ABSTRACT
BACKGROUND/AIMS: Over the last decade, multiple molecular defects of the GH-IGF axis have been identified and characterized, greatly expanding our appreciation of the genotypic and phenotypic variability of endocrine growth disorders. METHODS: In an effort to address the growing complexity of molecular defects and their characteristic phenotypes, a Growth Genetics Consortium was established in 2008, with the goal of developing a repository of case information on all patients with genetic variations in the GH-IGF axis. A database was established, along with a publicly accessible website (www.growthgenetics.com), with registration open to all potential users. RESULTS: The genes currently available in the database include GHR, Stat5b, IGF1, IGF2, IGFALS and IGF1R. The data collected include clinical details, auxology, family history, laboratory data, identified molecular defects and, if relevant, treatment information. CONCLUSIONS: It is planned for the database and website to eventually include all identified genes in the GH-IGF axis.
Subject(s)
Databases, Genetic , Growth Disorders/genetics , Human Growth Hormone/genetics , Internet , Mutation , Receptors, Somatotropin/genetics , Somatomedins/genetics , Adolescent , Child , Growth Charts , Growth Disorders/epidemiology , Human Growth Hormone/metabolism , Humans , Signal Transduction/genetics , Somatomedins/metabolism , User-Computer InterfaceABSTRACT
UNLABELLED: A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments. A group of 40 participants from universities, governmental agencies, a patient self-help organization, and the pharmaceutical industry considered methodologic issues and research results relevant to determining the clinical importance of changes in the specific outcome measures previously recommended by IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression Inventory and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures. Provisional benchmarks for identifying clinically important changes in specific outcome measures that can be used for outcome studies of treatments for chronic pain are proposed. PERSPECTIVE: Systematically collecting and reporting the recommended information needed to evaluate the clinical importance of treatment outcomes of chronic pain clinical trials will allow additional validation of proposed benchmarks and provide more meaningful comparisons of chronic pain treatments.
Subject(s)
Clinical Trials as Topic/methods , Pain Management , Pain Measurement/methods , Research Design , Treatment Outcome , HumansSubject(s)
Clinical Trials as Topic/standards , Outcome Assessment, Health Care/standards , Pain Measurement/standards , Pain/classification , Pain/diagnosis , Practice Guidelines as Topic , Surveys and Questionnaires/standards , Clinical Trials as Topic/methods , Humans , Outcome Assessment, Health Care/methods , Pain Measurement/methods , Practice Patterns, Physicians'/standards , United StatesABSTRACT
Capsaicin-containing plant extracts have been used as topical treatments for a variety of pain syndromes for many centuries. Current products containing capsaicin in low concentrations (usually 0.025-0.075% w/w) have shown efficacy against a variety of pain conditions in clinical studies. However, in order to produce significant analgesic effects, these formulations require frequent re-dosing, often as much as three to five times daily for several weeks. Previous functional and immunohistochemical studies following prolonged exposures to low-concentration capsaicin cream suggested that the duration and onset of analgesic efficacy correlate with a reduction of cutaneous nociceptive sensory nerve fiber responsiveness and immunostaining. The purpose of the present study was to determine whether a single topical application of a high-concentration capsaicin-containing (8%w/w) patch for 120 min or less would induce similar effects on cutaneous nociceptive nerve fibers. Seven days following patch application, changes in heat and cold perception thresholds were determined by quantitative sensory testing and punch biopsies were collected to assess epidermal nerve fiber (ENF) immunostaining density at the application site using PGP 9.5 as a marker. The results show a significant reduction of heat, but not cold, sensitivity and reduction of ENF immunostaining with high-capsaicin concentration patch applications for 60 or 120 min, compared to placebo patch applications. Application sites exposed to low-capsaicin concentration (0.04%w/w) patches for 120 min or high-concentration patches for 30 min were not significantly different from placebo with respect to either thermal threshold detection or ENF immunostaining. The ability of a single 60 min high-concentration patch application to mimic effects produced by prolonged exposure to low-concentration capsaicin creams suggests a new approach to the management of chronic pain syndromes.
