Metformin treatment in diabetes and heart failure: when academic equipoise meets clinical reality

<p>Abstract</p> <p>Objective</p> <p>Metformin has had a 'black box' contraindication in diabetic patients with heart failure (HF), but many believe it to be the treatment of choice in this setting. Therefore, we attempted to conduct a pilot study to evaluate the feasibility of undertaking a large randomized controlled trial with clinical endpoints.</p> <p>Study Design</p> <p>The pilot study was a randomized double blinded placebo controlled trial. Patients with HF and type 2 diabetes were screened in hospitals and HF clinics in Edmonton, Alberta, Canada (population ~1 million). Major exclusion criteria included the current use of insulin or high dose metformin, decreased renal function, or a glycosylated hemoglobin <7%. Patients were to be randomized to 1500 mg of metformin daily or matching placebo and followed for 6 months for a variety of functional outcomes, as well as clinical events.</p> <p>Results</p> <p>Fifty-eight patients were screened over a six month period and all were excluded. Because of futility with respect to enrollment, the pilot study was abandoned. The mean age of screened patients was 77 (SD 9) years and 57% were male. The main reasons for exclusion were: use of insulin therapy (n = 23; 40%), glycosylated hemoglobin <7% (n = 17; 29%) and current use of high dose metformin (n = 12; 21%). Overall, contraindicated metformin therapy was the most commonly prescribed oral antihyperglycemic agent (n = 27; 51%). On average, patients were receiving 1,706 mg (SD 488 mg) of metformin daily and 12 (44%) used only metformin.</p> <p>Conclusion</p> <p>Despite uncertainty in the scientific literature, there does not appear to be clinical uncertainty with regards to the safety or effectiveness of metformin in HF making a definitive randomized trial virtually impossible.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00325910</p

Vacuum-assisted wound closure and mesh-mediated fascial traction - A novel technique for late closure of the open abdomen

Background Open abdomen (OA) treatment often results in difficulties in closing the abdomen. Highest closure rates are seen with the vacuum-assisted wound closure (VAWC) technique. However, we have experienced occasional failures with this technique in cases with severe visceral swelling needing longer treatment periods with open abdomen. Feasibility and short-term outcome of a novel combination of techniques for managing the open abdomen are presented. Methods The VAWC technique was combined with medial traction of the fasciae through a temporary mesh in seven consecutive patients. The VAWC-system was changed and the mesh tightened every 2-3 days. Results Median (range) age in the 7 men was 65 (17-78) years. The diagnoses were ruptured abdominal aortic aneurysm (AAA) (3), operation for juxtarenal AAA (1), iatrogenic aortic lesion (1), trauma (1) and abdominal abscesses (1). Four patients were decompressed due to abdominal compartment syndrome (ACS) or intra-abdominal hypertension, and 3 could not be closed after laparotomy. Intra-abdominal pressure prior to OA treatment was 24 (17-36) mmHg. Maximal separation of the fasciae was 16 (7 -30) cm. Delayed primary closure was achieved in all patients after 32 (12-52) days with OA. No recurrent ACS was seen. No technique-specific complication was observed. Two small incisional hernias, one intra-abdominal abscess and one wound infection occurred in three patients. Conclusions Delayed primary closure in cases with severe visceral swelling and long periods of OA seems feasible with this technique