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The role of the multidrug resistance protein MRP4/ABCC4 in vivo remains undefined. To explore this role, we generated Mrp4-deficient mice. Unexpectedly, these mice showed enhanced accumulation of the anticancer agent topotecan in brain tissue and cerebrospinal fluid (CSF). Further studies demonstrated that topotecan was an Mrp4 substrate and that cells(More)
The 4-anilinoquinazoline (4-AQ) derivative gefitinib (Iressa) is an oral epidermal growth factor receptor tyrosine kinase inhibitor. Oral administration of 4-AQ molecules, such as gefitinib, inhibits ATP-binding cassette (ABC) transporter-mediated drug efflux and strongly increases the apparent bioavailability of coadministered drug molecules that are(More)
Presenting continuous outcomes in Summary of Findings tables presents particular challenges to interpretation. When each study uses the same outcome measure, and the units of that measure are intuitively interpretable (e.g., duration of hospitalization, duration of symptoms), presenting differences in means is usually desirable. When the natural units of(More)
BACKGROUND Antibiotics are widely prescribed; however they can cause disturbances in gastrointestinal flora which may lead to reduced resistance to pathogens such as Clostridium difficile (C. difficile). Probiotics are live organisms thought to balance the gastrointestinal flora. OBJECTIVES The primary objectives were to assess the efficacy and safety of(More)
BACKGROUND No methods directly address the impact of missing participant data for continuous outcomes in systematic reviews on risk of bias. METHODS We conducted a consultative, iterative process to develop a framework for handling missing participant data for continuous outcomes. We considered sources reflecting real observed outcomes in participants(More)
BACKGROUND - Meta-analyses of health-related quality of life (HRQL) outcomes present difficulties in interpretation when studies use different instruments to measure the same construct. Presentation of results in standard deviation units (standardized mean difference) is widely used but is limited by vulnerability to differential variability in populations(More)
OBJECTIVE Pain is a patient-important outcome, but current reporting in randomized controlled trials and systematic reviews is often suboptimal, impeding clinical interpretation and decision making. METHODS A working group at the 2014 Outcome Measures in Rheumatology (OMERACT 12) was convened to provide guidance for reporting treatment effects regarding(More)
BACKGROUND Postoperative infections, particularly surgical site infections (SSIs), cause significant morbidity and mortality. Probiotics or synbiotics are a potential prevention strategy. AIM To evaluate the efficacy of probiotics/synbiotics for reducing postoperative infection risk following abdominal surgery. METHODS We searched AMED, Central, CINAHL,(More)
BACKGROUND The accessibility to improved water and sanitation has been understood as a crucial mechanism to save infants and children from the adverse health outcomes associated with diarrheal disease. This knowledge stimulated the worldwide donor community to develop a specific category of aid aimed at the water and sanitation sector. The actual impact of(More)
OBJECTIVES Expressing treatment effects in relative terms yields larger numbers than expressions in absolute terms, affecting the judgment of the clinicians and patients regarding the treatment options. It is uncertain how authors of systematic reviews (SRs) absolute effect estimates are reported in. We therefore undertook a systematic survey to identify(More)