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Darrah J.,University of Alberta | O'Donnell M.,University of British Columbia | O'Donnell M.,Center for International Child Health | O'Donnell M.,Child Health BC | And 7 more authors.
Infants and Young Children | Year: 2013

Clinical practice frameworks are a valuable component of clinical education, promoting informed clinical decision making based on the best available evidence and/or clinical experience. They encourage standardized intervention approaches and evaluation of practice. Based on an international project to support the development of an enhanced service system for infants and young children with neuromotor disabilities in Guangzhou, China, this article describes the processes used to develop a practice framework to guide therapists' intervention choices to encourage the gross motor abilities of infants and children (0-3 years of age) exhibiting hypotonia and gross motor delays. The goal was to provide a practice framework that aligns with contemporary interest in activity-focused intervention approaches and that considers both a child's abilities and the influence of environmental context in the achievement of gross motor skills. The final product, the Hypotonia Wheel, is presented. It may be useful for therapists and early intervention providers who work with infants and young children with hypotonia. The process used to design the Hypotonia Wheel also could be used as a template to develop intervention guidelines for other clinical conditions. Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Tebruegge M.,University of Melbourne | Tebruegge M.,Royal Melbourne Hospital | Tebruegge M.,Murdoch Childrens Research Institute | Tebruegge M.,University of Southampton | And 25 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2015

Rationale: Current immunodiagnostic tests for tuberculosis (TB), including the tuberculin skin test and IFN-γ release assay (IGRA), have significant limitations, which include their inability to distinguish between latent TB infection (LTBI) and active TB, a distinction critical for clinical management. Objectives: To identify mycobacteria-specific cytokine biomarkers that characterize TB infection, determine their diagnostic performance characteristics, and establish whether these biomarkers can distinguish between LTBI and active TB. Methods: A total of 149 children investigated for TB infection were recruited; all participants underwent a tuberculin skin test and QuantiFERON-TB Gold assay. In parallel, whole-blood assays using early secretory antigenic target-6, culture filtrate protein-10, and PPD as stimulatory antigens were undertaken, and cytokine responses were determined by xMAP multiplex assays. Measurements and Main Results: IFN-γ, interferon-inducible protein-10 (IP-10), tumor necrosis factor (TNF)-α, IL-1ra, IL-2, IL-13, and MIP-1β (macrophage inflammatory protein-1β) responses were significantly higher in LTBI and active TB cases than in TB-uninfected individuals, irrespective of the stimulant. Receiver operating characteristic analyses showed that IP-10, TNF-α, and IL-2 responses achieved high sensitivity and specificity for the distinction between TB-uninfected and TB-infected individuals. TNF-α, IL-1ra, and IL-10 responses had the greatest ability to distinguish between LTBI and active TB cases; the combinations of TNF-α/IL-1ra and TNF-α/IL-10 achieved correct classification of 95.5% and 100% of cases, respectively. Conclusions: We identified several mycobacteria-specific cytokine biomarkers with the potential to be exploited for immunodiagnosis. Incorporation of these biomarkers into future immunodiagnostic assays for TB could result in substantial gains in sensitivity and allow the distinction between LTBI and active TB based on a blood test alone. Copyright © 2015 by the American Thoracic Society.


Seear M.,Center for International Child Health | Seear M.,Oak Street Health | Gandhi D.,Center for International Child Health | Carr R.,Childrens and Womens Hospital | And 3 more authors.
Journal of Clinical Pharmacy and Therapeutics | Year: 2011

What is known and objective: There is still surprisingly little basic research data to support widely repeated claims about the prevalence of drug counterfeiting. To meet the need for more reliable drug quality data, we designed a study framework that includes clear definitions of measured end points, sampling methods and assay technique. Our objective was to test this research design in Chennai (formerly Madras), India, using a joint Indian and Canadian team. Methods: The city was divided into ten areas along municipal lines. From each area, ten stores and pharmacies selling drugs were selected. At each of these 100 outlets, three study drugs (artesunate, ciprofloxacin and rifampicin) were purchased. The 300 samples were tested by Liquid Chromatography-Mass Spectrometry. Assay content was expressed as a percentage of stated tablet content. Based on assay results and their distribution, we developed drug quality definitions for normal manufacturing standards, counterfeiting, decomposition, poor quality control and adulteration. Results: The group mean for ciprofloxacin was close to normal manufacturing limits (99·2 ± 7·1%) but rifampicin (91·6 ± 5·7%), and artesunate (80·1 ± 9·1%), were both below normal pharmaceutical standards. Overall, 43% of all samples fell below the widely accepted manufacturing range of 90-110% of stated content. No tablet from any sample contained less than 50% of the stated dose. What is new and conclusion: The quality of at least some anti-infective drugs in Chennai is below commonly accepted standards but we found no evidence of criminal counterfeiting. Poor drug quality was most likely due to decomposition during storage or poor manufacturing standards. Our research methodology worked well under practical conditions and should hopefully be of value to others working in this area. © 2010 Blackwell Publishing Ltd.

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