Bureau of Medicine and Surgery

Importance: Although the Afghanistan and Iraq conflicts have the lowest US case-fatality rates in history, no comprehensive assessment of combat casualty care statistics, major interventions, or risk factors has been reported to date after 16 years of conflict. Objectives: To analyze trends in overall combat casualty statistics, to assess aggregate measures of injury and interventions, and to simulate how mortality rates would have changed had the interventions not occurred. Design, Setting, and Participants: Retrospective analysis of all available aggregate and weighted individual administrative data compiled from Department of Defense databases on all 56 763 US military casualties injured in battle in Afghanistan and Iraq from October 1, 2001, through December 31, 2017. Casualty outcomes were compared with period-specific ratios of the use of tourniquets, blood transfusions, and transport to a surgical facility within 60 minutes. Main Outcomes and Measures: Main outcomes were casualty status (alive, killed in action [KIA], or died of wounds [DOW]) and the case-fatality rate (CFR). Regression, simulation, and decomposition analyses were used to assess associations between covariates, interventions, and individual casualty status; estimate casualty transitions (KIA to DOW, KIA to alive, and DOW to alive); and estimate the contribution of interventions to changes in CFR. Results: In aggregate data for 56 763 casualties, CFR decreased in Afghanistan (20.0% to 8.6%) and Iraq (20.4% to 10.1%) from early stages to later stages of the conflicts. Survival for critically injured casualties (Injury Severity Score, 25-75 [critical]) increased from 2.2% to 39.9% in Afghanistan and from 8.9% to 32.9% in Iraq. Simulations using data from 23 699 individual casualties showed that without interventions assessed, CFR would likely have been higher in Afghanistan (15.6% estimated vs 8.6% observed) and Iraq (16.3% estimated vs 10.1% observed), equating to 3672 additional deaths (95% CI, 3209-4244 deaths), of which 1623 (44.2%) were associated with the interventions studied: 474 deaths (12.9%) (95% CI, 439-510) associated with the use of tourniquets, 873 (23.8%) (95% CI, 840-910) with blood transfusion, and 275 (7.5%) (95% CI, 259-292) with prehospital transport times. Conclusions and Relevance: Our analysis suggests that increased use of tourniquets, blood transfusions, and more rapid prehospital transport were associated with 44.2% of total mortality reduction. More critically injured casualties reached surgical care, with increased survival, implying improvements in prehospital and hospital care.

BACKGROUND: Mild traumatic brain injury (mTBI) secondary to blast exposure is the most common battlefield injury in Southwest Asia. There has been little prospective work in the combat setting to test the efficacy of new countermeasures. The goal of this study was to compare the efficacy of N-acetyl cysteine (NAC) versus placebo on the symptoms associated with blast exposure mTBI in a combat setting. METHODS: This study was a randomized double blind, placebo-controlled study that was conducted on active duty service members at a forward deployed field hospital in Iraq. All symptomatic U.S. service members who were exposed to significant ordnance blast and who met the criteria for mTBI were offered participation in the study and 81 individuals agreed to participate. Individuals underwent a baseline evaluation and then were randomly assigned to receive either N-acetyl cysteine (NAC) or placebo for seven days. Each subject was re-evaluated at 3 and 7 days. Outcome measures were the presence of the following sequelae of mTBI: dizziness, hearing loss, headache, memory loss, sleep disturbances, and neurocognitive dysfunction. The resolution of these symptoms seven days after the blast exposure was the main outcome measure in this study. Logistic regression on the outcome of 'no day 7 symptoms' indicated that NAC treatment was significantly better than placebo (OR = 3.6, p = 0.006). Secondary analysis revealed subjects receiving NAC within 24 hours of blast had an 86% chance of symptom resolution with no reported side effects versus 42% for those seen early who received placebo. CONCLUSION: This study, conducted in an active theatre of war, demonstrates that NAC, a safe pharmaceutical countermeasure, has beneficial effects on the severity and resolution of sequelae of blast induced mTBI. This is the first demonstration of an effective short term countermeasure for mTBI. Further work on long term outcomes and the potential use of NAC in civilian mTBI is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00822263.

(1968). The Epidemiology of Tuberculosis Infection in a Closed Environment. Archives of Environmental Health: An International Journal: Vol. 16, No. 1, pp. 26-35.

Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI). This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: (1) Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. (2) ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are non-disclosing. (3) The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including non-linear dynamical analysis, complexity measures, analysis of causal interactions, graph theory, and information dynamics. (4) Reports of high specificity in qEEG evaluations of TBI must be interpreted with care. High specificities have been reported in carefully constructed clinical studies in which healthy controls were compared against a carefully selected TBI population. The published literature indicates, however, that similar abnormalities in qEEG measures are observed in other neuropsychiatric disorders. While it may be possible to distinguish a clinical patient from a healthy control participant with this technology, these measures are unlikely to discriminate between, for example, major depressive disorder, bipolar disorder, or TBI. The specificities observed in these clinical studies may well be lost in real world clinical practice. (5) The absence of specificity does not preclude clinical utility. The possibility of use as a longitudinal measure of treatment response remains. However, efficacy as a longitudinal clinical measure does require acceptable test-retest reliability. To date, very few test-retest reliability studies have been published with qEEG data obtained from TBI patients or from healthy controls. This is a particular concern because high variability is a known characteristic of the injured central nervous system.

(1963). Effects of Mild Carbon Monoxide Intoxication. Archives of Environmental Health: An International Journal: Vol. 7, No. 5, pp. 524-530.

Optic nerve injury is a devastating potential complication of endoscopic sinus surgery. Anatomic variations of the posterior ethmoid sinus are certainly contributing factors. In the most well described posterior ethmoid anatomical variant, the sphenoethmoid or Onodi cell, the optic nerve is placed at risk during sinus surgery. Improving preoperative and intraoperative identification of the sphenoethmoid (Onodi) cell could decrease the risk of optic nerve injury. The purpose of this investigation was to assess the reliability of computerized tomography (CT) in detecting the sphenoethmoid (Onodi) cell, and further our understanding of this clinically relevant anatomic variant. A total of 41 sinonasal complexes from 21 human adult cadaveric heads were studied with a standard coronal and axial plane CT, and subsequent endoscopic dissection. The prevalence of the sphenoethmoid (Onodi) cell was determined by CT and endoscopic dissection, as were other anatomic characteristics of the posterior ethmoid anatomy. In our study, CT identified a sphenoethmoid (Onodi) cell in 3/41 (7%) of the sphenoethmoid complexes. However, anatomic dissection identified a sphenoethmoid (Onodi) cell in 16/41 (39%) complexes. Coronal orientation of the anterior sphenoid wall was never associated with a sphenoethmoid (Onodi) cell. Conversely, oblique or horizontal orientations were present in all cases of sphenoethmoid (Onodi) cells. Current CT scanning protocols for the paranasal sinuses did not reliably detect the Onodi cell. Endoscopic dissection indicates that the sphenoethmoid (Onodi) cell is a more frequent anatomic variant than previously appreciated. Awareness of anterior sphenoid wall orientation may assist surgeons in identifying the Onodi cell, thereby reducing the risk of optic nerve trauma.

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.

In response to the health concerns of Gulf War veterans, the Department of Defense instituted the Comprehensive Clinical Evaluation Program (CCEP). Although not designed as a research study, the CCEP provided valuable clinical data. An analysis was conducted of CCEP findings from systematic and comprehensive examinations of 20,000 U.S. Gulf War veterans. Among 20,000 participants, the types of primary and secondary diagnoses varied widely. Also, among veterans with an ICD-9-CM diagnosis of "symptoms, signs, and ill-defined conditions," no single subcategory of illness predominated, and no characteristic physical sign or laboratory abnormality was identified. In-total, there were 74 (0.4%) cases of connective tissue disease; 52 (0.3%) noncutaneous malignancies; 42 (0.2%) peripheral neuropathies; 14 (0.07%) cases of interstitial pulmonary fibrosis; 12 (0.06%) cases of renal insufficiency; and no new cases of viscerotropic leishmaniasis. No clinical indication of a new or unique illness was identified in this self-referred population, and the types of physiologic disease that could result from postulated hazardous wartime exposures were uncommon.

Exposure to explosive armaments during Operation Iraqi Freedom and Operation Enduring Freedom contributed to approximately 14% of the 352 612 traumatic brain injury (TBI) diagnoses in the US military between 2000 and 2016. The US Department of Defense issued guidelines in 2009 to (1) standardize TBI diagnostic criteria; (2) classify TBI according to mechanism and severity; (3) categorize TBI symptoms as somatic, psychological, or cognitive; and (4) systematize types of care given during the acute and rehabilitation stages of TBI treatment. Polytrauma and associated psychological and neurologic conditions may create barriers to optimal rehabilitation from TBI. Given the completion of recent combat operations and the transition of TBI patients into long-term care within the US Department of Veterans Affairs system, a review of the literature concerning TBI is timely. Long-term follow-up care for patients who have sustained TBI will remain a critical issue for the US military.

Seventy-five patients presented with the complaint of pruritus ani. The following prospective studies were employed to evaluate groups of these patients; (1) laboratory, including blood count, stool examination for ova and parasites, urinalysis, Sequential Multiple Analysis-12 serum studies, stool pH, and skin scrapings for fungi; (2) Minnesota Multiphasic Personality Inventory; (3) anal manometry; (4) elimination of dietary factors, and (5) topical ointment application. Many patients were concerned that a cancer caused the symptom. Once reassured, they tolerated the pruritus. Forty-eight to 50 per cent of these patients had poorly formed stools or incomplete stool evacuation; thus, soiling was frequent. An underlying skin problem was found in six patients with psoriasis and in one with erythrasma. Patients tended to worsen the problem by application of many medications and overzealous cleaning. Minor surgical problems of the anus should be corrected before other managements are instituted. Idiopathic pruritus ani responds to anal cleanliness, dietary discretion with avoidance of specific items by some patients, bowel habit regulation, and a mild topical hydrocortisone cream.

The primary aim of the current study was to obtain information about the longitudinal clinical functioning of primary care patients who had received care from behavioral health consultants (BHCs) integrated into a large family medicine clinic. Global mental health functioning was measured with the 20-item self-report Behavioral Health Measure (BHM), which was completed by patients at all appointments with the BHC. The BHM was then mailed to 664 patients 1.5 to 3 years after receipt of intervention from BHCs in primary care, of which 70 (10.5%) were completed and returned (62.9% female; mean age 43.1 ± 12.7 years; 48.6% Caucasian, 12.9% African American, 21.4% Hispanic/Latino, 2.9% Asian/Pacific Islander, 10.0% Other, 4.3% no response). Mixed effects modeling revealed that patients improved from their first to last BHC appointment, with gains being maintained an average of 2 years after intervention. Patterns of results remained significant even when accounting for the receipt of additional mental health treatment subsequent to BHC intervention. Findings suggest that clinical gains achieved by this subset of primary care patients that were associated with brief BHC intervention were maintained approximately 2 years after the final appointment.

OBJECTIVE: To model typical trajectories for improvement among patients treated in an integrated primary care behavioral health service, multilevel models were used to explore the relationship between baseline mental health impairment level and eventual mental health functioning across follow-up appointments. METHOD: Data from 495 primary care patients (61.1% female, 60.7% Caucasian, 37.141 ± 12.21 years of age) who completed the Behavioral Health Measure (Kopta & Lowry, 2002) at each primary care appointment were used for the analysis. Three separate models were constructed to identify clinical improvement in terms of number of appointments attended, baseline impairment severity level, and the interaction of these 2 variables. RESULTS: The data showed that 71.5% of patients improved across appointments, 56.8% of which (40.5% of the entire sample) was clinically meaningful and reliable. Number of appointments and baseline severity of impairment significantly accounted for variability in clinical outcome, with trajectories of change varying across appointments as a function of baseline severity. Patients with more severe impairment at baseline improved faster than patients with less severe baseline impairment. CONCLUSIONS: Patients treated within an integrated primary care behavioral health service demonstrate significant improvements in clinical status, even those with the most severe levels of distress at baseline.

Infections have complicated the care of combat casualties throughout history and were at one time considered part of the natural history of combat trauma. Personnel who survived to reach medical care were expected to develop and possibly succumb to infections during their care in military hospitals. Initial care of war wounds continues to focus on rapid surgical care with debridement and irrigation, aimed at preventing local infection and sepsis with bacteria from the environment (e.g., clostridial gangrene) or the casualty's own flora. Over the past 150 years, with the revelation that pathogens can be spread from patient to patient and from healthcare providers to patients (including via unwashed hands of healthcare workers, the hospital environment and fomites), a focus on infection prevention and control aimed at decreasing transmission of pathogens and prevention of these infections has developed. Infections associated with combat-related injuries in the recent operations in Iraq and Afghanistan have predominantly been secondary to multidrug-resistant pathogens, likely acquired within the military healthcare system. These healthcare-associated infections seem to originate throughout the system, from deployed medical treatment facilities through the chain of care outside of the combat zone. Emphasis on infection prevention and control, including hand hygiene, isolation, cohorting, and antibiotic control measures, in deployed medical treatment facilities is essential to reducing these healthcare-associated infections. This review was produced to support the Guidelines for the Prevention of Infections Associated With Combat-Related Injuries: 2011 Update contained in this supplement of Journal of Trauma.

Ch'i, I-Cheng (Nat. Defense Med. Ctr., Taipei, Taiwan) and R. Q. Blackwell. A controlled retrospective study of Blackfoot Disease, an endemic peripheral gangrene disease in Taiwan. Amer. J. Epid., 1968, 88; 7-24.—Blackfoot (BF) disease occurs in one small endemic area of Taiwan where it has been recognized for approximately 50 years. The condition affects young and old of both sexes and clinically resembles thromboangiitis obliterans; it generally causes loss of toes and, less frequently, loss of fingers. Previous studies had reported an association between the disease and the consumption of deep well water. The present controlled retrospective study of 353 patients with BF disease and 353 matched controls disclosed no striking differences between the groups except the doser association in the BF group of a history of long consumption of deep well water. That association was evaluated by several approaches and appears to be firmly established. Our previous laboratory studies had established that the deep well water contained appreciable levels of arsenic Furthermore, those residents of the endemic area who were consuming deep well water, including BF subjects as well as their relatives and neighbors, were found to excrete elevated levels of arsenic in hair and urine. It was concluded from our present epidemiologic study and our past laboratory work that arsenic, primarily from deep well water, is a likely etidogic factor in Blackfoot disease.

BACKGROUND: Infrequent use of emergency medical skills eventually leads to skill degradation. Even during residency training, certain skills may be infrequently encountered. The use of human patient simulators (HPS) is one means by which these skills may be practiced with sufficient numbers to learn and maintain emergency skills. OBJECTIVE: To assess the efficacy and feasibility of training isolated emergency medical personnel with a HPS. DESIGN/METHODS: A sophisticated HPS was placed at the Roosevelt Roads Naval Hospital, Puerto Rico. A convenience sample of emergency naval personnel enrolled in a training program consisting of five HPS-based scenarios. Both on-site (instructor in the room) and off-site (instructor in the United States) training was provided. A pre/post-test design was used to assess the efficacy of HPS training using a survey with a Likert scale measuring participant-perceived preparedness, self-efficacy, and perceptions of HPS training. RESULTS: Eighteen emergency medical personnel participated in the educational program. Eight were physicians, and the remainder were emergency medical technicians and U.S. Navy medical corpsmen. Perceived preparedness and self-efficacy improved overall and for each individual scenario. Participants rated the training highly and felt that it was better than conventional noninteractive mannequins. Off-site training was found to be feasible despite the low-bandwidth services available: Internet (56 K) and telephone service. Participants readily accepted off-site training. CONCLUSIONS: HPS education improves perceived preparedness and self-efficacy in U.S. Navy emergency medical personnel. This type of training may be an important adjunct for emergency medical providers who infrequently have the opportunity to apply learned emergency medical care skills. The use of HPS with distant interactive education capability allows isolated medical personnel the opportunity to practice skills unconstrained by time or distance.

We report a novel histological finding in a dermatofibrosarcoma protuberans (DFSP) after treatment with imatinib mesylate: copious amounts of hyalinized collagen. A 57-year-old female was referred for evaluation and treatment of a 7 x 8 x 10 cm tumor on the right anterior shoulder. Histological evaluation of the incisional biopsy showed a highly cellular dermal neoplasm composed of spindle cells arranged in a storiform pattern with minimal collagen. A CD34 immunohistochemical stain was strongly positive, highlighting atypical spindle cells in the dermis. A diagnosis of DFSP was made and the patient was enrolled in the Southwest Oncology Group trial. She received imatinib mesylate 400 mg per day for 1 year. At the end of therapy, the DFSP decreased in size to 5.5 x 4 x 4 cm. The tumor was excised. Histological evaluation showed a residual dermal neoplasm composed of atypical spindle cells and a copious amount of hyalinized collagen. Areas of necrosis were not seen. A CD34 stain confirmed the presence of residual DFSP, highlighting atypical spindle cells. A procollagen I stain was strongly positive, confirming the presence of abundant collagen in the dermis. A similar finding has been reported in gastrointestinal stromal tumor, which shows deposition of myxohyaline stroma after treatment with imatinib mesylate.

Over the past decade, studies into the impact of wartime deployment and related adversities on service members and their families have offered empirical support for systemic models of family functioning and a more nuanced understanding of the mechanisms by which stress and trauma reverberate across family and partner relationships. They have also advanced our understanding of the ways in which families may contribute to the resilience of children and parents contending with the stressors of serial deployments and parental physical and psychological injuries. This study is the latest in a series designed to further clarify the systemic functioning of military families and to explicate the role of resilient family processes in reducing symptoms of distress and poor adaptation among family members. Drawing upon the implementation of the Families Overcoming Under Stress (FOCUS) Family Resilience Program at 14 active-duty military installations across the United States, structural equation modeling was conducted with data from 434 marine and navy active-duty families who participated in the FOCUS program. The goal was to better understand the ways in which parental distress reverberates across military family systems and, through longitudinal path analytic modeling, determine the pathways of program impact on parental distress. The findings indicated significant cross-influence of distress between the military and civilian parents within families, families with more distressed military parents were more likely to sustain participation in the program, and reductions in distress among both military and civilian parents were significantly mediated by improvements in resilient family processes. These results are consistent with family systemic and resilient models that support preventive interventions designed to enhance family resilient processes as an important part of comprehensive services for distressed military families.

Children can be exposed to lead from a variety of environmental sources. It has been repeatedly reported that children of employees in a lead-related industry are at increased risk of lead absorption because of the high levels of lead found in the household dust of these workers. A case-control study was done in Oklahoma in 1978 to determine whether children of employees in battery manufacturing plant had a higher prevalence of high levels of blood lead than children whose parents were not employed in a lead-related industry. The data obtained indicated that the blood lead levels of the study children were significantly greater than those of the control children. None of the control children had blood lead levels greater than 30 micrograms/dl, while 53% of the exposed children had blood lead levels of greater than 30 micrograms/dl. Trends indicated that the children whose fathers had higher lead exposure at work also had higher blood lead levels. However, the study children whose fathers had good personal hygiene had blood lead levels comparable to the control children. It appeared that only good personal hygiene, i.e., showering, shampooing and changing clothes and shoes before leaving work, was effective for lead containment. The mere changing of clothes and shoes appeared to be inadequate for lead containment.

(1968). The Byrd Study. Archives of Environmental Health: An International Journal: Vol. 16, No. 1, pp. 4-6.

BACKGROUND: This study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons. METHODS: Participants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations. RESULTS: Over a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was -0.062 (SE = 0.005), -0.081(SE = 0.011), and -0.096 (SE = 0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference = -0.034 z-score units/year, SE = 0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p = 0.1). CONCLUSIONS: Older persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications.