Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults ...with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 10
, 10
or up to 10
cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.
Controversy surrounds the use of parenteral nutrition in critical illness. Previous overviews used composite scales to identify high-quality trials, which may mask important differences in true ...methodological quality. Using a component-based approach this meta-analysis investigated the effect of trial quality on overall conclusions reached when standard enteral nutrition is compared to standard parenteral nutrition in critically ill patients.
An extensive literature search was undertaken to identify all eligible trials. We retrieved 465 publications, and 11 qualified for inclusion. Nine trials presented complete follow-up, allowing the conduct of an intention to treat analysis.
Aggregation revealed a mortality benefit in favour of parenteral nutrition, with no heterogeneity. A priori specified subgroup analysis demonstrated the presence of a potentially important treatment-subgroup interaction between studies of parenteral vs. early enteral nutrition compared to parenteral vs. late enteral. Six trials with complete follow-up reported infectious complications. Infectious complications were increased with parenteral use. The I(2) measure of heterogeneity was 37.7%.
Intention to treat trials demonstrated reduced mortality associated with parenteral nutrition use. A priori subgroup analysis attributed this reduction to trials comparing parenteral to delayed enteral nutrition. Despite an association with increased infectious complications, a grade B+ evidence-based recommendation (level II trials, no heterogeneity) can be generated for parenteral nutrition use in patients in whom enteral nutrition cannot be initiated within 24 h of ICU admission or injury.
Priapism is a time-dependent emergency, which can lead to marked adverse effects on erectile function. We present the case of a patient with bipolar disorder who consumed a novel psychoactive ...substance, as well as an illegal substitute for sildenafil citrate. History revealed erectile dysfunction most likely secondary to hyperprolactinaema. This case, therefore, raises the question of whether this patient demographic should be routinely screened for this complaint.
Efficient literature searching and the application of formal rules of evidence in evaluating the clinical literature are the two key skills defining the practice of evidence-based medicine. Although ...clinicians embrace the concepts of evidence-based medicine, most identify limited personal time as the major barrier towards its implementation into daily practice. Busy clinicians who practice evidence-based medicine identify systematic reviews and evidence-based clinical practice guidelines as very useful resources.
This review presents a simple, easy-to-follow, three-step searching strategy that emphasises the use of powerful new PubMed features that allow clinicians to retrieve high-quality systematic reviews, clinical practice guidelines and primary studies with a single mouse click. The overall effectiveness of the process is further improved by highlighting the major features of successful and unsuccessful literature searches.
At the end of this tutorial the reader should be able to conduct efficient and effective literature searches that support clinical decision making in under 10 minutes.
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