Measuring the Effect of Off-Balancing Vectors on the Delivery of High-Quality CPR during Ambulance Transport: A Proof of Concept Study.

AIM: This study aims to demonstrate the feasibility of quantifying the off-balancing vectors experienced during ambulance transport and comparing them to high-quality cardiopulmonary resuscitation (HQ-CPR) metrics. METHODS: Ten participants completed a total of 20 evolutions of compression-only HQ-CPR in an ambulance driven in a manner that minimized or increased linear and angular off-balancing vectors. Linear and angular velocity, linear and angular acceleration, and linear jerk were recorded. HQ-CPR variables measured were compression fraction and proportion of compressions with depth >5 cm (depth%), rate 100-120 (rate%), full chest recoil (recoil%), and hand position (hand%). A composite score was calculated: [(depth% + rate% + recoil% + hand%)/4) * compression fraction]. Difficulty of HQ-CPR performance was measured with the Borg rating of perceived exertion (RPE) Scale. A series of mixed effects models were fitted regressing each HQ-CPR metric on each off-balancing vector. RESULTS: HQ-CPR data and vector quantity data were successfully recorded in all evolutions. Rate% was negatively associated with increasing linear velocity (slope = -3.82, standard error [SE] 1.12, p = 0.005), linear acceleration (slope = -5.52, SE 1.93, p = 0.013), linear jerk (slope = -17.60, SE 5.78, p = 0.007), angular velocity (slope = -75.74, SE 22.72, p = 0.004), and angular acceleration (slope = -152.53, SE 59.60, p = 0.022). Compression fraction was negatively associated with increasing linear velocity (slope = -1.35, SE 0.37, p = 0.004), linear acceleration (slope = -1.67, SE 0.48, p = 0.003), linear jerk (slope = -4.90, SE 1.86, p = 0.018), angular velocity (slope = -25.66, SE 6.49, p = 0.001), and angular acceleration (slope = -45.35, SE 18.91, p = 0.031). Recoil% was negatively associated with increasing linear velocity (slope = -5.80, SE 2.21, p = 0.023) and angular velocity (slope = -116.96, SE 44.24, p = 0.019)). Composite score was negatively associated with increasing linear velocity (slope = -4.49, SE 1.45, p = 0.009) and angular velocity (slope = -86.13, SE 31.24, p = 0.014) and approached a negative association with increasing magnitudes of linear acceleration (slope -5.54, SE 2.93, p = 0.075), linear jerk (slope = -17.43, SE 8.80, p = 0.064), and angular acceleration (slope = -170.43, SE 80.73, p = 0.051). Borg RPE scale was positively associated with all off-balancing vectors. Depth%, hand%, mean compression depth, and mean compression rate were not correlated with any off-balancing vector. CONCLUSION: Off-balancing vector data can be successfully quantified during ambulance transport and compared with HQ-CPR performance parameters. Increasing off-balancing vectors experienced during ambulance transport are associated with worse HQ-CPR metrics and increased perceived physical exertion. These data may help guide future drive styles, ambulance design, or use of mechanical CPR devices to improve HQ-CPR delivery during selected patient transport scenarios.

The Effect of Sustained Poor Air Quality on EMS Call Volume and Characteristics: A Time-Stratified Case-Crossover Study.

OBJECTIVES: As wildfires and air pollution become more common across the United States, it is increasingly important to understand the burden they place on public health. Previous studies have noted relationships between air quality and use of Emergency Medical Services (EMS), but until now, these studies have focused on day-to-day air quality. The goal of this study is to investigate the effect of sustained periods of poor air quality on EMS call characteristics and volume. METHODS: Using a time-stratified case-crossover design, the effect of exposure to periods of poor air quality on number and type of EMS calls in California, USA from 2014-2019 was observed. Poor air quality periods greater than three days were identified at the United States Environmental Protection Agency's (EPA's) Air Quality Index (AQI) levels of Unhealthy for Sensitive Groups (AQI 100) and Unhealthy (AQI 150). Periods less than three days apart were combined. Each poor air quality period was matched with two one-week controls, the first being the closest preceding week that did not intersect a different case. The second control was the closest week at least three days after the case and not intersecting with a different case. Due to seasonal variation in EMS usage, from the initial cases, cases were used only if it was possible to identify controls within 28 days of the case. A conditional Poisson regression calculated risk ratios for EMS call volume. RESULTS: Comparing the case periods to the controls, significant increases were found at AQI >100 for total number of calls, and the primary impressions categories of emotional state or behavior, level of consciousness, no patient complaint, other, respiratory, and abdominal. At an AQI >150, significance was found for the primary impressions categories of other, pain, respiratory, and digestive. CONCLUSION: These data demonstrate increased EMS calls during sustained poor air quality, and that several EMS primary impression categories are disproportionately affected. This study is limited by the imprecision of the primary impression's classification provided by the EMS clinician responding to the EMS call. More research is needed to understand the effects of periods of poor air quality on the EMS system for more efficient deployment of resources.

Development of a model to measure the effect of off-balancing vectors on the delivery of high-quality CPR in a moving vehicle.

AIM: We sought to develop a model to measure the acceleration and jerk vectors affecting the performance of High-Quality Cardiopulmonary Resuscitation (HQ-CPR) during patient transport. METHODS: Three participants completed a total of eighteen rounds of compression only HQ-CPR in a moving vehicle. The vehicle was driven in a manner that either minimized or increased linear and angular vectors. The HQ-CPR variables measured were compression fraction (CF%), and percentages of compressions with correct depth > 5 cm (D%), rate 100-120 (R%), full recoil (FR%), and hand position (HP%). A composite HQ-CPR score was calculated: ((D% + R% + FR% + HP%)/4) * CF%). Linear and gyroscopic data were measured in the X, Y, and Z axes. The perceived difficulty in performing HQ-CPR was measured with the Borg Rating of Perceived Exertion Scale. RESULTS: HQ-CPR data, linear vector data, and gyroscopic data were successfully recorded in all trial evolutions. Univariate regression analysis demonstrated that HQ-CPR was negatively affected by increasing magnitudes of linear acceleration (B = -0.093%/m/s2, 95% CI [-0.17 - -0.02), p = 0.02], linear jerk (B = -0.134%/m/s3, 95% CI [-0.26 - -0.01], p = 0.04), angular velocity (B = -0.543%/radian/s, 95% CI [-0.98 - -0.11], p = 0.02), and angular acceleration (B = 0.863%/radian/s2, 95% CI [-1.69 - -0.03], p = 0.04). Increasing vectors were negatively associated with FR% and R%. No difference was seen in D%, HP%, or CF%. Borg Rating of Perceived Exertion was greater in dynamic driving evolutions (8 ± 1 vs 3.5 ± 1.53, p = 0.02). CONCLUSION: This model reliably measured linear and angular off-balancing vectors experienced during the delivery of HQ-CPR in a moving vehicle. In this preliminary report, compression rate and full recoil appear to be HQ-CPR variables most affected in a moving vehicle.

Manual versus Mechanical Delivery of High-Quality Cardiopulmonary Resuscitation on a River-Based Fire Rescue Boat.

OBJECTIVES: Studies have demonstrated the efficacy of mechanical devices at delivering high-quality cardiopulmonary resuscitation (HQ-CPR) in various transport settings. Herein, this study investigates the efficacy of manual and mechanical HQ-CPR delivery on a fire rescue boat. METHODS: A total of 15 active firefighter-paramedics were recruited for a prospective manikin-based trial. Each paramedic performed two minutes manual compression-only CPR while navigating on a river-based fire rescue boat. The boat was piloted in either a stable linear manner or dynamic S-turn manner to simulate obstacle avoidance. For each session of manual HQ-CPR, a session of mechanical HQ-CPR was also performed with a LUCAS 3 (Stryker; Kalamazoo, Michigan USA). A total of 60 sessions were completed. Parameters recorded included compression fraction (CF) and the percentage of compressions with correct depth >5cm (D%), correct rate 100-120 (R%), full release (FR%), and correct hand position (HP%). A composite HQ-CPR score was calculated as follows: ((D% + R% + FR% + HP%)/4) * CF%). Differences in magnitude of change seen in stable versus dynamic navigation within study conditions were evaluated with a Z-score calculation. Difficulty of HQ-CPR delivery was assessed utilizing the Borg Rating of Perceived Exertion Scale. RESULTS: Participants were mostly male and had a median experience of 20 years. Manual HQ-CPR delivered during stable navigation out-performed manual HQ-CPR delivered during dynamic navigation for composite score and trended towards superiority for FR% and R%. There was no difference seen for any measured variable when comparing mechanical HQ-CPR delivered during stable navigation versus dynamic navigation. Mechanical HQ-CPR out-performed manual HQ-CPR during both stable and dynamic navigation in terms of composite score, FR%, and R%. Z-score calculation demonstrated that manual HQ-CPR delivery was significantly more affected by drive style than mechanical HQ-CPR delivery in terms of composite HQ-CPR score and trended towards significance for FR% and R%. Borg Rating of Perceived Exertion was higher for manual CPR delivered during dynamic sessions than for stable sessions. CONCLUSION: Mechanical HQ-CPR delivery is superior to manual HQ-CPR delivery during both stable and dynamic riverine navigation. Whereas manual HQ-CPR delivery was worse during dynamic transportation conditions compared to stable transport conditions, mechanical HQ-CPR delivery was unaffected by drive style. This suggests the utility of routine use of mechanical HQ-CPR devices in the riverine patient transport setting.

Prehospital Testing and Surveillance for SARS-CoV-2: A Special Report from the Sacramento (California USA) Mobile Integrated Health Unit.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has killed nearly 800,000 Americans since early 2020. The disease has disproportionately affected older Americans, men, persons of color, and those living in congregate living facilities. Sacramento County (California USA) has used a novel Mobile Integrated Health Unit (MIH) to test hundreds of patients who dwell in congregate living facilities, including skilled nursing facilities (SNF), residential care facilities (ie, assisted living facilities [ALF] and board and care facilities [BCF]), and inpatient psychiatric facilities (PSY), for SARS-CoV-2. METHODS: The MIH was authorized and rapidly created at the beginning of the COVID-19 pandemic as a joint venture between the Sacramento County Department of Public Health (SCDPH) and several fire-based Emergency Medical Services (EMS) agencies within the county to perform SARS-CoV-2 testing and surveillance in a prehospital setting at a number of congregate living facilities. All adult patients (≥18 years) who were tested for SARS-CoV-2 infection by the MIH from March 31, 2020 through April 30, 2020 and lived in congregate living facilities were included in this retrospective descriptive cohort. Demographic and laboratory data were collected to describe the cohort of patients tested by the MIH. RESULTS: During the study period, the MIH tested a total of 323 patients from 15 facilities in Sacramento County. The median age of patients tested was 66 years and the majority were female (72%). Overall, 72 patients (22%) tested positive for SARS-CoV-2 in congregate living settings, a higher rate of positivity than was measured across the county during the same time period. CONCLUSION: The MIH was a novel method of epidemic surveillance that succeeded in delivering effective and efficient testing to patients who reside in congregate living facilities and was able to accurately identify pockets of infection within otherwise low prevalence areas. Cooperative prehospital models are an effective model to deliver out-of-hospital testing and disease surveillance that may serve as a blueprint for community-based care delivery for a number of disease states and future epidemics or pandemics.

Evaluation of High Altitude Interstitial Pulmonary Edema in Healthy Participants Using Rapid 4-View Lung Ultrasound Protocol During Staged Ascent to Everest Base Camp.

INTRODUCTION: Prior research identified possible interstitial pulmonary fluid, concerning for early high altitude pulmonary edema (HAPE), in a large percentage of trekkers above 3000 m using a comprehensive 28-view pulmonary ultrasound protocol. These trekkers had no clinical symptoms of HAPE despite these ultrasound findings. The more common 4-view lung ultrasound protocol (LUP) is accurate in rapidly detecting interstitial edema during resource-rich care. The objective of this study was to evaluate whether the 4-view LUP detects interstitial fluid in trekkers ascending to Everest Base Camp. METHODS: Serial 4-view LUP was performed on 15 healthy trekkers during a 9-d ascent from Kathmandu to Everest Base Camp. Ascent protocols complied with Wilderness Medical Society guidelines for staged ascent. A 4-view LUP was performed in accordance with the published 2012 international consensus protocols on lung ultrasound. Symptom assessment and 4-view LUP were obtained at 6 waypoints along the staged ascent. A 4-view LUP was positive for interstitial edema if ≥3 B-lines were detected in 2 ultrasound windows. RESULTS: A single participant had evidence of interstitial lung fluid at 5380 m as defined by the 4-view LUP. There was no evidence of interstitial fluid in any participant below 5380 m. One participant was evacuated for acute altitude sickness at 4000 m but showed no preceding sonographic evidence of interstitial fluid. CONCLUSIONS: In this small study, sonographic detection of interstitial fluid, suggestive of early HAPE, was not identified by the 4-view LUP protocol.

Effects of Continuous Albuterol Inhalation on Serum Metabolome in Healthy Subjects: More Than Just Lactic Acid.

Treatment with ß2-agonists may cause elevated lactic acid, the end product of anaerobic metabolism of glucose. It has been proposed that lactic acidosis associated with ß2-agonists is caused by changes to direct biochemical impacts on glycolysis, gluconeogenesis, pyruvate metabolism, and free fatty acid production. However, much remains unknown, and there is a paucity of evidence regarding the underlying chemical changes associated with this lactic acidosis. The goal of our study was to investigate the impact of 1 hour of continuous albuterol on the untargeted serum metabolome of healthy subjects. Twenty-four healthy participants received 7.5 mg of continuous albuterol for 1 hour. Baseline, 1-hour, and 2-hour lactic acid levels were drawn. Samples obtained at baseline and 1 hour were sent for untargeted metabolomic profiling. Participants had a baseline lactic acid of 1.45 ± 0.46 mmol/L. On average, lactate levels increased 0.33 ± 0.67 mmol/L after 1 hour (P = .02) and remained elevated at 2 hours (0.32 ± 0.72 mmol/L, P = .02), although there was overlap in lactate levels across times. For metabolomic analysis, fatty acids, organic acids, and sugars were elevated, and amino acids were reduced. Lactic acid and pyruvic acid metabolites, however, did not significantly change (after false discovery rate adjustment). In healthy participants, continuous albuterol alters the serum metabolome, but this change may not be clinically significant. The data support recent hypotheses that ß2-receptor activation stimulates lactic acid production, altering aerobic glycolysis, gluconeogenesis, and free fatty acid production.

Evaluation of Serial Chest Radiographs of High-Altitude Pulmonary Edema Requiring Medical Evacuation from South Pole Station, Antarctica: From Diagnosis to Recovery.

INTRODUCTION: Chest radiography is a diagnostic tool commonly used by medical providers to assess high-altitude pulmonary edema (HAPE). Although HAPE often causes a pattern of pulmonary edema with right lower lung predominance, previous research has shown that there is no single radiographic finding associated with the condition. The majority of research involves a retrospective analysis of chest radiographs taken at the time of HAPE diagnosis. Little is known about the radiographic progression of HAPE during treatment or medical evacuation. MATERIALS AND METHODS: Three sequential chest radiographs were obtained from two patients diagnosed with HAPE at the Amundsen-Scott South Pole Station, Antarctica, who required treatment and medical evacuation. Deidentified and temporally randomized images were reviewed in a blinded fashion by two radiologists. A score of 0 (normal lung) to 4 (alveolar disease) was assigned for each of the four lung quadrants for an aggregate possible score ranging from 0 to 16 for each radiograph. RESULTS: Patient 1's initial radiograph showed severe HAPE with an initial score of 13. Despite a rapid clinical improvement after medical evacuation, he continued to show multifocal radiographic evidence of disease in all the lung quadrants on day 1 (score of 11) and day 2 (score of 5). Patient 2's radiographs showed less severe disease at presentation (score of 6). Despite the need for continued treatment, his radiographs showed a rapid improvement, with radiographic score decreasing to 3 on day 1 and 1 on day 3. CONCLUSION: The chest radiographs showed serial improvement after medical evacuation in both patients. There was not a strong correlation between clinical symptoms and radiographic severity in subsequent images.

Serious Altitude Illness at the South Pole.

BACKGROUND: Gradual ascent is impractical for personnel deploying to the South Pole due to logistical challenges. Prevention of altitude illness relies on prophylactic medications such as acetazolamide and behavioral modifications including hydration and avoidance of overexertion. We present three recent cases of altitude illness that occurred in previously healthy individuals at the South Pole.CASE REPORTS: 1) A 52-yr-old woman not on prophylactics presented with headache and intractable vomiting 7 h after arriving and hiking around the station. She was treated with acetazolamide, dexamethasone, oxygen, and supportive care. Her symptoms resolved during the evacuation flight. 2) A 23-yr-old man presented with dyspnea at rest 3 d after arriving without prophylactic treatments. He had a Sao2 of 49%, wheezes and crackles on lung exam, and interstitial infiltrates on chest X-ray. His treatment included oxygen, nifedipine, acetazolamide, and dexamethasone. His symptoms resolved during the evacuation flight. 3) A 40-yr-old man presented with dyspnea after a series of strenuous workouts since his arrival 5 d prior. He had a Sao2 of 41%, and his chest X-ray was consistent with high altitude pulmonary edema. He was treated with oxygen, nifedipine, and fluids before descent to sea level, where his symptoms fully resolved 4 d later.DISCUSSION: These patients illustrate that altitude illness may develop despite medical screening, participant education, and availability of prophylactic medications based on published guidelines. These cases could be attributed to noncompliance and misinformation, bringing to light some of the challenges with managing more diverse populations that deploy to remote environments.Rose JS, Law J, Scheuring R, Ramage MH, McKeith JJ. Serious altitude illness at the South Pole. Aerosp Med Hum Perform. 2020; 91(1):46-50.

Effect of Abdominal Ultrasound on Clinical Care, Outcomes, and Resource Use Among Children With Blunt Torso Trauma: A Randomized Clinical Trial.

Importance: The utility of the focused assessment with sonography for trauma (FAST) examination in children is unknown. Objective: To determine if the FAST examination during initial evaluation of injured children improves clinical care. Design, Setting, and Participants: A randomized clinical trial (April 2012-May 2015) that involved 975 hemodynamically stable children and adolescents younger than 18 years treated for blunt torso trauma at the University of California, Davis Medical Center, a level I trauma center. Interventions: Patients were randomly assigned to a standard trauma evaluation with the FAST examination by the treating ED physician or a standard trauma evaluation alone. Main Outcomes and Measures: Coprimary outcomes were rate of abdominal computed tomographic (CT) scans in the ED, missed intra-abdominal injuries, ED length of stay, and hospital charges. Results: Among the 925 patients who were randomized (mean [SD] age, 9.7 [5.3] years; 575 males [62%]), all completed the study. A total of 50 patients (5.4%, 95% CI, 4.0% to 7.1%) were diagnosed with intra-abdominal injuries, including 40 (80%; 95% CI, 66% to 90%) who had intraperitoneal fluid found on an abdominal CT scan, and 9 patients (0.97%; 95% CI, 0.44% to 1.8%) underwent laparotomy. The proportion of patients with abdominal CT scans was 241 of 460 (52.4%) in the FAST group and 254 of 465 (54.6%) in the standard care-only group (difference, -2.2%; 95% CI, -8.7% to 4.2%). One case of missed intra-abdominal injury occurred in a patient in the FAST group and none in the control group (difference, 0.2%; 95% CI, -0.6% to 1.2%). The mean ED length of stay was 6.03 hours in the FAST group and 6.07 hours in the standard care-only group (difference, -0.04 hours; 95% CI, -0.47 to 0.40 hours). Median hospital charges were $46 415 in the FAST group and $47 759 in the standard care-only group (difference, -$1180; 95% CI, -$6651 to $4291). Conclusions and Relevance: Among hemodynamically stable children treated in an ED following blunt torso trauma, the use of FAST compared with standard care only did not improve clinical care, including use of resources; ED length of stay; missed intra-abdominal injuries; or hospital charges. These findings do not support the routine use of FAST in this setting. Trial Registration: clinicaltrials.gov Identifier: NCT01540318.

Family Medicine Physicians With Substance Use Disorder: A 5-year Outcome Study.

OBJECTIVES: There is little published evidence on how well family medicine physicians (FMPs) with substance use disorder (SUD) perform in Physician Health Programs (PHPs). We examined outcomes for FMP compared with non-FMP physicians. METHODS: This study utilized data from a 5-year, longitudinal, cohort study involving 904 physicians with diagnoses of SUD consecutively admitted to one of 16 state PHPs between 1995 and 2001. We compared 175 FMPs to 687 other physicians. Outcome measures were relapse, successful completion of monitoring contract at 5 years, and licensed and employed at 5 years. RESULTS: Of the 3 outcome variables measured: relapse, successful completion of monitoring contract at 5 years, and licensed and employed at 5 years, FMPs had similar rates of success on all variables except monitoring contract completion at 5 years when compared with the other physician cohort. CONCLUSIONS: In this study, FMPs with SUD do as well as other physicians in PHPs at 5 years. However, FMPs were less likely to complete the monitoring contract at 5 years as compared to the other physician cohort.

Classic IL-6R signalling is dispensable for intestinal epithelial proliferation and repair.

Inflammatory bowel disease is characterized by disturbed cytokine signalling in the mucosa. Inhibition of the proinflammatory interleukin (IL)-6 pathway is a promising new therapeutic strategy, but safety concerns arise as IL-6 signalling also contributes to epithelial repair of the intestinal mucosa. To which extent IL-6 classic or trans-signalling contributes to intestinal repair remains elusive. We tested the influence of IL-6 classic signalling on intestinal repair and proliferation. Whereas IL-6 induced STAT3 phosphorylation in the colonic cancer cell lines, primary non-malignant intestinal organoids did not respond to IL-6 classic signalling. Mice deficient in intestinal IL-6R (IL-6RΔIEC mice) did not display increased susceptibility to acute dextran sulfate sodium (DSS)-induced colitis. In the azoxymethane DSS model IL-6RΔIEC mice were not protected from inflammation-induced carcinogenesis but showed comparable tumor load to wild-type mice. These data indicate that classic signalling is not the major pathway to transduce IL-6 stimuli into the intestinal epithelium.

Creation of a High-fidelity, Low-cost Pediatric Skull Fracture Ultrasound Phantom.

Over the past decade, point-of-care ultrasound has become a common tool used for both procedures and diagnosis. Developing high-fidelity phantoms is critical for training in new and novel point-of-care ultrasound applications. Detecting skull fractures on ultrasound imaging in the younger-than-2-year-old patient is an emerging area of point-of-care ultrasound research. Identifying a skull fracture on ultrasound imaging in this age group requires knowledge of the appearance and location of sutures to distinguish them from fractures. There are currently no commercially available pediatric skull fracture models. We outline a novel approach to building a cost-effective, simple, high-fidelity pediatric skull fracture phantom to meet a unique training requirement.

ADAM10 and ADAM17 have opposite roles during sprouting angiogenesis.

During angiogenesis, endothelial tip cells start sprouting and express delta-like 4 (DLL4) downstream of vascular endothelial growth factor (VEGF). DLL4 subsequently activates Notch in the adjacent stalk cells suppressing sprouting. VEGF also activates A disintegrin and metalloproteases (ADAMs) that induce Notch ectodomain shedding. Although two major ADAMs, i.e. ADAM10 and ADAM17, have been implicated in Notch-signalling activation, their apparent different roles in angiogenesis have not been fully understood yet. The objective of this study was to determine the roles of ADAM10 and ADAM17 activity in angiogenesis. In mouse retinas, ADAM10 or γ-secretase inhibition induced vascular sprouting and density in vivo, whereas attenuation of both ADAM10 and ADAM17 activity produced the opposite phenotype. Retinal blood vessel analysis in ADAM17 hypomorphic mice confirmed the requirement for ADAM17 activity in angiogenesis. However, ADAM17 inhibition did not phenocopy blood vessel increase by Notch blockage. These observations suggest that ADAM17 regulates other fundamental players during angiogenesis besides Notch, which were not affected by ADAM10. By means of an angiogenesis proteome assay, we found that ADAM17 inhibition induced the expression of a naturally occurring inhibitor of angiogenesis Thrombospondin 1 (TSP1), whereas ADAM10 inhibition did not. Accordingly, ADAM17 overexpression downregulated TSP1 expression, and the TSP1 inhibitor LSKL rescued angiogenesis in the tube formation assay downstream of VEGF in the presence of ADAM17 inhibition. Finally, genetic and pharmacological ADAM17 blockade resulted in increased TSP1 expression in mouse retina. Altogether, our results show that ADAM10 and ADAM17 have opposite effects on sprouting angiogenesis that may be unrelated to Notch signalling and involves differentially expressed anti-angiogenic proteins such as TSP1.

Psychiatrists with substance use disorders: positive treatment outcomes from physician health programs.

OBJECTIVE: The objective of this study was to compare outcomes of psychiatrists and nonpsychiatrist physicians enrolled in state physician health programs for substance use disorders. METHODS: The study used the data set from a five-year, longitudinal cohort study of 904 physicians, including 55 psychiatrists, with diagnoses of substance abuse or dependence consecutively admitted to one of 16 state physician health programs between 1995 and 2001. RESULTS: There was a higher proportion of women among psychiatrists than among other physicians, but there were no other significant differences between the cohorts. Five-year outcomes were similar between psychiatrists and the other physicians, with at least 75% of psychiatrists continuing their medical practice after five years of monitoring and treatment. CONCLUSIONS: Psychiatrists were not overrepresented compared with other physician groups and had similar clinical outcomes at the five-year follow-up. Physician health programs appeared to be effective treatment programs for psychiatrists with substance use disorders.

Prognosis for Emergency Physician with substance abuse recovery: 5-year outcome study.

INTRODUCTION: Emergency physicians (EPs) are reported to have a higher rate of substance use disorder (SUD) than most specialties, although little is known about their prognosis. We examined the outcomes of emergency physician compared to other physicians in the treatment of substance use disorders in Physician Health Programs (PHP). METHODS: This study used the dataset from a 5-year, longitudinal, cohort study involving 904 physicians with diagnoses of SUD consecutively admitted to one of 16 state PHPs between 1995 and 2001. We compared 56 EPs to 724 other physicians. Main outcome variables were rates of relapse, successful completion of monitoring, and return to clinical practice. RESULTS: EPs had a higher than expected rate of SUD (odds ratio [OR] 2.7 confidence interval [CI]: 2.1-3.5, p<0.001). Half of each group (49% of EPs and 50% of the others) enrolled in a PHP due to alcohol-related problems. Over a third of each group (38% of EPs and 34% of the others) enrolled due to opioid use. During monitoring by the PHPs, 13% of EPs had at least one positive drug test compared to 22% of the other physicians; however, this difference was not significant (p=0.13). At the end of the 5-year follow-up period, 71% of EPs and 64% of other physicians had completed their contracts and were no longer required to be monitored (OR 1.4 [CI: 0.8-2.6], p = 0.31). The study found that the proportion of EPs (84%) continuing their medical practice was generally as high as that of other physicians (72%) (OR 2.0 [CI: 1.0-4.1], p = 0.06). CONCLUSION: In the study EPs did very well in the PHPs with an 84% success rate in completion and return to clinical practice at 5 years. Of the 3 outcome variables measured, rates of relapse, successful completion of monitoring, and return to clinical practice, EPs had a high rate of success on all variables compared to the other physician cohort. These data support the conclusion that EM physicians do well following treatment of SUD with monitoring in PHPs and generally return to the practice of emergency medicine.

ADAM17 is a survival factor for microglial cells in vitro and in vivo after spinal cord injury in mice.

A disintegrin and metalloprotease 17 (ADAM17) is a sheddase with important substrates including tumor necrosis factor-α (TNF-α) and its receptors, the p75 neurotrophin receptor (p75NTR), and members of the epidermal growth factor family. The rationale of this study was to inhibit ADAM17-induced shedding of soluble TNF-α in order to reduce detrimental inflammation after spinal cord injury (SCI). However, using the specific ADAM17 blocker BMS-561392 in neuronal and glial cell cultures, we show that proper functioning of ADAM17 is vital for oligodendrocyte and microglia survival in a p44 MAPK-dependent manner. In contrast, genetic ablation of ADAM17 specifically increases microglial death. Surprisingly, although blocking ADAM17 in vivo does not substantially change the ratio between membrane-bound and soluble TNF-α, it increases expression of the pro-apoptotic marker Bax and microglial apoptosis while impairing functional recovery after SCI. These data suggest that ADAM17 is a key survival factor for microglial cells after SCI.

Novel path to IL-6 trans-signaling through thrombin-induced soluble IL-6 receptor release by platelets.

Interleukin (IL)-6 is a multifunctional cytokine with a critical role in inflammatory, immunoregulatory and haemopoietic responses. Its receptor consists of an ubiquitously expressed membrane transducing element (gp130) and of the specific element IL-6R-alpha (gp80), present only on hepatocytes and some leukocyte subsets. IL-6R-alpha also exists as soluble protein (sIL-6R) that, in the presence of IL-6, forms a complex able to bind gp130 and, thanks to the mechanism called trans-signaling, transduces IL-6 effect through tyrosine phosphorylation and activation of the signal transducer and transcription activator (STAT)-3. The aim of this study was to analyze the bidirectional relationships between platelet aggregation and IL-6-dependent effects. While platelets do not produce IL-6, we found that resting platelets express gp130, but not gp80, on their membranes. Upon activation by thrombin or calcium ionophore A23187, but not by ADP, the IL-6R-alpha is released in soluble form, while cangrelor, the specific inhibitor of P2Y12 receptor, can partially inhibit sIL-6R release. This sIL-6R is biologically active and, in the presence of IL-6, can trigger IL-6 trans-signaling, inducing an autocrine activation loop (as measured by an increase in gp80 and gp130 content) and STAT3 phosphorylation. On the other hand, IL-6 trans-signaling has no effect on platelet degranulation or aggregation by itself, nor on thrombin-induced platelet aggregation. Our data add an important piece to the puzzle of thrombosis and inflammation: in the presence of IL-6, which can be produced by stressed endothelial cells, the platelet-derived IL-6 trans-signaling could be crucial for the evolution of inflammation within a damaged vessel.