Rawle A. Seupaul

Microtubule-associated protein tau is hyperphosphorylated during mitosis in the human neuroblastoma cell line SH-SY5Y

A phosphorylated tau epitope specific for paired helical filaments in Alzheimers disease is recognized by monoclonal antibody PHF-1. Healthy adult brains lack the PHF-1 epitope (PHF-1 tau), but it is transiently expressed by immature neurons during development. We have found that proliferating SH-SY5Y human neuroblastoma cells also express PHF-1 tau. Consistent with the recent finding that cell-cycle-dependent kinases can phosphorylate tau in vitro, flow cytometry showed that mitotic SH-SY5Y cells were up to 18-fold more PHF-1 immunoreactive than nonmitotic cells. On immunoblots, PHF-1 tau in mitotic and nonmitotic cells also was strikingly different. First, mitosis induced a prominent PHF-1 reactive band at 120 kDa, which likely accounted for the large increase in PHF-1 signal seen at mitosis. Although the size of the 120-kDa band is consistent with it being the high-molecular-weight form of tau, other antibodies to tau did not recognize it. Second, mitosis caused a hyperphosphorylation of the PHF-1 immunoreactive tau band normally seen at 50 kDa. In mitotic cells this band had an increased intensity and molecular weight. Alkaline phosphatase treatment abolished tau M(r) heterogeneity, verifying that the variations in mobility were due to phosphorylation. These data show that cell-cycle-dependent hyperphosphorylation of tau occurs in intact cells, and they support the hypothesis that aberrant activity of cell-cycle-dependent kinases may contribute to tau phosphorylation and PHF formation in Alzheimers disease.

Pain measurement in pediatric emergency care: a review of the faces pain scale-revised.

Abstract: Addressing pain in children is an important task for emergency physicians. Current literature highlights a significant deficiency in our ability to assess and treat pain in this population. Multiple pediatric pain scales are available for use. This article will briefly review some of the major challenges in pediatric pain measurement and focus on the Faces Pain Scale-Revised as a valid tool that can be used in both clinical trials and everyday clinical practice.

Pharmacologic prophylaxis for acute mountain sickness: a systematic shortcut review.

STUDY OBJECTIVE Multiple studies have explored pharmacologic interventions to prevent acute mountain sickness. A systematic review of this subject published in 2000 found that both acetazolamide and dexamethasone were effective. Since 2000, a number of other agents have been reported to be beneficial. This EBEM review evaluates the most current evidence on this topic. METHODS We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, SPORTDiscus, Emergency Medical Abstracts, and ClinicalTrials.gov from 2000 to July 2011. Only randomized placebo-controlled trials with an N greater than or equal to 50 and systematic reviews were reviewed. Standard criteria for assessing trial quality were independently assessed by 2 authors. RESULTS Seven hundred eighty-six citations were retrieved, of which 105 were reviewed in their entirety. Eleven randomized controlled trials and 1 systematic review appeared to meet inclusion criteria; however, 4 randomized controlled trials were excluded for high risk of bias. The remaining 7 randomized controlled trials investigated antioxidants, magnesium, sumatriptan, gabapentin, acetazolamide, and Ginkgo biloba. No trials studying dexamethasone met our criteria. Acetazolamide was associated with a reduction in acute mountain sickness symptoms, with a number needed to treat ranging from 8 to 3 among 3 trials and at doses ranging from 250 to 750 mg daily. Sumatriptan showed benefit in 1 trial (number needed to treat=4), as did gabapentin (number needed to treat=6). Antioxidants, magnesium, and G biloba were not efficacious. Reported adverse events included somnolence with gabapentin and paresthesias with acetazolamide. The systematic review affirmed our results but did not capture trials studying antioxidants, magnesium, sumatriptan, or gabapentin. CONCLUSION Acetazolamide is effective for the prevention of acute mountain sickness but may be associated with paresthesias. Sumatriptan and gabapentin are beneficial but require further study.

DIFFERENTIATING LOW-RISK AND NO-RISK PE PATIENTS: THE PERC SCORE

BACKGROUND Pulmonary embolism (PE) remains one of the most challenging diagnoses in emergency medicine. The Pulmonary Embolism Rule-out Criteria (PERC) score, a decision aid to reliably distinguish low-risk from very low-risk PE patients, has been derived and validated. CLINICAL QUESTION Can a subset of patients with sufficiently low risk for PE be identified who require no diagnostic testing? EVIDENCE REVIEW The PERC score derivation and validation trials were located using PubMed and Web of Science. A critical appraisal of this research is presented. RESULTS One single-center and another multi-center validation trial both confirmed that the eight-item PERC score identified a very low-risk subset of patients in whom PE was clinically contemplated with a negative likelihood ratio 0.17 (95% confidence interval 0.11-0.25) in the larger trial. If applied, the rule would have identified 20% of potential PE patients as very low risk. CONCLUSION The PERC score provides clinicians with an easily remembered, validated clinical decision rule that allows physicians to forego diagnostic testing for pulmonary embolus in a very low-risk population.

No benefit to prehospital initiation of therapeutic hypothermia in out-of-hospital cardiac arrest: a systematic review and meta-analysis.

OBJECTIVES The aim of this review was to define the effect of prehospital therapeutic hypothermia (TH) on survival and neurologic recovery in patients who have suffered out-of-hospital cardiac arrest (OHCA). METHODS Included in this review are randomized trials assessing the effect of prehospital TH in adult patients suffering nontraumatic OHCA. Trials assessing the effect of in-hospital TH were excluded. Only studies with a low risk of bias were eligible for meta-analysis. A medical librarian searched PubMed, Ovid, EMBASE, Ovid Global Health, the Cochrane Library, Guidelines.gov, EM Association Websites, CenterWatch, IFPMA Clinical Trial Results Portal, CINAHL, ProQuest, and the Emergency Medical Abstracts Database without language restrictions. Clinicaltrials.gov was searched for unpublished studies. Bibliographies were hand searched and experts in the field were queried about other published or unpublished trials. Using standardized forms, two authors independently extracted data from all included trials. Results from high-quality trials were pooled using a random-effects model. Two authors, using the Cochrane risk of bias tool, assessed risk of bias independently. RESULTS Of 740 citations, six trials met inclusion criteria. Four trials were at a low risk of bias and were included in the meta-analysis (N=715 patients). Pooled analysis of these trials revealed no difference in overall survival (relative risk [RR]=0.98, 95% CI=0.79 to 1.21) or good neurologic outcome (RR=0.96, 95% CI=0.76 to 1.22) between patients randomized to prehospital TH versus standard therapy. Heterogeneity was low for both survival and neurologic outcome (I2=0). CONCLUSIONS Randomized trial data demonstrate no important patient benefit from prehospital initiation of TH. Pending the results of ongoing larger trials, resources dedicated to this intervention may be better spent elsewhere.

Streptococcal necrotizing myositis: a case report and clinical review.

BACKGROUND Streptococcal necrotizing myositis, also known as gangrenous myositis, is a very rare and severe soft tissue infection that predominately involves skeletal muscle and, eventually, superficial fascia and surrounding tissues. The presentation is often nonspecific until the rapidly progressing clinical course becomes apparent. A high morbidity and mortality rate has been reported in the small number of cases since 1900. Despite several attempts to better define the different entities causing necrotizing myositis, no single definitive causal relationship has been defined. OBJECTIVES A review of the literature is presented here to help clinicians distinguish those with necrotizing myositis from those with nonnecrotizing myositis when the clinician is at all confronted with the suspicion for such an infection. CASE REPORT The case presented is that of a 48-year-old woman who had streptococcal necrotizing myositis. She died roughly 72 h after admission. After the patients death, the clinical team sought consent for autopsy. Hospital staff made contact with family, and information was obtained from the family that the onset of the patients symptoms was allegedly temporally related to her acquisition of a new tattoo on the right back, where the tattoo process allegedly included injection of cremated ashes of a pet dog. CONCLUSION A high level of suspicion for necrotizing myositis must be maintained for a patient with unexplained severe muscle pain and soft tissue swelling accompanied by systemic inflammatory response syndrome.

Does succinylcholine maximize intubating conditions better than rocuronium for rapid sequence intubation

Succinylcholine is superior to rocuronium for creating excellent intubating conditions and should be the first-line paralytic agent used for rapid sequence intubations.

Are Plain Radiographs Sufficient to Exclude Cervical Spine Injuries in Low-Risk Adults?

BACKGROUND The routine use of clinical decision rules and three-view plain radiography to clear the cervical spine in blunt trauma patients has been recently called into question. CLINICAL QUESTION In low-risk adult blunt trauma patients, can plain radiographs adequately exclude cervical spine injury when clinical prediction rules cannot? EVIDENCE REVIEW Four observational studies investigating the performance of plain radiographs in detecting cervical spine injury in low-risk adult blunt trauma patients were reviewed. CONCLUSION The consistently poor performance of plain radiographs to rule out cervical spine injury in adult blunt trauma victims is concerning. Large, rigorously performed prospective trials focusing on low- or low/moderate-risk patients will be needed to truly define the utility of plain radiographs of the cervical spine in blunt trauma.

Klippel-Feil syndrome.

A healthy 19-year-old man presented with signs and symptoms of central cord syndrome after a moderate fall. He had congenital fusion of multiple cervical vertebrae consistent with Klippel-Feil syndrome. This disorder, although rare, is important for emergency medicine physicians to recognize as a risk factor for cervical cord syndromes.

STOP STEMI©-a novel medical application to improve the coordination of STEMI care: a brief report on door-to-balloon times after initiating the application.

Objective: The objective of our study was to evaluate the effect of the STOP STEMI© medical application on door-to-balloon (D2B) time in patients arriving to our emergency department with an acute ST Elevation Myocardial Infarction (STEMI). STOP STEMI© is a novel medical application developed by physicians to improve the coordination and communication tasks essential to rapid assessment and care of the patients suffering from a STEMI. Methods: We conducted a retrospective before and after review of the Good Shepherd Health System STEMI quality assurance/improvement dashboard for a 10-month period between November, 2012 and September, 2013 (4 months before STOP STEMI© and 6 months after). Data was collected using a standard data collection form and entered on the dashboard by a STEMI coordinator blinded to study objectives. We calculated the average D2B times before and after initiation of STOP STEMI© along with the improvement in the benchmarks of D2B less than 90 min and D2B less than 60 minutes. A subgroup analysis of Center for Medicare and Medicaid services (CMS) reportable cases was conducted to evaluate these benchmarks in the subset of patients meeting the criteria for CMS reporting by our facility. Results: During the study period, we received 155 STEMI patients, average 0.5 patients per day. One hundred twelve of the patients underwent percutaneous coronary intervention (PCI), 37 preSTOP STEMI©, and 75 postSTOP STEMI©. Of the 112 PCI cases, 7 were excluded leaving 105 cases for analysis, 36 preapplication and 69 postapplication. We found a 22% reduction in the average door-to-balloon time after implementing the STOP STEMI© application (91–71 minutes) respectively, the average difference of 20 minutes P = 0.05 (95% CI, -1–40minutes). In the analysis of CMS reportable cases (n = 64 cases), we observed a decrease in the average D2B of 15 minutes (68–53 minutes), a 22% reduction P = 0.03 (95% CI 1–29min). In the CMS reportable cases, we saw an improvement in the D2B time less than 90 minutes from 78–95% and less than 60 minutes D2B improvement from 56–80%. We also observed an appropriate absolute reduction in PCI resource utilization by 11%. Conclusions: In this cohort of patients, the utilization of STOP STEMI© decreased the average door-to-balloon times by 22% in the patients with acute STEMI arriving at our emergency department. This effect was maintained when looking at the subset of all STEMI cases reportable to CMS. We also observed modest improvements in meeting the less than 60-minute, less than 90-minute benchmarks, and improvements in the resource utilization.