A 4-Year-Old With Altered Mental Status and Bradycardia After Clonidine Overdose.

This case presentation describes the clinical management of a pediatric patient during transport after a single-drug overdose of clonidine. Clonidine overdose closely resembles opiate intoxication, and treatment is largely supportive; however, the patient in this case presentation had a declining altered mental status with evidence of airway compromise within 1 to 2 hours after ingestion, which warranted protective airway management. The patient was extubated the following day with a successful outcome.

Real-Time Fatigue Mitigation with Air-Medical Personnel: The SleepTrackTXT2 Randomized Trial.

Objective: The aims of this study were: 1) to determine the short-term impact of the SleepTrackTXT2 intervention on air-medical clinician fatigue during work shifts and 2) determine the longer-term impact on sleep quality over 120 days. Methods: We used a multi-site randomized controlled trial study design with a targeted enrollment of 100 (ClinicalTrials.gov NCT02783027). The intervention was behavioral (non-pharmacological) and participation was scheduled for 120 days. Participation was voluntary. All consented participants answered baseline as well as follow-up surveys. All participants answered text message queries, which assessed self-rated fatigue, sleepiness, concentration, recovery, and hours of sleep. Intervention participants received additional text messages with recommendations for behaviors that can mitigate fatigue. Intervention participants received weekly text messages that promoted sleep. Our analysis was guided by the intent-to-treat principle. For the long-term outcome of interest (sleep quality at 120 days), we used a two-sample t-test on the change in sleep quality to determine the intervention effect. Results: Eighty-three individuals were randomized and 2,828 shifts documented (median shifts per participant =37, IQR 23-49). Seventy-one percent of individuals randomized (n = 59) participated up to the 120-day study period and 52% (n = 43) completed the follow-up survey. Of the 69,530 text messages distributed, participants responded to 61,571 (88.6%). Mean sleep quality at 120 days did not differ from baseline for intervention (p > 0.05) or control group participants (p > 0.05), and did not differ between groups (p > 0.05). There was no change from baseline to 120 days in the proportion with poor sleep quality in either group. Intra-shift fatigue increased (worsened) over the course of 12-hour shifts for participants in both study arms. Fatigue at the end of 12-hour shifts was higher among control group participants than participants in the intervention group (p < 0.05). Pre-shift hours of sleep were often less than 7 hours and did not differ between the groups over time. Conclusions: The SleepTrackTXT2 behavioral intervention showed a positive short-term impact on self-rated fatigue during 12-hour shifts, but did not impact longer duration shifts or have a longer-term impact on sleep quality among air-medical EMS clinicians.

Impact of shift duration on alertness among air-medical emergency care clinician shift workers.

BACKGROUND: Greater than half of Emergency Medical Services (EMS) shift workers report fatigue at work and most work long duration shifts. We sought to compare the alertness level of EMS shift workers by shift duration. METHODS: We used a multi-site, 14-day prospective observational cohort study design of EMS clinician shift workers at four air-medical EMS organizations. The primary outcome was behavioral alertness as measured by psychomotor vigilance tests (PVT) at the start and end of shifts. We stratified shifts by duration (< 24 h and 24 h), night versus day, and examined the impact of intra-shift napping on PVT performance. RESULTS: One hundred and twelve individuals participated. The distribution of shifts <24 h and 24 h with complete data were 54% and 46%, respectively. We detected no differences in PVT performance measures stratified by shift duration (P > 0.05). Performance for selected PVT measures (lapses and false starts) was worse on night shifts compared to day shifts (P < 0.05). Performance also worsened with decreasing time between waking from a nap and the end of shift PVT assessment. CONCLUSIONS: Deficits in performance in the air-medical setting may be greatest during night shifts and proximal to waking from an intra-shift nap. Future research should examine alertness and performance throughout air-medical shifts, as well as investigate the timing and duration of intra-shift naps on outcomes.

Decreased Time from 9-1-1 Call to PCI among Patients Experiencing STEMI Results in a Decreased One Year Mortality.

BACKGROUND: The impact on mortality due to prompt recognition of ST-segment Elevation Myocardial Infarction (STEMI) patients by EMS has not been well described. The objective of this study was to describe the association between the time interval, 9-1-1 call to percutaneous intervention (PCI), and mortality at one year. METHODS: This retrospective analysis included patients that were transported by EMS as a "code STEMI" and underwent PCI.  Total time from 9-1-1 call to PCI was calculated for each patient and was the independent variable of interest. Each patient's mortality status at one year was the outcome variable, collected by querying medical records and the national death index. Confounding variables were abstracted from hospital records. Logistic regression was conducted to determine the likelihood of survival given differences in time to PCI. RESULTS: A total of 550 patients were included in the analyses of which 68% were male with an average age 59.8 (SD 12.8). Mean reperfusion time was 81.8 min (SD 20.0) and was significantly lower in patients alive at one year (80.8 min, SD 19.7) vs. deceased at one year (93.9 min, SD 19.6), respectively. Odds of survival at one year decreased by 3% (OR 0.97; 95% CI 0.96-0.99) for every one minute increase in time to PCI. This relationship practically represents a 30% increase in mortality for every 10 minute delay from 9-1-1 call to PCI. CONCLUSION: The model produced suggests that a linear relationship exists between time to PCI and mortality in the prehospital environment with the probability of survival decreasing significantly as time to PCI increases.

Abnormalities in the Structure and Function of Cerebellar Neurons and Neuroglia in the Lc/+ Chimeric Mouse Model of Variable Developmental Purkinje Cell Loss.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by impaired and disordered language, decreased social interactions, stereotyped and repetitive behaviors, and impaired fine and gross motor skills. It has been well established that cerebellar abnormalities are one of the most common structural changes seen in the brains of people diagnosed with autism. Common cerebellar pathology observed in autistic individuals includes variable loss of cerebellar Purkinje cells (PCs) and increased numbers of reactive neuroglia in the cerebellum and cortical brain regions. The Lc/+ mutant mouse loses 100 % of cerebellar PCs during the first few weeks of life and provided a valuable model to study the effects of developmental PC loss on underlying structural and functional changes in cerebellar neural circuits. Lurcher (Lc) chimeric mice were also generated to explore the link between variable cerebellar pathology and subsequent changes in the structure and function of cerebellar neurons and neuroglia. Chimeras with the most severe cerebellar pathology (as quantified by cerebellar PC counts) had the largest changes in cFos expression (an indirect reporter of neural activity) in cerebellar granule cells (GCs) and cerebellar nucleus (CN) neurons. In addition, Lc chimeras with the fewest PCs also had numerous reactive microglia and Bergmann glia located in the cerebellar cortex. Structural and functional abnormalities observed in the cerebella of Lc chimeras appeared to be along a continuum, with the degree of pathology related to the number of PCs in individual chimeras.

Evaluating clinical care in the prehospital setting: Is Rapid Emergency Medicine Score the missing metric of EMS?

INTRODUCTION: The Rapid Emergency Medicine Score (REMS) was developed to predict emergency department patient mortality. Our objective was to utilize REMS to assess initial patient acuity and evaluate clinical change during prehospital care. METHODS: All non-cardiac arrest emergency transports from April 1, 2013 to March 31, 2014 were analyzed from a single EMS agency. Using age, pulse rate, mean arterial pressure, respiratory rate, oxygen saturation, and Glasgow Coma Scale, initial and final REMS were calculated. Change in REMS was calculated by initial minus final with a positive number indicating clinical improvement. Descriptive analyses were performed calculating means and 95% confidence intervals. RESULTS: There were 61,346 patients analyzed with an average initial REMS of 4.3 (95% CI: 4.2-4.3) and an average REMS change of 0.37 (95% CI: 0.36-0.38). Those patients classified with the highest dispatch priority had the highest initial REMS (5.8; 95% CI: 5.5-6.2) and the greatest change (0.95; 95% CI: 0.72-1.17). Patients transported with high priority had greater initial REMS, as well as greater improvement in REMS (high priority 7.3 [95% CI: 7.1-7.4], change 0.61 [95% CI: 0.53-0.69]; middle priority 5.3 [95% CI: 5.2-5.4], change 0.55 [95% CI: 0.51-0.59]; low priority 3.9 [95% CI: 3.8-3.9], change 0.32 [95% CI: 0.31-0.33]). CONCLUSION: Descriptive analyses indicate that as dispatch and transport priorities increased in severity so too did initial REMS. The largest change in REMS was seen in patients with the highest dispatch and transport priorities. This indicates that REMS may provide system level insight into evaluating clinical changes during care.

North Carolina College of Emergency Physicians' Guidance Document on Emergency Medical Services.

The North Carolina College of Emergency Physicians (NCCEP) Emergency Medical Services (EMS) Committee uses an evidence-based approach in writing its protocols and procedures. The most recent revision of the NCCEP document, which was started in late 2010, lasted for more than 1 year and utilized committee members from across the state. Four meetings were held at locations across North Carolina. In addition, 2 surveys were sent to get input from EMS providers. Since 2010, the document has been updated on an ongoing basis, aligning it with the latest evidence-based medicine.

Assessing the validity of the Cincinnati prehospital stroke scale and the medic prehospital assessment for code stroke in an urban emergency medical services agency.

OBJECTIVES: The primary objective of this study was to assess the effectiveness of two prehospital stroke screens in correctly classifying patients suspected of having a stroke. Secondarily, differences in the sensitivity and specificity of the two screening tools were assessed. METHODS: We performed a retrospective assessment of the Cincinnati Prehospital Stroke Scale (CPSS) and the Medic Prehospital Assessment for Code Stroke (Med PACS) between March 1, 2011, and September 30, 2011, in a single emergency medical services (EMS) agency with seven local hospitals all classified as stroke-capable. We obtained data for this analysis from the EMS electronic patient care reports (ePCRs) and the Get With The Guidelines(-)Stroke (GWTG-S) registries maintained by the two local health care systems by matching on patient identifiers. The Med PACS was developed specifically for the EMS agency under study by a local team of neurologists, emergency physicians, and paramedics. All of the physical assessment elements of the CPSS were included within the Med PACS. Two additional physical assessment items, gaze and leg motor function, were included in the Med PACS. We classified patients as CPSS-positive or -negative and Med PACS-positive or -negative if any one of the physical assessment findings was present. We determined the presence of a hospital discharge diagnosis of stroke from GWTG-S. We calculated sensitivity and specificity with resultant 95% confidence intervals. RESULTS: We enrolled 416 patients in this study, of whom 186 (44.7%) were diagnosed with a stroke. The Med PACS scale demonstrated a sensitivity of 0.742 (95% confidence interval [CI] 0.672-0.802), while the sensitivity for the CPSS was 0.790 (95% CI 0.723-0.845). The sensitivity of the CPSS was significantly higher than that of the Med PACS, with a difference of 0.048 (95% CI 0.009-0.088; p = 0.011). The specificities of these two scales were low, Med PACS 0.326 (95% CI 0.267-0.391) vs. CPSS 0.239 (95% CI 0.187-0.300), and the specificity of the Med PACS was significantly higher compared with the CPSS, with a difference in specificity of 0.086 (95% CI 0.042-0.131), p < 0.001. CONCLUSION: The two stroke scales under study demonstrated low sensitivity and specificity, with each scale performing marginally better in one of the two metrics assessed.

Implementation of prehospital dispatch protocols that triage low-acuity patients to advice-line nurses.

INTRODUCTION: Although EMS agencies have been designed to efficiently provide medical assistance to individuals, the overuse of 9-1-1 as an alternative to primary medical care has resulted in the need for new methods to respond to this increasing demand. Our study analyzes the efficacy of classifying specific low-acuity calls that can be transferred to an advice-line nurse for further medical instruction. The objectives of our study were to analyze the impact of implementing this protocol and resultant patient feedback regarding the transfer to an advice-line nurse. METHODS: We collected data for retrospective review from April 2011 to April 2012 from a single municipal EMS agency with an average annual call volume of approximately 90,000. Medical Priority Dispatch System response codes were assigned to calls based on patient acuity. Patients classified under Omega response codes were assessed for eligibility of transfer to nurse advice lines. Exclusion criteria included the following: if the call was placed by a third-party caller; if the patient refused to be transferred to the advice-line nurse; anytime the MPDS system was not used; if the patient was referred from a skilled nursing facility, school, or university nursing office, or physician's office. Telephone surveys were conducted for those patients who spoke to an advice-line nurse and did not receive an ambulance response 24 hours after calling 9-1-1 to obtain patient feedback. RESULTS: The database included 1660 patients initially classified as Omega and eligible for transfer to an advice-line nurse. After applying the exclusion criteria, 329 (19.8%) patients were ultimately transferred to an advice-line nurse and 204 (12.3%) received no ambulance response. Of those patients who were not transported by ambulance 118 (57.8%), patients completed telephone follow-up, with 104 (88.1%) reporting the nontransport option met their health-care needs and 108 (91.5%) responding they would accept the transfer again for a similar complaint. CONCLUSION: We identified an average of two patients per day as eligible for transfer to the nurse advice line, with less than one patient successfully completing the Omega protocol per day. While impact was limited, there was a decrease in ambulance response.

Novel cystamine-core dendrimer-formulation rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection by augmenting autophagy.

BACKGROUND: Cystic fibrosis (CF) is challenged with pathophysiological barriers for effective airway drug-delivery. Hence, we standardized the therapeutic efficacy of the novel dendrimer-based autophagy-inducing anti-oxidant drug, cysteamine. RESEARCH DESIGN AND METHODS: Human primary-CF epithelial-cells, CFBE41o-cells were used to standardize the efficacy of the dendrimer-cystamine in correcting impaired-autophagy, rescuing ΔF508-CFTR and Pseudomonas-aeruginosa (Pa) infection. RESULTS: We first designed a novel cystamine-core dendrimer formulation (G4-CYS) that significantly increases membrane-ΔF508CFTR expression in CFBE41o-cells (p < 0.05) by forming its reduced-form cysteamine, in vivo. Additionally, G4-CYS treatment corrects ΔF508-CFTR-mediated impaired-autophagy as observed by a significant decrease (p < 0.05) in Ub-LC3-positive aggresome-bodies. Next, we verified that in non-permeabilized CFBE41o-cells, G4-CYS significantly (p < 0.05) induces ΔF508-CFTR's forward-trafficking to the plasma membrane. Furthermore, cysteamine's known antibacterial and anti-biofilm properties against Pa were enhanced as our findings demonstrate that both G4-CYS and its control DAB-core dendrimer, G4-DAB, exhibited significant (p < 0.05) bactericidal-activity against Pa. We also found that both G4-CYS and G4-DAB exhibit marked mucolytic-activity against porcine-mucus (p < 0.05). Finally, we demonstrate that G4-CYS not only corrects the autophagy-impairment by rescuing ΔF508-CFTR in CFBE41o-cells but also corrects the intrinsic phagocytosis defect (p < 0.05). CONCLUSIONS: Overall, our data demonstrates the efficacy of novel cystamine-dendrimer formulation in rescuing ΔF508-CFTR to the plasma membrane and inhibiting Pa bacterial-infection by augmenting autophagy.

ED endovaginal pelvic ultrasound in nonpregnant women with right lower quadrant pain.

INTRODUCTION: We hypothesized that emergency physician-performed endovaginal ultrasound (EVUS) would change diagnostic decision making in nonpregnant women with right lower quadrant (RLQ) pain. METHODS: A prospective cohort of female patients was enrolled at an urban emergency department (ED). Inclusion criteria were RLQ pain, hemodynamic stability, and a strong suspicion for appendicitis or right adnexal pathology. Treating physicians were queried regarding pre- and post-ED EVUS probability of disease, differential diagnoses, consultation, and management. Positive findings included large cysts or multitissue densities, tubal dilation, uterine enlargement/mass, and extensive peritoneal fluid. RESULTS: With a positive ED EVUS, mean physician probability increased for gynecologic (24%) and decreased for both surgical (14%) and medical (20%) disease. With a negative ED EVUS, mean physician probability increased for surgical disease (5.3%) and decreased for gynecologic disease (18.6%). CONCLUSION: Emergency department EVUS changes physician diagnostic decision making in nonpregnant women with undifferentiated RLQ pain.

Persistent hyperplastic primary vitreous due to somatic mosaic deletion of the arf tumor suppressor.

PURPOSE: Mice lacking the Arf tumor-suppressor gene develop eye disease reminiscent of persistent hyperplastic primary vitreous (PHPV). The current work explores mechanisms by which Arf promotes eye development, and its absence causes a PHPV-like disease. METHODS: Chimeric mice were made by fusing wild-type and Arf(-/-) morulae. In these experiments, wild-type cells are identified by transgenic expression of GFP from a constitutive promoter. PCR-based genotyping and quantitative analyses after immunofluorescence staining of tissue and cultured cells documented the relative contribution of wild-type and Arf(-/-) cells to different tissues in the eye and different types of cells in the vitreous. RESULTS: The contributions of the Arf(-/-) lineage to the tail DNA, cornea, retina, and retina pigment epithelium (RPE) correlated with each other in wild-type<-->Arf(-/-) chimeric mice. Newborn chimeras had primary vitreous hyperplasia, evident as a retrolental mass. The mass was usually present when the proportion of Arf(-/-) cells was relatively high and absent when the Arf(-/-) proportion was low. The Pdgfrbeta- and Sma-expressing cells within the mass arose predominantly from the Arf(-/-) population. Ectopic Arf expression induced smooth muscle proteins in cultured pericyte-like cells, and Arf and Sma expression overlapped in hyaloid vessels. CONCLUSIONS: In the mouse model, loss of Arf in only a subset of cells causes a PHPV-like disease. The data indicate that both cell autonomous and non-cell autonomous effects of Arf may contribute to its role in vitreous development.

Fatigue mitigation with SleepTrackTXT2 in air medical emergency care systems: study protocol for a randomized controlled trial.

BACKGROUND: Most air medical Emergency Medical Services (EMS) clinicians work extended duration shifts, and more than 50% report inadequate sleep, poor sleep quality, and/or poor recovery between shifts. The SleepTrackTXT pilot trial (ClinicalTrials.gov, NCT02063737) showed that use of mobile phone text messages could impact EMS clinician self-reported fatigue and sleepiness during long duration shifts. The purpose of the SleepTrackTXT2 trial is to leverage lessons learned from the first SleepTrackTXT study and test an enhanced intervention targeting air medical EMS clinicians. METHODS/DESIGN: We will conduct a multi-site randomized trial with a sample of adult EMS clinicians recruited from four air medical EMS systems located in the midwest, northeastern, and southern USA. Participants will be allocated to one of two possible arms for a 4-month (120-day) study period. The intervention arm will involve text-message assessments of sleepiness, fatigue, and difficulty concentrating at the beginning, every 4 hours during, and at the end of scheduled shifts. Participants reporting high levels of sleepiness, fatigue, or difficulty with concentration will receive one of nine randomly selected intervention messages to promote behavior change during shift work to improve alertness. Intervention participants will receive a text-message report on Friday of each week that shows their sleep debt over the previous 7 days followed by a text message to promote paying back sleep debt recovery when feasible. Participants in the control group receive text messages that only include assessments. Both arms will receive text-message assessments of perceived recovery since last shift, sleepiness, fatigue, or difficulty with concentration at noon (1200 hours) on days between scheduled shifts (off-duty days). We have two aims for this study: (1) to determine the short-term impact of the enhanced SleepTrackTXT2 intervention on air medical clinician fatigue reported in real time during and at the end of shift work, and (2) to determine the long-term impact of the SleepTrackTXT2 intervention on sleep quality and sleep health indicators including hours of sleep and recovery between shift work. DISCUSSION: The SleepTrackTXT2 trial may provide evidence of real-world effectiveness that would support widespread expansion of fatigue mitigation interventions in emergency care clinician shift workers. The trial may specifically support use of real-time assessments and interventions delivered via mobile technology such as text messaging. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02783027 . Registered on 23 May 2016.

Dendrimer-Based Selective Proteostasis-Inhibition Strategy to Control NSCLC Growth and Progression.

Elevated valosin containing protein (VCP/p97) levels promote the progression of non-small cell lung carcinoma (NSCLC). Although many VCP inhibitors are available, most of these therapeutic compounds have low specificity for targeted tumor cell delivery. Hence, the primary aim of this study was to evaluate the in vitro efficacy of dendrimer-encapsulated potent VCP-inhibitor drug in controlling non-small cell lung carcinoma (NSCLC) progression. The VCP inhibitor(s) (either in their pure form or encapsulated in generation-4 PAMAM-dendrimer with hydroxyl surface) were tested for their in vitro efficacy in modulating H1299 (NSCLC cells) proliferation, migration, invasion, apoptosis and cell cycle progression. Our results show that VCP inhibition by DBeQ was significantly more potent than NMS-873 as evident by decreased cell proliferation (p<0.0001, MTT-assay) and migration (p<0.05; scratch-assay), and increased apoptosis (p<0.05; caspase-3/7-assay) as compared to untreated control cells. Next, we found that dendrimer-encapsulated DBeQ (DDNDBeQ) treatment increased ubiquitinated-protein accumulation in soluble protein-fraction (immunoblotting) of H1299 cells as compared to DDN-control, implying the effectiveness of DBeQ in proteostasis-inhibition. We verified by immunostaining that DDNDBeQ treatment increases accumulation of ubiquitinated-proteins that co-localizes with an ER-marker, KDEL. We observed that proteostasis-inhibition with DDNDBeQ, significantly decreased cell migration rate (scratch-assay and transwell-invasion) as compared to the control-DDN treatment (p<0.05). Moreover, DDNDBeQ treatment showed a significant decrease in cell proliferation (p<0.01, MTT-assay) and increased caspase-3/7 mediated apoptotic cell death (p<0.05) as compared to DDN-control. This was further verified by cell cycle analysis (propidium-iodide-staining) that demonstrated significant cell cycle arrest in the G2/M-phase (p<0.001) by DDNDBeQ treatment as compared to control-DDN. Moreover, we confirmed by clonogenic-assay that DDNDBeQ treatment significantly (p<0.001) inhibits H1299 colony-formation as compared to control/DDN. Overall, encapsulation of potent VCP-inhibitor DBeQ into a dendrimer allows selective VCP-mediated proteostasis-inhibition for controlling NSCLC-tumor growth and progression to allow tumor-targeted sustained drug delivery.

Time for a revolution: smart energy and microgrid use in disaster response.

Modern health care and disaster response are inextricably linked to high volume, reliable, quality power. Disasters place major strain on energy infrastructure in affected communities. Advances in renewable energy and microgrid technology offer the potential to improve mobile disaster medical response capabilities. However, very little is known about the energy requirements of and alternative power sources in disaster response. A gap analysis of the energy components of modern disaster response reveals multiple deficiencies. The MED-1 Green Project has been executed as a multiphase project designed to identify energy utilization inefficiencies, decrease demands on diesel generators, and employ modern energy management strategies to expand operational independence. This approach, in turn, allows for longer deployments in potentially more austere environments and minimizes the unit's environmental footprint. The ultimate goal is to serve as a proof of concept for other mobile medical units to create strategies for energy independence.