Upper Extremity Crotalid Envenomation: A Review of Incidence and Recent Trends in Management of Snakebites.

PURPOSE: The goal of this study was to evaluate the recent trends in the management of upper extremity Crotalid envenomation in the state of Georgia, United States. METHODS: A retrospective review of the Georgia Poison Center database looking at the reported snakebites to the upper extremity between 2015 and 2020 was performed. Patient demographics, timing and location of injury, severity of envenomation, treatment, including use of antivenin and surgical intervention, and reported complications related to the use of antivenin was extracted. RESULTS: A retrospective review of snakebites between 2015 and 2020 showed 2408 snakebite cases with a mean patient age of 37.4 years. Males incurred 62.8% of all bites. The highest incidence was in summer 52.5%, and between the hours of 5 PM to midnight 57.2%. Overall, 1010 (41.9%) of all bites were categorized as venomous snakebites (55.6% copperhead, 20% rattlesnake, 2.4% cottonmouth, and 22% miscellaneous [including 3 Elapid envenomations] or unidentified. The total number of venomous bites to the upper extremity was 575 (56.9%) and 567 patients received antivenin. Envenomation severity was mild in 29%, moderate in 45%, severe in 10%, and undetermined in 16% of cases. Crotalidae polyvalent immune Fab (Ovine) was the main antivenin used, with overall mean initial therapy dose of 6.2 vials and 59% of patients receiving maintenance therapy. Three patients (0.5%) had a severe anaphylactic reaction to antivenin requiring cessation of therapy. Seven patients had acute compartment syndrome of the upper extremity requiring fasciotomy (3 copperhead, 2 rattlesnake, and 2 unidentified). There was no reported mortality during this period. CONCLUSIONS: Hand surgeons should be familiar with the management of upper extremity Crotalid envenomation. Antivenin remains the main treatment for symptomatic patients. Crotalid snakebites rarely require operative intervention. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Veratrum parviflorum poisoning: identification of steroidal alkaloids in patient blood and breast milk.

INTRODUCTION: The Veratrum genus is composed of plants containing a diverse set of steroidal alkaloids. Veratrum plant material has been utilized for centuries as herbal medicines, however the alkaloids have such a low therapeutic index that they are not used in modern medicine. Here we report an incident of inadvertent ingestion of V. parviflorum by hikers in Georgia that allowed detection, and in several instances identification of alkaloids from the plant, and correlated their presence within patient blood and breast milk specimens. CASE HISTORY: Eight patients, three male and five female, presented in the spring of 2020 and 2021 with symptoms requiring emergent medical attention after ingestion of Veratrum parviflorum. All patients believed the plants to be a local native species of wild leek, Allium tricoccum, locally known as ramps. Plants were identified using photographs as well as fresh and cooked plant material provided by patients, in consultation with botanists at the University of Georgia Herbarium. Written consent was obtained from all patients for collection of blood and breast milk specimens for laboratory identification of Veratrum alkaloids. METHODS: V. parviflorum plant material, and patient serum and breast milk were analyzed by high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF) to identify steroidal alkaloids. RESULTS: The V. parviflorum extract was confirmed to contain cyclopamine, veratramine, jervine, and muldamine. Two out of the eight patients had detectable concentrations of Veratrum alkaloids. Of the alkaloids identified in the plant, cyclopamine and jervine were detected within patient serum, and cyclopamine and veratramine were observed to be present in breast milk. DISCUSSION: Toxicity resulting from Veratrum steroidal alkaloids has primarily been reported from V. album and V. viride. This is the second report of V. parviflorum poisoning. The present work reports for the first time the presence of muldamine and jervine within V. parviflorum. This work provides the first instance of identification of Veratrum alkaloids in breast milk. Thus, the findings presented herein add to literature record causative agents contributing to the toxicity of V. parviflorum when ingested and potential for secondary poisoning through breastfeeding. CONCLUSION: V. parviflorum toxicity was observed to cause nausea, vomiting, hypotension, bradycardia, abdominal pain, light-headedness, blurred vision, and tingling in the arms. Patients experiencing mild symptoms improved with supportive care, IV fluids, and antiemetics, but hemodynamically unstable patients required atropine and vasopressors. This study demonstrated that more lipophilic Veratrum alkaloids can be passed along in breast milk, which suggests additional precautions may be critical to limit further poisonings.

Identifying Opioid Use Disorder in the Emergency Department: Multi-System Electronic Health Record-Based Computable Phenotype Derivation and Validation Study.

BACKGROUND: Deploying accurate computable phenotypes in pragmatic trials requires a trade-off between precise and clinically sensical variable selection. In particular, evaluating the medical encounter to assess a pattern leading to clinically significant impairment or distress indicative of disease is a difficult modeling challenge for the emergency department. OBJECTIVE: This study aimed to derive and validate an electronic health record-based computable phenotype to identify emergency department patients with opioid use disorder using physician chart review as a reference standard. METHODS: A two-algorithm computable phenotype was developed and evaluated using structured clinical data across 13 emergency departments in two large health care systems. Algorithm 1 combined clinician and billing codes. Algorithm 2 used chief complaint structured data suggestive of opioid use disorder. To evaluate the algorithms in both internal and external validation phases, two emergency medicine physicians, with a third acting as adjudicator, reviewed a pragmatic sample of 231 charts: 125 internal validation (75 positive and 50 negative), 106 external validation (56 positive and 50 negative). RESULTS: Cohen kappa, measuring agreement between reviewers, for the internal and external validation cohorts was 0.95 and 0.93, respectively. In the internal validation phase, Algorithm 1 had a positive predictive value (PPV) of 0.96 (95% CI 0.863-0.995) and a negative predictive value (NPV) of 0.98 (95% CI 0.893-0.999), and Algorithm 2 had a PPV of 0.8 (95% CI 0.593-0.932) and an NPV of 1.0 (one-sided 97.5% CI 0.863-1). In the external validation phase, the phenotype had a PPV of 0.95 (95% CI 0.851-0.989) and an NPV of 0.92 (95% CI 0.807-0.978). CONCLUSIONS: This phenotype detected emergency department patients with opioid use disorder with high predictive values and reliability. Its algorithms were transportable across health care systems and have potential value for both clinical and research purposes.

Integration of in-hospital cardiac arrest contextual curriculum into a basic life support course: a randomized, controlled simulation study.

OBJECTIVE: The objective was to compare resuscitation performance on simulated in-hospital cardiac arrests after traditional American Heart Association (AHA) Healthcare Provider Basic Life Support course (TradBLS) versus revised course including in-hospital skills (HospBLS). DESIGN: This study is a prospective, randomized, controlled curriculum evaluation. SETTING: Johns Hopkins Medicine Simulation Center. SUBJECTS: One hundred twenty-two first year medical students were divided into fifty-nine teams. INTERVENTION: HospBLS course of identical length, containing additional content contextual to hospital environments, taught utilizing Rapid Cycle Deliberate Practice (RCDP). MEASUREMENTS: The primary outcome measure during simulated cardiac arrest scenarios was chest compression fraction (CCF) and secondary outcome measures included metrics of high quality resuscitation. MAIN RESULTS: Out-of-hospital cardiac arrest HospBLS teams had larger CCF: [69% (65-74) vs. 58% (53-62), p<0.001] and were faster than TradBLS at initiating compressions: [median (IQR): 9s (7-12) vs. 22s (17.5-30.5), p<0.001]. In-hospital cardiac arrest HospBLS teams had larger CCF: [73% (68-75) vs. 50% (43-54), p<0.001] and were faster to initiate compressions: [10s (6-11) vs. 36s (27-63), p<0.001]. All teams utilized the hospital AED to defibrillate within 180s per AHA guidelines [HospBLS: 122s (103-149) vs. TradBLS: 139s (117-172), p=0.09]. HospBLS teams performed more hospital-specific maneuvers to optimize compressions, i.e. utilized: CPR button to flatten bed: [7/30 (23%) vs. 0/29 (0%), p=0.006], backboard: [21/30 (70%) vs. 5/29 (17%), p<0.001], stepstool: [28/30 (93%) vs. 8/29 (28%), p<0.001], lowered bedrails: [28/30 (93%) vs. 10/29 (34%), p<0.001], connected oxygen appropriately: [26/30 (87%) vs. 1/29 (3%), p<0.001] and used oral airway and/or two-person bagging when traditional bag-mask-ventilation unsuccessful: [30/30 (100%) vs. 0/29 (0%), p<0.001]. CONCLUSION: A hospital focused BLS course utilizing RCDP was associated with improved performance on hospital-specific quality measures compared with the traditional AHA course.

Multiple Fentanyl Overdoses - New Haven, Connecticut, June 23, 2016.

On the evening of June 23, 2016, a white powder advertised as cocaine was purchased off the streets from multiple sources and used by an unknown number of persons in New Haven, Connecticut. During a period of less than 8 hours, 12 patients were brought to the emergency department (ED) at Yale New Haven Hospital, experiencing signs and symptoms consistent with opioid overdose. The route of intoxication was not known, but presumed to be insufflation ("snorting") in most cases. Some patients required doses of the opioid antidote naloxone exceeding 4 mg (usual initial dose = 0.1-0.2 mg intravenously), and several patients who were alert after receiving naloxone subsequently developed respiratory failure. Nine patients were admitted to the hospital, including four to the intensive care unit (ICU); three required endotracheal intubation, and one required continuous naloxone infusion. Three patients died. The white powder was determined to be fentanyl, a drug 50 times more potent than heroin, and it included trace amounts of cocaine. The episode triggered rapid notification of public health and law enforcement agencies, interviews of patients and their family members to trace and limit further use or distribution of the fentanyl, immediate naloxone resupply and augmentation for emergency medical services (EMS) crews, public health alerts, and plans to accelerate naloxone distribution to opioid users and their friends and families. Effective communication and timely, coordinated, collaborative actions of community partners reduced the harm caused by this event and prevented potential subsequent episodes.

The transcriptional coactivators, PGC-1α and ß, cooperate to maintain cardiac mitochondrial function during the early stages of insulin resistance.

We previously demonstrated a cardiac mitochondrial biogenic response in insulin resistant mice that requires the nuclear receptor transcription factor PPARα. We hypothesized that the PPARα coactivator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is necessary for mitochondrial biogenesis in insulin resistant hearts and that this response was adaptive. Mitochondrial phenotype was assessed in insulin resistant mouse models in wild-type (WT) versus PGC-1α deficient (PGC-1α(-/-)) backgrounds. Both high fat-fed (HFD) WT and 6 week-old Ob/Ob animals exhibited a significant increase in myocardial mitochondrial volume density compared to standard chow fed or WT controls. In contrast, HFD PGC-1α(-/-) and Ob/Ob-PGC-1α(-/-) hearts lacked a mitochondrial biogenic response. PGC-1α gene expression was increased in 6 week-old Ob/Ob animals, followed by a decline in 8 week-old Ob/Ob animals with more severe glucose intolerance. Mitochondrial respiratory function was increased in 6 week-old Ob/Ob animals, but not in Ob/Ob-PGC-1α(-/-) mice and not in 8 week-old Ob/Ob animals, suggesting a loss of the early adaptive response, consistent with the loss of PGC-1α upregulation. Animals that were deficient for PGC-1α and heterozygous for the related coactivator PGC-1ß (PGC-1α(-/-)ß(+/-)) were bred to the Ob/Ob mice. Ob/Ob-PGC-1α(-/-)ß(+/-) hearts exhibited dramatically reduced mitochondrial respiratory capacity. Finally, the mitochondrial biogenic response was triggered in H9C2 myotubes by exposure to oleate, an effect that was blunted with shRNA-mediated PGC-1 "knockdown". We conclude that PGC-1 signaling is important for the adaptive cardiac mitochondrial biogenic response that occurs during the early stages of insulin resistance. This response occurs in a cell autonomous manner and likely involves exposure to high levels of free fatty acids.