Pathophysiology of Hemorrhage as It Relates to the Warfighter.

Saving lives of wounded military warfighters often depends on the ability to resolve or mitigate the pathophysiology of hemorrhage, specifically diminished oxygen delivery to vital organs that leads to multiorgan failure and death. However, caring for hemorrhaging patients on the battlefield presents unique challenges that extend beyond applying a tourniquet and giving a blood transfusion, especially when battlefield care must be provided for a prolonged period. This review describes these challenges and potential strategies for treating hemorrhage on the battlefield in a prolonged casualty care situation.

Analysis of the Effects of COVID-19 Mask Mandates on Hospital Resource Consumption and Mortality at the County Level.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) threatens vulnerable patient populations, resulting in immense pressures at the local, regional, national, and international levels to contain the virus. Laboratory-based studies demonstrate that masks may offer benefit in reducing the spread of droplet-based illnesses, but few data are available to assess mask effects via executive order on a population basis. We assess the effects of a county-wide mask order on per-population mortality, intensive care unit (ICU) utilization, and ventilator utilization in Bexar County, Texas. METHODS: We used publicly reported county-level data to perform a mixed-methods before-and-after analysis along with other sources of public data for analyses of covariance. We used a least-squares regression analysis to adjust for confounders. A Texas state-level mask order was issued on July 3, 2020, followed by a Bexar County-level order on July 15, 2020. We defined the control period as June 2 to July 2 and the postmask order period as July 8, 2020-August 12, 2020, with a 5-day gap to account for the median incubation period for cases; longer periods of 7 and 10 days were used for hospitalization and ICU admission/death, respectively. Data are reported on a per-100,000 population basis using respective US Census Bureau-reported populations. RESULTS: From June 2, 2020 through August 12, 2020, there were 40,771 reported cases of COVID-19 within Bexar County, with 470 total deaths. The average number of new cases per day within the county was 565.4 (95% confidence interval [CI] 394.6-736.2). The average number of positive hospitalized patients was 754.1 (95% CI 657.2-851.0), in the ICU was 273.1 (95% CI 238.2-308.0), and on a ventilator was 170.5 (95% CI 146.4-194.6). The average deaths per day was 6.5 (95% CI 4.4-8.6). All of the measured outcomes were higher on average in the postmask period as were covariables included in the adjusted model. When adjusting for traffic activity, total statewide caseload, public health complaints, and mean temperature, the daily caseload, hospital bed occupancy, ICU bed occupancy, ventilator occupancy, and daily mortality remained higher in the postmask period. CONCLUSIONS: There was no reduction in per-population daily mortality, hospital bed, ICU bed, or ventilator occupancy of COVID-19-positive patients attributable to the implementation of a mask-wearing mandate.

Chronic infarct size after spontaneous coronary artery dissection: implications for pathophysiology and clinical management.

AIMS: To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury. METHODS AND RESULTS: One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case-control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P < 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P < 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P <0.01) compared to healthy controls. Infarcts were small with few large infarcts (median 4.06%; range 0-30.9%) and 39% having no detectable late gadolinium enhancement (LGE). Female SCAD patients presenting with STEMI had similar sized infarcts to female Type-1 STEMI patients age <75 years. Multivariate modelling demonstrated STEMI at presentation, initial TIMI 0/1 flow, multivessel SCAD, and a Beighton score >4 were associated with larger infarcts [>10% left ventricular (LV) mass]. CONCLUSION: The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts.

Comparison of exercise testing and CMR measured myocardial perfusion reserve for predicting outcome in asymptomatic aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in Aortic Stenosis (PRIMID AS) Study.

AIMS: To assess cardiovascular magnetic resonance (CMR) measured myocardial perfusion reserve (MPR) and exercise testing in asymptomatic patients with moderate-severe AS. METHODS AND RESULTS: Multi-centre, prospective, observational study, with blinded analysis of CMR data. Patients underwent adenosine stress CMR, symptom-limited exercise testing (ETT) and echocardiography and were followed up for 12-30 months. The primary outcome was a composite of: typical AS symptoms necessitating referral for AVR, cardiovascular death and major adverse cardiovascular events. 174 patients were recruited: mean age 66.2 ± 13.34 years, 76% male, peak velocity 3.86 ± 0.56 m/s and aortic valve area index 0.57 ± 0.14 cm2/m2. A primary outcome occurred in 47 (27%) patients over a median follow-up of 374 (IQR 351-498) days. The mean MPR in those with and without a primary outcome was 2.06 ± 0.65 and 2.34 ± 0.70 (P = 0.022), while the incidence of a symptom-limited ETT was 45.7% and 27.0% (P = 0.020), respectively. MPR showed moderate association with outcome area under curve (AUC) = 0.61 (0.52-0.71, P = 0.020), as did exercise testing (AUC = 0.59 (0.51-0.68, P = 0.027), with no significant difference between the two. CONCLUSIONS: MPR was associated with symptom-onset in initially asymptomatic patients with AS, but with moderate accuracy and was not superior to symptom-limited exercise testing. ClinicalTrials.gov (NCT01658345).

The European Medicines Agency Review of Decitabine (Dacogen) for the Treatment of Adult Patients With Acute Myeloid Leukemia: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use.

UNLABELLED: : On September 20, 2012, a marketing authorization valid throughout the European Union (EU) was issued for decitabine for the treatment of adult patients aged 65 years and older with newly diagnosed de novo or secondary acute myeloid leukemia (AML) who are not candidates for standard induction chemotherapy. Decitabine is a pyrimidine analog incorporated into DNA, where it irreversibly inhibits DNA methyltransferases through covalent adduct formation with the enzyme. The use of decitabine was studied in an open-label, randomized, multicenter phase III study (DACO-016) in patients with newly diagnosed de novo or secondary AML. Decitabine (n = 242) was compared with patient's choice with physician's advice (n = 243) of low-dose cytarabine or supportive care alone. The primary endpoint of the study was overall survival. The median overall survival in the intent-to-treat (ITT) population was 7.7 months among patients treated with decitabine compared with 5.0 months for those in the control arm (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69-1.04; p = .1079). Mature survival data after an additional year of follow-up were consistent with these results, with a median overall survival of 7.7 months in patients treated with decitabine and 5.0 months in the control arm (HR, 0.82; 95% CI, 0.68-0.99; p = .0373). Secondary endpoints, including response rates, progression-free survival, and event-free survival, were increased in favor of decitabine when compared with control treatment. The most common adverse drug reactions reported during treatment with decitabine are pyrexia, anemia, thrombocytopenia, febrile neutropenia, neutropenia, nausea, and diarrhea. This paper summarizes the scientific review of the application leading to approval of decitabine in the EU. The detailed scientific assessment report and product information (including the summary of product characteristics) for this product are available on the EMA website (http://www.ema.europa.eu). IMPLICATIONS FOR PRACTICE: Acute myeloid leukemia (AML) remains an area of significant unmet need, especially in older patients. Older patients and those with comorbidities are often considered ineligible for standard induction therapy, and outcome for these patients is poor. Decitabine has favorable effects in terms of overall survival, which were considered clinically meaningful in the context of a manageable toxicity profile and after consideration of the lack of therapeutic alternatives for these patients. Decitabine is widely used in the treatment of AML in patients aged >60 years, as per current guidelines, including the European LeukemiaNet and the U.S. National Cancer Comprehensive Network.

UK medicines regulation: responding to current challenges.

The medicines regulatory environment is evolving rapidly in response to the changing environment. Advances in science and technology have led to a vast field of increasingly complicated pharmaceutical and medical device products; increasing globalization of the pharmaceutical industry, advances in digital technology and the internet, changing patient populations, and shifts in society also affect the regulatory environment. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines, medical devices and blood products to protect and improve public health, and supports innovation through scientific research and development. It works closely with other bodies in a single medicines network across Europe and takes forward UK health priorities. This paper discusses the range of initiatives in the UK and across Europe to support innovation in medicines regulation. The MHRA leads a number of initiatives, such as the Innovation Office, which helps innovators to navigate the regulatory processes to progress their products or technologies; and simplification of the Clinical Trials Regulations and the Early Access to Medicines Scheme, to bring innovative medicines to patients faster. The Accelerated Access Review will identify reforms to accelerate access for National Health Service patients to innovative medicines and medical technologies. PRIME and Adaptive Pathways initiatives are joint endeavours within the European regulatory community. The MHRA runs spontaneous reporting schemes and works with INTERPOL to tackle counterfeiting and substandard products sold via the internet. The role of the regulator is changing rapidly, with new risk-proportionate, flexible approaches being introduced. International collaboration is a key element of the work of regulators, and is set to expand.

Septic arthritis in intravenous drug abusers: a historical comparison of habits and pathogens.

BACKGROUND: Intravenous drug abuse (IVDA) is a common problem; there were more than 16 million users worldwide in 2008. Numerous reports highlight the infectious skeletal complication associated with IVDA. OBJECTIVE: To determine septic arthritis pathogens in IVDA in a U.S. hospital and compare the current causative organisms to a cohort from the 1980s at the same institution. METHODS: An institutional review board-approved retrospective cohort study compared a consecutive series of IVDA septic arthritis patients over a 10-year period, 1999-2008 (Group B), with an IVDA septic arthritis database that was collected in the 1980s (Group A). Endpoints were: bacterial species and staph species antibiotic susceptibility. RESULTS: Group B included 58 patients (35 men, 23 women) with a median age of 46.5 years. Group A included 38 patients (30 men, 8 women), with a median age of 32.5 years. The sets were significantly different in pathogens (p = 0.0443). The most common organisms were Staphylococcus (staph) species (B 74.51%, A 52.63%), followed by Streptococcus (strep) species (B 7.84%, A 31.58%), Pseudomonas (B 13.73%, A 13.16%), and Serratia (B 3.92%, A 2.63%). Of the total number of septic joints, methicillin-resistant Staphylococcus aureus (MRSA) made up 39% of Group B and 34% of Group A. However, within the staph species, MRSA made up 53% of Group B and 65% of Group A. Strep species made up 7.84% (Group B) vs. 31.58% (Group A), and Pseudomonas (13%) and Serratia (3-4%) were similar. In the Group B cohort, methicillin-susceptible Staphylococcus aureus (MSSA) had a predilection to infect the knee (94.4%), whereas MRSA was found more often in the hip (57.1%). CONCLUSIONS: In IVDAs, MRSA is the most common pathogen causing septic arthritis. The ratio of staph species in septic joints is increasing, and the ratio of MRSA to MSSA remains high (>50%). Strep species are much less common.

To live and die in America: labor in the time of cholera and cancer.

A popular explanation of the epidemiological transition is that the germs that caused infectious disease mortality were defeated by the "magic bullets" of mainstream medicine over the course of the 20th century, permitting the population to get old enough to get the chronic diseases of heart disease and cancer. This explanation is false. The most important causes of infectious disease were the political and economic structures that favored capital at the expense of labor so blatantly that it left a large portion of the working population virtually at death's door. This was remedied only when resistance by labor created a more livable workday, child labor laws, and a higher wage, resulting in improvements in nutrition and housing. Chronic disease increased as firms transformed the production process by introducing more mechanized and chemically intensive production processes. This has transformed our food, water, air, and work processes in unprecedented ways and created a historically unique chronic disease pattern.

The European Medicines Agency review of pixantrone for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin's B-cell lymphomas: summary of the scientific assessment of the committee for medicinal products for human use.

On May 10, 2012, the European Commission issued a conditional marketing authorization valid throughout the European Union for pixantrone for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin's B-cell lymphoma (NHL). Pixantrone is a cytotoxic aza-anthracenedione that directly alkylates DNA-forming stable DNA adducts and cross-strand breaks. The recommended dose of pixantrone is 50 mg/m(2) administered on days 1, 8, and 15 of each 28-day cycle for up to 6 cycles. In the main study submitted for this application, a significant difference in response rate (proportion of complete responses and unconfirmed complete responses) was observed in favor of pixantrone (20.0% vs. 5.7% for pixantrone and physician's best choice, respectively), supported by the results of secondary endpoints of median progression-free and overall survival times (increase of 2.7 and 2.6 months, respectively). The most common side effects with pixantrone were bone marrow suppression (particularly of the neutrophil lineage) nausea, vomiting, and asthenia. This article summarizes the scientific review of the application leading to approval in the European Union. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu).

Sequential reduction and fixation for windswept pelvic ring injuries (LC3) corrects the deformity until healed.

PURPOSE: The restoration, and fixation, of normal pelvic anatomy after a windswept type injury can be a difficult endeavor and our purpose is to describe a method to accomplish this. METHODS: A stepwise and sequential technique was utilized to effectively reduce and stabilize this injury pattern. By first closing down the open disruption posteriorly and fixing with a partially threaded SI screw, a stable platform was created upon which to work from and subsequently distract and reduce the contralateral side via an anterior internal fixator (seven), external fixator (one), or plate (one). This was followed by a fully threaded SI screw in the compression side of the sacral fracture to hold the distraction. Nine consecutive patients with LC3 (61-B3.2) were included in the study with an average FU of 15 months. RESULTS: The Keshishyan deformity index revealed an initial mean deformity of 0.0456 which was corrected to 0.0170 (postop) and 0.0181 at latest follow up. This entailed an average correction of 62 % at the latest follow up. The follow-up group was significantly different from pre-op (p = 0.0040), but not post-op (p = 0.6833). Furthermore, post-op was significantly different from pre-op (p = 0.0089). CONCLUSION: This is an effective method of correcting and maintaining reduction until healing for this relatively rare and difficult-to-treat injury pattern.

CAN POLYETHYLENE GLYCOL-20K REPLACE ALBUMIN FOR PREHOSPITAL TREATMENT OF HEMORRHAGIC SHOCK WHEN FULL RESUSCITATION IS UNAVAILABLE?

ABSTRACT: A solution of high concentration albumin has been used for temporal volume expansion when timely resuscitation was unavailable after hemorrhagic shock. However, during prolonged hemorrhagic shock, cell edema and interstitial dehydration can occur and impede the volume expansion effect of albumin. Polyethylene glycol-20K (PEG) can establish an osmotic gradient from swollen cells to capillary lumens and thus facilitate capillary fluid shift and volume expansion. We hypothesized that with similar osmolality, 7.5% PEG elicits more rapid and profound compensatory responses after hemorrhagic shock than 25% albumin. Rats were randomized into three groups (n = 8/group) based on treatment: saline (vehicle), PEG (7.5%), and albumin (25%). Trauma was induced in anesthetized rats with muscle injury and fibula fracture, followed by pressure-controlled hemorrhagic shock (MAP = 55 mm Hg) for 45 min. Animals then received an intravenous injection (0.3 mL/kg) of saline, PEG, or albumin. MAP, heart rate, blood gases, hematocrit, skeletal muscle capillary flow, renal blood flow, glomerular filtration rate, urinary flow, urinary sodium concentration, and mortality were monitored for another 2 hours. Polyethylene glycol-20K and albumin both improved MAP, renal and capillary blood flow, and renal oxygen delivery, and decreased hyperkalemia, hyperlactatemia, hematocrit, and mortality (saline: 100% PEG: 12.5%; albumin: 38%) over saline treatment. Compared with albumin, PEG had a more rapid decrease in hematocrit and more profound increases in MAP, diastolic pressure, renal blood flow, glomerular filtration rate, and urinary flow. These results suggest that PEG may be a better option than albumin for prolonged prehospital care of hemorrhagic shock.

Patterns of Palliation: A Review of Casualties That Received Pain Management Before Reaching Role 2 in Afghanistan.

INTRODUCTION: Battlefield pain management changed markedly during the first 20 years of the Global War on Terror. Morphine, long the mainstay of combat analgesia, diminished in favor of fentanyl and ketamine for military pain control, but the options are not hemodynamically or psychologically equivalent. Understanding patterns of prehospital analgesia may reveal further opportunities for combat casualty care improvement. MATERIALS AND METHODS: Using Department of Defense Trauma Registry data for the Afghanistan conflict from 2005 to 2018, we examined 2,402 records of prehospital analgesia administration to assess temporal trends in medication choice and proportions receiving analgesia, including subanalysis of a cohort screened for an indication with minimal contraindication for analgesia. We further employed frequency matching to explore the presence of disparities in analgesia by casualty affiliation. RESULTS: Proportions of documented analgesia increased throughout the study period, from 0% in 2005 to 70.6% in 2018. Afghan casualties had the highest proportion of documented analgesia (53.0%), versus U.S. military (31.9%), civilian/other (23.3%), and non-U.S. military (19.3%). Fentanyl surpassed morphine in the frequency of administration in 2012. The median age of those receiving ketamine was higher (30 years) than those receiving fentanyl (26 years) or nonsteroidal anti-inflammatory drugs (23 years). Among the frequency-matched subanalysis, the odds ratio for ketamine administration with Afghan casualties was 1.84 (95% CI, 1.30-2.61). CONCLUSIONS: We observed heterogeneity of prehospital patient care across patient affiliation groups, suggesting possible opportunities for improvement toward an overall best practice system. General increase in documented prehospital pain management likely reflects efforts toward complete documentation, as well as improved options for analgesia. Current combat casualty care documentation does not include any standardized pain scale.

Descriptive Analysis of Combat-Associated Aspiration Pneumonia.

BACKGROUND: Airway obstruction is the second leading cause of potentially preventable death on the battlefield. The treatment for airway obstruction is intubation or advanced airway adjunct, which has a known risk of aspiration. We sought to describe the variables associated with aspiration pneumonia after prehospital airway intervention. METHODS: This is a sub-analysis of previously described data from the Department of Defense Trauma Registry (DoDTR) from 2007 to 2020. We included casualties that had at least one prehospital airway intervention with documentation of subsequent aspiration pneumonia or pneumonia within three days of the intervention. We used a generalized linear model with Firth bias estimates to test for associations. RESULTS: There were 1,509 casualties that underwent prehospital airway device placement. Of these, 41 (2.7%) met inclusion criteria into the aspiration pneumonia cohort. The demographics had no statistical difference between the groups. The non-aspiration cohort had fewer median ventilator days (2 versus 6, p < 0.001), intensive care unit days (2 versus 7, p < 0.001, and hospital days [3 versus 8, p < 0.001]). Survival was lower in the non-aspiration cohort (74.2% versus 90.2%, p = 0.017). The administration of succinylcholine was higher in the non-aspiration cohort (28.0% versus 12.2%, p = 0.031). In our multivariable model, only the administration of succinylcholine was significant and was associated with lower probability of aspiration pneumonia (odds ratio 0.56). CONCLUSION: Overall, the incidence of aspiration pneumonia was low in our cohort. The administration of succinylcholine was associated with a lower odds of developing aspiration pneumonia.

Improving Outcomes Associated with Prehospital Combat Airway Interventions: An Unrealized Opportunity.

BACKGROUND: Airway obstruction is the second leading cause of potentially survivable death on the battlefield. Assessing outcomes associated with airway interventions is important, and temporal trends can reflect the influence of training, technology, the system of care, and other factors. We assessed mortality among casualties undergoing prehospital airway intervention occurring over the course of combat operations during 2007-2019. METHODS: This is a retrospective analysis of a previously described dataset from the Department of Defense Trauma Registry (DODTR). We included only casualties with documented placement of an endotracheal tube, cricothyrotomy, or supraglottic airway (SGA) in the prehospital setting. RESULTS: Within the DODTR from January 2007 to December 2019, there were 25,849 adult encounters with documentation of any prehospital activity. Within that group, there were 251 documented cricothyrotomies, 1,147 documented intubations, and 35 documented supraglottic airways placed. Cricothyrotomy recipients had a median age of 25. Within this group, the largest proportion were non-North Atlantic Treaty Organization (NATO) military personnel (35%), were injured by explosives (54%), had a median injury severity score (ISS) of 24, and 60% survived to hospital discharge. Intubation recipients had a median age of 24. Within this group, the largest proportion were non-NATO military personnel (37%), were injured by explosives (57%), had a median ISS of 18, and 76% survived to hospital discharge. SGA recipients had a median age of 28. Within this group, the largest proportion were non-NATO military (37%), were injured by firearms (48%), had a median ISS of 25, and 54% survived to hospital discharge. A downward trend existed in the quantity of all procedures performed during the study period. In both unadjusted and adjusted regression models, we identified no year-to-year differences in survival after prehospital cricothyrotomy or SGA placement. In the unadjusted and adjusted models, we noted a decrease in mortality during the 2007-2008 (odds ratio [OR] for death 0.47, 95% CI 0.26-0.86) and an increase from 2012-2013 (OR 2.10, 95% CI 1.09-4.05) for prehospital intubation. CONCLUSION: Mortality among combat casualties undergoing prehospital or emergency department airway interventions showed no sustained change during the study period. These findings suggest that advances in airway resuscitation are necessary to achieve mortality improvements in potentially survivable airway injuries in the prehospital setting.

Oversight May Reduce Military Health System Leakage: Preventing Inappropriate Interhospital Transfers.

INTRODUCTION: The Military Health System (MHS) offers an example of a socialized healthcare model, operating within a larger "purchased care" civilian healthcare market. This arrangement has facilitated a trend wherein MHS clinicians often transfer moderate-to-complex patients to surrounding civilian hospitals, despite having the capability to care for such patients in-house. In an effort to stem this behavior, two initiatives were introduced at Carl R Darnall Army Medical Center (CRDAMC): A Transfer Policy Statement and Transfer Rounds. The Transfer Policy Statement emphasized that patients ought to be transferred only for capability gaps within the hospital. Transfer Rounds were then used to review the care received by each transferred patient and assess if that care could have been delivered internally. The purpose of this study is to assess the effect of these initiatives on reducing transfers from our hospital. MATERIALS AND METHODS: We performed a retrospective chart review from July 2019 through June 2020 to identify the number of total emergency department (ED) transfers, subcategorized as either transfers we had the capability to care for or transfers we did not have the capability to care for. The Transfer Policy Statement was published in August 2019, and Transfer Rounds were instituted in November 2019. We hypothesized that the two interventions would decrease the number of monthly inappropriate transfers. This was assessed by analyzing the proportion of inappropriate to appropriate patient transfers via Cochran and Armitage using SAS 9.4 (SAS Institute, Cary, NC). The projected received an Exemption Determination from the CRDAMC's Human Research Protections Office. The Defense Health Agency approved the data-sharing agreement. RESULTS: Over the study period, a total of 706 transfers met the criteria for analysis. The monthly median for total ED transfers was 64.5 (Interquartile Range (IQR) 45-74); appropriate transfers averaged 29.5 (median, IQR 24.5-36) and inappropriate 25.5 (median, IQR 9-41.5). A statistically significant downward trend in the fraction of inappropriate transfers was demonstrated by Cochran and Armitage (P < .0001). CONCLUSION: Our analysis supports the hypothesis that implementing a Transfer Policy and Transfer Rounds can significantly reduce the amount of MHS Leakage-that is the number of transferred patients that the MHS could have equally cared for. The effects of reduced patient transfers have many implications for the MHS: patients experience improved continuity of care by remaining in the same hospital system; clinicians maintain and extend their scope of practice by treating more complex patients; and patient flow and ED wait times are reduced by eliminating the transfer process. The financial implications of reduced MHS Leakage were not directly evaluated by our study, however may be assessed in future study.

A mixed methods end-user assessment to determine the ideal supraglottic airway device for inclusion into the medic's aid bag.

BACKGROUND: Many advancements in supraglottic airway technology have occurred since the start of the Global War on Terrorism. While the Tactical Combat Casualty Care guidelines previously recommend the i-gel device, this is based on little data and minimal end-user input. OBJECTIVE: We sought to use a mixed methods approach to investigate the properties of an ideal device for inclusion into the medic's aid bag. METHODS: We performed prospective, serial qualitative studies to uncover and articulate themes relative to airway device usability with 68W-combat medics. 68W are trained roughly to the level of a civilian advanced emergency medical technician with a heavier focus on trauma care. Physicians with airway expertise demonstrated the use of each device and provided formal training on all the presented devices. We then administered performed focus groups to solicit end-user feedback along with survey data. RESULTS: We enrolled 250 medics during the study. The preponderance of medics were of the rank E4 (28%) and E5 (44%). Only 35% reported ever placing a supraglottic airway in a real human. When reporting on usability, the i-gel had the highest median score, ease of manipulation, grip comfort and ease of insertion while also scoring the best in regard to requiring minimal training. The other compared devices had no clear highest score. Qualitative data saturated around a strong preference for the BaskaMask and/or the i-gel airway device, with the least favorite being the AirQ and the LMA Fastrach airway devises. There was a strong qualitative alignment in how both the BaskaMask and i-gel provided ease of use and simplicity of training. CONCLUSION: There were strong qualitative preferences for two specific airway devices: Baska Mask and i-gel. However, many medics commented on their previous experience with the i-gel compared with the other devices, which may have biased them toward the i-gel. The overall data suggest that medics would prefer a device engineered with features from several devices. LEVEL OF EVIDENCE: Therapeutic/care management; Level V.

Battlefield Vital Sign Monitoring in Role 1 Military Treatment Facilities: A Thematic Analysis of After-Action Reviews from the Prehospital Trauma Registry.

INTRODUCTION: The Prehospital Trauma Registry (PHTR) captures after-action reviews (AARs) as part of a continuous performance improvement cycle and to provide commanders real-time feedback of Role 1 care. We have previously described overall challenges noted within the AARs. We now performed a focused assessment of challenges with regard to hemodynamic monitoring to improve casualty monitoring systems. MATERIALS AND METHODS: We performed a review of AARs within the PHTR in Afghanistan from January 2013 to September 2014 as previously described. In this analysis, we focus on AARs specific to challenges with hemodynamic monitoring of combat casualties. RESULTS: Of the 705 PHTR casualties, 592 had available AAR data; 86 of those described challenges with hemodynamic monitoring. Most were identified as male (97%) and having sustained battle injuries (93%), typically from an explosion (48%). Most were urgent evacuation status (85%) and had a medical officer in their chain of care (65%). The most common vital sign mentioned in AAR comments was blood pressure (62%), and nearly one-quarter of comments stated that arterial palpation was used in place of blood pressure cuff measurements. CONCLUSIONS: Our qualitative methods study highlights the challenges with obtaining vital signs-both training and equipment. We also highlight the challenges regarding ongoing monitoring to prevent hemodynamic collapse in severely injured casualties. The U.S. military needs to develop better methods for casualty monitoring for the subset of casualties that are critically injured.

Changes in Emergency Department Volumes at the Largest U.S. Military Hospital During the COVID-19 Pandemic.

INTRODUCTION: The coronavirus-2019 (COVID-19) pandemic has significantly impacted global healthcare delivery. Brooke Army Medical Center (BAMC) is the DoD's largest hospital and a critical platform for maintaining a ready medical force. We compare temporal trends in patient volumes and characteristics in the BAMC emergency department (ED) before versus during the pandemic. MATERIALS AND METHODS: We abstracted data on patient visits from the BAMC ED electronic medical record system. Data included patient demographics, visit dates, emergency severity index triage level, and disposition. We visually compared the data from January 1, 2019 to November 30, 2019 versus January 1, 2020 to November 30, 2020 to assess the period with the most apparent differences. We then used descriptive statistics to characterize the pre-pandemic control period (1 March-November 30, 2019) versus the pandemic period (1 March-November 30, 2020). RESULTS: Overall, when comparing the pre-pandemic and pandemic periods, the median number of visits per day was 232 (Interquartile Range (IQR) 214-250, range 145-293) versus 165 (144-193, range 89-308, P < .0001). Specific to pediatric visits, we found the median number of visits per day was 39 (IQR 33-46, range 15-72) versus 18 (IQR 14-22, range 5-61, P < .001). When comparing the median number of visits by month, the volumes were lower during the pandemic for all months, all of which were strongly significant (P < .001 for all). CONCLUSIONS: The BAMC ED experienced a significant decrease in patient volume during the COVID-19 pandemic starting in March 2020. This may have significant implications for the capacity of this facility to maintain a medically ready force.

Building the concept for WHO Evidence Considerations for Vaccine Policy (ECVP): Tuberculosis vaccines intended for adults and adolescents as a test case.

Currently, no formal mechanisms or systematic approaches exist to inform developers of new vaccines of the evidence anticipated to facilitate global policy recommendations, before a vaccine candidate approaches regulatory approval at the end of pre-licensure efficacy studies. Consequently, significant delays may result in vaccine introduction and uptake, while post-licensure data are generated to support a definitive policy decision. To address the uncertainties of the evidence-to-recommendation data needs and to mitigate the risk of delays between vaccine recommendation and use, WHO is evaluating the need for and value of a new strategic alignment tool: Evidence Considerations for Vaccine Policy (ECVP). EVCPs aim to fill a critical current gap by providing early (pre-phase 3 study design) information on the anticipated clinical trial and observational data or evidence that could support WHO and/or policy decision making for new vaccines in priority disease areas. The intent of ECVPs is to inform vaccine developers, funders, and other key stakeholders, facilitating stakeholder alignment in their strategic planning for late stage vaccine development. While ECVPs are envisaged as a tool to support dialogue on evidence needs between regulators and policy makers at the national, regional and global level, development of an ECVP will not preclude or supersede the independent WHO's Strategic Advisory Group of Experts on Immunization (SAGE) evidence to recommendation (EtR) process that is required for all vaccines seeking WHO policy recommendation. Tuberculosis (TB) vaccine candidates intended for use in the adolescent and adult target populations comprise a portfolio of priority vaccines in late-stage clinical development. As such, TB vaccines intended for use in this target population provide a 'test case' to further develop the ECVP concept, and develop the first WHO ECVP considerations guidance.

The European Medicines Agency review of eltrombopag (Revolade) for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura: summary of the scientific assessment of the Committee for Medicinal Products for Human Use.

On 11(th) March 2010, the European Commission issued a marketing authorization valid throughout the European Union for Revolade for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura. Revolade is an orphan medicinal product indicated for splenectomized patients with immune (idiopathic) thrombocytopenic purpura who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) and as second-line treatment for non-splenectomized patients where surgery is contraindicated. The active substance of Revolade is eltrombopag (ATC code B02BX05). Eltrombopag increases platelet production through activation of the thrombopoietin receptor. The recommended oral dose is 50 mg once daily to achieve and maintain a platelet count of the 50×10(9)/L or more necessary to reduce or prevent the risk of bleeding. The benefit of Revolade is a durable response in maintaining platelet levels. The most common side effects include headache, nausea, hepatobiliary toxicity, diarrhea, fatigue, paresthesia, constipation, rash, pruritus, cataract, arthralgia and myalgia. The decision to grant the marketing authorization was based on the favorable recommendation of the Committee for Medicinal Products for Human Use of the European Medicines Agency. The objective of this paper is to describe the data submitted to the European Medicines Agency and to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency website (www.ema.europa.eu).