International Consultation on Urological Diseases and European Association of Urology International Consultation on Minimally Invasive Surgery in Urology: laparoscopic and robotic adrenalectomy

The aim of this study was to provide an evidence‐based systematic review of the use of laparoscopic and robotic adrenalectomy in the treatment of adrenal disease as part of the International Consultation on Urological Diseases and European Association of Urology consultation on Minimally Invasive Surgery in Urology. A systematic literature search (January 2004 to January 2014) was conducted to identify comparative studies assessing the safety and efficacy of minimally invasive adrenal surgery. Subtopics including the role of minimally invasive surgery for pheochromocytoma, adrenocortical carcinoma (ACC) and large adrenal tumours were examined. Additionally, the role of transperitoneal and retroperitoneal approaches, as well as laparoendoscopic single‐site (LESS) and robotic adrenalectomy were reviewed. The major findings are presented in an evidence‐based fashion. Large retrospective and prospective data were analysed and a set of recommendations provided by the committee was produced. Laparoscopic surgery should be considered the first‐line therapy for benign adrenal masses requiring surgical resection and for patients with pheochromocytoma. While a laparoscopic approach may be feasible for selected cases of ACC without adjacent organ involvement, an open surgical approach remains the ‘gold standard’. Large adrenal tumours without preoperative or intra‐operative suspicion of ACC may be safely resected via a laparoscopic approach. Both transperitoneal and retroperitoneal approaches to laparoscopic adrenalectomy are safe. The approach should be chosen based on surgeon training and experience. LESS and robotic adrenalectomy should be considered as alternatives to laparoscopic adrenalectomy but require further study.     

Dietitians' Perspectives on Teaching Nutrition to Medical Students

Objectives: The provision of nutrition care by health professionals can facilitate improved patient nutrition behaviors. Some education institutions include nutrition in their medical curriculum; however, doctors and medical students continue to lack competence in providing nutrition care. Dietitians are increasingly teaching nutrition to medical students, yet evidence on the topic remains anecdotal. It is important to understand the experiences of these dietitians to support improvements in undergraduate medical nutrition education. The aim of this study was to explore dietitians' perspectives of teaching nutrition to medical students.

Methods: A qualitative study was conducted in collaboration with the Need for Nutrition Education/Innovation Programme (NNEdPro). Twenty-four dietitians who had provided nutrition education to medical students participated in individual semistructured interviews. Participants were from Australia (n = 5), New Zealand (n = 1), the United States (n = 6), Canada (n = 5), the United Kingdom (n = 5), Germany (n = 1), and Finland (n = 1). Data analysis was conducted using a constant comparative approach to thematic analysis.

Results: The dietitians expressed confidence in their ability to teach medical students and believed that they were the most appropriate professionals to administer the education. However, they were not confident that medical students graduate with sufficient nutrition competence and attributed this to poor curriculum planning for nutrition. Dietitians had access to useful resources and tools to support education, with opportunity to contribute further to integration of nutrition throughout medical curricula.

Conclusion: This study suggests that dietitians are likely appropriate nutrition teachers in medical education. However, optimizing dietitians' role requires their further involvement in curriculum planning and development. Including dietitians as members of medical faculty would facilitate their input on nutrition throughout the curriculum, which could enhance the nutrition education of medical students.     

Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference

Diamond Blackfan anaemia (DBA) is a rare, genetically and clinically heterogeneous, inherited red cell aplasia. Classical DBA affects about seven per million live births and presents during the first year of life. However, as mutated genes have been discovered in DBA, non-classical cases with less distinct phenotypes are being described in adults as well as children. In caring for these patients it is often difficult to have a clear understanding of the treatment options and their outcomes because of the lack of complete information on the natural history of the disease. The purpose of this document is to review the criteria for diagnosis, evaluate the available treatment options, including corticosteroid and transfusion therapies and stem cell transplantation, and propose a plan for optimizing patient care. Congenital anomalies, mode of inheritance, cancer predisposition, and pregnancy in DBA are also reviewed. Evidence-based conclusions will be made when possible; however, as in many rare diseases, the data are often anecdotal and the recommendations are based upon the best judgment of experienced clinicians. The recommendations regarding the diagnosis and management described in this report are the result of deliberations and discussions at an international consensus conference.     

Derivation of a bisphenol A oral reference dose (RfD) and drinking-water equivalent concentration

Human exposure to bisphenol A (BPA) is due to that found in the diet, and BPA and its metabolites were detected at parts per billion (or less) concentrations in human urine, milk, saliva, serum, plasma, ovarian follicular fluid, and amniotic fluid. Adverse health effects in mice and rats may be induced after parenteral injection or after massive oral doses. Controlled ingestion trials in healthy adult volunteers with 5 mg d16-BPA were unable to detect parent BPA in plasma despite exquisitely sensitive (limit of detection = 6 nM) methods, but by 96 h 100% of the administered dose was recovered in urine as the glucuronide. The extensive BPA glucuronidation following ingestion is not seen after parenteral injection; only the parent BPA binds plasma proteins and estrogen receptors (ER). The hypothesis that BPA dose-response may be described by a J- or U-shape curve was not supported by toxicogenomic data collected in fetal rat testes and epididymes (after repeated parenteral exposure at 2-400,000 microg/kg-d), where a clear monotonic dose-response both in the numbers of genes and magnitude of individual gene expression was evident. There is no clear indication from available data that the BPA doses normally consumed by humans pose an increased risk for immunologic or neurologic disease. There is no evidence that BPA poses a genotoxic or carcinogenic risk and clinical evaluations of 205 men and women with high-performance liquid chromatography (HPLC)-verified serum or urinary BPA conjugates showed (1) no objective signs, (2) no changes in reproductive hormones or clinical chemistry parameters, and (3) no alterations in the number of children or sons:daughters ratio. Results of benchmark dose (BMD10 and BMDL10) calculations and no-observed-adverse-effect level (NOAEL) inspections of all available and reproducible rodent studies with oral BPA found BMD and NOAEL values all greater than the 5 mg/kg-d NOAELs from mouse and rat multigeneration reproduction toxicity studies. While allometric and physiologically based pharmacokinetic (PBPK) models were constructed for interspecies scaling of BPA and its interaction with ER, multigeneration feeding studies with BPA at doses spanning 5 orders of magnitude failed to identify signs of developmental toxicity or adverse changes in reproductive tract tissues; the 5-mg/kg-d NOAELs identified for systemic toxicity in rats and mice were less than the oral NOAELs for reproductive toxicity. Thus, it is the generalized systemic toxicity of ingested BPA rather than reproductive, immunologic, neurobehavioral, or genotoxic hazard that represents the point of departure. Using U.S. Environmental Protection Agency (EPA) uncertainty factor guidance and application of a threefold database uncertainty factor (to account for the fact that the carcinogenic potential of transplacental BPA exposure has yet to be fully defined and comprehensive neurobehavioral and immunotoxicologic evaluations of BPA by relevant routes and at relevant doses have yet to be completed) to the administered dose NOAEL results in an oral RfD of 0.016 mg/kg-d. Assuming the 70-kg adult consumes 2 L of water each day and adopting the default 20% U.S. EPA drinking water relative source contribution yields a 100 microg/L BPA total allowable concentration (TAC).     

A non-inferiority comparison of duloxetine and venlafaxine in the treatment of adult patients with generalized anxiety disorder

The present study is a non-inferiority comparison of duloxetine 60-120 mg/day and venlafaxine extended-release (XR) 75-225 mg/day for the treatment of adults with generalized anxiety disorder (GAD). The non-inferiority test was a prespecified plan to pool data from two nearly identical 10-week, multicentre, randomized, placebo-controlled, double-blind studies of duloxetine 60-120 mg/day and venlafaxine 75-225 mg/ day for the treatment of GAD. An independent expert consensus panel provided six statistical and clinical criteria for determining non-inferiority between treatments. Response was defined as > or =50% reduction in Hamilton Anxiety Rating Scale (HAMA) total score. In the pooled sample, patients were randomly assigned to duloxetine (n = 320), venlafaxine XR (n = 333) or placebo (n = 331). For the non-inferiority analysis, the per-protocol patients who were treated with duloxetine (n = 239) or venlafaxine XR (n = 262) improved significantly more (mean HAMA reductions were -15.4 and -15.2, respectively) than placebo-treated patients (n = 267; -11.6, P < or = 0.001, both comparisons). Response rates were 56%, 58% and 40%, respectively. Discontinuation rate because of AEs was significantly higher for duloxetine (13.4%, P < or = 0.001) and venlafaxine XR (11.4%, P < or = 0.01) groups compared with placebo (5.4%). Duloxetine 60-120 mg/day met all statistical and clinical criteria for non-inferiority and exhibited a similar tolerability profile compared with venlafaxine XR 75-225 mg/day for the treatment of adults with GAD.