Physiology of Energy Expenditure in the Weight-Reduced State.

Although many individuals achieve weight loss of 10% or more, the ability to maintain a reduced body mass over months and years is much rarer. Unfortunately, our understanding of the adverse consequences of having overweight and obesity argues that long-term maintenance of a reduced weight provides the greatest health benefit. However, to achieve long-term weight reduction requires overcoming neuroendocrine systems that favor restoration of one's initial weight. Identifying and characterizing the components of these systems will be important if we are to develop therapies and strategies to reduce the rates of obesity and its complications in our modern society. During this session, Eric Ravussin and Steven R. Smith, respectively, discussed the physiology of the weight-reduced state that favors weight regain and a molecular component that contributes to this response.

Current State and Future of Research in Nephrology.

The focus of this article is to review the available funding opportunities for the nephrology workforce at all career levels and review the current challenges involved in the career of a physician-scientist. While the scarcity of nephrology fellows for training programs is a continuing challenge, increased funding for the National Institutes of Health is encouraging particularly for early career investigators. In addition to National Institutes of Health funding, other funding sources are also discussed as they provide much needed bridge funding during key transition periods for young careers. Recent initiatives such as the Advancing American Kidney Health, KidneyX, and National Institute of Diabetes and Digestive and Kidney Diseases' Kidney Precision Medicine Project offer new research opportunities for bringing much needed innovation to improve lives of people with kidney diseases. The time is now for us to seize the opportunity and ensure that a strong workforce will be able to take advantage of these potential game changers for nephrology.

Glomerular Diseases: Registries and Clinical Trials.

Nephrology has conducted few high-quality clinical trials, and the trials that have been conducted have not resulted in the approval of new treatments for primary or inflammatory glomerular diseases. There are overarching process issues that affect the conduct of all clinical trials, but there are also some specialty-specific issues. Within nephrology, primary glomerular diseases are rare, making adequate recruitment for meaningful trials difficult. Nephrologists need better ways, beyond histopathology, to phenotype patients with glomerular diseases and stratify the risk for progression to ESRD. Rigorous trial design is needed for the testing of new therapies, where most patients with glomerular diseases are offered the opportunity to enroll in a clinical trial if standard therapies have failed or are lacking. Training programs to develop a core group of kidney specialists with expertise in the design and implementation of clinical trials are also needed. Registries of patients with glomerular disease and observational studies can aid in the ability to determine realistic estimates of disease prevalence and inform trial design through a better understanding of the natural history of disease. Some proposed changes to the Common Rule, the federal regulations governing the ethical conduct of research involving humans, and the emerging use of electronic health records may facilitate the efficiency of initiating multicenter clinical trials. Collaborations among academia, government scientific and regulatory agencies, industry, foundations, and patient advocacy groups can accelerate therapeutic development for these complex diseases.

Effect Sizes and Primary Outcomes in Large-Budget, Cardiovascular-Related Behavioral Randomized Controlled Trials Funded by NIH Since 1980.

PURPOSE: We reviewed large-budget, National Institutes of Health (NIH)-supported randomized controlled trials (RCTs) with behavioral interventions to assess (1) publication rates, (2) trial registration, (3) use of objective measures, (4) significant behavior and physiological change, and (5) effect sizes. METHODS: We identified large-budget grants (>$500,000/year) funded by NIH (National Heart Lung and Blood Institute (NHLBI) or National Institute of Diabetes & Digestive and Kidney Diseases (NIDDK)) for cardiovascular disease (dates January 1, 1980 to December 31, 2012). Among 106 grants that potentially met inclusion criteria, 20 studies were not published and 48 publications were excluded, leaving 38 publications for analysis. ClinicalTrials.gov abstracts were used to determine whether outcome measures had been pre-specified. RESULTS: Three fourths of trials were registered in ClinicalTrials.gov and all published pre-specified outcomes. Twenty-six trials reported a behavioral outcome with 81 % reporting significant improvements for the target behavior. Thirty-two trials reported a physiological outcome. All were objectively measured, and 81 % reported significant benefit. Seventeen trials reported morbidity outcomes, and seven reported a significant benefit. Nine trials assessed mortality, and all were null for this outcome. CONCLUSIONS: Behavioral trials complied with trial registration standards. Most reported a physiological benefit, but few documented morbidity or mortality benefits.

Total pancreatectomy with islet autotransplantation: summary of a National Institute of Diabetes and Digestive and Kidney diseases workshop.

A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases focused on research gaps and opportunities in total pancreatectomy with islet autotransplantation (TPIAT) for the management of chronic pancreatitis (CP). The session was held on July 23, 2014, and structured into 5 sessions: (1) patient selection, indications, and timing; (2) technical aspects of TPIAT; (3) improving success of islet autotransplantation; (4) improving outcomes after total pancreatectomy; and (5) registry considerations for TPIAT. The current state of knowledge was reviewed; knowledge gaps and research needs were specifically highlighted. Common themes included the need to identify which patients best benefit from and when to intervene with TPIAT, current limitations of the surgical procedure, diabetes remission and the potential for improvement, opportunities to better address pain remission, gastrointestinal complications in this population, and unique features of children with CP considered for TPIAT. The need for a multicenter patient registry that specifically addresses the complexities of CP and total pancreatectomy outcomes as well as postsurgical diabetes outcomes was repeatedly emphasized.

Sample and data sharing: observations from a central data repository.

OBJECTIVES: From 2003 to 2013, RTI International served as the data repository for the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK). RTI worked closely with two sample repository partners to build and maintain the Central Repository (CR) that made data and samples available to approved requestors. In this paper, we recap aspects of establishing the mechanism; detail the challenges and limitations of data and sample sharing, and explore the future of resource sharing in light of the evolving environment of research funding. DESIGN AND METHODS: Effective maintenance required the system to be flexible and dynamic while at the same time compliant with established data standards. RESULTS: Our years serving as the CR for NIDDK have yielded a number of observations about the difficulties of running a repository, an operation that is by definition dependent on many outside parties whose degree of expertise and efficiency have a direct impact on repository functioning. CONCLUSION: The bio-banking industry will likely continue to become more globally centralized for studying specific genetic diseases and monitoring the health of our environment. The dynamic relationship between emerging technologies and the infrastructure will be needed to support future research that requires the ability of organizations providing support to remain flexible even while following established standards.