Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal (GI) dysfunction, and altered gut microbiome compositions. Methods: We sought to better understand non-behavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (LC/MS and DMS-MS) with broad panels of identified metabolites. Herein, we present the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing (TD) controls. Results: Differences in amino acid, lipid, and xenobiotic metabolism discriminate ASD and TD samples. Our results implicate oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also reveal correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with GI dysfunction in ASD are provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice were identified. Conclusions: These findings support a connection between metabolism, GI physiology, and complex behavioral traits, and may advance discovery and development of molecular biomarkers for ASD

Assessing Communities of Practice in health policy : A conceptual framework as a first step towards empirical research

Peer reviewe

Quality indicators for responsible antibiotic use in the inpatient setting: a systematic review followed by an international multidisciplinary consensus procedure

Background This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use

Designing Tailored Web-Based Instruction to Improve Practicing Physicians' Preventive Practices

BACKGROUND: The World Wide Web has led to the rapid growth of medical information and continuing medical educational offerings. Ease of access and availability at any time are advantages of the World Wide Web. Existing physician-education sites have often been designed and developed without systematic application of evidence and cognitive-educational theories; little rigorous evaluation has been conducted to determine which design factors are most effective in facilitating improvements in physician performance and patient-health outcomes that might occur as a result of physician participation in Web-based education. Theory and evidence-based Web design principles include the use of: needs assessment, multimodal strategies, interactivity, clinical cases, tailoring, credible evidence-based content, audit and feedback, and patient-education materials. Ease of use and design to support the lowest common technology denominator are also important. OBJECTIVE: Using these principles, design and develop a Web site including multimodal strategies for improving chlamydial-screening rates among primary care physicians. METHODS: We used office-practice data in needs assessment and as an audit/feedback tool. In the intervention introduced in 4 phases over 11 months, we provided a series of interactive, tailored, case vignettes with feedback on peer answers. We included a quality-improvement toolbox including clinical practice guidelines and printable patient education materials. RESULTS: In the formative evaluation of the first 2 chlamydia modules, data regarding the recruitment, enrollment, participation, and reminders have been examined. Preliminary evaluation data from a randomized, controlled trial has tested the effectiveness of this intervention in improving chlamydia screening rates with a significant increase in intervention physicians' chlamydia knowledge, attitude, and skills compared to those of a control group. CONCLUSIONS: The application of theory in the development and evaluation of a Web-based continuing medical education intervention offers valuable insight into World Wide Web technology's influence on physician performance and the quality of medical care