions.

Does Physician Gender and Gender Composition of Clinical Teams Affect Guideline Concordance and Patient Outcomes in Out-of-Hospital Cardiac Arrest?

Objective: Prior literature has shown improved outcomes in morbidity and mortality for admitted patients cared for by female physicians. One theory is that female physicians adhere closely to guideline recommendations. We sought to determine whether patients who have out-of-hospital cardiac arrest (OHCA) experience more guideline-concordant postcardiac arrest care and potentially better outcomes based on the gender of their treating physician and gender distribution of the treatment teams. Methods: This study is a retrospective cohort study from the Colorado Cardiac Arrest Registry, local registry of OHCA patients treated at one academic urban tertiary care hospital. We analyzed adult OHCA patients who survived to hospital admission but were comatose. Patient demographic data and arrest characteristics were abstracted for subjects, and the gender of the provider was abstracted from the medical record. Results: Patients were admitted by a female attending in 28.5% of the cohort. The difference in guideline-concordant care between male and female providers was not significant. No statistical difference was found between all-male or mixed gender teams in adherence to guideline-concordant care. No patient was cared for by an all-female team. Neither gender of the admitting physician nor gender of the physician who led the family meeting to discuss prognosis was associated with a survival difference. Conclusions: Prior literature has described differences in outcome based on gender of the treating physician. Our analysis targeted a similar question in a cohort of OHCA patients with survival to hospital admission. We determined that there was no difference in postcardiac arrest guideline concordance and survival to hospital discharge based on treating physician gender. This finding differs from the prior literature and supports the importance of diverse clinical teams in medicine.

Why do patients come to the emergency department after using cannabis?

Background: Cannabis (MJ) policy liberalization in a majority of US states has impacted emergency department (ED) visits. It is important to understand why people come to the ED after using MJ because the drug is now available to experienced and naïve people across the country. The objectives of this study were to (1) improve upon administrative dataset methodology by performing additional chart review to describe ED visits related to cannabis, (2) understand why patients come to the ED after using cannabis, and (3) begin to inform our understanding of cannabis-attributable ED visits to start to educate patients and providers about cannabis' safety.Methods: We performed a retrospective chart review of ED visits identified by cannabis ICD-9 and 10-CM codes between 2012 and 2016. Visits were reviewed and determined if the visit was partially attributable to cannabis based upon a pre-specified definition, then categorized into clinical complaint categories. Descriptive statistics, Chi-Square, and T-tests were used to elucidate the data.Results: About one-fourth (25.74%) of visits with cannabis ICD-CM codes were found to be at least partially attributable to cannabis. These patients are more often young, Caucasian males when compared to the overall ED population (p < .0001). Patients with a cannabis-attributable visit were more often admitted to the hospital (p < .0001). The most common complaints in cannabis-attributable visits were gastrointestinal and psychiatric complaints, as well as intoxication. The number of cannabis-attributable visits rose with time (p=.012).Conclusions: Based on a pre-specified definition, with good inter-rater reliability, we found that 25% of visits with a cannabis ICD-CM code were partially attributable to cannabis. These findings represent areas to target in cannabis user education as public perceptions change across time.

The Psychoactive Surveillance Consortium and Analysis Network (PSCAN): the first year.

BACKGROUND AND AIMS: The Psychoactive Surveillance Consortium and Analysis Network (PSCAN) is a national network of academic emergency departments (ED), analytical toxicologists and pharmacologists that collects clinical data paired with biological samples to identify and improve treatments of medical conditions arising from use of new psychoactive substances (NPS). The aim of this study was to gather clinical data with paired drug identification from NPS users who presented to EDs within PSCAN during its first year (2016-17). DESIGN: Observational study involving patient records and biological samples. SETTING: Seven academic emergency medical centers across the United States. PARTICIPANTS: ED patients (n = 127) > 8 years of age with possible NPS use who were identified and enrolled in PSCAN by clinical providers or research personnel. MEASUREMENTS: Clinical signs, symptoms and treatments were abstracted from the patients' health records. Biological samples were collected from leftover urine, serum and whole blood. Biological and drug samples, when available, were tested for drugs and drug metabolites via liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). FINDINGS: Patients in whom synthetic opioids were detected (n = 9) showed higher rates of intubation (four of nine), impaired mental status (four of nine) and respiratory acidosis (five of nine) compared with the rest of the cohort (nine of 118, P-value < 0.05). Patients in whom synthetic cannabinoid (SC) were found (n = 27) had lower median diastolic blood pressures (70.5 versus 77 mmHg, P = 0.046) compared with the rest of the cohort. In 64 cases of single drug ingestion, benzodiazepines were administered in 25 cases and considered effective by the treating physician in 21 (84%) cases. CONCLUSIONS: During its first year of operation, the Psychoactive Surveillance Consortium and Analysis Network captured clinical data on new classes of drugs paired with biological samples over a large geographical area in the United States. Synthetic cannabinoids were the most common new psychoactive drug identified. Synthetic opioids were associated with a high rate of intubation and respiratory acidosis.

The Emergency Medicine Specimen Bank: An Innovative Approach To Biobanking In Acute Care.

The Emergency Medicine Specimen Bank (EMSB) was developed to facilitate precision medicine in acute care. The EMSB is a biorepository of clinical health data and biospecimens collected from all adult English- or Spanish-speaking individuals who are able and willing to provide consent and are treated at the UCHealth-University of Colorado Hospital Emergency Department. The EMSB is the first acute care biobank that seeks to enroll all patients, with all conditions who present to the ED. Acute care biobanking presents many challenges that are unique to acute care settings such as providing informed consent in a uniquely stressful and fast-paced environment and collecting, processing, and storing samples for tens of thousands of patients per year. Here, we describe the process by which the EMSB overcame these challenges and was integrated into clinical workflow allowing for operation 24 hours a day, 7 days a week at a reasonable cost. Other institutions can implement this template, further increasing the power of biobanking research to inform treatment strategies and interventions for common and uncommon phenotypes in acute care settings.

Validation of an ICD code for accurately identifying emergency department patients who suffer an out-of-hospital cardiac arrest.

AIM: International classification of disease (ICD-9) code 427.5 (cardiac arrest) is utilized to identify cohorts of patients who suffer out-of-hospital cardiac arrest (OHCA), though the use of ICD codes for this purpose has never been formally validated. We sought to validate the utility of ICD-9 code 427.5 by identifying patients admitted from the emergency department (ED) after OHCA. METHODS: Adult visits to a single ED between January 2007 and July 2012 were retrospectively examined and a keyword search of the electronic medical record (EMR) was used to identify patients. Cardiac arrest was confirmed; and ICD-9 information and location of return of spontaneous circulation (ROSC) were collected. Separately, the EMR was searched for patients who received ICD-9 code 427.5. The kappa coefficient (κ) was calculated, as was the sensitivity and specificity of the code for identifying OHCA. RESULTS: The keyword search identified 1717 patients, of which 385 suffered OHCA and 333 were assigned the code 427.5. The agreement between ICD-9 code and cardiac arrest was excellent (κ = 0.895). The ICD-9 code 427.5 was both specific (99.4%) and sensitive (86.5%). Of the 52 cardiac arrests that were not identified by ICD-9 code, 33% had ROSC before arrival to the ED. When searching independently on ICD-9 code, 347 patients with ICD-9 code 427.5 were found, of which 320 were "true" arrests. This yielded a positive predictive value of 92% for ICD-9 code 427.5 in predicting OHCA. CONCLUSIONS: ICD-9 code 427.5 is sensitive and specific for identifying ED patients who suffer OHCA with a positive predictive value of 92%.