18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.

(18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. METHODS: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.     

Extended-release divalproex in bipolar and other psychiatric disorders: A comprehensive review

Bipolar disorder can be a devastating disease state for individuals with the disease and also for family members. Proper recognition and treatment is vital to the successful management of this disease state. Through increased community and practitioner awareness, along with efforts to increase awareness for proper assessment, the rate of diagnosed bipolar disorder is increasing. Recent years have brought about the introduction of several new medications with approved indications for the treatment of bipolar disorder. In addition to new agents, traditional mood stabilizing medications have also been released in different formulations to better enhance tolerability without jeopardizing efficacy. One particular product is extended-release divalproex sodium. In the following article, we review the clinical presentation of bipolar disorder, its epidemiology, and the pharmacokinetics and mechanism of action for divalproex. In addition, we specifically review the role of extended-release divalproex in bipolar disorder through a critical analysis of the currently available published primary literature.     

Physical Activity Participation by Parental Language Use in 4th, 8th,and 11th Grade Students in Texas,USA

Research on physical activity (PA) by level of acculturation in Hispanic children is limited and findings have been mixed. We examined PA participation by primary language used with parents in a representative sample of 4th, 8th, and 11th grade Texas public school students. Mixed-effects regression models were conducted using cross-sectional data from the 2004–2005 School Physical Activity and Nutrition Study (n = 22,049). Self-reported PA was compared among three language-ethnic groups: Spanish-Hispanic (SH) (referent); English-Hispanic (EH); and English-Other (EO). EH and/or EO girls were generally between 1.25 and 2.58 [OR] times more likely to participate in PA across grade levels, with the largest differences found for school sports in 8th grade girls. EH and EO 8th grade boys were 1.71 (CI: 1.40, 2.10) and 2.06 (CI: 1.68, 2.51) times, respectively, more likely to participate in school sports. Findings indicate important disparities in Spanish-speaking Hispanic children’s PA participation.     

Pharmacokinetics of mycophenolate mofetil in stable pediatric liver transplant recipients receiving mycophenolate mofetil and cyclosporine.

There are few pharmacokinetic data for mycophenolate mofetil (MMF) when used in combination with cyclosporine (CsA) in pediatric liver transplant recipients. The aim of this study was to assess the pharmacokinetics of MMF in stable pediatric liver transplant patients and estimate the dose of MMF required to provide a mycophenolic acid (MPA) exposure similar to that observed in adult liver transplant recipients receiving the recommended dose of MMF (target area under the plasma concentration-time curve from 0 to 12 hours [AUC(0-12)] for MPA of 29 mug.hour/mL in the immediate posttransplantation period and 58 microg x hour/mL after 6 months). A 12-hour pharmacokinetic profile was collected for 8 pediatric patients (mean age 20.9 months) on stable doses of MMF and CsA who had received a liver transplant > or = 6 months prior to entry and who had started on MMF within 2 weeks of transplantation. Mean MMF dosage was 285 mg/m(2) (range, 200-424 mg/m(2)). Of 8 patients, 7 had a MPA AUC(0-12) (range, 11.0-37.2 microg x hour/mL) well below the target. One patient had an AUC(0-12) > or = 58 microg x hour/mL but was considered an outlier and was excluded from analyses. Mean MPA AUC(0-12) and maximum plasma concentration values were 22.7 +/- 10.5 microg x hour/mL and 7.23 +/- 3.27 microg/mL, respectively; values normalized to 600 mg/m(2) (the approved pediatric dose in renal transplantation) were 47.0 +/- 21.8 microg x hour/mL and 14.5 +/- 4.21 microg/mL. In conclusion, assuming that MPA exhibits linear pharmacokinetics, when used in combination with CsA, a MMF dose of 740 mg/m(2) twice daily would be recommended in pediatric liver transplant recipients to achieve MPA exposures similar to those observed in adult liver transplant recipients. This finding should be confirmed by a prospective trial.     

Comparison of Laparoscopic vs Open Sigmoid Colectomy for Benign and Malignant Disease at Academic Medical Centers

Few studies have examined outcomes of laparoscopic and open sigmoid colectomy performed at US academic centers. Using ICD-9 diagnosis and procedural codes, data was obtained from the University HealthSystem Consortium (UHC) Clinical Database of 10,603 patients who underwent laparoscopic or open sigmoid colectomy for benign and malignant disease between 2003–2006. A total of 1,092 patients (10.3%) underwent laparoscopic sigmoid colectomy. Laparoscopic sigmoid colectomy was associated with a significantly shorter length of stay (5.4 vs 7.4 days), lower overall complication rate (19.7 vs 26.0%), lower 30-day readmission rate (3.4 vs 4.6), and a lower hospital cost ($13,814 vs $15,626). When a subset analysis of malignant and benign groups was performed, a significantly shorter length of stay in both the malignant laparoscopic group (6.4 ± 6.4 vs 7.8 ± 6.6 days) and in the benign laparoscopic groups (5.1 ± 3.5 vs 7.2 ± 7.6) exists. A lower wound complication rate (2.1 vs 5.5%, malignant and 4.0 vs 6.1, benign) is also evident. Laparoscopic sigmoid colectomy was associated with a shorter length of stay, less complications, and a lower 30-day readmission rate. The shorter length of stay and wound infection rate maintain significance when comparing laparoscopic vs open sigmoid resections for malignant and benign disease. Presented at the 48th annual meeting of the Society for Surgery of the Alimentary Tract at Digestive Disease Weak, Washington, DC, May 21st 2007. The information contained in this article was based on the Clinical Data Base provided by the University HealthSystem Consortium.     

Understanding the minimum clinically important difference: a review of concepts and methods.

BACKGROUND CONTEXT: The effectiveness of spinal surgery as a treatment option is currently evaluated through the assessment of patient-reported outcomes (PROs). The minimum clinically important difference (MCID) represents the smallest improvement considered worthwhile by a patient. The concept of an MCID is offered as the new standard for determining effectiveness of a given treatment and describing patient satisfaction in reference to that treatment. PURPOSE: Our goal is to review the various definitions of MCID and the methods available to determine MCID. STUDY DESIGN: The primary means of determining the MCID for a specific treatment are divided into anchor-based and distribution-based methods. Each method is further subdivided and examined in detail. METHODS: The overall limitations of the MCID concept are first identified. The basic assumptions, statistical biases, and shortcomings of each method are examined in detail. RESULTS: Each method of determining the MCID has specific shortcomings. Three general limitations in the accurate determination of an MCID have been identified: the multiplicity of MCID determinations, the loss of the patient's perspective, and the relationship between pretreatment baseline and posttreatment change scores. CONCLUSIONS: An ideal means of determining the MCID for a given intervention is yet to be determined. It is possible to develop a useful method provided that the assumptions and methodology are initially declared. Our efforts toward the establishment of a MCID will rely on the establishment of specific external criteria based on the symptoms of the patient and treatment intervention being evaluated.     

Cephalad Movement of Morphine and Fentanyl in Humans after Intrathecal Injection

Background: Despite decades of use, controversy remains regarding the extent and time course of cephalad spread of opioids in cerebrospinal fluid (CSF) after intrathecal injection. The purpose of this study was to examine differences between two often used opioids, morphine and fentanyl, in distribution in the CSF after intrathecal injection.

Methods: Eight healthy volunteers received intrathecal injection of morphine (50 [mu]g) plus fentanyl (50 [mu]g) at a lower lumbar interspace. CSF was sampled through a needle in an upper lumbar interspace for 60-120 min. At the end of this time, a sample was taken from the lower lumbar needle, and both needles were withdrawn. CSF volume was determined by magnetic resonance imaging. Pharmacokinetic modeling was performed with NONMEM.

Results: Morphine and fentanyl peaked in CSF at the cephalad needle at similar times (41 +/- 13 min for fentanyl, 57 +/- 12 min for morphine). The ratio of morphine to fentanyl in CSF at the cephalad needle increased with time, surpassing 2:1 by 36 min and 4:1 by 103 min. CSF concentrations did not correlate with weight, height, or lumbosacral CSF volume. The concentrations of morphine and fentanyl at both sampling sites were well described by a simple pharmacokinetic model. The individual model parameters did not correlate with the distance between the needles, CSF volume, patient height, or patient weight.