Who receives naloxone from emergency medical services? Characteristics of calls and recent trends

Abstract

Background: With the rapid rise in opioid overdose-related deaths, state policy makers have expanded policies to increase the use of naloxone by emergency medical services (EMS). However, little is known about changes in EMS naloxone administration in the context of continued worsening of the opioid crisis and efforts to increase use of naloxone. This study examines trends in patient demographics and EMS response characteristics over time and by county urbanicity. Methods: We used data from the 2013–2016 National EMS Information System to examine trends in patient demographics and EMS response characteristics for 911-initiated incidents that resulted in EMS naloxone administration. We also assessed temporal, regional, and urban–rural variation in per capita rates of EMS naloxone administrations compared with per capita rates of opioid-related overdose deaths. Results: From 2013 to 2016, naloxone administrations increasingly involved young adults and occurred in public settings. Particularly in urban counties, there were modest but significant increases in the percentage of individuals who refused subsequent treatment, were treated and released, and received multiple administrations of naloxone before and after arrival of EMS personnel. Over the 4-year period, EMS naloxone administrations per capita increased at a faster rate than opioid-related overdose deaths across urban, suburban, and rural counties. Although national rates of naloxone administration were consistently higher in suburban counties, these trends varied across U.S. Census Regions, with the highest rates of suburban administration occurring in the South. Conclusions: Naloxone administration rates increased more quickly than opioid deaths across all levels of county urbanicity, but increases in the percentage of individuals requiring multiple doses and refusing subsequent care require further attention.     

Murine startle mutant Nmf11 affects the structural stability of the glycine receptor and increases deactivation

AbstractDysfunctional glycinergic inhibitory transmission underlies the debilitating neurological condition, hyperekplexia, which is characterised by exaggerated startle reflexes, muscle hypertonia and apnoea. Here we investigated the N46K missense mutation in the GlyR α1 subunit gene found in the ethylnitrosourea (ENU) murine mutant, Nmf11, which causes reduced body size, evoked tremor, seizures, muscle stiffness, and morbidity by postnatal day 21. Introducing the N46K mutation into recombinant GlyR α1 homomeric receptors, expressed in HEK cells, reduced the potencies of glycine, β‐alanine and taurine by 9‐, 6‐ and 3‐fold respectively, and that of the competitive antagonist strychnine by 15‐fold. Replacing N46 with hydrophobic, charged or polar residues revealed that the amide moiety of asparagine was crucial for GlyR activation. Co‐mutating N61, located on a neighbouring β loop to N46, rescued the wild‐type phenotype depending on the amino acid charge. Single‐channel recording identified that burst length for the N46K mutant was reduced and fast agonist application revealed faster glycine deactivation times for the N46K mutant compared with the WT receptor. Overall, these data are consistent with N46 ensuring correct alignment of the α1 subunit interface by interaction with juxtaposed residues to preserve the structural integrity of the glycine binding site. This represents a new mechanism by which GlyR dysfunction induces startle disease.

Abbreviations

DMEM

Dulbecco''s modified Eagle medium

DR

dose‐ratio

ENU

ethylnitrosourea

GFP

green fluorescent protein

GLRA1

GlyR α1 subunit gene

GLRB

GlyR β subunit gene

GluCl

glutamate‐activated Cl^˗ channel

GlyR

glycine receptor

HEK‐293

human embryonic kidney 293 cells

K_B

equilibrium dissociation constant

V_patch

trans‐patch potential

WT

wild type

     

Best practice in primary care pathology: review 7

This seventh best-practice review examines four series of common primary care questions in laboratory medicine: (1) blood count abnormalities 2; (2) cardiac troponins; (3) high-density lipoprotein cholesterol; and (4) viral diseases 2. The review is presented in a question-answer format, with authorship attributed for each question series. The recommendations are a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. The recommendations are not standards, but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.     

Proposal for a New Pathologic Prognostic Index After Neoadjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma (PINC)

Background

Limited information is available on the relevant prognostic variables after surgery for patients with pancreatic ductal adenocarcinoma (PDAC) subjected to neoadjuvant chemotherapy (NACT). NACT is known to induce a spectrum of histological changes in PDAC. Different grading regression systems are currently available; unfortunately, they lack precision and accuracy. We aimed to identify a new quantitative prognostic index based on tumor morphology.

Patients and Methods

The study population was composed of 69 patients with resectable or borderline resectable PDAC treated with preoperative NACT (neoadjuvant group) and 36 patients submitted to upfront surgery (upfront-surgery group). A comprehensive histological assessment on hematoxylin and eosin (H&E) stained sections evaluated 20 morphological parameters. The association between patient survival and morphological variables was evaluated to generate a prognostic index.

Results

The distribution of morphological parameters evaluated was significantly different between upfront-surgery and neoadjuvant groups, demonstrating the effect of NACT on tumor morphology. On multivariate analysis for patients that received NACT, the predictors of shorter overall survival (OS) and disease-free survival (DFS) were perineural invasion and lymph node ratio. Conversely, high stroma to neoplasia ratio predicted longer OS and DFS. These variables were combined to generate a semiquantitative prognostic index based on both OS and DFS, which significantly distinguished patients with poor outcomes from those with a good outcome. Bootstrap analysis confirmed the reproducibility of the model.

Conclusions

The pathologic prognostic index proposed is mostly quantitative in nature, easy to use, and may represent a reliable tumor regression grading system to predict patient outcomes after NACT followed by surgery for PDAC.

     

Gastro-oesophageal reflux in the irritable bowel syndrome.

Symptomatic assessment and oesophageal investigations were done in 25 consecutive patients with the irritable bowel syndrome attending a gastroenterological clinic. Symptoms of gastro-oesophageal reflux, dysphagia, and a globus sensation were significantly commoner than in a control group of fracture clinic patients. Ambulatory oesophageal pH monitoring showed clearly abnormal reflux in 11 of 22 patients (50%). Nine patients had macroscopic endoscopic changes and a further 11 biopsy changes alone, of oesophagitis which was thus present in 80% overall. Lower oesophageal sphincter pressure was significantly less in irritable bowel patients than in age and sex matched controls, but upper oesophageal sphincter pressure was comparable in the two groups and disordered peristalsis was not found. Oesophageal symptoms in the irritable bowel syndrome are mainly caused by gastro-oesophageal reflux predisposed to by a subnormal lower oesophageal sphincter pressure, rather than by oesophageal spasm.     

Utility of impedance cardiography for the identification of short-term risk of clinical decompensation in stable patients with chronic heart failure.

OBJECTIVES: This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). BACKGROUND: Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. METHODS: We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. RESULTS: During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. CONCLUSIONS: These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation.     

Acute systemic immune activation following vaginal exposure to staphylococcal enterotoxin B--implications for menstrual shock

Menstrual toxic shock syndrome (mTSS) is an acute systemic inflammatory disease associated with the superantigenic exotoxin, toxic shock syndrome toxin (TSST)-1, produced by Staphylococcus aureus and the use of high absorbency tampons. Even though S. aureus is capable of elaborating several other superantigenic exotoxins, only TSST-1 has been implicated in the pathogenesis of mTSS possibly because most other superantigenic exotoxins are known enterotoxins. Nonetheless, we have shown recently that one of the enterotoxigenic staphylococcal superantigens, staphylococcal enterotoxin B (SEB), can cause robust systemic immune activation following exposure through non-enteric mucosa, including nasal or conjunctival routes. In a similar manner, we show here that vaginal administration of SEB in HLA class II transgenic mice can cause robust systemic immune activation characterized by profound elevation of proinflammatory cytokines in the serum, activation and expansion of SEB-reactive CD4(+) and CD8(+) T cells in peripheral lymphoid organs and SEB-induced deletion of immature thymocytes. Vaginal administration of SEB also caused leukocytic infiltration in major organs, such as liver and lung, reminiscent of human toxic shock syndrome. Systemic immune activation following vaginal superantigen delivery was independent of the stage of the estrus cycle in the mouse. Using HLA class II transgenic mice, we have shown that exposure to SEB through the vaginal canal can cause robust systemic immune activation. SEB could thus play a role in the pathogenesis of mTSS.     

Caveolae, lipid rafts, and vascular disease

Caveolae and lipid rafts are discrete regions within the plasma membrane that coordinate and regulate a variety of signaling processes. The exact relationship between caveolae and lipid rafts is unclear. However, caveolae contain a protein called caveolin that serves as a biochemical marker for caveolae. In addition, caveolin plays a role in maintaining the lipid composition of caveolae, the morphology of caveolae, and the signals that emanate from caveolae. The physiologic importance of caveolae is evidenced by recent studies using caveolin knockout mice that show dramatic abnormalities in the cardiovascular system, such as pulmonary hypertension and cardiac hypertrophy. In this review, we will focus on the role of caveolae in the cardiovascular system.