Naval Medical Center Portsmouth

The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007. These guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in PONV under the auspices of the Society for Ambulatory Anesthesia. The panel members critically and systematically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. These guidelines identify patients at risk for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic single therapy and combination therapy regimens for PONV prophylaxis, including nonpharmacologic approaches; recommend strategies for treatment of PONV when it occurs; provide an algorithm for the management of individuals at increased risk for PONV as well as steps to ensure PONV prevention and treatment are implemented in the clinical setting.

The incidence of noncontact anterior cruciate ligament injuries in young to middle-aged athletes remains high. Despite early diagnosis and appropriate operative and nonoperative treatments, posttraumatic degenerative arthritis may develop. In a meeting in Atlanta, Georgia (January 2005), sponsored by the American Orthopaedic Society for Sports Medicine, a group of physicians, physical therapists, athletic trainers, biomechanists, epidemiologists, and other scientists interested in this area of research met to review current knowledge on risk factors associated with noncontact anterior cruciate ligament injuries, anterior cruciate ligament injury biomechanics, and existing anterior cruciate ligament prevention programs. This article reports on the presentations, discussions, and recommendations of this group.

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.

Ticks, including many that bite humans, are hosts to several obligate intracellular bacteria in the spotted fever group (SFG) of the genus Rickettsia. Only Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, has been definitively associated with disease in humans in the United States. Herein we describe disease in a human caused by Rickettsia parkeri, an SFG rickettsia first identified 160 years ago in Gulf Coast ticks (Amblyomma maculatum) collected from the southern United States. Confirmation of the infection was accomplished using serological testing, immunohistochemical staining, cell culture isolation, and molecular methods. Application of specific laboratory assays to clinical specimens obtained from patients with febrile, eschar-associated illnesses following a tick bite may identify additional cases of R. parkeri rickettsiosis and possibly other novel SFG rickettsioses in the United States.

UNLABELLED: In the first paper in this section, authors from the Mayo Clinic describe their experience and 15-year outcomes in the controversial subject of radical prostatectomy in patients with clinical T3 prostate cancer. The findings were interesting in many respects, but the authors concluded that radical prostatectomy as part of multimodal treatment for patients with clinical T3 disease offers cancer control and good survival rates. There follows a series of papers on both prostate cancer and bladder cancer, but the final paper in this section from the UK attempts to define the accuracy of urologists and oncologists in assessing patient life-expectancy. Using various methods they found that, rather disappointingly, doctors were poor at predicting 10-year survival, leading to the possible outcome that some patients may be denied treatment after a pessimistic assessment of life-expectancy. OBJECTIVE: To report a long-term experience with extirpative surgery in patients presenting with locally advanced (cT3) prostate cancer, as the best management of such patients remains a problem. PATIENTS AND METHODS: In a single-institution retrospective study identifying 5652 men who had radical prostatectomy (RP) for histologically confirmed prostate cancer since the advent of prostate-specific antigen (PSA) testing (1987-97), 15% (842) had RP for cT3 disease. The median follow-up of these men was 10.3 years. Cancer-specific, overall and disease-free survival was plotted and compared with those of patients having RP for cT2 disease during the same period. Perioperative morbidity, continence and erectile function rates were examined, with a multivariate analysis for risk factors of disease recurrence. RESULTS: Freedom from local or systemic disease at 5, 10, and 15 years after RP for cT3 disease was 85%, 73% and 67%; the respective cancer-specific survival rates were 95%, 90% and 79%. Significantly many men who did not receive neoadjuvant therapy (27%) were clinically over-staged (pT2) and most men with pT3 disease (78%) received adjuvant therapy. The mean time to adjuvant therapy after RP was not significantly different between men with cT3 and cT2 disease (4.0 and 4.3 years). Pathological grade (> or =7), positive surgical margins, and nondiploid chromatin were all independently associated with a significant risk for clinical disease recurrence, while preoperative PSA level had little effect on outcome. Complications and continence rates after RP in patients with cT3 mirrored those in patients with cT2 disease. CONCLUSIONS: Significantly many patients with cT3 prostate cancer are overstaged (pT2) in the PSA era. RP as part of a multimodal treatment strategy for patients with cT3 disease offers cancer control and survival rates approaching those achieved for cT2 disease. Pathological grade, ploidy and margin status are all significant predictors of outcome after RP. Complications and incontinence rates in patients with cT3 disease mirror those after RP for cT2 disease.

METHODS: Comparisons of death-related variables during the 3 eras were performed. RESULTS: The number of deaths declined over the study period, with 987 deaths in the pre-HAART era, 159 deaths in the early HAART era (1997-1999), and 78 deaths in the late HAART era (2000-2003) (P < 0.01). The annual death rate peaked in 1995 (10.3 per 100 patients) and then declined to <2 deaths per 100 persons in the late HAART era (P < 0.01). The proportion of deaths attributable to infection decreased, but infection remained the leading cause of death in our cohort, followed by cancer. Of those who died, there was an increasing proportion of non-HIV-related deaths (32% vs. 9%; P < 0.01), including cardiac disease (22% vs. 8%; P < 0.01) and trauma (8% vs. 2%; P = 0.01) in the post-HAART versus pre-HAART era. Despite the absence of intravenous drug use and the low prevalence of hepatitis C coinfection in our cohort, an increasing proportion of deaths in the HAART era were attributable to liver disease, although the numbers are small. CONCLUSIONS: Despite increasing concerns regarding antiretroviral resistance, the death rate among HIV-infected persons in our cohort continues to decline. Our data show a lower death rate than that reported among many other US HIV-infected populations; this may be the result of open access to health care. A shift in the causes of death toward non-HIV-related causes suggests that a more comprehensive health care approach may be needed for optimal life expectancy; this may include enhanced screening for malignancy and heart disease as well as preventive measures for liver disease and accidents.

VACANTI, CHARLES J. LCDR, MC, USN; VanHOUTEN, ROBERT J. CAPT MC, USN; HILL, ROBERT C. M.D. Author Information

BACKGROUND: Increased external rotation and decreased internal rotation have been noted to occur progressively in the throwing shoulder of baseball pitchers. HYPOTHESIS: Proximal remodeling of the humerus contributes to the rotational asymmetry between shoulders in pitchers. STUDY DESIGN: Descriptive anatomic study. METHODS: Both shoulders of 19 male college baseball pitchers were evaluated and retroversion of the humerus calculated by using the technique of Söderlund et al. Measurements were taken of passive glenohumeral external rotation at 0 degrees and 90 degrees of abduction and internal rotation at 90 degrees of abduction under a 3.5-kg load. Subjects completed a questionnaire on the amount and duration of overhead throwing performed during the ages 8 through 16 years. RESULTS: All of the subjects had greater external rotation at 0 degrees and 90 degrees of abduction, decreased internal rotation at 90 degrees of abduction, and greater retroversion of the humerus in their dominant compared with nondominant shoulders. A significant difference was found between dominant and nondominant external rotation at 0 degrees and 90 degrees of abduction, internal rotation at 90 degrees of abduction, and retroversion of the humerus. In the dominant arm, there was a significant correlation between retroversion of the humerus and external rotation at 0 degrees and 90 degrees of abduction. There was also a significant correlation between the side-to-side difference in retroversion of the humerus compared with the side-to-side difference in external rotation at 90 degrees of abduction. CONCLUSIONS: Rotational changes in the throwing shoulder are due to bony as well as soft tissue adaptations.

OBJECTIVES: Uncontrolled hemorrhage remains a leading cause of traumatic death. Several topical adjunct agents have been shown to be effective in controlling hemorrhage, and two, chitosan wafer dressing (HemCon [HC]) and zeolite powder dressing (QuikClot [QC]), are being utilized regularly on the battlefield. However, recent literature reviews have concluded that no ideal topical agent exists. The authors compared a new chitosan granule dressing (CELOX [CX]) to HC, QC and standard dressing in a lethal hemorrhagic groin injury. METHODS: A complex groin injury with transection of the femoral vessels and 3 minutes of uncontrolled hemorrhage was created in 48 swine. The animals were then randomized to four treatment groups (12 animals each). Group 1 included standard gauze dressing (SD); Group 2, CX; Group 3, HC; and Group 4, QC. Each agent was applied with 5 minutes of manual pressure followed by a standard field compression dressing. Hetastarch (500 mL) was infused over 30 minutes. Hemodynamic parameters were recorded over 180 minutes. Primary endpoints included rebleed and death. RESULTS: CX reduced rebleeding to 0% (p < 0.001), HC to 33% (95% CI = 19.7% to 46.3%, p = 0.038), and QC to 8% (95% CI = 3.3% to 15.7%, p = 0.001), compared to 83% (95% CI = 72.4% to 93.6%) for SD. CX improved survival to 100% compared to SD at 50% (95% CI = 35.9% to 64.2%, p = 0.018). Survival for HC (67%) (95% CI = 53.7% to 80.3%) and QC (92%; 95% CI = 84.3% to 99.7%) did not differ from SD. CONCLUSIONS: In this porcine model of uncontrolled hemorrhage, CX improved hemorrhage control and survival. CELOX is a viable alternative for the treatment of severe hemorrhage.

Durable control of human immunodeficiency virus (HIV) replication and lack of disease progression in the absence of antiretroviral therapy were studied in a military cohort of 4586 subjects. We examined groups of elite controllers (ie, subjects with plasma HIV RNA levels of <50 copies/mL; prevalence, 0.55% [95% confidence interval {CI}, 0.35%-0.80%]), viremic controllers (ie, subjects with plasma HIV RNA levels of 50-2000 copies/mL; prevalence, 3.34% [95% CI, 2.83%-3.91%]), and subjects with a lack of disease progression (ie, long-term nonprogressors [LTNPs]) through 7 years of follow-up (LTNP7s; prevalence, 3.32% [95% CI, 2.70%-4.01%]) or 10 years of follow-up (LTNP10s; prevalence, 2.04% [95% CI, 1.52%-2.68%]). For elite and viremic controllers, spontaneous virologic control was established early and was typically observed when the initial viral load measurement was obtained within 1 year of estimated seroconversion. Elite controllers had favorable time to development of AIDS (P=.048), a CD4 cell count of 350 cells/microL (P= .009), and more-stable CD4 cell trends, compared with viremic controllers. LTNPs defined by 10-year versus 7-year criteria had a longer survival time (P=.001), even after adjustment for differing periods of invulnerability (P= .042). Definitions of controllers and LTNPs describe distinct populations whose differing clinical outcomes improve with the stringency of criteria, underscoring the need for comparability between study populations.

Background. Rickettsia parkeri rickettsiosis, a recently identified spotted fever transmitted by the Gulf Coast tick (Amblyomma maculatum), was first described in 2004. We summarize the clinical and epidemiological features of 12 patients in the United States with confirmed or probable disease attributable to R. parkeri and comment on distinctions between R. parkeri rickettsiosis and other United States rickettsioses.

OBJECTIVE: To describe trends in incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) during the HIV epidemic and to evaluate predictors, including the impact of antiretroviral therapy, of cancer development. DESIGN: Retrospective analysis of a multicenter, prospective natural history study including 4498 HIV-infected US military beneficiaries with 33 486 person-years of follow-up. METHODS: Predictors evaluated included demographics, clinical data, time-updated CD4 cell counts, HIV viral loads, and antiretroviral history. Time periods were classified as early pre (1984-1990), late pre (1991-1995), early post (1996-2000), and late post (2001-2006) HAART eras. Cox proportional hazard models were used to evaluate the association of specific factors with cancer. RESULTS: Ten percent of HIV-infected persons developed cancer. ADC rates increased between the early and late pre-HAART eras (7.6 and 14.2 cases per 1000 person-years) and have since declined from 5.4 to 2.7 in the early and late HAART eras, respectively (P < 0.001). Rates of NADCs have risen over the four periods (2.9, 2.8, 4.2, 6.7, P = 0.0004). During the late HAART era, 71% of cancers were NADCs. Predictors for ADCs included low CD4 cell count, noncancer AIDS diagnosis, and lack of HAART. NADCs were predicted by increasing age and white race (due to skin cancers). CONCLUSION: Although the rate of ADCs continues to fall, the rate of NADCs is rising and now accounts for the majority of cancers in HIV-infected persons. The development of NADCs is associated with increasing age among HIV patients. HAART use is protective for ADCs, but did not significantly impact NADCs.

The extent of blockade when four different techniques were used for blocking the lumbar plexus was prospectively evaluated in 80 adult patients. The extent of blockade was measured by testing motor function of all nerves except the lateral and posterior femoral cutaneous nerves, which were evaluated by pinprick response. The posterior approaches of Dekrey at L3 (n = 20) and Chayen at L4-5 (n = 20) proved similarly effective in producing blockade of the femoral, obturator, and lateral femoral cutaneous nerves, as well as the nerves to the psoas muscle. The anterior approach of Winnie (femoral sheath or 3-in-1 block) using paresthesia (n = 20) or peripheral nerve stimulation (n = 20) proved effective in producing blockade of the femoral and lateral femoral cutaneous nerves, but ineffective for obturator nerve blockade. None of the four techniques produced blockade of the sacral plexus. Perhaps our means of assessing blockade (motor) is what produced the difference between our findings and those of others.

BACKGROUND: The prevalence and factors associated with overweight/obesity among human immunodeficiency virus (HIV)-infected persons are unknown. METHODS: We evaluated prospective data from a U.S. Military HIV Natural History Study (1985-2004) consisting of early diagnosed patients. Statistics included multivariate linear regression and longitudinal linear mixed effects models. RESULTS: Of 1682 patients, 2% were underweight, 37% were overweight, and 9% were obese at HIV diagnosis. Multivariate predictors of a higher body mass index (BMI) at diagnosis included more recent year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05). The majority of patients (62%) gained weight during HIV infection. Multivariate factors associated with a greater increase in BMI during HIV infection included more recent year of diagnosis, lower BMI at diagnosis, higher CD4 count, lower HIV RNA level, lack of AIDS diagnosis, and longer HIV duration (all p<0.05). Nucleoside agents were associated with less weight gain; other drug classes had no significant impact on weight change in the HAART era. CONCLUSIONS: HIV-infected patients are increasingly overweight/obese at diagnosis and during HIV infection. Weight gain appears to reflect improved health status and mirror trends in the general population. Weight management programs may be important components of HIV care.

Recent advances in the operative management of aortic aneurysms have resulted in a decreased rate of morbidity and mortality. In 1972, we hypothesized that a further reduction in operative mortality might be obtained with controlled perioperative fluid management based on data provided by the thermistor-tipped pulmonary artery balloon catheter. From 1972 to 1979 a flow directed pulmonary artery catheter was inserted in each of 110 consecutive patients prior to elective or urgent repair of nonruptured infrarenal aortic aneurysms. The slope of the left ventricular performance curve was determined preoperatively by incremental infusions of salt-poor albumin and Ringer's lactate solution. With each increase in the pulmonary arterial wedge pressure (PAWP), the cardiac index (CI) was measured. The PAWP was then maintained intra- and postoperatively at levels providing optimal left ventricular performance for the individual patient. There were no 30-day operative deaths among the patients in this series and only one in-hospital mortality (0.9%), four months following surgery. The five-year cumulative survival rate for patients in the present series was 84%, a rate which does not differ significantly from that expected for a normal age-corrected population. Since the patient population was unselected and there were no substantial alterations in operative technique during the present period, these improved results support the hypothesis that operative mortality attending the elective or urgent repair of abdominal aortic aneurysm can be minimized by maintenance of optimal cardiac performance with careful attention to fluid therapy during the perioperative period.

PURPOSE: Hormonal therapy (HT) is the current mainstay of systemic treatment for prostate specific antigen (PSA) only recurrence (PSAR), however, there is virtually no published literature comparing HT to observation in the clinical setting. The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational database to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach. MATERIALS AND METHODS: Of 5,382 men in the database who underwent primary radical prostatectomy (RP), 4,967 patients were treated in the PSA-era between 1988 and December 2002. Of those patients 1,352 men who had PSAR (PSA after surgery greater than 0.2 ng/ml) and had postoperative followup greater than 6 months were used as the study cohort. These patients were further divided into an early HT group in which patients (355) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients (997) who received no HT before clinical metastasis or by current followup. The primary end point was the development of clinical metastases. Of the 1,352 patients with PSAR clinical metastases developed in 103 (7.6%). Patients were also stratified by surgical Gleason sum, PSA doubling time and timing of recurrence. Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome. RESULTS: Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less (Hazards ratio = 2.12, p = 0.01). However, in the overall cohort early HT did not impact clinical metastases. Race, age at RP and PSA at diagnosis had no effect on metastasis-free survival (p >0.05). CONCLUSIONS: The retrospective observational multicenter database analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup. Further study with longer followup and randomized trials are needed to address this important issue.

BACKGROUND: The objective of this study was to determine the rates and predictors of non-AIDS-defining cancers (NADCs) among a cohort of human immunodeficiency virus (HIV)-infected individuals. METHODS: The authors conducted a retrospective study of 4144 HIV-infected individuals who had 26,916 person-years of follow-up and who had open access to medical care at 1 of the United States military HIV clinics during the years 1988-2003. Cancer incidence rates were race specific and were adjusted for age; these were compared with national rates using logistic regression to assess predictors of NADC development. RESULTS: One hundred thirty-three NADCs were diagnosed with a rate of 980 diagnoses per 100,000 person-years. The most frequent NADCs were skin carcinomas (basal cell and squamous cell), Hodgkin disease, and anal carcinoma. The results showed that there were higher rates of melanoma, basal and squamous cell skin carcinomas, anal carcinoma, prostate carcinoma, and Hodgkin disease among the HIV-infected cohort compared with age-adjusted rates for the general United States population. Predictors of NADCs included age older than 40 years (odds ratio [OR], 12.2; P < 0.001), Caucasian/non-Hispanic race (OR, 2.1; P < 0.001), longer duration of HIV infection (OR, 1.2; P < 0.001), and a history of opportunistic infection (OR, 2.5; P < 0.001). The use of highly active antiretroviral therapy (HAART) was associated with lower rates of NADCs (OR, 0.21; P < 0.001). A low CD4 nadir or CD4 count at diagnosis (< 200 cells/mL) was not predictive of NADCs. CONCLUSIONS: The most frequent NADCs were primary skin malignancies. Melanoma, basal and squamous cell skin carcinomas, anal carcinoma, prostate carcinoma, and Hodgkin disease occurred at higher rates among HIV-infected individuals. The implementation of screening programs for these malignancies should be considered. Most risk factors for the development of NADCs are nonmodifiable; however, the use of HAART appeared to be beneficial in protecting against the development of malignant disease.

We report an outbreak of 235 community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections among military recruits. In this unique environment, the close contact between recruits and the physical demands of training may have contributed to the spread of MRSA. Control measures included improved hygiene and aggressive clinical treatment.

BACKGROUND: Clinical trials have shown cardiovascular benefits and potential risks from sodium glucose cotransporter 2 inhibitors (SGLT2i). Trials may have limited ability to address individual end points or safety concerns. METHODS: We performed a population-based cohort study among patients with type 2 diabetes mellitus with established cardiovascular disease newly initiated on antihyperglycemic agents within the US Department of Defense Military Health System between April 1, 2013, and December 31, 2016. Incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) for time to first composite end point of all-cause mortality and hospitalization for heart failure event, major adverse cardiovascular events (defined as all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke), and individual end points were evaluated using conditional Cox models comparing new SGLT2i users with other antihyperglycemic agents. The exploratory safety end point was below-knee lower extremity amputation. Intent-to-treat and on-treatment analyses were performed. RESULTS: After propensity matching, 25 258 patients were followed for a median of 1.6 years. Compared with non-SGLT2i, initiation of SGLT2i was associated with a lower rate of all-cause mortality and hospitalization for heart failure (1.73 versus 3.01 events per 100 person-years; HR, 0.57; 95% CI, 0.50-0.65) and major adverse cardiovascular events (2.31 versus 3.45 events per 100 person-years; HR, 0.67; 95% CI, 0.60-0.75). SGLT2i initiation was also associated with an ≈2-fold higher risk of below-knee lower extremity amputation (0.17 versus 0.09 events per 100 person-years; HR, 1.99; 95% CI, 1.12-3.51). Because of the disproportionate canagliflozin exposure in the database, the majority of amputations were observed on canagliflozin. Results were consistent in the on-treatment analysis. CONCLUSIONS: In this high-risk cohort, initiation of SGLT2i was associated with lower risk of all-cause mortality, hospitalization for heart failure, and major adverse cardiovascular events and higher risk of below-knee lower extremity amputation. Findings underscore the potential benefit and risks to be aware of when initiating SGLT2i. It remains unclear whether the below-knee lower extremity amputation risk extends across the class of medication, because the study was not powered to make comparisons among individual treatments.

The clinical syndrome of aspirin-exacerbated respiratory disease (AERD) is a condition where inhibition of cyclooxygenase-1 (COX-1) induces attacks of upper and lower airway reactions, including rhinorrhea and varying degrees of bronchospasm and laryngospasm. Although the reaction is not IgE-mediated, patients can also present with anaphylactic hypersensitivity reactions, including hypotension, after exposure to COX-1 inhibiting drugs. All patients with AERD have underlying nasal polyps and intractable sinus disease which may be difficult to treat with standard medical and surgical interventions. This review article focuses on the management of AERD patients with a particular emphasis on aspirin desensitization and continuous treatment with aspirin.