David N. Cowan

Hemangiopericytoma of the central nervous system: A review of 94 cases

Ninety-four cases of central nervous system hemangiopericytoma (CNS-HPC) are reported. Hemangiopericytoma was found more commonly in men than in women. The mean age at diagnosis was 40.9 years for men and 47 years for women. The tumor was found throughout the entire CNS, usually superficially and closely related to the meninges. Based on multiple histologic variables, the original tumors were divided into differentiated (n = 67) and anaplastic (n = 27). Anaplastic HPC was characterized by the presence of necrosis and/or greater than five mitoses per ten 400x microscopic fields, and at least two of the following microscopic features: hemorrhage, moderate to high nuclear atypia, and moderate to high cellularity. For those patients known to be dead, median survival time was 144 months for differentiated HPC and 62 months for anaplastic HPC. Fifty-seven (60.6%) patients had one or more recurrences and metastasis developed in 22 (23.4%). Thirty-five of 56 patients with differentiated HPC had recurrence, while 22 of 26 patients with anaplastic HPC had recurrence. Bone, liver, lung, central nervous system, and abdominal cavity were the most common sites of metastasis. Postoperative radiotherapy and/or chemotherapy were significantly associated with increased patient survival time.

Exercise, Training and Injuries

SummaryAlthough exercise results in a number of well documented physical fitness and health benefits, accruing such benefits entails a risk of exercise-related injuries. Musculoskeletal injuries occur frequently among fitness programme participants, runners, athletes, military recruits and others who engage in routine vigorous exercise. The same parameters of exercise (intensity, duration and frequency) that determine the positive fitness and health effects of physical training also appear to influence the risk of injuries. Studies of runners and other physically active groups have consistently demonstrated that greater duration and frequency of exercise are associated with higher risks of injury. However, the sports medicine literature shows little association between exercise intensity and injuries, a finding which may be misleading. The strongest and most consistent association reported exists between greater total amounts of exercise and higher risks of injury. This is not surprising, since the total amount of exercise is the product of the intensity, duration and frequency of exercise. Recent military research confirms the finding that higher volumes of running are associated with higher rates of injury. Furthermore, the study of army recruits suggests that greater amounts of exercise not only result in greater risks of injury, but in some instances may also impart no additional increase in fitness, a finding consistent with an earlier study of civilian runners. Several military studies also demonstrate that those recruits who have been more physically active in the past are less likely to be injured during basic training. These military studies also document a number of other factors, such as older age, smoking, sedentary jobs and lifestyle, high or low flexibility and high arches of the feet, which may contribute to or modify the risks for exercise-related injuries.In conclusion, the present review suggests that, for activities such as running, specific parameters of exercise may contribute to the overall risk of injuries in rough proportion to their contribution to the total amount of activity performed. Also, better knowledge of the effects of the parameters of training and other factors on the risks of exercise-related injuries is necessary to make more judicious choices about how to best achieve the benefits of exercise and to prevent injuries.

Validation of a Blood-Based Laboratory Test to Aid in the Confirmation of a Diagnosis of Schizophrenia

We describe the validation of a serum-based test developed by Rules-Based Medicine which can be used to help confirm the diagnosis of schizophrenia. In preliminary studies using multiplex immunoassay profiling technology, we identified a disease signature comprised of 51 analytes which could distinguish schizophrenia (n = 250) from control (n = 230) subjects. In the next stage, these analytes were developed as a refined 51-plex immunoassay panel for validation using a large independent cohort of schizophrenia (n = 577) and control (n = 229) subjects. The resulting test yielded an overall sensitivity of 83% and specificity of 83% with a receiver operating characteristic area under the curve (ROC-AUC) of 89%. These 51 immunoassays and the associated decision rule delivered a sensitive and specific prediction for the presence of schizophrenia in patients compared to matched healthy controls.

Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset.

Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples. First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls. Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95–1.00) for schizophrenia detection. Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals. The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86–0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71–0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82–0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset.

Identification of a blood-based biological signature in subjects with psychiatric disorders prior to clinical manifestation

Abstract Objectives. To determine whether a molecular signature is present in blood of patients with psychiatric disorders before manifestation of symptoms. Methods. Multiplex immunoassay analyses were carried out using serum obtained from two case-control studies of schizophrenia (n = 75) and bipolar disorder (n = 110) patients and their matched controls. The samples were drawn within 1 month before estimated onset of illness. Results. This led to identification of 20 molecules which were altered in pre-schizophrenia and 14 molecules in pre-bipolar disorder subjects compared to controls. Only two of these molecular changes were identical in both data sets and predictive testing confirmed that the biomarker signatures for pre-schizophrenia and pre-bipolar disorder were dissimilar. Conclusion. The present results suggest that there are distinct serum alterations that occur before clinical manifestation of schizophrenia and bipolar disorder. These findings could lead to development of diagnostic tests to help clinical psychiatrists identify and classify vulnerable patients early in the disease process, allowing for earlier and more effective therapeutic intervention.

Exertional heat illness among overweight U.S. Army recruits in basic training.

INTRODUCTION Heat illness has not declined in the U.S. military despite preventive measures. The increase in overweight recruits entering the U.S. military may lead to an increase in heat-related events. This study compares the risk of heat illness among U.S. Army recruits who exceeded body fat standards at accession to those who met standards. METHODS Recruits with excess body fat and qualified applicants to the Army were required to take a preaccession fitness test during the study period (February 2005 through September 2006). The test included a 5-min step test and 1-min push-up challenge, scored as pass or fail. Incidence and outpatient usage for heat illness (any heat illness, heat stroke, heat exhaustion, and other heat illness) at 90 d of service were compared in 9667 male recruits of whom 826 had excess body fat and 8841 were qualified. There were too few heat events among women for analysis. RESULTS The incidence odds ratio among male recruits with excess body fat compared to qualified male recruits was 3.63 (95% CI: 1.92, 6.85). Men with excess body fat had an increased incidence of heat illness with a rate ratio of 7.25 (95% CI: 4.17, 12.61). DISCUSSION Although there were few heat illness events, the results indicate a significantly increased risk of heat illness and outpatient utilization among male recruits with excess body fat. It was estimated that approximately 70% of the relative risk for heat illnesses in men with excess body fat during basic training was associated with exceeding body fat standards. These findings may have implications for military accession and training.

Musculoskeletal injuries among overweight army trainees: incidence and health care utilization.

BACKGROUND Musculoskeletal injuries are a major cause of morbidity in military training. They are more common among overweight/obese individuals, and the prevalence of overweight/obesity in the military has increased. During strong economic periods, the military can be challenged to recruit enough qualified personnel, and physical standards are sometimes relaxed. AIMS This study was conducted to compare the incidence of and outpatient utilization for training-related overuse injuries among men who were over body fat (OBF) standards compared with those who were weight qualified (WQ). METHODS All study subjects were men ≥18 years old, who were classified as OBF or WQ and were followed for 90 days. During this period, everyone entering through the study sites was required to take a physical fitness test (5 min step test). Only individuals passing the fitness test were included in these analyses. RESULTS There were 812 OBF and 6511 WQ study participants. OBF were 47% more likely to experience a musculoskeletal injury and had 49% higher health care utilization. Other significant factors included age >19 and a history of smoking. CONCLUSIONS Among this population who had passed a fitness test, those who were OBF had a substantially higher risk of injury and higher utilization for these injuries. Because the recruiting environment is much better, military entrance standards have been tightened, but should the economy improve substantially the military may again be challenged to recruit adequate numbers of personnel, and the lessons learned in this project may prove valuable.

Psychiatric and General Medical Conditions Comorbid With Bipolar Disorder in the National Hospital Discharge Survey

OBJECTIVE From 40% to 65% of patients with bipolar disorder are estimated to have diagnoses of one or more comorbid conditions. The purpose of this study was to identify comorbid disorders and compare their prevalence in hospitalizations of persons with or without bipolar disorder. METHODS Data from the 1979-2006 National Hospital Discharge Survey (NHDS) were analyzed to examine temporal trends in the proportional morbidity of bipolar disorder, demographic characteristics, and the most frequent comorbid conditions in hospitalizations of patients with or without bipolar disorder. Among discharges of patients ages 13-64, the conditions of those with a primary diagnosis of bipolar disorder (N=27,054) were compared with those with other primary diagnoses (N=2,325,247). Proportional morbidity ratios (PMRs) were calculated. RESULTS There was an average 10% (p<.001) increase per year in the proportion of discharges with bipolar disorder. Proportions of discharge records that noted bipolar disorder were higher among females and whites and were highest among persons ages 13-19 and those from the Northeast. Discharge records noting a primary diagnosis of bipolar disorder showed higher proportions of most psychiatric and some general medical conditions, including acquired hypothyroidism (proportional morbidity ratio=2.6), viral hepatitis (1.6), obesity (1.4), and various diseases of the skin and subcutaneous tissue (range 2.6-4.2) and of the nervous (1.4-3.8), respiratory (1.4-2.3), and musculoskeletal (1.2-1.9) systems. CONCLUSIONS Patients with bipolar disorder have an increased illness burden from many psychiatric and general medical conditions. Knowledge of the most prevalent comorbid conditions and methods for their prevention, early diagnosis, and treatment are critical in improving the prognosis of patients with bipolar disorder.

Step Test Performance and Risk of Stress Fractures Among Female Army Trainees

BACKGROUND Stress fractures and other musculoskeletal injuries are major sources of morbidity among female military trainees. Several risk factors have been postulated, particularly pre-existing fitness, usually assessed with post-entry run time for ≥ 1.0 mile. PURPOSE Physical fitness is not formally evaluated prior to Army entry. If a valid and simple test that identified women at increased risk of stress fracture were available and could be applied prior to entry, it would facilitate cost-benefit studies of deferral or interventions. These analyses were undertaken to determine if a 5-minute step test conducted before entry identified women at increased risk. METHODS A prospective study was conducted of weight-qualified women entering the Army in 2005-2006, with analyses completed in 2011. At the pre-entry examination, information was collected on age, BMI, smoking, race, and activity level. Everyone took the step test. All outpatient medical encounters were captured, and stress fractures and other musculoskeletal injuries identified. Women with stress fractures and those with other musculoskeletal injuries were evaluated separately. RESULTS 1568 women were included in the study; 109 developed stress fractures and 803 other musculoskeletal injury. Women who failed the step test had a 76% higher stress fracture incidence and a 35% higher incidence of other musculoskeletal injuries. There was effect modification between age and test failure for stress fracture. CONCLUSIONS A step test that can be administered before military entry identifies women with increased incidence of stress fracture and other musculoskeletal injury. This test could be used pre-entry to defer or target high-risk recruits for tailored fitness training before or after military entrance.

Body mass index, medical qualification status, and discharge during the first year of US Army service

BACKGROUND The high prevalence of overweight and obesity in military recruits and in the US population as a whole necessitates understanding the health effects of body composition and associated morbidity. OBJECTIVE In this study, we examined the effect of body mass index (BMI; in kg/m(2)) and medical status on premature discharge from the US Army in a large cohort of first-time-enlisted, active-duty soldiers. DESIGN We determined the odds ratios (ORs) associated with BMI and medical status at enlistment by using a retrospective cohort of first-time, active-duty army recruits. RESULTS ORs for BMI, calculated by using 24-24.9 as a reference, exhibited a U-shaped pattern. Soldiers with a BMI >34 had the highest ORs for all-cause (OR: 1.47; 95% CI: 1.32, 1.64) and medical (OR: 1.68; 95% CI: 1.46, 1.93) discharges. A BMI <17 was 1.35 times as likely (95% CI: 1.02, 1.80) to result in an all-cause discharge and 1.45 times as likely (95% CI: 1.01, 2.08) to result in a medical discharge. ORs for soldiers who required a medical reexamination did not vary when all-cause discharge (OR: 1.10; 95% CI: 1.06, 1.14) and medical discharge (OR: 1.10; 95% CI: 1.05, 1.15) were compared. The medical discharge OR for soldiers who required a medical waiver to enter the army (OR: 1.56; 95% CI: 1.48, 1.64) was higher than the OR for all-cause discharge (OR: 1.27; 95% CI: 1.22, 1.32). CONCLUSION Enlistment BMI and medical qualification status play an important role in early discharge and may provide a valuable tool in the development of fitness, nutrition, and injury-prevention interventions in higher-risk groups.