Madigan Army Medical Center

This document represents the first collaboration between 2 organizations-the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine-to describe best practices in nutrition therapy in critically ill children. The target of these guidelines is intended to be the pediatric critically ill patient (>1 month and <18 years) expected to require a length of stay >2-3 days in a PICU admitting medical, surgical, and cardiac patients. In total, 2032 citations were scanned for relevance. The PubMed/MEDLINE search resulted in 960 citations for clinical trials and 925 citations for cohort studies. The EMBASE search for clinical trials culled 1661 citations. In total, the search for clinical trials yielded 1107 citations, whereas the cohort search yielded 925. After careful review, 16 randomized controlled trials and 37 cohort studies appeared to answer 1 of the 8 preidentified question groups for this guideline. We used the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluation) to adjust the evidence grade based on assessment of the quality of study design and execution. These guidelines are not intended for neonates or adult patients. The guidelines reiterate the importance of nutrition assessment-particularly, the detection of malnourished patients who are most vulnerable and therefore may benefit from timely intervention. There is a need for renewed focus on accurate estimation of energy needs and attention to optimizing protein intake. Indirect calorimetry, where feasible, and cautious use of estimating equations and increased surveillance for unintended caloric underfeeding and overfeeding are recommended. Optimal protein intake and its correlation with clinical outcomes are areas of great interest. The optimal route and timing of nutrient delivery are areas of intense debate and investigations. Enteral nutrition remains the preferred route for nutrient delivery. Several strategies to optimize enteral nutrition during critical illness have emerged. The role of supplemental parenteral nutrition has been highlighted, and a delayed approach appears to be beneficial. Immunonutrition cannot be currently recommended. Overall, the pediatric critical care population is heterogeneous, and a nuanced approach to individualizing nutrition support with the aim of improving clinical outcomes is necessary.

grade for the recommendation was based on the number and level of investigative studies referable to that guideline.Large studies warranting level I evidence were defined as those with ≥100 patients or those which fulfilled endpoint criteria predetermined by power analysis.The level of evidence for uncontrolled studies was determined by whether they included contemporaneous controls (level III), historical controls (level IV), or no controls (level V, equal to expert opinion).See Table 1. 1 Review papers and consensus statements were considered expert opinion and were designated the appropriate level of evidence.Meta-analyses were used to organize the information and to draw conclusions about an overall treatment effect from multiple studies on a particular subject.The grade of recommendation, however, was based on the level of evidence of the individual studies.An A or B grade recommendation required at least 1 or 2 large positive randomized trials supporting the claim, while a C grade recommendation required only 1 small supportive randomized investigation.The rationale for each guideline statement was used to clarify certain points from the studies, to identify controversies, and to provide clarity in the derivation of the final recommendation.Significant controversies in interpretation of the literature were resolved by consensus of opinion of the committee members, which in some cases led to a downgrade of the recommendation.Following an extensive review process by external reviewers, the final guideline

PRELIMINARY REMARKS (INTENT OF GUIDELINES) A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. The mission of SCCM is to secure the highest quality care for all critically ill and injured patients. Guideline Limitations: These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, practice guidelines are not intended as absolute requirements. The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival. The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines. The guidelines offer basic recommendations that are supported by review and analysis of the current literature, other national and international guidelines, and a blend of expert opinion and clinical practicality. The population of critically ill patients in an intensive care unit (ICU) is not homogeneous. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in disease severity, lack of baseline nutritional status, and insufficient statistical power for analysis. Periodic Guideline Review and Update: This particular report is an update and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009 (1). Governing bodies of both A.S.P.E.N. and SCCM have mandated that these guidelines be updated every three to five years. The database of randomized controlled trials (RCTs) that served as the platform for the analysis of the literature was assembled in a joint “harmonization process” with the Canadian Clinical Guidelines group. Once completed, each group operated separately in their interpretation of the studies and derivation of guideline recommendations (2). The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature searches by the authors through December 31, 2013. Although the committee was aware of landmark studies published after this date, these data were not included in this manuscript. The process by which the literature was evaluated necessitated a common end date for the search review. Adding a last-minute landmark trial would have introduced bias unless a formalized literature search was re-conducted for all sections of the manuscript. Target Patient Population for Guideline: The target of these guidelines is intended to be the adult (≥ 18 years) critically ill patient expected to require a length of stay (LOS) greater than 2 or 3 days in a medical ICU (MICU) or surgical ICU (SICU). The current guidelines were expanded to include a number of additional subsets of patients who met the above criteria, but were not included in the previous 2009 guidelines. Specific patient populations addressed by these expanded and updated guidelines include organ failure (pulmonary, renal, and liver), acute pancreatitis, surgical subsets (trauma, traumatic brain injury [TBI], open abdomen [OA], and burns), sepsis, postoperative major surgery, chronic critically ill, and critically ill obese. These guidelines are directed toward generalized patient populations but, like any other management strategy in the ICU, nutrition therapy should be tailored to the individual patient. Target Audience: The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill, primarily physicians, nurses, dietitians, and pharmacists. Methodology: The authors compiled clinical questions reflecting key management issues in nutrition therapy. A committee of multidisciplinary experts in clinical nutrition composed of physicians, nurses, pharmacists, and dietitians was jointly convened by the two societies. Literature searches were then performed using key words (critically ill, critical care, intensive care, nutrition, enteral, parenteral, tube feeding, and those related to assigned topics such as pancreatitis, sepsis, etc.) to evaluate the quality of evidence supporting a response to those questions, which were then used to derive a subsequent treatment recommendation. The literature search included MEDLINE, PubMed, Cochrane Database of Systemic Reviews, the National Guidelines Clearing House and an Internet search using the Google search engine for scholarly articles through an end date of December 31, 2013 (including ePub publications). While preference was given to RCTs, other forms of resource material were used to support the response, including nonrandomized cohort trials, prospective observational studies, and retrospective case series. Use of publications was limited to full-text articles available in English on adult humans. For all included RCTs, two readers completed data abstraction forms (DAFs) examining the data and assessing the quality of the research methodology to produce a shared evaluation achieved by consensus for each study (example of DAF provided in the supplemental data, Supplemental Digital Content 1, https://links.lww.com/CCM/B571). DAFs were constructed only for RCTs. When the strongest available evidence was a published meta-analysis, the studies from the meta-analysis were used to determine the quality of the evidence and assessed by two evidence assessors. The data from included trials were entered into Review Manager 5.2 software to create forest plots aggregating the effect size for each intervention and outcome (3). The key forest plots supporting the recommendation are included throughout the text and in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). No new forest plots were created when a meta-analysis was evaluated. Since release of the 2009 A.S.P.E.N. and SCCM Clinical Guidelines, the concepts of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group have A of the methodology published The data from the Review Manager analysis was to software the of evidence for a given intervention and outcome was evaluated for created each that was then by a The are provided in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). to the number of observational studies were critically but not to the However, in the observational studies were the only available evidence in a their quality of evidence was using When or observational study was available to a consensus of the group on the clinical practice was and the recommendation was on expert of recommendation for clinical practice was based on both the available evidence and the risks and benefits to patients. While each recommendation and provided the supporting a by the group and every committee was for their with the recommendation. of consensus was of authors with a particular recommendation. recommendation not this of with a consensus of other recommendations a of of or with all A.S.P.E.N. and SCCM clinical guidelines, this was to review by clinical experts from all the practice that would use the guidelines, both and to the A of the guidelines is in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). 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To determine whether hyperinsulinemia can directly reduce serum sex hormone-binding globulin (SHBG) levels in obese women with the polycystic ovary syndrome, six obese women with this disorder were studied. Before study, ovarian steroid production was suppressed in each woman by the administration of 7.5 mg of a long-acting GnRH agonist, leuprolide depot, im, on days -56, -28, and 0. This resulted in substantial reductions in serum concentrations of testosterone (from 1.72 +/- 0.29 nmol/L on day -56 to 0.32 +/- 0.09 nmol/L on day 0), non-SHBG-bound testosterone (from 104 +/- 16 pmol/L on day -56 to 19 +/- 5 pmol/L on day 0), androstenedione (from 7.25 +/- 1.65 nmol/L on day -56 to 2.78 +/- 0.94 nmol/L on day 0), estrone (from 371 +/- 71 pmol/L on day -56 to 156 +/- 29 pmol/L on day 0), estradiol (from 235 +/- 26 pmol/L on day -56 to 90 +/- 24 pmol/L on day 0), and progesterone (from 0.28 +/- 0.12 nmol/L on day -56 to 0.08 +/- 0.02 nmol/L on day 0). Serum SHBG levels, however, did not change (18.8 +/- 2.8 nmol/L on day -56 vs. 17.8 +/- 2.6 nmol/L on day 0). While continuing leuprolide treatment, the women were administered oral diazoxide (300 mg/day) for 10 days to suppress serum insulin levels. Diazoxide treatment resulted in suppressed insulin release during a 100-g oral glucose tolerance test (insulin area under the curve, 262 +/- 55 nmol/min.L on day 0 vs. 102 +/- 33 nmol/min.L on day 10; P less than 0.05) and deterioration of glucose tolerance. Serum testosterone, androstenedione, estrone, estradiol, and progesterone levels did not change during combined diazoxide and leuprolide treatment. In contrast, serum SHBG levels rose by 32% from 17.8 +/- 2.6 nmol/L on day 0 to 23.5 +/- 2.0 nmol/L on day 10 (P less than 0.003). Due primarily to the rise in serum SHBG levels, serum non-SHBG-bound testosterone levels fell by 43% from 19 +/- 5 pmol/L on day 0 to 11 +/- 4 pmol/L on day 10 (P = 0.05). These observations suggest that hyperinsulinemia directly reduces serum SHBG levels in obese women with the polycystic ovary syndrome independently of any effect on serum sex steroids.

BACKGROUND: The acquisition of genital herpes during pregnancy has been associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. The frequency of seroconversion, maternal symptoms of the disease, and the timing of its greatest effect on the outcome of pregnancy have not been systematically studied. METHODS: We studied 7046 pregnant women whom serologic tests showed to be at risk for herpes simplex virus (HSV) infection. Serum samples obtained at the first prenatal visit, at approximately 16 and 24 weeks, and during labor were tested for antibodies to HSV types 1 and 2 (HSV-1 and HSV-2) by the Western blot assay, and the results were correlated with the occurrence of antenatal genital infections. RESULTS: Ninety-four of the women became seropositive for HSV; 34 of the 94 women (36 percent) had symptoms consistent with herpes infection. Women who were initially seronegative for both HSV-1 and HSV-2 had an estimated chance of seroconversion for either virus of 3.7 percent; those who were initially seropositive only for HSV-1 had an estimated chance of HSV-2 seroconversion of 1.7 percent; and those who were initially HSV-2-seropositive had an estimated chance of zero for acquiring HSV-1 infection. Among the 60 of the 94 pregnancies for which the time of acquisition of HSV infection was known, 30 percent of the infections occurred in the first trimester, 30 percent in the second, and 40 percent in the third. HSV seroconversion completed by the time of labor was not associated with an increase in neonatal morbidity or with any cases of congenital herpes infection. However, among the infants born to nine women who acquired genital HSV infection shortly before labor, neonatal HSV infection occurred in four infants, of whom one died. CONCLUSIONS: Two percent or more of susceptible women acquire HSV infection during pregnancy. Acquisition of infection with seroconversion completed before labor does not appear to affect the outcome of pregnancy, but infection acquired near the time of labor is associated with neonatal herpes and perinatal morbidity.

Sex hormone-binding globulin (SHBG) production in humans has been thought to be stimulated by estrogens and thyroid hormone and inhibited by androgens. However, recent data indicate that SHBG production in vitro is stimulated by both androgens and estrogens. This study was designed to determine what other hormonal factors regulate SHBG production. Since hyperinsulinemia and hyperprolactinemia both occur in disease states in which low serum SHBG levels are found, the effects of insulin and PRL were compared to and/or studied in combination with estradiol (E2), T4, and testosterone (T) in a human hepatoma cell line (Hep G2). Hep G2 cells were grown to near confluence in medium including 10% fetal calf serum, and then 72-h experimental incubations were carried out which used only fetal calf serum-free medium. Compared to control incubations, both insulin (10(-8) mol/L) and PRL (10(-8) mol/L) decreased SHBG production from 65.0 +/- 0.6 (+/- SE) to 46.8 +/- 1.1 and 46.8 +/- 1.2 nmol/10(6) cells, respectively (P less than 0.01). Insulin also inhibited both E2 and T4-stimulated SHBG production. T stimulated SHBG production to the same degree as E2. Finally, both E2 and insulin significantly increased cell number, an important consideration when expressing the effect of a hormone on SHBG production in cultured cells. We conclude that insulin and PRL inhibit SHBG production and confirm that T4, T, and E2 stimulate SHBG production in vitro. These findings suggest that insulin and PRL may be important factors in the regulation of SHBG production in vivo.

Serratia species, in particular Serratia marcescens, are significant human pathogens. S. marcescens has a long and interesting taxonomic, medical experimentation, military experimentation, and human clinical infection history. The organisms in this genus, particularly S. marcescens, were long thought to be nonpathogenic. Because S. marcescens was thought to be a nonpathogen and is usually red pigmented, the U.S. military conducted experiments that attempted to ascertain the spread of this organism released over large areas. In the process, members of both the public and the military were exposed to S. marcescens, and this was uncovered by the press in the 1970s, leading to U.S. congressional hearings. S. marcescens was found to be a certain human pathogen by the mid-1960s. S. marcescens and S. liquefaciens have been isolated as causative agents of numerous outbreaks and opportunistic infections, and the association of these organisms with point sources such as medical devices and various solutions given to hospitalized patients is striking. Serratia species appear to be common environmental organisms, and this helps to explain the large number of nosocomial infections due to these bacteria. Since many nosocomial infections are caused by multiply antibiotic-resistant strains of S. marcescens, this increases the danger to hospitalized patients, and hospital personnel should be vigilant in preventing nosocomial outbreaks due to this organism. S. marcescens, and probably other species in the genus, carries several antibiotic resistance determinants and is also capable of acquiring resistance genes. S. marcescens and S. liquefaciens are usually identified well in the clinical laboratory, but the other species are rare enough that laboratory technologists may not recognize them. 16S rRNA gene sequencing may enable better identification of some of the less common Serratia species.

BACKGROUND: Few investigations include both subjective and objective measurements of the effectiveness of treatments for osteoarthritis of the knee. Beneficial interventions may decrease the disability associated with osteoarthritis and the need for more invasive treatments. OBJECTIVE: To evaluate the effectiveness of physical therapy for osteoarthritis of the knee, applied by experienced physical therapists with formal training in manual therapy. DESIGN: Randomized, controlled clinical trial. SETTING: Outpatient physical therapy department of a large military medical center. PATIENTS: 83 patients with osteoarthritis of the knee who were randomly assigned to receive treatment (n = 42; 15 men and 27 women [mean age, 60 +/- 11 years]) or placebo (n = 41; 19 men and 22 women [mean age, 62 +/- 10 years]). INTERVENTION: The treatment group received manual therapy, applied to the knee as well as to the lumbar spine, hip, and ankle as required, and performed a standardized knee exercise program in the clinic and at home. The placebo group had subtherapeutic ultrasound to the knee at an intensity of 0.1 W/cm2 with a 10% pulsed mode. Both groups were treated at the clinic twice weekly for 4 weeks. MEASUREMENTS: Distance walked in 6 minutes and sum of the function, pain, and stiffness subscores of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). A tester who was blinded to group assignment made group comparisons at the initial visit (before initiation of treatment), 4 weeks, 8 weeks, and 1 year. RESULTS: Clinically and statistically significant improvements in 6-minute walk distance and WOMAC score at 4 weeks and 8 weeks were seen in the treatment group but not the placebo group. By 8 weeks, average 6-minute walk distances had improved by 13.1% and WOMAC scores had improved by 55.8% over baseline values in the treatment group (P < 0.05). After controlling for potential confounding variables, the average distance walked in 6 minutes at 8 weeks among patients in the treatment group was 170 m (95% CI, 71 to 270 m) more than that in the placebo group and the average WOMAC scores were 599 mm higher (95% CI, 197 to 1002 mm). At 1 year, patients in the treatment group had clinically and statistically significant gains over baseline WOMAC scores and walking distance; 20% of patients in the placebo group and 5% of patients in the treatment group had undergone knee arthroplasty. CONCLUSIONS: A combination of manual physical therapy and supervised exercise yields functional benefits for patients with osteoarthritis of the knee and may delay or prevent the need for surgical intervention.

BACKGROUND: Hemorrhage remains a leading cause of death in both civilian and military trauma patients. The HemCon chitosan-based hemostatic dressing is approved by the US Food and Drug Administration (FDA) for hemorrhage control. Animal data have shown the HemCon dressing to reduce hemorrhage and improve survival. The purpose of this article is to report preliminary results of the hemostatic efficacy of the HemCon dressing used in the prehospital setting on combat casualties. METHODS: A request for case information on use of HemCon dressings in Operation Iraqi Freedom and Operation Enduring Freedom was sent to deployed Special Forces combat medics, physicians, and physician assistants. RESULTS: Sixty-eight uses of the HemCon dressing were reported and reviewed by two US Army physicians. Four of the 68 cases were determined duplicative resulting in a total of 64 combat uses. Dressings were utilized externally on the chest, groin, buttock, and abdomen in 25 cases; on extremities in 35 cases; and on neck or facial wounds in 4 cases. In 66% of cases, dressings were utilized following gauze failure and were 100% successful. In 62 (97%) of the cases, the use of the HemCon dressing resulted in cessation of bleeding or improvement in hemostasis. There were two reported dressing failures that occurred with blind application of bandages up into large cavitational injuries. Dressings were reported to be most useful on areas where tourniquets could not be applied to control bleeding. The dressings were reported to be most difficult to use in extremity injuries where they could not be placed easily onto or into the wounds. No complications or adverse events were reported. CONCLUSION: This report on the field use of the HemCon dressing by medics suggests that it is a useful hemostatic dressing for prehospital combat casualties and supports further study to confirm efficacy.

BACKGROUND: Increased understanding of the pathophysiology of the acute coagulopathy of trauma has lead many to question the current transfusion approach to hemorrhagic shock. We hypothesized that warm fresh whole blood (WFWB) transfusion would be associated with improved survival in patients with trauma compared with those transfused only stored component therapy (CT). METHODS: We retrospectively studied US Military combat casualty patients transfused >or=1 unit of red blood cells (RBCs). The following two groups of patients were compared: (1) WFWB, who were transfused WFWB, RBCs, and plasma but not apheresis platelets and (2) CT, who were transfused RBC, plasma, and apheresis platelets but not WFWB. The primary outcomes were 24-hour and 30-day survival. RESULTS: Of 354 patients analyzed there were 100 in the WFWB and 254 in the CT group. Patients in both groups had similar severity of injury determined by admission eye, verbal, and motor Glasgow Coma Score, base deficit, international normalized ratio, hemoglobin, systolic blood pressure, and injury severity score. Both 24-hour and 30-day survival were higher in the WFWB cohort compared with CT patients, 96 of 100 (96%) versus 223 of 254 (88%), (p = 0.018) and 95% to 82%, (p = 0.002), respectively. An increased amount (825 mL) of additives and anticoagulants were administered to the CT compared with the WFWB group, (p < 0.001). Upon multivariate logistic regression the use of WFWB and the volume of WFWB transfused was independently associated with improved 30-day survival. CONCLUSIONS: In patients with trauma with hemorrhagic shock, resuscitation strategies that include WFWB may improve 30-day survival, and may be a result of less anticoagulants and additives with WFWB use in this population.

BACKGROUND: To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research. METHODS: Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use. RESULTS: Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56%, 73%; race: 69% White, 97% Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50%, 50%; race: 58% White, 100% Mestizo. SYMPTOMS: Symptoms identified by >50%: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument. CONCLUSIONS: Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.

PURPOSE: Donabedian's 1966 framework of structure, process, and outcome has guided three decades of study in the United States of the elements needed to evaluate and compare medical care quality. Donabedian's perspective was essentially linear, assuming that structures affect processes, which in turn affect outcomes. Patient characteristics are sometimes considered as mediating outcomes and clinical interventions are considered to be processes. A model is presented in the following article that relates multiple factors affecting quality of care to desired outcomes. It extends previous models by positing dynamic relationships with indicators that not only act upon, but reciprocally affect the various components. SCOPE AND SOURCES: The proposed model was derived from a synthesis of the authors' experience in quality of care practice and research, as well as selected previous theories. CONCLUSIONS: The quality health outcomes model is sufficiently broad (a) to guide development of databases for quality improvement and outcomes management, (b) to suggest key variables in clinical intervention research, and (c) to provide a framework for outcomes research and outcomes management that compares not only treatment options, but organizational or system level interventions. The model also has several policy implications.

BACKGROUND AND PURPOSE: Manual therapy and exercise have not previously been compared with a home exercise program for patients with osteoarthritis (OA) of the knee. The purpose of this study was to compare outcomes between a home-based physical therapy program and a clinically based physical therapy program. SUBJECTS: One hundred thirty-four subjects with OA of the knee were randomly assigned to a clinic treatment group (n=66; 61% female, 39% male; mean age [+/-SD]=64+/-10 years) or a home exercise group (n=68, 71% female, 29% male; mean age [+/-SD]=62+/-9 years). METHODS: Subjects in the clinic treatment group received supervised exercise, individualized manual therapy, and a home exercise program over a 4-week period. Subjects in the home exercise group received the same home exercise program initially, reinforced at a clinic visit 2 weeks later. Measured outcomes were the distance walked in 6 minutes and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Both groups showed clinically and statistically significant improvements in 6-minute walk distances and WOMAC scores at 4 weeks; improvements were still evident in both groups at 8 weeks. By 4 weeks, WOMAC scores had improved by 52% in the clinic treatment group and by 26% in the home exercise group. Average 6-minute walk distances had improved about 10% in both groups. At 1 year, both groups were substantially and about equally improved over baseline measurements. Subjects in the clinic treatment group were less likely to be taking medications for their arthritis and were more satisfied with the overall outcome of their rehabilitative treatment compared with subjects in the home exercise group. DISCUSSION AND CONCLUSION: Although both groups improved by 1 month, subjects in the clinic treatment group achieved about twice as much improvement in WOMAC scores than subjects who performed similar unsupervised exercises at home. Equivalent maintenance of improvements at 1 year was presumably due to both groups continuing the identical home exercise program. The results indicate that a home exercise program for patients with OA of the knee provides important benefit. Adding a small number of additional clinical visits for the application of manual therapy and supervised exercise adds greater symptomatic relief.

BACKGROUND: Up to 9% of casualties killed in action during the Vietnam War died from exsanguination from extremity injuries. Retrospective reviews of prehospital tourniquet use in World War II and by the Israeli Defense Forces revealed improvements in extremity hemorrhage control and very few adverse limb outcomes when tourniquet times are less than 6 hours. HYPOTHESIS: We hypothesized that prehospital tourniquet use decreased hemorrhage from extremity injuries and saved lives, and was not associated with a substantial increase in adverse limb outcomes. METHODS: This was an institutional review board-approved, retrospective review of the 31st combat support hospital for 1 year during Operation Iraqi Freedom. Inclusion criteria were any patient with a traumatic amputation, major extremity vascular injury, or documented prehospital tourniquet. RESULTS: Among 3,444 total admissions, 165 patients met inclusion criteria. Sixty-seven patients had prehospital tourniquets (TK); 98 patients had severe extremity injuries but no prehospital tourniquet (No TK). Extremity Acute Injury Scores were the same (3.5 TK vs. 3.4 No TK) in both groups. Differences (p < 0.05) were noted in the numbers of patients with arm injuries (16.2% TK vs. 30.6% No TK), injuries requiring vascular reconstruction (29.9% TK vs. 52.5% No TK), traumatic amputations (41.8% TK vs. 26.3% No TK), and in those patients with adequate bleeding control on arrival (83% TK vs. 60% No TK). Secondary amputation rates (4 (6.0%) TK vs. 9 (9.1%) No TK); and mortality (3 (4.4%) TK vs. 4 (4.1%) No TK) did not differ. Tourniquet use was not deemed responsible for subsequent amputation in severely mangled extremities. Analysis revealed that four of seven deaths were potentially preventable with functional prehospital tourniquet placement. CONCLUSIONS: Prehospital tourniquet use was associated with improved hemorrhage control, particularly in the worse injured (Injury Severity Score >15) subset of patients. Fifty-seven percent of the deaths might have been prevented by earlier tourniquet use. There were no early adverse outcomes related to tourniquet use.

We examined the frequency of acquisition of bacterial pathogens on investigators' hands after contacting environmental surfaces near hospitalized patients. Hand imprint cultures were positive for one or more pathogens after contacting surfaces near 34 (53%) of 64 study patients, with Staphylococcus aureus and vancomycin-resistant Enterococcus being the most common isolates.

CONTEXT: The effects of war-zone deployment on neuropsychological health remain poorly understood. Neuropsychological performance deficits serve as sensitive measures of neural dysfunction and are often associated with psychosocial and occupational problems. Previous studies have not conducted objective neuropsychological assessments both before and after a major war-zone deployment. OBJECTIVE: To examine objective neuropsychological outcomes of Iraq War deployment in a large military cohort. DESIGN, SETTING, AND PARTICIPANTS: The Neurocognition Deployment Health Study, a prospective, cohort-controlled study conducted at military installations. This report centers on 961 male and female active-duty Army soldiers drawn from the larger cohort. Deploying Army soldiers (n = 654) were examined prior to deployment to Iraq (April-December 2003) and shortly after return (within a mean of 73 days [median, 75 days]; January-May 2005) from Iraq deployment. A comparison group of soldiers (n = 307) similar in military characteristics but not deploying overseas during the study was assessed in sessions timed to be as close as possible to the assessment of deployers. Military unit sampling procedures facilitated representation of combat, combat support, and combat service support functions among both deployers and nondeployers. MAIN OUTCOME MEASURES: Individually administered, performance-based neuropsychological tasks. Estimates (beta; the unstandardized parameter estimate) for the absolute differences in adjusted mean outcome scores between deployed and nondeployed groups were determined using generalized estimating equations. RESULTS: Multiple linear regression analyses adjusted for battalion membership revealed that Iraq deployment, compared with nondeployment, was associated with neuropsychological compromise on tasks of sustained attention (beta = 0.11; P<.001), verbal learning (beta = -1.51; P = .003), and visual-spatial memory (beta = -3.82; P<.001). Iraq deployment was also associated with increased negative state affect on measures of confusion (beta = 1.40; P<.001) and tension (beta = 1.24; P<.001). In contrast, deployment was associated with improved simple reaction time (beta = 4.30; P = .003). Deployment effects remained statistically significant after taking into account deployment-related head injury and stress and depression symptoms. CONCLUSIONS: Deployment to Iraq is associated with increased risk of neuropsychological compromise. Findings point to the need to investigate further the impact of deployment on neural functioning. Public health implications include consideration of neuropsychological compromise in health prevention and postdeployment clinical and occupational management.

BACKGROUND: To treat the coagulopathy of trauma, some have suggested early and aggressive use of cryoprecipitate as a source of fibrinogen. Our objective was to determine whether increased ratios of fibrinogen to red blood cells (RBCs) decreased mortality in combat casualties requiring massive transfusion. METHODS: We performed a retrospective chart review of 252 patients at a U.S. Army combat support hospital who received a massive transfusion (>or=10 units of RBCs in 24 hours). The typical amount of fibrinogen within each blood product was used to calculate the fibrinogen-to-RBC (F:R) ratio transfused for each patient. Two groups of patients who received either a low (<0.2 g fibrinogen/RBC Unit) or high (>or=0.2 g fibrinogen/RBC Unit) F:R ratio were identified. Mortality rates and the cause of death were compared between these groups, and logistic regression was used to determine if the F:R ratio was independently associated with survival. RESULTS: Two-hundred and fifty-two patients who received a massive transfusion with a mean (SD) ISS of 21 (+/-10) and an overall mortality of 75 of 252 (30%) were included. The mean (SD) F:R ratios transfused for the low and high groups were 0.1 grams/Unit (+/-0.06), and 0.48 grams/Unit (+/-0.2), respectively (p < 0.001). Mortality was 27 of 52 (52%) and 48 of 200 (24%) in the low and high F:R ratio groups respectively (p < 0.001). Additional variables associated with survival were admission temperature, systolic blood pressure, hemoglobin, International Normalized Ratio (INR), base deficit, platelet concentration and Combined Injury Severity Score (ISS). Upon logistic regression, the F:R ratio was independently associated with mortality (odds ratio 0.37, 95% confidence interval 0.171-0.812, p = 0.013). The incidence of death from hemorrhage was higher in the low F:R group, 23/27 (85%), compared to the high F:R group, 21/48 (44%) (p < 0.001). CONCLUSIONS: In patients with combat-related trauma requiring massive transfusion, the transfusion of an increased fibrinogen: RBC ratio was independently associated with improved survival to hospital discharge, primarily by decreasing death from hemorrhage. Prospective studies are needed to evaluate the best source of fibrinogen and the optimal empiric ratio of fibrinogen to RBCs in patients requiring massive transfusion.

Endometrial cancer is the most common gynecologic malignancy. It is the fourth most common cancer in women in the United States after breast, lung, and colorectal cancers. Risk factors are related to excessive unopposed exposure of the endometrium to estrogen, including unopposed estrogen therapy, early menarche, late menopause, tamoxifen therapy, nulliparity, infertility or failure to ovulate, and polycystic ovary syndrome. Additional risk factors are increasing age, obesity, hypertension, diabetes mellitus, and hereditary nonpolyposis colorectal cancer. The most common presentation for endometrial cancer is postmenopausal bleeding. The American Cancer Society recommends that all women older than 65 years be informed of the risks and symptoms of endometrial cancer and advised to seek evaluation if symptoms occur. There is no evidence to support endometrial cancer screening in asymptomatic women. Evaluation of a patient with suspected disease should include a pregnancy test in women of childbearing age, complete blood count, and prothrombin time and partial thromboplastin time if bleeding is heavy. Most guidelines recommend either transvaginal ultrasonography or endometrial biopsy as the initial study. The mainstay of treatment for endometrial cancer is total hysterectomy with bilateral salpingo-oophorectomy. Radiation and chemotherapy can also play a role in treatment. Low- to medium-risk endometrial hyperplasia can be treated with nonsurgical options. Survival is generally defined by the stage of the disease and histology, with most patients at stage I and II having a favorable prognosis. Controlling risk factors such as obesity, diabetes, and hypertension could play a role in the prevention of endometrial cancer.

Autism has been described in association with a variety of medical and genetic conditions. We previously reported on a patient whose clinical phenotype was compatible with both fetal valproate syndrome (FVS) and autism. Here we present five additional patients with FVS and autism. In all five of our patients, there was evidence of cognitive deficits, manifestations of autism, and typical phenotypic characteristics of FVS. The association between this known teratogen and autism has both clinical and research implications.

Many Mendelian traits are likely unrecognized owing to absence of traditional segregation patterns in families due to causation by de novo mutations, incomplete penetrance, and/or variable expressivity. Genome-level sequencing can overcome these complications. Extreme childhood phenotypes are promising candidates for new Mendelian traits. One example is early onset hypertension, a rare form of a global cause of morbidity and mortality. We performed exome sequencing of 40 unrelated subjects with hypertension due to primary aldosteronism by age 10. Five subjects (12.5%) shared the identical, previously unidentified, heterozygous CACNA1H(M1549V) mutation. Two mutations were demonstrated to be de novo events, and all mutations occurred independently. CACNA1H encodes a voltage-gated calcium channel (CaV3.2) expressed in adrenal glomerulosa. CACNA1H(M1549V) showed drastically impaired channel inactivation and activation at more hyperpolarized potentials, producing increased intracellular Ca(2+), the signal for aldosterone production. This mutation explains disease pathogenesis and provides new insight into mechanisms mediating aldosterone production and hypertension.