Qualifying coronavirus disease 2019 convalescent plasma donors in Israel.

BACKGROUND AND OBJECTIVES: Passive immunization using investigational COVID-19 convalescent plasma (CCP) is a promising therapeutic strategy and could improve outcome if transfused early and contain high levels of anti-SARS-CoV-2 antibodies. We report the management of a national CCP collection and distribution program in Israel. MATERIALS AND METHODS: From 1 April 2020 to 15 January 2021, 4020 volunteer donors donated 5221 CCP units and 837 (20.8%) donors donated more than once. Anti-nucleocapsid IgG antibodies were determined using chemiluminescent immunoassay method (Abbott). A statistical model based on repeated IgG tests in sequential donations was created to predict the time of antibody decline below sample/cut-off (S/CO) level of 4.0. RESULTS: Ninety-six percent of CCP donors suffered a mild disease or were asymptomatic. Older donors had higher antibody levels. Higher antibody levels (S/CO ≥4) were detected in 35.2% of the donors. Low positive (S/CO ≥1.4-3.99) were found in 37%, and 27.8% had undetectable antibodies (S/CO ≤1.4). The model predicted decrease antibody thresholds of 0.55%/day since the first CCP donation, providing guidance for the effective timing of future collections from donors with high antibody levels. CONCLUSIONS: An efficient CCP collection and distribution program was achieved, based on performing initial and repeated plasma collections, preferably from donors with higher antibody levels, and only antibody-rich units were supplied for therapeutic use. The inventory met the quantity and quality standards of the authorities, enabled to respond to the growing demand of the medical system and provide a product that may contribute to improve prognosis in patients with COVID-19.

Prevalence of significant traumatic brain injury among patients intubated in the field due to impaired level of consciousness.

OBJECTIVE: Current guidelines advocate prehospital endotracheal intubation (ETI) in patients with suspected severe head injury and impaired level of consciousness. However, the ability to identify patients with traumatic brain injury (TBI) in the prehospital setting is limited and prehospital ETI carries a high complication rate. We investigated the prevalence of significant TBI among patients intubated in the field for that reason. METHODS: Data were retrospectively collected from emergency medical services and hospital records of trauma patients for whom prehospital ETI was attempted and who were transferred to Rambam Health Care Campus, Israel. The indication for ETI was extracted. The primary outcome was significant TBI (clinical or radiographic) among patients intubated due to suspected severe head trauma. RESULTS: In 57.3% (379/662) of the trauma patients, ETI was attempted due to impaired consciousness. 349 patients were included in the final analysis: 82.8% were male, the median age was 34 years (IQR 23.0-57.3), and 95.7% suffered blunt trauma. 253 patients (72.5%) had significant TBI. In a multivariable analysis, Glasgow Coma Scale>8 and alcohol intoxication were associated with a lower risk of TBI with OR of 0.26 (95% CI 0.13-0.51, p < 0.001) and 0.16 (95% CI 0.06-0.46, p < 0.001), respectively. CONCLUSION: Altered mental status in the setting of trauma is a major reason for prehospital ETI. Although most of these patients had TBI, one in four of them did not suffer a significant TBI. Patients with a higher field GCS and those suffering from intoxication have a higher risk of misdiagnosis. Future studies should explore better tools for prehospital assessment of TBI and ways to better define and characterize patients who may benefit from early ETI.

Isolated Versus Non-isolated Traumatic Brain Injuries Identification and Decision Making: A Comparative Study.

BACKGROUND: Traumatic brain injury (TBI) is a significant cause of death in the battlefield. TBI can be challenging to diagnose in the combat setting and remains a substantial challenge for advanced life support (ALS) providers. OBJECTIVES: To compare prehospital and hospitalization characteristics between isolated and non-isolated TBI. To examine the effects of TBI with coexisting injuries on patient evaluation and outcomes based on the Israeli Defense Forces Trauma Registry and the Israeli National Trauma Registry of soldiers hospitalized for TBI between the years 2006-2017. METHODS: A total of 885 casualties were eligible for our study, of whom 271 (30%) had isolated TBI. Only 35% of hospitalized patients with isolated TBI were defined as urgent by the ALS providers versus 67% in the non-isolated TBI group (P < 0.001). RESULTS: Overall, 29% of the TBIs in the non-isolated group were missed by the ALS providers vs. 11% in the isolated group. CONCLUSIONS: Concomitant injuries may delay the diagnosis of TBI by ALS providers. These findings should be considered in the prehospital evaluation to potentially improve the care and outcome of head injury patients.

Emergent exploratory thoracotomy with military casualties: contemporary prehospital management and outcome (see editorial page 619).

BACKGROUND: Chest trauma is among the most common types of trauma, corresponding to 10% of trauma patients admitted to hospitals. In the military setting, thoracic trauma was reported as a significant cause of death. With well-timed treatment, chest trauma is regarded as survivable. Emergency thoracotomy (ET) is considered when the patient with trauma to the chest needs immediate resuscitation. Survival rate is reported as low as 1% in some reports and 20% in others. The survival rate depends on injury mechanism, protocols for intervention, and other decompressive procedures. OBJECTIVES: To determine parameters that may impact survival of ET. METHODS: We conducted a retrospective cohort study to compare prehospital and in-hospital data regarding ET in the emergency department (ED) versus the operating room (OR). RESULTS: Between 2009 and 2017, 6532 casualties presented to the ED; 1125 with trauma to the chest. Fifty-four of those with chest trauma underwent ET in the hospital (4.8%), 22 (41%) in the ED, and 32 (59%) in the OR. The overall mortality of the ET subgroup was 48%. With regard to thoracotomies, 19/22 of patients (86%) who underwent ET in the ED died compared to 2/28 in the OR (13%). CONCLUSIONS: Utilizing ET after chest trauma with appropriate clinical indications, well-trained personnel, and prompt transportation poses a significant challenge, but may be associated with better survival than that reported previously with military casualties. Adoption of indications and timed allocation to the OR may improve outcomes with chest trauma casualties.

Patterns in vehicle-ramming attacks.

BACKGROUND: Vehicle-ramming attacks have become a common tactic for terror organizations worldwide. However, the medical implications of vehicle-ramming attacks remain unknown. OBJECTIVES: To investigate the characteristics of vehicle-ramming attack incidents and casualties in order to assist in guiding the policy of medical organizations. METHODS: In this study we included all vehicle-ramming attacks recorded in the Israel Defense Forces-Trauma Registry between 2015 and 2019. Records were screened using text mining of incident, casualty, and injury descriptions. The selected records were examined manually to ensure that they were vehicle-ramming attacks. Incident and casualty data were retrieved from the trauma registry. RESULTS: During the years 2015-2019, a total of 36 vehicle-ramming attacks with 113 casualties were documented in the trauma registry. The median number of casualties, urgent casualties, and fatalities per incident was 3 (interquartile range [IQR] 2-5), 1 (IQR 1-2), and 1 (IQR 1-1), respectively. Of the incidents, 15 (42%) had three or more casualties. The most prevelant day of the week was Friday with 9 incidents (25%). Within the day, 21 incidents (58%) occurred between the hours of 12:00 and 18:00. Commonly injured body regions were lower extremities (55%), head (28%), and upper extremities. Ten victims (9%) died before arriving at a hospital. CONCLUSIONS: Vehicle-ramming attacks tend to have multiple casualties, be deadly, occur more often on Fridays and in the afternoon, and result mostly in injuries to the extremities and the head. These findings could guide policymaking to improve medical response to vehicle-ramming attacks.

Trends in prehospital pain management: two decades of point-of-injury care.

BACKGROUND: Pain control in trauma is an integral part of treatment in combat casualty care. More soldiers injured on the battlefield need analgesics for pain than life-saving interventions (LSIs). Early treatment of pain improves outcomes after injury, while inadequate treatment leads to higher rates of post-traumatic stress disorder (PTSD). OBJECTIVES: To describe the experience of the Israel Defense Forces (IDF) Medical Corps with prehospital use of analgesia. METHODS: All cases documented in the IDF-Trauma Registry between January 1997 and December 2019 were examined. Data collection included analgesia administered, mechanism of injury, wound distribution, and life-saving interventions performed. RESULTS: Of 16,117 patients, 1807 (11.2%) had at least one documented analgesia. Demographics included 91.2% male; median age 21 years. Leading mechanism of injury was penetrating (52.9%). Of injured body regions reported, 46.2% were lower extremity wounds. Most common types of analgesics were morphine (57.2%) and fentanyl (27%). Over the two decades of the study period, types of analgesics given by providers at point of injury (POI) had changed. Fentanyl was introduced in 2013, and by 2019 was given to 39% of patients. Another change was an increase of casualties receiving analgesia from 5-10% until 2010 to 34% by 2019. A total of 824 LSIs were performed on 556 patients (30.8%) receiving analgesia and no adverse events were found in any of the casualties. CONCLUSIONS: Most casualties at POI did not receive any analgesics. The most common analgesics administered were opioids. Over time analgesic administration has gained acceptance and become more commonplace on the battlefield.

BladeShield 101: A Novel Prehospital Digital Wearable Combat Casualty Card.

BACKGROUND: The Israeli Defense Forces-Medical Corps (IDF-MC) focuses on reducing preventable death by improving prehospital trauma care. High quality documentation of care can serve casualty care and to improve future care. Currently, paper casualty cards are used for documentation. Incomplete data acquisition and inadequate data handover are common. To resolve these deficits, the IDF-MC launched the BladeShield 101 project. OBJECTIVES: To assess the quality of casualty care data acquired by comparing standard paper casualty cards with the BladeShield 101. METHODS: The BladeShield 101 system consists of three components: a patient unit that records vital signs and medical care provided, a medical sensor that transmits to the patient unit, and a ruggedized mobile device that allows providers to access and document information. We compared all trauma registries of casualties treated between September 2019 and June 2020. RESULTS: The system was applied during the study period on 24 patients. All data were transferred to the military trauma registry within one day, compared to 72% (141/194) with a paper casualty card (P < 0.01). Information regarding treatment time was available in 100% vs. 43% (P < 0.01) of cases and 98% vs. 67% (P < 0.01) of treatments provided were documented comparing BladeShield 101 with paper cards, respectively. CONCLUSIONS: Using an autonomous system to record, view, deliver, and store casualty information may resolve most current information flow deficits. This solution will ultimately significantly improve individual patient care and systematic learning and development processes.

A randomized, controlled, blinded evaluation of augmenting point-of-care ultrasound and remote telementored ultrasound in inexperienced operators.

BACKGROUND: Handheld ultrasound devices present an opportunity for prehospital sonographic assessment of trauma, even in the hands of novice operators commonly found in military, maritime, or other austere environments. However, the reliability of such point-of-care ultrasound (POCUS) examinations by novices is rightly questioned. A common strategy being examined to mitigate this reliability gap is remote mentoring by an expert. OBJECTIVES: To assess the feasibility of utilizing POCUS in the hands of novice military or civilian emergency medicine service (EMS) providers, with and without the use of telementoring. To assess the mitigating or exacerbating effect telementoring may have on operator stress. METHODS: Thirty-seven inexperienced physicians and EMTs serving as first responders in military or civilian EMS were randomized to receive or not receive telementoring during three POCUS trials: live model, Simbionix trainer, and jugular phantom. Salivary cortisol was obtained before and after the trial. Heart rate variability monitoring was performed throughout the trial. RESULTS: There were no significant differences in clinical performance between the two groups. Iatrogenic complications of jugular venous catheterization were reduced by 26% in the telementored group (P < 0.001). Salivary cortisol levels dropped by 39% (P < 0.001) in the telementored group. Heart rate variability data also suggested mitigation of stress. CONCLUSIONS: Telementoring of POCUS tasks was not found to improve performance by novices, but findings suggest that it may mitigate caregiver stress.

A prehospital scoring system for predicting the need for emergent blood product transfusion.

BACKGROUND: Several tools have been proven to predict the need for massive transfusion in trauma casualties, yet tools that are easily applicable in the prehospital setting for predicting the need for any blood product transfusion in the emergency department (ED) are lacking. METHODS: A retrospective analysis of the cross-referenced Israeli Defense Forces Trauma Registry and the Israeli National Trauma Registry databases was performed to identify predictors for any blood product transfusion in the ED. A scoring system was developed after internally validating the prediction model. Division to risk groups was performed. RESULTS: Seven variables (systolic blood pressure, heart rate, arterial oxygen saturation, trunk involvement, mechanism of injury, chest decompression, and tourniquet application) were included in the scoring system, ranging from 0 to 11.5. Risk groups for ED transfusion included very low (0.8%), low (3.2%), intermediate (8.5%), and high (31.2%) risk. CONCLUSION: A scoring system for predicting the need for any blood product transfusion in the ED was developed, based on information readily available in the early stages of prehospital resuscitation, allowing the receiving medical facility to prepare for that need.

Low-Titer Group O Whole-Blood Resuscitation in the Prehospital Setting in Israel: Review of the First 2.5 Years' Experience.

INTRODUCTION: The Israeli Defense Forces Medical Corps (IDF-MC) implemented the use of low-titer group O whole blood (LTOWB) as the first-choice resuscitation fluid in the IDF airborne Combat Search and Rescue Unit (IDF-CSAR) for aerial evacuation of both military and civilian casualties in June 2018 for injured patients with hemorrhagic shock and at least one of the following: systolic blood pressure <90 mm Hg, heart rate >130 beats/min, deterioration of consciousness without head injury or hemoglobin concentration ≤7 g/dL. METHOD: All casualties treated with LTOWB by IDF-CSAR providers from June 2018 to January 2021 were included. Demographic and prehospital treatment data were collected in order to check compliance and adherence to the IDF-MC guidelines. This is a follow-up retrospective report. RESULTS: Overall, 1,608 LTOWB units were supplied to the IDF-CSAR during the study period. Of these, 33 were transfused to 27 casualties; 17 (69%) with blunt injury, 8 (29.6%) with penetrating injuries, and 1 (3.7%) with gastrointestinal bleeding without trauma. The leading cause of injury was motor vehicle accidents. A total of 23 casualties received 1 unit of LTOWB, 3 received 2 units and 1 patient received 4 units. Two casualties were children. The median heart rate was 120 beats/min, 8 (29.6%) casualties had heart rates >130 beats/min. Median systolic blood pressure was 95 mm Hg, 7 (26%) casualties had blood pressure <90 mm Hg. The median Glasgow Coma Score was 14. No adverse reactions were documented following the administration of LTOWB. 77.8% of patients received LTOWB in adherence to the guidelines. CONCLUSION: Appropriate administration of LTOWB has improved over time in IDF-CSAR. Using LTOWB is feasible and simpler than administering packed red blood cells and plasma concurrently. Further efforts are needed to introduce LTOWB in other prehospital and in-hospital scenarios, with an increase in the maximum antibody titer threshold, to meet the expected increase in demand.

[COVID-19 - BLOOD GROUPS, ANTIBODIES AND CONVALESCENT PLASMA].

INTRODUCTION: Israel is currently struggling with the Coronavirus Disease (COVID-19) caused by SARS CoV-2. Transmission is increasing, with higher morbidity and mortality among populations at risk. Over-representation of blood type A was reported in COVID-19 patients with increased respiratory failure, while blood type O seems to have a protective effect. This may be caused by interference of anti-A antibodies in viral binding to the ACE receptor, different neutralization antibodies potency or variations in the stability of von Willebrand factor (VWF) multimers in different blood types. Since transfusion of convalescent COVID19 Plasma (CCP) is an accepted therapeutic modality, the Ministry of Health initiated a national project whereby CCP is collected by Magen David Adom (MDA) Blood Services using apheresis procedures and transfusions are approved by an experts committee, as part of the clinical trial or as compassionate treatment. Preliminary analysis of 49/170 patients treated so far shows improvement in 49%, with important relations with the anti-SARS-CoV-2 IgG antibodies level in the transfused plasma. Anti-SARS-CoV-2 antibodies were found in 83% of 1100 CCP donors, but a 13% decrease in antibodies level was detected in repeat donations. Blood type A was more predominant among CCP donors, when compared to MDA blood donors' data. A transfusion of CCP is a feasible and relatively safe therapeutic modality, mainly for patients with moderate COVID 19. CCP also serves as a source for the production of hyperimmune globulin for the treatment of COVID 19 and for passive immunization for populations at risk.

Characterization of Antineovascularization Activity and Ocular Pharmacokinetics of Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GNE-947.

The objectives of the present study were to characterize GNE-947 for its phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitory activities, in vitro anti-cell migration activity in human umbilical vein endothelial cells (HUVECs), in vivo antineovascularization activity in laser-induced rat choroidal neovascular (CNV) eyes, pharmacokinetics in rabbit plasma and eyes, and ocular distribution using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) and autoradioluminography. Its PI3K and mTOR K i were 0.0005 and 0.045 µM, respectively, and its HUVEC IC50 was 0.093 µM. GNE-947 prevented neovascularization in the rat CNV model at 50 or 100 µg per eye with repeat dosing. After a single intravenous injection at 2.5 and 500 µg/kg in rabbits, its plasma terminal half-lives (t 1/2) were 9.11 and 9.59 hours, respectively. After a single intravitreal injection of a solution at 2.5 µg per eye in rabbits, its apparent t 1/2 values were 14.4, 16.3, and 23.2 hours in the plasma, vitreous humor, and aqueous humor, respectively. After a single intravitreal injection of a suspension at 33.5, 100, 200 µg per eye in rabbits, the t 1/2 were 29, 74, and 219 days in the plasma and 46, 143, and 191 days in the eyes, respectively. MALDI-IMS and autoradioluminography images show that GNE-947 did not homogenously distribute in the vitreous humor and aggregated at the injection sites after injection of the suspension, which was responsible for the long t 1/2 of the suspension because of the slow dissolution process. This hypothesis was supported by pharmacokinetic modeling analyses. In conclusion, the PI3K/mTOR inhibitor GNE-947 prevented neovascularization in a rat CNV model, with t 1/2 up to approximately 6 months after a single intravitreal injection of the suspension in rabbit eyes. SIGNIFICANCE STATEMENT: GNE-947 is a potent phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor and exhibits anti-choroidal neovascular activity in rat eyes. The duration of GNE-947 in the rabbit eyes after intravitreal injection in a solution is short, with a half-life (t 1/2) of less than a day. However, the duration after intravitreal dose of a suspension is long, with t 1/2 up to 6 months due to low solubility and slow dissolution. These results indicate that intravitreal injection of a suspension for low-solubility drugs can be used to achieve long-term drug exposure.

Early experience with transfusing low titer group O whole blood in the pre-hospital setting in Israel.

BACKGROUND: The Israeli Defense Force Medical Corps (IDF-MC) recently implemented the use of low titer group O whole blood (LTOWB) in the airborne combat search and rescue unit (CSAR) for both military and civilian patients during transport to definitive care. LTOWB is preferentially used by the CSAR instead of red blood cell units and freeze-dried plasma (FDP) for patients with signs of hemorrhagic shock. Ten percent of group O donors were eligible to donate LTOWB as they had anti-A and -B IgM titers of <50. METHODS: All patients treated by CSAR providers with LTOWB between July 2018 and June 2019 were included. RESULTS: Between July 2018 and June 2019, eight patients have received 10 units of LTOWB. All patients suffered blunt injuries, 6 out of 8 (75%) of whom were due to motor vehicle accidents. Four patients (4 out of 8, 50%) received a single LTOWB unit, two patients (2 out of 8, 25%) received two units. Two pediatric patients received fewer than one unit of LTOWB. Median (range) heart rate was 130 (30-150) bpm, median systolic blood pressure was 107 (80-124) mmHg, and median Glasgow coma scale was 8 (on a scale of 3-15). For four (4 out of 8, 50%) patients, LTOWB was the only blood product used for volume resuscitation. All six adult patients were treated with 1 g of tranexamic acid at the point of injury. CONCLUSIONS: The CSAR has successfully implemented a LTOWB program for the pre-hospital treatment of bleeding patients, and as its experience grows this product will be made available to other units and in civilian hospitals.

Cognitive and physical performance are well preserved following standard blood donation: A noninferiority, randomized clinical trial.

BACKGROUND: A walking blood bank (WBB) refers to the use of fellow combatants for battlefield blood donation. This requires pretesting combatants for infectious diseases and blood type. A fundamental prerequisite for this technique is that the donating soldier will suffer minimal physiological and mental impact. The purpose of the current study is to assess the effect of blood shedding on battlefield performance. METHODS: This is a double-blind randomized control trial. Forty Israel Defense Forces combatants volunteered for the study. Participants underwent baseline evaluation, including repeated measurement of vital signs, cognitive evaluation, physical evaluation, and a strenuous shooting test. Three weeks after the baseline evaluation, subjects were randomized to either blood donation or the control group. For blinding purposes, all subjects underwent venous catheterization for the duration of a blood donation. Repeated vital signs and function evaluation were then performed. RESULTS: Thirty-six patients were available for randomization. Baseline measurements were similar for both groups. Mean strenuous shooting score was 80.5 ± 9.5 for the control group and 82 ± 6.6 for the test group (p = 0.58). No clinically or statistically significant differences were found in tests designed to evaluate cognitive performance or physical functions. Vital signs taken multiple times were also similar between the test and control groups. CONCLUSIONS: Executive, cognitive, and physical functions were well preserved after blood donation. This study supports the hypothesis that a WBB does not decrease donor combat performance. The categorical prohibition of physical exercise following blood donation might need to be reconsidered in both military and civilian populations.

Platelets derived from fresh and cold-stored whole blood participate in clot formation in rats with acute traumatic coagulopathy.

The in vitro haemostatic functions of fresh whole blood (FWB) are well preserved after cold storage. This study aimed to determine whether platelets derived from FWB and stored whole blood (SWB) contribute to clot formation in tissue injury after transfusion into coagulopathic rats with polytrauma/haemorrhage (T/H). The rats were resuscitated 1 h after trauma with FWB or SWB collected from green fluorescence protein (GFP) transgenic rats. After transfusion, a liver incision was made and the tissue was collected 10 min after injury to identify GFP+ platelets by immunohistochemistry. In comparison to FWB, platelet aggregation to adenosine diphosphate and protease-activated receptor-4 was reduced by 35% and 20%, and clotting time was shortened by 25% in SWB. After transfusion, SWB led to a significant increase in platelet activation as measured by an elevation of CD62P and phosphatidylserine expression. The platelets from SWB were in a higher activation state, and showed higher clearance rate and formation of platelet-leucocyte aggregates than those from FWB after transfusion. Platelets from both FWB and SWB were equivalently incorporated into the clot at the incisional site, as determined by co-localization of CD61 and GFP. This study suggests that SWB contributes to haemostatic function and is an effective alternative resource to treat trauma patients.

In vitro and in vivo characterization of CYP inhibition by 1-aminobenzotriazole in rats.

1-Aminobenzotriazole (ABT) is a non-isoform specific, time-dependent inhibitor of cytochrome P450 (CYP) enzymes used extensively in preclinical studies to determine the relative contribution of oxidative metabolism. Although ABT has been widely used, the extent and duration of its inhibitory effect is not well understood. The purpose of this study is to characterize ABT inhibition of CYP in rats at both the hepatic and intestinal levels. In vivo studies using midazolam (p.o. and i.v.), as a probe for CYP activity, demonstrated that CYP inhibition was not complete even at the highest dose (300 mg/kg). Additional in vivo studies demonstrated that even at 26 h following ABT administration, there was significant CYP inhibition remaining. In vitro studies, conducted in both rat liver microsomes and rat hepatocytes, confirm that ABT is a time-dependent inhibitor of rat CYP orthologs. However, in rat liver microsomes, there was more than 15% CYP activity remaining following a 60 min preincubation at 2 mm ABT and 5-10% of CYP activity was remaining in rat hepatocytes suspended in rat plasma following a 60 min preincubation at 2 mm ABT. 1-Aminobenzotriazole is a useful tool in elucidating the oxidative component of metabolism in preclinical species; however, conclusions made from the preclinical use of ABT should not operate under the assumption that CYP enzymatic activity is completely inhibited. Copyright © 2016 John Wiley & Sons, Ltd.

Needle thoracostomy for tension pneumothorax: the Israeli Defense Forces experience.

BACKGROUND: Point of injury needle thoracostomy (NT) for tension pneumothorax is potentially lifesaving. Recent data raised concerns regarding the efficacy of conventional NT devices. Owing to these considerations, the Israeli Defense Forces Medical Corps (IDF-MC) recently introduced a longer, wider, more durable catheter for the performance of rapid chest decompression. The present series represents the IDF-MC experience with chest decompression by NT. METHODS: We reviewed the IDF trauma registry from January 1997 to October 2012 to identify all cases in which NT was attempted. RESULTS: During the study period a total of 111 patients underwent chest decompression by NT. Most casualties (54%) were wounded as a result of gunshot wounds (GSW); motor vehicle accidents (MVAs) were the second leading cause (16%). Most (79%) NTs were performed at the point of injury, while the rest were performed during evacuation by ambulance or helicopter (13% and 4%, respectively). Decreased breath sounds on the affected side were one of the most frequent clinical indications for NT, recorded in 28% of cases. Decreased breath sounds were more common in surviving than in nonsurviving patients. (37% v. 19%, p < 0.001). A chest tube was installed on the field in 35 patients (32%), all after NT. CONCLUSION: Standard NT has a high failure rate on the battlefield. Alternative measures for chest decompression, such as the Vygon catheter, appear to be a feasible alternative to conventional NT.

CONTEXTE: La thoracotomie à l'aiguille (TA) pour le pneumothorax sous tension sur les lieux mêmes du traumatisme peut sauver des vies. Des données récentes ont mis en doute l'efficacité des dispositifs de TA classiques. C'est pourquoi le corps médical de l'armée israélienne (CMAI) a récemment proposé un cathéter plus long, plus large et plus résistant pour décomprimer rapidement le pneumothorax. Le présent article résume l'expérience du CMAI en matière de décompression des pneumothorax au moyen de la TA. MÉTHODES: Nous avons passé en revue le registre des traumatismes de l'armée israélienne entre janvier 1997 et octobre 2012 pour relever tous les cas où une TA a été tentée. RÉSULTANTS: Durant la période de l'étude 111 patients en tout ont subi une décompression à l'aide d'une TA. La plupart des cas (54 %) résultaient de blessures par balles; les accidents de la route venaient au second rang (16 %). La plupart (79 %) des TA ont été effectuées sur les lieux, tandis que les autres ont été effectuées durant l'évacuation par ambulance ou par hélicoptère (13 % et 4 %, respectivement). L'atténuation des bruits respiratoires du côté affecté était l'une des indications cliniques les plus fréquentes de la TA, enregistrée dans 28 % des cas. L'atténuation des bruits respiratoires était plus fréquente chez les patients qui ont survécu (37 % c. 19 %, p < 0,001). Un drain thoracique a été installé sur le terrain chez 35 patients (32 %), à chaque fois après une TA. CONCLUSION: La TA standard s'accompagne d'un taux d'échec élevé sur le champ de bataille. Une autre mesure de décompression, comme le cathéter Vygon, semble être une solution de rechange envisageable à la TA classique.

Investigations into the mechanisms of pyridine ring cleavage in vismodegib.

Vismodegib (Erivedge, GDC-0449) is a first-in-class, orally administered small-molecule Hedgehog pathway inhibitor that is approved for the treatment of advanced basal cell carcinoma. Previously, we reported results from preclinical and clinical radiolabeled mass balance studies in which we determined that metabolism is the main route of vismodegib elimination. The metabolites of vismodegib are primarily the result of oxidation followed by glucuronidation. The focus of the current work is to probe the mechanisms of formation of three pyridine ring-cleaved metabolites of vismodegib, mainly M9, M13, and M18, using in vitro, ex vivo liver perfusion and in vivo rat studies. The use of stable-labeled ((13)C2,(15)N)vismodegib on the pyridine ring exhibited that the loss of carbon observed in both M9 and M13 was from the C-6 position of pyridine. Interestingly, the source of the nitrogen atom in the amide of M9 was from the pyridine. Evidence for the formation of aldehyde intermediates was observed using trapping agents as well as (18)O-water. Finally, we conclude that cytochrome P450 is involved in the formation of M9, M13, and M18 and that M3 (the major mono-oxidative metabolite) is not the precursor for the formation of these cleaved products; rather, M18 is the primary cleaved metabolite.

Patient Time Spent With Professional Medical Interpreters and the Care Experiences of Patients With Limited English Proficiency.

INTRODUCTION/OBJECTIVES: More time spent with interpreters may support clinician-patient communication for patients with limited English proficiency (LEP), especially when interpreter support before and after clinical encounters is considered. We assessed whether more time spent with interpreters is associated with better patient-reported experiences of clinician-patient communication and interpreter support among patients with LEP. METHODS: Patients with LEP (n = 338) were surveyed about their experiences with both the clinician and interpreter. Duration of interpreter support during the encounter (in min) and auxiliary time spent before and after encounters supporting patients (in min) were documented by interpreters. Multivariable linear regression models were estimated to assess the association of the time duration of interpreter support and patient experiences of (1) clinician-patient communication, and (2) interpreter support, controlling for patient and encounter characteristics. RESULTS: The average encounter duration was 47.7 min (standard deviation, SD = 25.1), the average auxiliary time was 43.8 min (SD = 16.4), and the average total interpreter time was 91.1 min (SD = 28.6). LEP patients reported better experiences of interpreter support with a mean score of 97.4 out of 100 (SD = 6.99) compared to clinician-patient communication, with a mean score of 93.7 out of 100 (SD = 14.1). In adjusted analyses, total patient time spent with an interpreter was associated with better patient experiences of clinician-patient communication (ß = 7.23, P < .01) when auxiliary time spent by interpreters supporting patients before and after the encounter was considered, but not when only the encounter time was considered. CONCLUSIONS: Longer duration of time spent with an interpreter was associated with better clinician-patient communication for patients with LEP when time spent with an interpreter before and after the clinician encounter is considered. Policymakers should consider reimbursing health care organizations for time interpreters spend providing patient navigation and other support beyond clinical encounters.

Poor Compliance to Clinical Guidelines in the Diagnosis of Acute Appendicitis: Insights from a National Survey.

Background: Many scoring systems, algorithms, and guidelines have been developed to aid in the evaluation and diagnosis of acute appendicitis (AA). Many of these algorithms advocate against the routine use of radiological investigations when there is a high clinical suspicion of AA. However, there has been a significant rise in the use of imaging techniques for diagnosing AA in the past two decades. This is a national study aimed at assessing the adherence of residents assigned to the emergency department to the clinical guidelines for diagnosing AA. Methods: We introduced a case study of a male patient with highly suspicious clinical findings of AA to all surgical and emergency medicine residents assigned to the emergency department with the autonomy to make critical decisions to determine the preferred way of diagnosing AA. Results: A total of 62.4% of all relevant residents participated in this survey; 69.6% reported that the Alvarado score was eight or higher, and 82.1% estimated that the next step recommended by most clinical guidelines was appendectomy without further abdominal imaging tests. However, 83.4% chose to perform an imaging test to establish the diagnosis of AA. Conclusions: Our study revealed a notable non-adherence to clinical guidelines in diagnosing AA. Given the significance of these guidelines, we assert that adopting medical recommendations should not solely depend on individual education but should also be incorporated as a departmental policy.