Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents.

BACKGROUND: Bariatric surgery is increasingly considered for the treatment of adolescents with severe obesity, but few prospective adolescent-specific studies examining the efficacy and safety of weight-loss surgery are available to support clinical decision making. METHODS: We prospectively enrolled 242 adolescents undergoing weight-loss surgery at five U.S. centers. Patients undergoing Roux-en-Y gastric bypass (161 participants) or sleeve gastrectomy (67) were included in the analysis. Changes in body weight, coexisting conditions, cardiometabolic risk factors, and weight-related quality of life and postoperative complications were evaluated through 3 years after the procedure. RESULTS: The mean (±SD) baseline age of the participants was 17±1.6 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 53; 75% of the participants were female, and 72% were white. At 3 years after the procedure, the mean weight had decreased by 27% (95% confidence interval [CI], 25 to 29) in the total cohort, by 28% (95% CI, 25 to 30) among participants who underwent gastric bypass, and by 26% (95% CI, 22 to 30) among those who underwent sleeve gastrectomy. By 3 years after the procedure, remission of type 2 diabetes occurred in 95% (95% CI, 85 to 100) of participants who had had the condition at baseline, remission of abnormal kidney function occurred in 86% (95% CI, 72 to 100), remission of prediabetes in 76% (95% CI, 56 to 97), remission of elevated blood pressure in 74% (95% CI, 64 to 84), and remission of dyslipidemia in 66% (95% CI, 57 to 74). Weight-related quality of life also improved significantly. However, at 3 years after the bariatric procedure, hypoferritinemia was found in 57% (95% CI, 50 to 65) of the participants, and 13% (95% CI, 9 to 18) of the participants had undergone one or more additional intraabdominal procedures. CONCLUSIONS: In this multicenter, prospective study of bariatric surgery in adolescents, we found significant improvements in weight, cardiometabolic health, and weight-related quality of life at 3 years after the procedure. Risks associated with surgery included specific micronutrient deficiencies and the need for additional abdominal procedures. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; Teen-LABS ClinicalTrials.gov number, NCT00474318.).

Validation of a weight history questionnaire to identify adolescent obesity.

BACKGROUND: Past body weight may be a more informative factor than current weight for risk of chronic disease development. Often, investigators must rely on subject recall to gauge past body weights. The Cincinnati Weight History Questionnaire (CWHQ) was developed to aid in the retrospective identification of adults who were obese during adolescence. METHODS: To assess validity, the CWHQ was administered to a subset of National Heart, Lung, and Blood Growth and Health Study (NGHS) participants, a group of young adult females for whom historical measured anthropometrics were available. One hundred ninety-eight NGHS participants were contacted, of whom 191 (97 %) responded (age 26-29). Participants were asked to recall height and weight from ages 13 and 18, which were compared to previously measured values. Multiple indices of validity (Bland-Altman plots, sensitivity, and specificity) were calculated. RESULTS: The CWHQ was moderately sensitive (range, 19-66 %), but highly specific (range, 89-100 %). Recalled height and weight values used to determine body mass index (BMI) underestimated BMI based on recorded height and weight at ages 13 and 18. Differences in calculated BMI based on recalled and measured height and weight were found to increase with BMI calculated using measured values. CONCLUSIONS: The CWHQ proved to be a moderately sensitive, but highly specific instrument for detecting adolescent obesity in a cohort of young adult females. Epidemiologic research seeking to discriminate between adults with adult-onset vs. adolescent-onset obesity may find the CWHQ useful.

Improving noninvasive methods of assessing liver fibrosis in patients with hepatitis C virus/human immunodeficiency virus co-infection.

BACKGROUND & AIMS: Liver fibrosis is a significant concern for patients with hepatitis C virus/human immunodeficiency virus co-infection. Fibrosis staging by biopsy is accurate, but costly and invasive. Several fibrosis prediction models using noninvasive biomarkers have been developed but are suboptimal in co-infected patients. We compared results from different staging models and ordinal regression with biopsy data. METHODS: Data from the Adult Acquired Immune Deficiency Syndrome Clinical Trials Group protocol A5178 were used to evaluate 5 models of fibrosis staging; areas under receiver-operator characteristic curves (AUROC) were assessed. Individual covariates were assessed with univariable regression and then entered into an ordinal logistic regression model from which a stage-wise index was developed. RESULTS: Data from 173 patients were evaluated; 85% were on antiretroviral therapy, 31.2% had severe fibrosis (F3/F4), and 14% had cirrhosis (F4). Differences in CD4+ cell and platelets counts and international normalized ratio values were observed between those with and without F3/F4. Among existing models, the FIB-4 index ([age x AST])/[platelet count x (ALT)(1/2)]) performed best, with 88% specificity for F4 and greater than 86% negative predictive values for F3/F4, although AUROC values were low (0.56 +/- 0.03 for F3/F4). By using patients' demographic, clinical, and laboratory data, the ordinal regression model outperformed others, with an AUROC of 0.85 (standard error, 0.03) for predicting stage F3/F4 and 0.89 (standard error, 0.05) for stage 3 alone. CONCLUSIONS: Current noninvasive methods of fibrosis assessment have poor discriminatory capacity in hepatitis C virus/human immunodeficiency virus co-infected patients. Ordinal regression analysis outperformed other noninvasive fibrosis prediction models. Longitudinal studies with paired biopsies will assist in refining the Ordinal Regression Index.

Effect of dietary green tea extract and aerosolized difluoromethylornithine during lung tumor progression in A/J strain mice.

Chemoprevention strategies to prevent the development of lung cancer in at-risk individuals are a key component in disease management. In addition to being highly effective, an ideal chemopreventive agent will require low toxicity as patients are likely to require treatment for several years before their risk of cancer is lowered to background levels. In principle, a combination of safe agents that work through distinct mechanisms will improve efficacy while simultaneously maintaining a favorable safety profile. Here, we describe the use of the decaffeinated green tea extract Polyphenon E (Poly E) (1% in diet) and aerosolized difluoromethylornithine (DFMO) (20 mg/kg/day, 5 days/week) in a mouse lung cancer chemoprevention study using a progression protocol. Female A/J mice were injected with benzo[a]pyrene (B[a]P) at 8 weeks of age and precancerous lesions allowed to form over a period of 21 weeks before chemoprevention treatment for an additional 25 weeks. Poly E treatment did not significantly inhibit average tumor multiplicity but reduced per animal tumor load. Analysis of tumor pathology revealed a specific inhibition of carcinomas, with the largest carcinomas significantly decreased in Poly E-treated animals. Aerosolized DFMO did not have a significant effect on lung tumor progression. Magnetic resonance imaging of B[a]P-induced lung tumors confirmed the presence of a subset of large, rapidly growing tumors in untreated mice. Our results suggest a potential role for green tea extracts in preventing the progression of large, aggressive lung adenocarcinomas.

Career research interests and training of genetic counseling students.

Research is important to validate clinical services, provide information on the effectiveness of practice techniques, and develop the knowledge base of a clinical profession. Genetic counseling students from American Board of Genetic Counseling (ABGC) accredited training programs were surveyed to determine their career research interests and interest in pursuing a hypothetical doctoral degree in genetic counseling. Genetic counseling program directors were surveyed to assess the emphasis on research training within their programs. A substantial number (46%, n = 92) of genetic counseling students are interested in performing research in their careers and many (40%, n = 80) would pursue a doctoral degree in genetic counseling if it was available. Students and directors from programs with a thesis requirement reported a significantly higher emphasis on career research preparation than those from programs without a thesis requirement. The results of this study indicate that future genetic counselors are interested in contributing to the research base that will advance the field. This study suggests a need to strengthen research training within ABGC accredited graduate programs and explore the development of a doctoral degree option in genetic counseling.

Bisphenol A facilitates bypass of androgen ablation therapy in prostate cancer.

Prostatic adenocarcinomas depend on androgen for growth and survival. First line treatment of disseminated disease exploits this dependence by specifically targeting androgen receptor function. Clinical evidence has shown that androgen receptor is reactivated in recurrent tumors despite the continuance of androgen deprivation therapy. Several factors have been shown to restore androgen receptor activity under these conditions, including somatic mutation of the androgen receptor ligand-binding domain. We have shown previously that select tumor-derived mutants of the androgen receptor are receptive to activation by bisphenol A (BPA), an endocrine-disrupting compound that is leached from polycarbonate plastics and epoxy resins into the human food supply. Moreover, we have shown that BPA can promote cell cycle progression in cultured prostate cancer cells under conditions of androgen deprivation. Here, we challenged the effect of BPA on the therapeutic response in a xenograft model system of prostate cancer containing the endogenous BPA-responsive AR-T877A mutant protein. We show that after androgen deprivation, BPA enhanced both cellular proliferation rates and tumor growth. These effects were mediated, at least in part, through androgen receptor activity, as prostate-specific antigen levels rose with accelerated kinetics in BPA-exposed animals. Thus, at levels relevant to human exposure, BPA can modulate tumor cell growth and advance biochemical recurrence in tumors expressing the AR-T877A mutation.

Genetic counselors and research: current practices and future directions.

Members of the genetic counseling community have debated the need for doctoral degree programs to further advance the profession. However, genetic counselors' interest in conducting independent research and attitudes toward obtaining a doctoral degree in genetic counseling has not been assessed in more than a decade. We designed a comprehensive web-based survey to characterize the current research values and practices of genetic counselors. Respondents were asked to self-report their current research involvement, their specific role in research activities, and their interest in performing research in the future. The study showed that a significant number of genetic counselors (84.5%) have conducted previous research, and 69.4% of respondents plan to perform research in the future. These results reflect the maturation of the genetic counseling field, in that a substantial number of genetic counselors consider active involvement in research to be a core role. The study also showed that 34.1% of respondents have high interest in a hypothetical PhD in Genetic Counseling, suggesting that the profession is primed for the development of doctoral degree training options.

Assessment of scientific and ethical issues in two randomized clinical trial designs for patients with Tourette's syndrome: a model for studies of multiple neuropsychiatric diagnoses.

Most clinical trials in Tourette's syndrome (TS) involve fewer than 60 patients. This is partially due to difficulties recruiting patients who have multiple neuropsychiatric diagnoses. Few studies permit treatment of comorbid diagnoses or compare active treatments. As a result, standard clinical practice requires choices between multiple agents shown to be superior to placebo agents in highly selected samples but never compare the two. Clinical practice also requires use of untested medication combinations. The authors review scientific and ethical shortcomings of placebo-controlled, monotherapy trials in TS, proposing specific conditions and methods and discussing the scientific, ethical, and economic implications of an alternative design: randomized, active-comparator, rater-only blinded clinical trials.

Meta-analysis of EEG test performance shows wide variation among studies.

BACKGROUND: EEG results are used for counseling patients with seizures about prognosis and deciding on medications. Published sensitivities of interictal EEG vary widely. OBJECTIVE: To account for variation in test characteristics between studies. METHODS: Meta-analysis. Medline search, 1970 to 2000, of English language studies. Standard methods for meta-analysis of diagnostic test performance were used to determine the ability of EEG results to distinguish between patients who will and will not have seizures. Using linear regression, the authors assessed the influence of readers' thresholds for classifying the EEG as positive, sample probability of seizure, percent of subjects with prior neurologic impairment, percent treated, and years followed. RESULTS: Twenty-five studies involving 4,912 EEG met inclusion criteria. Specificity (range 0.13 to 0.99) and sensitivity (range 0.20 to 0.91) of epileptiform EEG interpretations varied widely and were heterogeneous by chi(2) analysis (p < 0.001 for each). Diagnostic accuracy of EEG and the thresholds for classifying EEG as positive varied widely. In the multivariate model, differences in readers' thresholds accounted for 37% of the variance in EEG diagnostic accuracy, and no other reported factors were significant. CONCLUSION: This analysis suggests that there is wide interreader variation in sensitivity and specificity of EEG interpretations, and that this variation influences the ability of EEG to discriminate between those who will and will not have seizure recurrences. In clinical practice, interpreting the degree to which a positive EEG result predicts increased seizure risk in an individual patient is difficult. Interpreting EEG with higher specificity yields more accurate predictions.