Different prognostic role of EGFR mutation according to the IASLC histological grade in patients with resected early-stage lung adenocarcinoma.

AIMS: The prognostic role of EGFR mutations remains controversial. We aimed to evaluate the prognostic role of EGFR mutation in consideration of the IASLC histological grade in patients with resected early-stage lung adenocarcinoma. METHODS AND RESULTS: A total of 3297 patients with stages I-IIA resected lung adenocarcinoma who had had EGFR mutation tests between January 2014 and December 2019 at the Samsung Medical Center, Seoul, Korea were included. Recurrence-free survival (RFS) was compared by EGFR mutation status (EGFR-M+ versus EGFR-WT) and IASLC histological grade (G1, G2 and G3). Cox proportional hazards models were used to estimate the adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS: Compared to the EGFR-WT group, the EGFR-M+ group had a significantly lower proportion of G3 tumour (16 versus 33%, P < 0.001). During a median follow-up of 41.4 months, 376 patients experienced recurrence. After adjusting for histological grade, the aHR for recurrence comparing the EGFR-M+ to the EGFR-WT was 1.30 (95% CI = 1.04-1.62, P = 0.022). The EGFR-M+ group had a significantly lower 5-year RFS than the EGFR-WT group among G3 patients (58.4 versus 71.5%, P < 0.001), but not among G1 and G2 patients. CONCLUSIONS: EGFR mutation status was associated with a risk of recurrence after consideration of the IASLC histological grading, especially in G3 tumours. The results of this study would be useful for developing a new staging system and identifying a subset of patients who may benefit from adjuvant targeted therapy.

Novel uses of ketamine in the emergency department.

INTRODUCTION: Ketamine is gaining renewed interest among healthcare providers in the emergency department (ED) setting due to its novel clinical applications. AREAS COVERED: This article provides a comprehensive discussion of ketamine's pharmacological properties, safety profile, and an overview of current evidence for ketamine in the management of ED patients with acute agitation, pain, depression/suicide ideation. EXPERT OPINION: Ketamine is an effective adjunct to opioids, providing greater pain relief than morphine alone. Ketamine (0.1-0.3 mg/kg IV) alone can provide analgesia similar to that of morphine in patients with acute visceral and musculoskeletal pain, as well as for chronic painful conditions (cancer, vaso-occlusive pain crisis associated with sickle cell disease, and in patients with high opioid tolerance and/or opioid dependency). Available literature shows that ketamine (1-2 mg/kg IV or 4-5 mg/kg IM) is a safe, rapid (<5 minutes) and effective tranquilization agent for ED patients with acute agitation. Finally, there is growing evidence that suggests ketamine may have potential utility in the management of patients with self-harm ideation or acute depressive episodes. Intravenous infusion of ketamine (0.5 mg/kg over 40 mins) has been shown to produce an antidepressant effect and decrease in suicidal ideation within 4 hours with effects lasting up to one week.

Use of Extracorporeal Membrane Oxygenation in Acutely Poisoned Pediatric Patients in United States: A Retrospective Analysis of the Extracorporeal Life Support Registry From 2003 to 2019.

OBJECTIVES: To describe the use of extracorporeal membrane oxygenation (ECMO) in the management of pediatric poisoning in the United States and to identify predictors of mortality. DESIGN: Retrospective cohort study. SETTING: Data reported to the Extracorporeal Life Support Organization by 76 U.S. ECMO centers from 2003 to 2019. PATIENTS: Pediatric patients (0-18 yr) receiving ECMO for poisoning. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During our study period, 86 cases of acute poisoning were identified and included in the analysis. The median age was 12.0 year and 52.9% were female. The most commonly reported substance exposures were hydrocarbon (n = 17; 19.8%), followed by chemical asphyxiants (n = 14; 16.3%), neuroactive agents (n = 14; 16.3%), opioid/analgesics (n = 13; 15.1%), and cardiovascular agents (n = 12; 14.0%). Single substance exposures were reported in 83.7% of the cases. The intention of the exposure was unknown in 65.1%, self-harm in 20.9% and 10.5% was unintentional exposure. Fifty-six patients (65.1%) survived. Venoarterial ECMO was used more frequently than venovenous ECMO, and its use increased significantly during the study period (p < 0.01). A bimodal distribution of ECMO support was observed among two age groups: less than or equal to 3 years (n = 34) and 13-17 years (n = 41). Hemodynamic and metabolic parameters improved for all patients with ECMO. Persistent systolic hypotension, acidemia/metabolic acidosis, and elevated Pao2) after 24 hours of ECMO support were associated with mortality. Time from PICU admission to ECMO cannulation was not significantly different between survivors (24.0 hr; interquartile range [IQR], 11.0-58.0 hr) and nonsurvivors (30.5 hr; IQR, 10.0-60.2 hr; p = 0.58). ECMO duration and PICU length of stay were significantly longer in survivors than in nonsurvivors (139.5 vs 70.5 hr; p = 0.007 and 25.0 vs 4.0 d; p = 0.002, respectively). CONCLUSIONS: ECMO may improve the hemodynamic and metabolic status of poisoned pediatric patients. Persistent hypotension, acidemia/acidosis, and elevated Pao2 after 24 hours of ECMO were associated with mortality.

Safety and efficacy of pharmacologic agents used for rapid tranquilization of emergency department patients with acute agitation or excited delirium.

Introduction: Management of patients with acute agitation or aggressive behavior can pose a significant challenge to health-care providers in emergency departments. Areas covered: This article provides a comprehensive review of the pharmacologic properties, efficacy, and safety profiles of select intramuscular (IM) sedative agents (i.e., antipsychotics, benzodiazepines, and ketamine) for rapid tranquilization. Expert opinion: Using antipsychotics and benzodiazepines - whether a single agent or combined - will have similar efficacy in producing sedation. But there are differences in the time to sedation depending on which agent is used. Based upon the available studies, droperidol (5-10 mg IM) and midazolam (5-10 mg IM) have the fastest onset of sedation when either is used as a single agent. When combination therapy is used, using midazolam with an antipsychotic agent, instead of lorazepam, may result in faster sedative effect. QT prolongation and torsades de pointes are uncommon adverse drug effects of antipsychotic administration. Ketamine is often reserved as a second-line agent when antipsychotics and benzodiazepines fail to produce the desired tranquilization. However, ketamine (5 mg/kg IM) is more frequently associated with airway compromise requiring endotracheal intubation. A low-dose of ketamine (2 mg/kg IM) may reduce the risk of airway compromise while providing adequate sedation.

Relative addictive potential of opioid analgesic agents.

Opioid overdoses and deaths continue to be a problem in the USA with a significant portion related to prescribed opioid analgesic agents. The role of pharmacogentic factors in opioid addiction is an active area of research. While all opioid analgesic agents have some addictive potential, it is clear that there are some with greater addictive potential. Oxycodone is the most widely abused opioid analgesic and it appears to predispose to chronic use with high likability by users. Fentanyl and hydromorphone are both very lipophilic allowing rapid penetration into the CNS, but are not rated as highly as other agents. Providers should consider the risk of addiction with the opioids they prescribe and give those with a lower addictive potential.

Access and Barriers to Take-Home Naloxone Use among Emergency Department Patients with Opioid Misuse in Baltimore, Maryland, USA.

BACKGROUND: The opioid epidemic has prompted the expansion of take-home naloxone (THN) distribution programs. The proportion of emergency department (ED) patients with opioid misuse who have access to a naloxone kit (NK) and barriers to using it are unclear. Objective: Characterizing the access and barrier to NK use among at-risk ED patients. Methods: We enrolled a convenience sample of ED patients with active opioid misuse from May 21-July 31, 2018. We administered a survey to collect patients' demographic data, substance use history, and access to and use of NK. The primary outcome was NK access (prior receipt of a kit or prescription); secondary outcomes were knowledge and use of NK, and barriers to obtaining and using it. Results: Of 165 respondents, 71.5% knew of THN programs and 57.6% (n = 95) had access to THN by either having received a NK (n = 90) or a prescription (n = 5); 34 respondents received both. Among 39 (23.6%) who received a naloxone prescription, 25 (64.1%) filled it. 60.0% (n = 99) reported knowing how to administer naloxone; lack of training was the primary reason (n = 63/66, 96.9%) for their unfamiliarity. Patients who presented after an opioid overdose (25.5%; n = 42) were less likely to have knowledge of THN programs (57.1% vs. 76.4%), and to have received a NK (35.7% vs. 61.0%). Conclusion: Awareness of THN programs was high among our cohort. But approximately 60% the respondents received a NK or knew how to use it. Despite efforts to expand THN access, gaps in knowledge, access, and use exist.

Prepacked naloxone administration for suspected opioid overdose in the era of illicitly manufactured fentanyl: a retrospective study of regional poison center data.

Background: Prepacked naloxone kits (PNKs) are frequently used to reverse opioid intoxication. It is unknown if the presence of illicitly manufactured fentanyl and its analogs (IMFs) in heroin supply is affecting the PNK doses given by laypersons. We investigated the trend of PNK dose administered to reverse opioid toxicity in suspected/undifferentiated opioid intoxication.Methods: We retrospectively reviewed PNK administrations reported to the Maryland Poison Center between 1 January 2015 and 15 October 2017. Primary outcome was the mean PNK dose administered to reverse opioid-induced central nervous system and ventilatory depression. Secondary outcomes included the reversal rate of opioid toxicity, patient disposition, and survival rate.Results: Our analysis involved 1139 PNK administrations. The mean age of subjects was 34.3 years; 68.8% (n = 781) were male. Ventilatory depression was present in 98.2% (n = 958) of cases, and 97% (n = 1097) were unresponsive. Law enforcement administered the majority of PNK (91.0%; n = 1035); the primary route was intranasal (97.9%; n = 1051). Toxicity was reversed in 79.2% (n = 886) of overdose victims after a mean PNK dose of 3.12 mg. EMS personnel gave 291 subjects additional naloxone (mean: 2.2 mg), reversing opioid toxicity in 94.2% (n = 254). Between 2015 and 2017, the mean PNK dose increased from 2.12 to 3.63 mg (p < .0001) while the reversal rate decreased from 82.1% to 76.4% (p = .04). One hundred and eighty-two patients (15.9%) refused transport; of those transported to a hospital, 73.4% (n = 569) were treated and released and 12.4% (n = 96) required hospitalization. Ninety-six percent (n = 1092) of the subjects survived. Forty subjects were pronounced dead at the scene. Fentanyl or its analog was detected in 36 of 55 opioid-related deaths (65.5%).Conclusions: PNK administration reversed toxicity in the majority of patients with undifferentiated opioid intoxication. Between 2015 and 2017, increasing doses of PNK were administered but the reversal rate decreased. These trends are likely multifactorial, including increasing availability of IMFs.

Clinical utility of venoarterial-extracorporeal membrane oxygenation (VA-ECMO) in patients with drug-induced cardiogenic shock: a retrospective study of the Extracorporeal Life Support Organizations' ECMO case registry.

Background: Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is increasingly utilized to treat severe or refractory drug-induced cardiovascular shock. There is limited evidence regarding VA-ECMO's clinical utility in poisoning. Therefore, we investigated the clinical benefit of VA-ECMO use in drug-induced cardiovascular shock using the Extracorporeal Life Support Organization (ELSO)'s ECMO case registry.Methods: The ELSO registry was systematically searched retrospectively, using ICD-9/10 codes for poisoning-related cases from January 1, 2003 to July 30, 2018. All adult cases (age ≥ 18 years) that received VA-ECMO for cardiac support were included. Cardiogenic shock was defined as systolic blood pressure (SBP) <90 mmHg, mean arterial pressure (MAP) <65 mmHg, or requiring infusion of ≥2 vasopressor agents. Study outcomes included survival to discharge (i.e., from the ECMO center), changes in metabolic (acid/base), hemodynamic and ventilatory status, and complications related to ECMO support. Demographic and clinical characteristics of pre-ECMO and 24-h after VA-ECMO cannulation were compared between survivors vs. non-survivors.Results: A total of 113 cases were identified from the ELSO registry; 9 cases were excluded because cardiogenic shock was not related to poisoning, leaving 104 cases for analysis. The median age was 34 years and 53.5% (n = 54) were male. Cardiovascular agents were involved in 47.1% (n = 49) of the cases followed by opioids (n = 9, 6.7%); 34 cases experienced pre-ECMO cardiac arrest. About 92.4% of the cases (n = 85) received vasopressor infusion for hemodynamic support, most frequently norepinephrine (83.7%). Median duration of VA-ECMO was 68 h (interquartile range [IQR]: 48, 113 h); 52.9% (n = 55) of the cases survived to discharge. VA-ECMO significantly improved hemodynamics (MAP, SBP, and DBP), acidemia/acidosis (pH, HCO3 level) and ventilatory parameters (pO2, SpO2, and SvO2). Non-survivors showed persistent acidemia/acidosis at 24-h after VA-ECMO cannulation compared to survivors. Renal replacement therapy (50.9%) and arrhythmia (26.3%) were the most frequently reported complications.Conclusions: VA-ECMO improved hemodynamic and metabolic parameters in patients with drug-induced cardiogenic shock (DCS).

Biocompatibility evaluation of bioprinted decellularized collagen sheet implanted in vivo cornea using swept-source optical coherence tomography.

Corneal transplantation by full-thickness penetrating keratoplasty with human donor tissue is a widely accepted treatment for damaged or diseased corneas. Although corneal transplantation has a high success rate, a shortage of high-quality donor tissue is a considerable limitation. Therefore, bioengineered corneas could be an effective solution for this limitation, and a decellularized extracellular matrix comprises a promising scaffold for their fabrication. In this study, three-dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. We performed in vivo noninvasive monitoring of the rabbit corneas using swept-source optical coherence tomography (OCT) after implanting the collagen sheets. Anterior segment OCT images and averaged amplitude-scans were acquired biweekly to monitor corneal thickness after implantation for 1 month. The averaged cornea thickness in the control images was 430.3 ± 5.9 µm, while the averaged thickness after corneal implantation was 598.5 ± 11.8 µm and 564.5 ± 12.5 µm at 2 and 4 weeks, respectively. The corneal thickness reduction of 34 µm confirmed the biocompatibility through the image analysis of the depth-intensity profile base. Moreover, hematoxylin and eosin staining supported the biocompatibility evaluation of the bioprinted decellularized collagen sheet implantation. Hence, the developed bioprinted decellularized collagen sheets could become an alternative solution to human corneal donor tissue, and the proposed image analysis procedure could be beneficial to confirm the success of the surgery.

The role of take-home naloxone in the epidemic of opioid overdose involving illicitly manufactured fentanyl and its analogs.

INTRODUCTION: There has been an exponential increase in overdose fatalities as illicitly manufactured fentanyl and its analogs (IMF) are becoming more prevalent in the illicit drug supply. In response, overdose education and naloxone distribution (OEND) programs have been implemented throughout the United States as a harm reduction strategy. However, there are increasing reports that higher naloxone doses or repeat administration might be required for overdose victims involving IMF. AREAS COVERED: In this article, we provide a comprehensive review of the epidemiology, public health impact, and pharmacologic properties of IMF. The pharmacokinetic properties of currently available take-home naloxone (THN) kits, the role of THN as a harm reduction strategy and available data on its clinical use are discussed. Implications of occupational IMF exposure for first responders are also described. EXPERT OPINION: THN administration by a bystander is an effective harm reduction intervention. However, there is growing evidence that higher dose or multiple administrations of naloxone are required to fully reverse IMF related toxicity. Recently, the US Food and Drug Administration approved THN kits with a concentrated naloxone dose that produce high bioavailability. However, limited presence of OEND programs and cost of these new devices impede their accessibility to the general public.

Evolution of clinical characteristics and outcomes of synthetic cannabinoid receptor agonist exposure in the United States: analysis of National Poison Data System data from 2010 to 2015.

BACKGROUND AND AIMS: New synthetic cannabinoid receptor agonists (SCRAs) are synthesized each year to evade US governmental regulation and sold for recreational use. Our aim was to estimate the changes in the clinical effects and patient disposition associated with SCRA exposure from 2010 to 2015. DESIGN: A retrospective observational cohort study. SETTING: National Poison Data System that collects data on reports of poisonings from US poison centers. PARTICIPANTS: A total of 19 388 isolated SCRA cases between 1 January 2010 and 31 December 2015 were identified. The mean age was 24.6 years and 77.8% were male. MEASUREMENTS: Primary outcome was the change in the trend of patient disposition, i.e. treated and released versus hospitalization (e.g. non-critical care, critical care unit or psychiatry) between 2010 and 2015. Secondary outcomes included the trends in the clinical effects and their duration, and therapeutic interventions nationally and regionally. FINDINGS: Reports of SCRA exposure peaked in 2011 (n = 5305) and 2015 (n = 5475). The majority of patients required supportive care and were treated and released from an emergency department. Hospitalization increased by annual percentage change in the log odds (APCO) of 21.0% (P < 0.0001) during the 6 years, with significant increases in admissions to critical care units and non-critical care units. Overall, tachycardia (32.1%), agitation/irritation (25.6%) and drowsiness/lethargy (20.4%) were the most frequently reported clinical effects from SCRA exposure. Clinical effects resolved within 2-8 hours in 52.8% of cases, but their duration increased markedly by 2015. Regionally, the largest number of SCRA cases was reported in the South (n = 9374, 48.6%). SCRA cases in the Northeast were hospitalized more frequently (27.4%), with cases in the Midwest being admitted more frequently to critical care units (15.3%). However, there were no significant differences in clinical toxicity or disposition among the regions. CONCLUSION: Hospitalization resulting from toxicity from synthetic cannabinoid receptor agonists exposure in the United States increased significantly between 2010 and 2015.

New observation of microcystic macular edema as a mild form of cystoid macular lesions after standard phacoemulsification: Prevalence and risk factors.

We present the new observations of postoperative microcystic macular edema (MME) as a mild form of cystoid macular lesions (CMLs) after standard phacoemulsification.To report the incidence, risk factors, and pathophysiology of MME compared to conventional concept of pseudophakic cystoid macular edema (CME), we retrospectively reviewed patients' records. Pseudophakic CMLs were defined as any cystic fluid collections that were newly formed after cataract surgery, confirmed by preoperative and postoperative optical coherence tomography (OCT) examinations. CMLs were classified into 2 groups, which are CME and MME, according to the change the central retinal thickness. The dataset consisted of 316 patients (mean age, 67.52 ±â€Š12.95 years; range, 42-87 years). Topical nonsteroidal anti-inflammatory drug (NSAID) were administered in 197 eyes during the perioperative period; 147 eyes were not treated. CMLs were present in 22 out of 344 (6.39%) eyes. Six of 344 eyes (1.74%) had CME and 16 of 344 eyes (4.65%) had MME. The incidence of MME significantly decreased in the group of patients treated with topical NSAIDs (P = .039), while the incidence of CME was not different in both groups (P = .408). All of the patients with MME were experienced improvement with only topical NSAIDs. However, 67% (4/6) of patients with CME did not improve with topical NSAIDs alone and needed additional treatments. Pseudophakic MMEs were more likely to have a history of diabetic retinopathy, epiretinal membrane, and eyes were not treated with topical NSAID.This study showed a wide clinical spectrum of CMLs. MME has not been included in the conventional definition of pseudophakic CME. Topical NSAIDs could decrease the CML incidence. People with risk factors for CML should use topical NSAIDs and undergo regular follow-up OCT examinations.

Metoclopramide induced pheochromocytoma crisis.

Metoclopramide (MCP) is a commonly used anti-emetic in the emergency department (ED). Its use is generally well tolerated; although infrequent adverse reactions such as extrapyramidal reactions or tardive dyskinesia are reported. However, many ED providers are not familiar with the potentially life-threatening hypertensive emergency that can be precipitated by MCP administration in patients with pheochromocytoma. A previously healthy 36-year-old woman presented to the ED with headache and nausea. She developed acute hypertensive emergency (acute agitation, worsening headache, chest pain and wide complex tachycardia) when her blood pressure (BP) increased to 223/102mmHg (initial BP, 134/86mmHg) after receiving intravenous MCP. Her hospital course was complicated by multi-organ injury, including acute respiratory distress syndrome requiring venous-venous extracorporeal membrane oxygenation, non-ST elevation myocardial infarction, cardiogenic shock, acute liver failure, and oliguric kidney injury requiring continuous renal replacement therapy. CT scan showed previously undiagnosed large right adrenal mass (5.9cm). The diagnosis of pheochromocytoma was confirmed after adrenalectomy. Drug-induced acute pheochromocytoma crisis is a rare event. Early recognition and appropriate blood pressure management with clevidipine, nicardipine, or phentolamine is essential.

The Opioid Epidemic in the United States.

There is an epidemic of opioid abuse. This article discusses the history of opioid use. Abusers of opioids are at great risk of harm. There have been increasing legislative efforts to curb this abuse and we present a review of the current state of these laws. Naloxone has made a profound impact in the care of these patients if they present for medical care early enough. This paper discusses naloxone pharmacodynamics, its use in the medical setting, and how its use is now being expanded to include nontraditional providers with take home naloxone programs.

Reversal of Opioid-Induced Ventilatory Depression Using Low-Dose Naloxone (0.04 mg): a Case Series.

INTRODUCTION: Naloxone is commonly administered in emergency department (ED) to reverse opioid intoxication. Several naloxone dose recommendations exist for acute management of opioid intoxication based on limited published clinical data. A case series of ED patients with opioid-induced ventilatory depression that was reversed using a low-dose naloxone (0.04 mg with titration) is presented. METHODS: ED patients with opioid-induced ventilatory depression requiring naloxone administration were identified through medical toxicology consultation. Retrospective review of medical records was performed. Collected data included history, and pre- and post-naloxone data, including respiratory rate (RR), pulse oximetry (pulse ox), end-tidal CO2 level (ET-CO2), and Richmond Agitation Sedation Scale (RASS). RESULTS: Fifteen ED patients with moderate to severe opioid-induced ventilatory depression (median RR, 6 breaths/min) who were managed using low-dose naloxone strategy were identified. Twelve of 15 patients reported ingestion of methadone (range, 30 to 180 mg). The median naloxone dose of 0.08 mg (range, 0.04 to 0.12 mg) reversed opioid-induced ventilatory and CNS depression. Two patients experienced acute opioid withdrawal after receiving 0.08 mg. CONCLUSION: ED patients with moderate to severe opioid-induced ventilatory depression can be reversed using 0.04 mg IV naloxone with appropriate dose titration.

Reducing the harm of opioid overdose with the safe use of naloxone : a pharmacologic review.

INTRODUCTION: Opioid overdose fatality has increased threefold since 1999. As a result, prescription drug overdose surpassed motor vehicle collision as the leading cause of unintentional injury-related death in the USA. Naloxone , an opioid antagonist that has been available for decades, can safely reverse opioid overdose if used promptly and correctly. However, clinicians often overestimate the dose of naloxone needed to achieve the desired clinical outcome, precipitating acute opioid withdrawal syndrome (OWS). AREAS COVERED: This article provides a comprehensive review of naloxone's pharmacologic properties and its clinical application to promote the safe use of naloxone in acute management of opioid intoxication and to mitigate the risk of precipitated OWS. Available clinical data on opioid-receptor kinetics that influence the reversal of opioid agonism by naloxone are discussed. Additionally, the legal and social barriers to take home naloxone programs are addressed. EXPERT OPINION: Naloxone is an intrinsically safe drug, and may be administered in large doses with minimal clinical effect in non-opioid-dependent patients. However, when administered to opioid-dependent patients, naloxone can result in acute opioid withdrawal. Therefore, it is prudent to use low-dose naloxone (0.04 mg) with appropriate titration to reverse ventilatory depression in this population.

Epidemic gasoline exposures following Hurricane Sandy.

INTRODUCTION: Major adverse climatic events (MACEs) in heavily-populated areas can inflict severe damage to infrastructure, disrupting essential municipal and commercial services. Compromised health care delivery systems and limited utilities such as electricity, heating, potable water, sanitation, and housing, place populations in disaster areas at risk of toxic exposures. Hurricane Sandy made landfall on October 29, 2012 and caused severe infrastructure damage in heavily-populated areas. The prolonged electrical outage and damage to oil refineries caused a gasoline shortage and rationing unseen in the USA since the 1970s. This study explored gasoline exposures and clinical outcomes in the aftermath of Hurricane Sandy. METHODS: Prospectively collected, regional poison control center (PCC) data regarding gasoline exposure cases from October 29, 2012 (hurricane landfall) through November 28, 2012 were reviewed and compared to the previous four years. The trends of gasoline exposures, exposure type, severity of clinical outcome, and hospital referral rates were assessed. RESULTS: Two-hundred and eighty-three gasoline exposures were identified, representing an 18 to 283-fold increase over the previous four years. The leading exposure route was siphoning (53.4%). Men comprised 83.0% of exposures; 91.9% were older than 20 years of age. Of 273 home-based calls, 88.7% were managed on site. Asymptomatic exposures occurred in 61.5% of the cases. However, minor and moderate toxic effects occurred in 12.4% and 3.5% of cases, respectively. Gastrointestinal (24.4%) and pulmonary (8.4%) symptoms predominated. No major outcomes or deaths were reported. CONCLUSIONS: Hurricane Sandy significantly increased gasoline exposures. While the majority of exposures were managed at home with minimum clinical toxicity, some patients experienced more severe symptoms. Disaster plans should incorporate public health messaging and regional PCCs for public health promotion and toxicological surveillance.

Buprenorphine may not be as safe as you think: a pediatric fatality from unintentional exposure.

Buprenorphine is a partial µ-opioid receptor agonist that is approved for the treatment of opioid dependency. It is generally believed to be safer than methadone because of its ceiling effect on respiratory depression. As more adults in US households use buprenorphine, an increasing number of children are being exposed. We report a fatal exposure to buprenorphine in a small child that occurred after ingestion of a caretaker's buprenorphine/naloxone. Postmortem toxicology analysis showed free serum concentrations of 52 ng/mL and 39 ng/mL for buprenorphine and norbuprenorphine, respectively. No other drugs were detected. Autopsy did not find signs of injury or trauma. The theoretical safety provided by the ceiling effect in respiratory depression from buprenorphine may not apply to children, and buprenorphine may cause dose-dependent respiratory depression.

The association between serum thyrotropin (TSH) levels and bone mineral density in healthy euthyroid men.

OBJECTIVE: Although osteoporosis is increasingly shown to occur in a considerable proportion of men, data on risk factors for male osteoporosis are limited. In this study, we investigated the association between serum thyrotropin (TSH) concentration and bone mineral density (BMD) in healthy euthyroid men. Design A cross-sectional community (health promotion centre)-based survey. SUBJECTS AND MEASUREMENTS: For 1478 apparently healthy euthyroid men who participated in a routine health screening examination, we measured BMD at the lumbar spine and femoral neck using dual energy X-ray absorptiometry and serum TSH concentrations using immunoluminometry. RESULTS: Lumbar spine BMD linearly increased with TSH level after adjustment for age, weight and height (P for trend = 0.002), and statistical significance persisted after additional adjustment for smoking and drinking habits (P for trend = 0.010). When serum alkaline phosphatase was added as a confounding variable, the relationship was still significant (P for trend = 0.016). Femoral neck BMD also tended to increase in higher TSH concentration after adjustment for age, weight and height (P for trend = 0.042), but this association disappeared after additional adjustment for smoking and drinking habits. The odds of lower BMD (i.e. osteopaenia and osteoporosis combined) were significantly increased in subjects with low-normal TSH (i.e. 0.4-1.2 mU/l), when compared to high-normal TSH (i.e. 3.1-5.0 mU/l), after adjustment for confounding factors (odds ratio = 1.45, 95% CI = 1.02-2.10). CONCLUSION: These results suggest that a serum TSH concentration at the lower end of the reference range may be associated with low BMD in men.