Edward J. Gracely

The Effects of Low-Carbohydrate versus Conventional Weight Loss Diets in Severely Obese Adults: One-Year Follow-up of a Randomized Trial

Context In 2003, the authors reported that severely obese adults lost more weight and had better serum lipid patterns after 6 months of a low-carbohydrate diet rather than a conventional low-fat diet. Contribution After 1 year, these same patients still had more favorable triglyceride and high-density lipoprotein cholesterol levels on the low-carbohydrate diet than on the conventional diet. However, weight loss and the other metabolic parameters were similar in the 2 diet groups. Cautions The effect of the modest improvements in high-density lipoprotein cholesterol and triglyceride levels on the development of diabetes and cardiovascular disease is unknown. The Editors The prevalence of obesity and its associated metabolic abnormalities has increased markedly over the past 2 decades (1, 2). Although guidelines to follow a highcomplex carbohydrate, low-fat, energy-deficient diet to achieve weight loss are generally accepted (3), considerable public interest has focused on low-carbohydrate diets (4). We recently reported that persons with severe obesity lost more weight and had greater improvements in triglyceride levels, insulin sensitivity, and glycemic control after 6 months of a low-carbohydrate diet as compared with a conventional weight loss diet based on calorie and fat restriction (5). However, these findings were preliminary because of the short duration of that study (6). A simultaneously published study by Foster and colleagues suggested that persons on a low-carbohydrate diet tended to regain weight by 1 year (7). These findings were limited, however, because few participants completed the study and because the study used a self-help approach, which is less effective than direct counseling for maintaining weight loss (8). Foster and colleagues also excluded persons with diabetes, which is highly prevalent in the obese population. During the development of this study, we decided to analyze and report preliminary results at 6 months and final results at 1 year. We thought that the short-term results would be important, given the high-risk nature of our study sample, but that long-term outcomes would provide more information about the sustainability of any diet-related outcomes. We now report our findings 1 year after randomization to a low-carbohydrate diet versus a low-fat weight loss diet (conventional diet) in severely obese adults with a high prevalence of diabetes or the metabolic syndrome. Methods Study Participants The study design has been previously described (5). Participants were recruited from the outpatient practices of the Philadelphia Veterans Affairs Medical Center and included persons 18 years of age and older with a body mass index (BMI) of 35 kg/m2 or greater. The exclusion criteria were a serum creatinine level greater than 133 mol/L (>1.5 mg/dL), hepatic disease, severe life-limiting medical illness, inability to self-monitor glucose levels, or active use of a weight loss program or weight loss medication. Between May 2001 and November 2001, 132 persons were randomly assigned to either a low-carbohydrate diet (n = 64) or a conventional diet (n = 68). The Institutional Review Committee at the Philadelphia Veterans Affairs Medical Center approved the study, and all participants provided written informed consent. Interventions Diet groups met in weekly counseling sessions for 4 weeks, followed by 11 monthly sessions. Participants on the low-carbohydrate diet were instructed only to reduce carbohydrate intake to less than 30 g per day. Participants on the conventional diet were instructed to reduce caloric intake by 500 calories per day, with less than 30% of calories derived from fat, in accordance with the National Heart, Lung, and Blood Institute guidelines (3). Outcome Measures We collected data, including weight (single calibrated scale, SR Instruments, Inc., Tonawanda, New York), medical history (self-reported), and blood pressure, at baseline, 6 months, and 1 year. Fasting blood specimens were obtained for glucose, hemoglobin A1c, and serum lipid levels (Synchron LX20, Beckman Coulter, Inc., Fullerton, California). Low-density lipoprotein (LDL) cholesterol level was calculated by using the Friedewald formula (9). We defined the presence of diabetes by a historical fasting blood glucose level greater than 6.94 mmol/L (>125 mg/dL) or use of antidiabetic medications. The metabolic syndrome was considered present if a participant had 3 or more of the following (10): central obesity, fasting blood glucose level of 6.11 mmol/L (110 mg/dL) or greater, fasting triglyceride level of 1.70 mmol/L (150 mg/dL) or greater, high-density lipoprotein (HDL) cholesterol level less than 1.04 mmol/L (<40 mg/dL) for men or less than 1.30 mmol/L (<50 mg/dL) for women, blood pressure of 130/85 mm Hg or greater, or antihypertensive therapy. We assumed that all participants had central obesity because of the uniform severity of their obesity (BMI range, 35.0 to 79.4 kg/m2). Serum insulin was measured by radioimmunoassay (Laboratory Corporation of America Holdings [LabCorp], Burlington, North Carolina]). Insulin resistance in nondiabetic persons was estimated by the quantitative insulin sensitivity check (QUICK) index: 1/[(log (fasting insulin (U/mL)) + (log fasting glucose(mg/dL))]. Statistical Analysis Our primary end point was total weight loss at 1 year. Secondary analyses included the change from baseline in serum lipid levels, insulin sensitivity, and glycemic control. We estimated that we would need 100 persons (50 per group), assuming a 2-sided type I error of 5%, for the study to have 80% power to detect a 5-kg greater mean weight loss in the low-carbohydrate group than in the conventional diet group. These calculations were based on an anticipated maximum weight loss by 6 months, with weight stabilization in both diet groups between 6 months and 1 year. To compensate for an anticipated dropout rate of 25%, we set our enrollment target at 135 persons. Randomization was performed by using a pre-established algorithm generated from a random set of numbers that was constructed and held in a separate center and concealed from those enrolling persons during randomization. We used stratified randomization, with blocking within strata, to ensure assignment of approximately equal numbers of women, diabetic persons, and severely obese persons (BMI 40 kg/m2) to each study group. Changes in weight, dietary intake, and metabolic data were compared between the 2 diets by random-coefficient analysis (11). This type of analysis was selected to allow for a variable number of observations for participants and to take into account that the repeated observations of the outcome variables over time for individuals were correlated. The random-coefficient analysis model takes these correlations into account by allowing the intercept to vary randomly among persons. We used a restricted maximum likelihood analysis, which assumed that changes were distributed according to a bivariate normal distribution and that data were missing at random. The outcome variables were changes from baseline in weight, dietary macronutrient consumption, and metabolic measurements. For all of these analyses, the covariates included an indicator variable for time (6 months and 1 year), diet group, and a diet group by time interaction term. This diet group by time interaction term was kept in the model, regardless of its statistical significance (P = 0.063 for the weight loss analysis). Separate analyses to adjust for baseline differences between diet groups were also made by entering the following covariates to each of these models: age; race (white or African American); sex; baseline BMI; baseline caloric intake; and the presence or absence of hypertension, use of lipid-lowering therapy, diabetes, active smoking, and sleep apnea (12). All variables were assessed for normality before entry into the analyses. Triglyceride, insulin, and glucose levels were skewed and thus were log-transformed before the analyses. Baseline differences between diet groups were compared by chi-square analysis for dichotomous variables and by the unpaired t-test for continuous variables. All P values are 2-sided, and a P value of 0.05 was considered statistically significant. Analyses were performed with SPSS statistical software, version 11.1 (SPSS, Inc., Chicago, Illinois). Missing Data Of the 132 enrolled persons, follow-up was done at 6 months for 79 persons and at 1 year for 87 persons. For measurements at 6 months, we retrieved weights on an additional 16 persons on the low-carbohydrate diet and 23 persons on the conventional diet (total, 39 persons at a mean [SD] of 6.6 1.2 months). For measurements at 1 year, we retrieved weights on 18 persons on the low-carbohydrate diet and 21 persons on the conventional diet (total, 39 persons at a mean [SD] of 13.5 3.2 months). Thus, we had 6-month weights on 118 of 132 persons (89%) and 1-year weights on 126 of 132 persons (96%). Of the 18 persons who missed the 6-month visit but returned for the 1-year visit (6 in the low-carbohydrate group and 12 in the conventional diet group), all but 2 had 6-month weights retrieved from medical records. Of the 6 persons for whom no 1-year weights were available, 2 were in the low-carbohydrate group and 4 in the conventional diet group. The weights retrieved from medical records were obtained on scales that were different from those used for the study and were probably obtained in a nonuniform manner with regard to clothing. We used several approaches to handle the 45 participants with missing data for diet recall and metabolic measurements. For the primary analysis by random-coefficient analysis, we assumed data were missing at random. To verify this assumption, we performed sensitivity analyses based on comparisons of baseline characteristics and weight loss differences between those who dropped out and those who completed the study. We also performed 2 additional sensitivity ana

Elevated Methylmalonic Acid and Total Homocysteine Levels Show High Prevalence of Vitamin B12 Deficiency after Gastric Surgery

Elderly persons [1, 2] and persons who have had gastric surgery [3-11] are at increased risk for developing vitamin B12 (cobalamin) deficiency. The hematologic and neurologic manifestations of vitamin B12 deficiency have been well described; however, this deficiency often remains undetected, and some patients receive a misdiagnosis of Alzheimer disease, spinal cord compression, amyotrophic lateral sclerosis, or diabetic or alcoholic peripheral neuropathy [12]. Although megaloblastic anemia is usually reversible with vitamin B12 treatment, the neurologic injuries are reversible only if they are treated soon after their onset [12, 13]. In addition, as do patients with folate deficiency [14], patients with untreated vitamin B12 deficiency have elevated total homocysteine levels. Substantial biochemical and epidemiologic evidence now suggests that an elevated serum total homocysteine level contributes to the development of carotid artery stenosis, coronary artery disease, and peripheral vascular disease [15-18]. Thus, in theory at least, patients with untreated vitamin B12 deficiency may be at increased risk for developing atherosclerotic vascular disease. In the future, the prevalence of vitamin B12 deficiency in the aging population may be expected to increase. Among persons at major risk are those who had subtotal gastrectomy for ulcer disease between the 1930s [19] and 1974 [5, 7] (in 1974, the first histamine-2 blocker, cimetidine, was released [20]). It is not possible to determine how many Americans had gastric surgery during this period, but representative data from the University of Minnesota Hospital suggest that the number is large. At that hospital alone, 1550 patients had subtotal gastrectomy between 1938 and 1950 [4]. Throughout the United States, therefore, hundreds of thousands of patients probably had this surgery. A new operation, gastric bypass for obesity, is currently creating another cohort at risk for developing vitamin B12 deficiency [11]. As these cohorts age, an unknown number of persons will develop vitamin B12 deficiency, and clinicians caring for such persons currently have no accurate guidelines on which to base screening decisions. Previous prevalence estimates are unreliable because clinical manifestations are insensitive and radiodilution vitamin B12 assays were nonspecific [21, 22]. The Schilling test is unreliable after gastrectomy [8, 9], anemia is often absent in vitamin B12-deficient patients [2, 12, 23], and macrocytosis may be masked by coexisting iron deficiency [7, 24]. See editorial comment on pp 509-511. Recently, however, measurements of the metabolites from two vitamin B12-dependent pathways (Figure 1)serum methylmalonic acid [25] and total homocysteine [14]were shown to be highly sensitive detectors of vitamin B12 deficiency [26]. Two enzymes have a known requirement for vitamin B12: L-methylmalonyl-CoA mutase and methionine synthase [22]. Methionine synthase requires folate in addition to vitamin B12 for normal functioning. If the conversion of L-methylmalonyl-CoA to succinyl-CoA is impaired by a deficiency of the vitamin B12 cofactor adenosylcobalamin, the excess methylmalonyl-CoA is cleaved to methylmalonic acid and methylmalonic acid levels in the serum and urine are elevated [25]. Similarly, if the methylation of homocysteine to methionine is impaired by a deficiency of methylcobalamin or methyltetrahydrofolate, serum total homocysteine levels are elevated [14]. The metabolic pathways in which these two enzymes function are not always equally affected by vitamin B12 deficiency. At the time vitamin B12 deficiency is diagnosed, therefore, levels of methylmalonic acid, total homocysteine, or both may be elevated [22]. Figure 1. The two vitamin B12-dependent enzymes, L-methylmalonyl-CoA mutase (left) and methionine synthase (right). In vitamin B12-deficient patients, elevated levels of both serum methylmalonic acid and total homocysteine decrease promptly with adequate vitamin B12 therapy [22, 26]. However, in folate-deficient patients, total homocysteine levels return to normal only after folate replacement [22]. Therefore, in addition to serum vitamin B12 levels, we used methylmalonic acid, total homocysteine, and folate levels to determine whether the prevalence of vitamin B12 deficiency differed between persons who had had gastric surgery and those who had not. Methods Between September 1991 and March 1993, 65 patients who had had gastric surgery were identified at the Philadelphia Veterans Affairs Medical Center. These patients were identified either by review of gastrointestinal radiographs, surveys of the house-staff assigned to the medicine and surgery inpatient services, or referral of outpatients from physicians in the medical clinic. Four of the 65 patients were excluded: Three were receiving vitamin B12 therapy, and one had a hepatoma. Hepatoma can produce increased levels of vitamin B12-binding protein, which may complicate interpretation of serum vitamin B12 levels. Patients who had not had gastric surgery (controls) were drawn from 127 consecutive patients attending one authors Philadelphia Veterans Affairs Medical Center clinic between November 1992 and March 1993. One hundred seven controls participated, and 20 either declined to participate or did not complete the required blood tests. We determined the type of gastric surgery that had been done either from patient reporting or by reviewing radiologic, endoscopic, or surgical records. In most patients (51 of 61), we determined the year surgery had been done from patient report or chart review. For patients who could not provide the year of surgery but could specify the decade, we used the mid-decade year. For example, if the patient said that the surgery had been done in the 1950s, we recorded the year as 1955. Serum vitamin B12 and folate levels were determined at the Philadelphia Veterans Affairs Medical Center using a commercially available radioligand kit (Bio-Rad, Diagnostics Group, Hercules, California). In the hospitals laboratory, normal values for vitamin B12 and folate levels were 171 to 840 pmol/L and 5 to 39 nmol/L, respectively. The remaining serum samples were frozen at 20 C and were shipped to Denver so that serum methylmalonic acid and total homocysteine levels could be analyzed by the stable isotope dilution gas chromatography-mass spectrometry method [27-30]. The normal range for serum methylmalonic acid levels (determined in 50 normal blood donors 18 to 65 years of age) is 73 to 271 nmol/L, and the normal range for serum total homocysteine levels is 5.4 to 16.2 mol/L [22]. Vitamin B12 deficiency was defined as one of the following: 1) a serum vitamin B12 level less than 221 pmol/L and an elevated methylmalonic acid level; 2) a serum vitamin B12 level less than 221 pmol/L and a total homocysteine level that decreased after vitamin B12 therapy; or 3) in patients unavailable for treatment, a serum vitamin B12 level less than 221 pmol/L, a folate level greater than 9 nmol/L, and an elevated total homocysteine level. Hemoglobin level, hematocrit, and mean corpuscular volume were measured by automatic devices. Macrocytosis was defined as a mean corpuscular volume of 95 fL or less. The peripheral smears of 71% of patients (43 of 61) and 88% of controls (94 of 107) were reviewed by one hematologist who was blinded to each participants vitamin B12 level, hemoglobin level, hematocrit, and gastric surgery status. Hypersegmentation was defined as five neutrophils with five or more lobes or one neutrophil with six lobes per 100 cells counted. Treatment Vitamin B12 treatment generally consisted of daily intramuscular injections of 1000 g of vitamin B12 for 5 days, followed by monthly injections. Folic acid was given orally, 1 mg/d. Serum vitamin B12, folate, methylmalonic acid, and total homocysteine levels were measured 1 to 6 weeks after treatment. Statistical Analysis Data were examined to determine whether the variables were suitable for parametric analyses. Although relatively modest, the skew for the numeric variables necessitated that several variables be transformed to logs for entry into two-way analysis of variance or be subjected to nonparametric analyses. The comparison between patients and controls for levels of vitamin B12, folate, methylmalonic acid, and total homocysteine was done by two-factor analysis of variance on log-transformed variables. In each analysis of variance, race was included as a factor (along with study group) to control for possible race-by-group interactions. We used unpaired t-tests or Mann-Whitney U tests to do comparisons of other numeric variables, such as hemoglobin and mean corpuscular volume; comparisons between other groups, such as patients with a positive and patients with a negative peripheral blood smear; and comparisons between deficient and nondeficient patients. We used chi-square tests to compare groups on dichotomous variables (such as white patients compared with black patients). Spearman correlations were used to assess the association between the time since surgery and other variables. The Human Studies Subcommittee and the Research and Development Committee of the Philadelphia Veterans Affairs Medical Center approved the study. Results Clinical Characteristics The 61 patients (who had had gastric surgery) and 107 controls (who had not) were similar in the ratio of men to women (60:1 compared with 104:3), age, and race (Table 1). The indications for surgery included peptic ulcer disease (56 patients), obesity (3 patients), gastric cancer (3 patients [2 of whom had previously had surgery for peptic ulcer disease]), and gastric lymphoma (1 patient). The type of gastric surgery could be determined in 36 of 61 patients (59%). The types of surgery were Billroth II (23 patients), repair of perforated ulcer (6 patients), vagotomy and pyloroplasty (2 patients), gastric bypass or gastric banding for obesity (3 patients), Billroth I (1 patient),

How Long Do Most Seizures Last? A Systematic Comparison of Seizures Recorded in the Epilepsy Monitoring Unit

Summary:  Purpose: More information is needed regarding how long seizures typically last, since this influences treatment decisions. Seizure type and other factors could influence seizure duration.

Interleukin-15 Increases Effector Memory CD8 T Cells and NK Cells in Simian Immunodeficiency Virus-Infected Macaques

ABSTRACT Interleukin-15 (IL-15) in vitro treatment of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected individuals specifically enhances the function and survival of HIV-specific CD8+ T cells, while in vivo IL-15 treatment of mice preferentially expands memory CD8+ T cells. In this study, we investigated the in vivo effect of IL-15 treatment in 9 SIVmac251-infected cynomolgus macaques (low dose of IL-15, 10 μg/kg of body weight, n = 3; high dose of IL-15, 100 μg/kg, n = 3; control [saline], n = 3; dose administered twice weekly for 4 weeks). IL-15 treatment induced a nearly threefold increase in peripheral blood CD8+CD3− NK cells. Furthermore, CD8+ T-cell numbers increased more than twofold, mainly due to an increase in the CD45RA−CD62L− and CD45RA+CD62L− effector memory CD8+ T cells. Expression of Ki-67 in the CD8+ T cells indicated expansion of CD8+ T cells and not redistribution. IL-15 did not affect CD4+ T-cell, B-cell, and CD14+ macrophage numbers. No statistically significant differences in changes from baseline in the viral load were observed when control-, low-dose-, and high-dose-treated animals were compared. No clinical adverse effects were observed in any of the animals studied. The selective expansion of effector memory CD8+ T cells and NK cells by IL-15 further supports IL-15s possible therapeutic use in viral infections such as HIV infection.

Oral versus intravenous corticosteroids in children hospitalized with asthma.

BACKGROUND Previous studies have demonstrated that in the emergency treatment of an asthma exacerbation, corticosteroids used in conjunction with beta-agonists result in lower hospitalization rates for children and adults. Furthermore, orally administered corticosteroids have been found to be effective in the treatment of outpatients with asthma. However, similar data in inpatients is lacking. OBJECTIVE The purpose of this study was to determine the efficacy of oral prednisone versus intravenous methylprednisolone in equivalent doses for the treatment of an acute asthma exacerbation in hospitalized children. METHODS We conducted a randomized, double-blind, double-placebo study comparing oral prednisone at 2 mg/kg/dose (maximum 120 mg/dose) twice daily versus intravenous methylprednisolone at 1 mg/kg/dose (maximum 60 mg/dose) four times daily in a group of patients 2 through 18 years of age hospitalized for an acute asthma exacerbation. All patients were assessed by a clinical asthma score 3 times a day. The main study outcome was length of hospitalization; total length of stay and time elapsed before beta-agonists could be administered at 6-hour intervals. Duration of supplemental oxygen administration and peak flow measurements were secondary outcome measures. RESULTS Sixty-six patients were evaluated. Children in the prednisone group had a mean length of stay of 70 hours compared with 78 hours for the methylprednisolone group (P =.52). Children in the prednisone group were successfully weaned to beta-agonists in 6-hour intervals after 59 hours compared with 68 hours for the methylprednisolone group (P =.47). Patients receiving prednisone required supplemental oxygen for 30 hours compared with 52 hours for the methylprednisolone group (P =.04). CONCLUSION There was no difference in length of hospital stay between asthmatic patients receiving oral prednisone and those receiving intravenous methylprednisolone. Because hospitalization charges are approximately 10 times greater for intravenous methylprednisolone compared with oral prednisone, the use of oral prednisone to treat inpatients with acute asthma would result in substantial savings.

IL-15 Treatment during Acute Simian Immunodeficiency Virus (SIV) Infection Increases Viral Set Point and Accelerates Disease Progression despite the Induction of Stronger SIV-Specific CD8+ T Cell Responses

In this study, we examined the effect of in vivo treatment of acutely SIV-infected Mamu-A*01+ rhesus macaques with IL-15. IL-15 treatment during acute infection increased viral set point by 3 logs and accelerated the development of simian AIDS in two of six animals with one developing early minimal lesion SIV meningoencephalitis. Although IL-15 induced a 2- to 3-fold increase in SIV-specific CD8+ T cell and NK cell numbers at peak viremia and reduced lymph node (LN) SIV-infected cells, this had no impact on peak viremia and did not lower viral set point. At viral set point, however, activated SIV-specific CD8+ T cells and NK cells were reduced in the blood of IL-15-treated animals and LN SIV-infected cells were increased. Week 30 LN from IL-15-treated animals had significantly increased Gag-specific CD8+ T cell numbers, whereas total cell, lymphocyte, and CD4+ T cell numbers were reduced. IL-15 treatment significantly reduced anti-SIV Ab concentrations at week 3 and viral set point. IL-15 increased Ki-67+CD4+ T cells at week 1 of treatment and reduced blood CCR5+ and CD45RA−CD62L− CD4+ T cells. The frequency of day 7 Ki-67+CD4+ T cells strongly correlated with viral set point. These findings suggest that CD4+ T cell activation during acute infection determines subsequent viral set point and IL-15 treatment by increasing such activation elevates viral set point. Finally, IL-15-treated acutely SIV-infected primates may serve as a useful model to investigate the poorly understood mechanisms that control viral set point and disease progression in HIV infection.

Helium/oxygen-driven albuterol nebulization in the treatment of children with moderate to severe asthma exacerbations: a randomized, controlled trial.

Background. Helium and oxygen mixtures (heliox) increase both pulmonary aerosol delivery and gas delivery relative to oxygen. We aimed to compare the effectiveness of a 70%:30% helium/oxygen (heliox)–driven continuous aerosol delivery versus 100% oxygen-driven delivery in the treatment of asthmatic children with moderate to severe exacerbations. Methods. We enrolled 30 children aged 2 to 18 years who presented to an urban, pediatric emergency department (ED) with moderate to severe asthma as defined by a pulmonary index (PI) score of ≥8. PI scores can range from 0 to 15. In this randomized, controlled, single-blind trial conducted in a convenience sample of children, all patients in the trial received an initial nebulized albuterol (5 mg) treatment driven by 100% oxygen and a dose of oral prednisone or prednisolone. Subsequently, patients were randomly assigned to receive continuously nebulized albuterol (15 mg/hour) delivered by either heliox or oxygen using a nonrebreathing face mask. The primary outcome measure was degree of improvement as assessed in blinded video-recorded PI scores over 240 minutes (at 30-minute intervals for the first 3 hours) or until ED discharge (if <240 minutes). Results. The mean change in PI score from baseline to 240 minutes or ED discharge was 6.67 for the heliox group compared with 3.33 for the oxygen group. Eleven (73%) patients in the heliox group were discharged from the hospital in <12 hours compared with 5 (33%) patients in the conventional group. Conclusion. Continuously nebulized albuterol delivered by heliox was associated with a greater degree of clinical improvement compared with that delivered by oxygen among children with moderate to severe asthma exacerbations.

A Phase II study of anti–epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme

OBJECT This single-institution Phase II study tests the efficacy of adjuvant radioimmunotherapy with (125)I-labeled anti-epidermal growth factor receptor 425 murine monoclonal antibody ((125)I-mAb 425) in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS A total of 192 patients with GBM were treated with (125)I-mAb 425 over a course of 3 weekly intravenous injections of 1.8 GBq following surgery and radiation therapy. The primary end point was overall survival, and the secondary end point was toxicity. Additional subgroup analyses were performed comparing treatment with (125)I-mAb 425 (RIT, 132 patients), (125)I-mAb 425 and temozolomide (TMZ+RIT, 60 patients), and a historical control group (CTL, 81 patients). RESULTS The median age was 53 years (range 19-78 years), and the median Karnofsky Performance Scale score was 80 (range 60-100). The percentage of patients who underwent debulking surgery was 77.6% and that of those receiving temozolomide was 31.3%. The overall median survival was 15.7 months (95% CI 13.6-17.8 months). The 1- and 2-year survivals were 62.5 and 25.5%, respectively. For subgroups RIT and TMZ+RIT, the median survivals were 14.5 and 20.2 months, respectively. No Grade 3 or 4 toxicity was seen with the administration of (125)I-mAb 425. The CTL patients lacked Karnofsky Performance Scale scores, had poorer survival, were older, and were less likely to receive radiation therapy. On multivariate analysis, the hazard ratios for RIT versus CTL, TMZ+RIT versus CTL, and TMZ+RIT versus RIT were 0.49 (p < 0.001), 0.30 (p < 0.001), and 0.62 (p = 0.008), respectively. CONCLUSIONS In this large Phase II study of 192 patients with GBM treated with anti-epidermal growth factor receptor (125)I-mAb 425 radioimmunotherapy, survival was 15.7 months, and treatment was safe and well tolerated.

Emergency department preparedness for the evaluation and treatment of victims of biological or chemical terrorist attack.

This study evaluated the preparedness of Emergency Departments (EDs) in the greater Philadelphia area to evaluate and treat victims of a terrorist biological or chemical agent release. All hospitals with EDs in the survey target area were included. A survey instrument consisting of 38 questions was mailed to the physician director of each ED. Fifty-four of 62 directors returned usable surveys. This represented an overall response rate of 88.5%. Deficiencies in preparedness were identified involving physician training and education, antidote stocking, written policies, interagency agreements, and decontamination facilities. The overall level of preparedness for hospital EDs responding to this survey was low based on a set of predetermined, implicit criteria. Comprehensive plans should be developed and implemented to remedy the identified deficiencies.

MCMI-diagnosed personality disorders among agoraphobic outpatients: prevalence and relationship to severity and treatment outcome

Abstract The prevalence of personality disorders among 165 agoraphobic outpatients was assessed with the Million Clinical Multiaxial Inventory, Versions I or II. Over 90% of clients met criteria for one or more Axis II diagnoses, the most common of which were avoidant and dependent. Scores on the personality scales were not significantly related to agoraphobic avoidance or panic frequency, but were often related to social phobia and dysphoria. Avoidant, dependent, and histrionic, but not severe personality disorders, were significantly associated with one or more indices of outcome for a sample of 64 clients in a naturalistic psychosocial treatment study, whereas paranoid PD was linked with early termination (