Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

BackgroundA venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines.AimThe aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration.MethodsThrough a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.     

Effects of tolazamide and exogenous insulin on pattern of postprandial carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus. Results of randomized crossover trial

To determine whether therapy with exogenous insulin or sulfonylureas results in a postprandial pattern of carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM) that resembles that in nondiabetic individuals, we employed a dual-isotope technique combined with forearm catheterization to examine meal disposition in NIDDM patients, before and after 3 mo of therapy with tolazamide and after 3 mo of therapy with exogenous insulin, with a randomized crossover design. Results were compared with those observed in nondiabetic subjects. Although both forms of therapy improved chronic glycemic control (glycosylated hemoglobin concentration went from 9.6 +/- 0.7 to 7.6 +/- 0.5 and 7.1 +/- 0.2%, respectively, P less than .01), exogenous insulin resulted in a lower postprandial glycemic response than tolazamide (P less than .001). Both agents comparably increased (P less than .01) fasting and integrated postprandial insulin concentrations. However, the initial rate of postprandial increase was greater with exogenous insulin (P less than .05). Tolazamide (P less than .05) but not exogenous insulin increased postprandial C-peptide concentrations. However, tolazamide did not improve the deficient early insulin release. Both agents (P less than .05) lowered postabsorptive hepatic glucose release (from 2.8 +/- 0.3 to 2.3 +/- 0.2 mg . kg-1 . min-1), but not to normal rates (1.8 +/- 0.1 mg . kg-1 . min-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Right Hepatic Lobectomy Using the Staple Technique in 101 Patients

Background Application of linear stapling devices for extrahepatic vascular control in liver surgery has been well-established. However, the technique for use of stapling devices in hepatic parenchymal transection is not well defined. Purpose To describe the safety and efficacy of our technique for use of vascular stapling devices in hepatic parenchymal transection during open right hepatic lobectomy is the purpose of this study. Methodology We reviewed our experience with 101 consecutive open right hepatic lobectomies performed by a single surgeon between January 2003 and July 2006, in which vascular staplers were utilized for the parenchymal transection phase. Results Of the 101 patients who underwent resection, 53 (52%) were female. The mean age was 58 years. Malignant disease was the indication for resection in the majority of patients (88%). Of those with cancer, 78% (69 of 89) had metastatic colorectal cancer, 6% (5 of 89) had metastatic neuroendocrine tumor, 4% (4 of 89) had hepatocellular carcinoma, 4% (4 of 89) had cholangiocarcinoma, and the remaining 8% were other metastatic cancers. Twelve patients (12%) underwent resection for hepatic adenoma or symptomatic benign disease (FNH or hemangioma). Forty-eight patients (48%) underwent a major ancillary procedure at the time of hepatic resection. Thirty-nine patients (39%) had a nonanatomic wedge resection of a left lobe lesion, 27 patients (27%) had one or more lesions treated with radiofrequency ablation (RFA), and 6 patients (6%) were treated with a synchronous bowel resection. The median total operative time was 336 min (range 155–620 min). A Pringle maneuver for temporary vascular inflow occlusion was utilized in all cases, with a median time of 9 min (range 4–17 min). Ten patients (10%) required blood transfusion during surgery or in the postoperative period. The maximum transfusion was 2 U of packed red blood cells (PRBC) in seven patients and 1 U of PRBC in three patients. The mean nadir postoperative hematocrit was 28.2. All patients with malignant disease had tumor-free margins at the completion of the procedure. The average hospital length of stay was 6.0 days. One patient (1%) developed a clinically significant bile leak requiring a postoperative endoscopic retrograde cholangiography (ERCP). No patient required reoperation. The 30 and 60-day postoperative survival was 100%. Conclusion These findings indicate that application of vascular stapling devices for parenchymal transection in major hepatic resection is a safe technique, with low transfusion requirements and minimal postoperative bile leak. The technique allows for rapid transection of the entire right hepatic lobe in under 10 min. Short video clips of the technique will be demonstrated. Presented at the 2007 American Hepato–Pancreato–Biliary Association, Las Vegas, Nevada, April 19–22, 2007 (oral presentation/video presentation).     

Cholinoceptor-mediated mechanical and electrical responses of rat oesophageal striated musculature. A comparison of two in vitro methods

1. Both muscarinic and nicotinic cholinoceptor agonists produce a contractile response of the rat oesophageal tunica muscularis externa (TME) in vitro. 2. The muscarinic receptor-mediated responses were confined to the distal 0.5 cm of the TME, which contains an admixture of smooth muscle. 3. Nicotinic receptor-mediated responses were obtained throughout the length of the TME striated musculature and consisted of a fast and slow component, representing TTX-sensitive contractions, associated with muscle action potentials, and electrically silent contractures, respectively. 4. Contractions were observed only in superfused preparations. 5. Contractures were resistant to changes in extracellular cation concentrations designed to eliminate generation of nerve and muscle action potentials or release of neurotransmitters.     

Interactions of angiotensin IV and oxytocin on behaviour in mice.

INTRODUCTION: Angiotensin (Ang) IV enhances learning and memory in rats but there are strain differences in its effects in mice. Oxytocin (OT) also influences learning and memory in rats and mice and, in the light of the proposed effects of Ang IV on oxytocinase, the hypothesis that the effects of Ang IV on cognition in mice involve OT was tested. MATERIALS AND METHODS: The effects of Ang IV and OT, alone and combined, were determined in rat isolated uterine smooth muscle and in object recognition and forced swim tests in BKW mice. RESULTS: Ang potentiated the contractile effects of OT in the uterus. Neither peptide had any effect on object recognition nor locomotor activity. Ang IV had no effect in the forced swim test but abolished the effects of OT. CONCLUSIONS: Ang IV influences the actions of OT in vitro and in vivo, possibly by inhibition of oxytocinase, but the lack of effect of Ang IV on object recognition in BKW mice is unlikely to be a consequence of a deficiency endogenous OT. Unlike OT, Ang IV alone has no effect on learned helplessness in the forced swim test, an effect often used to predict potential antidepressant efficacy in humans.     

Pattern of postprandial carbohydrate metabolism and effects of portal and peripheral insulin delivery

The importance of portal insulin delivery in the regulation of postprandial carbohydrate metabolism is uncertain. To address this question, three groups of dogs were studied: one group in which pancreatic venous drainage was transected and reanastomosed (portal insulin delivery), one in which the pancreatic drainage was transected and anastomosed to the inferior vena cava (peripheral insulin delivery), and one that received only a sham operation. Plasma insulin was greater (P less than 0.05) during peripheral insulin delivery than in either the portal or sham groups, respectively, before and after meal ingestion. On the other hand, C-peptide concentrations did not differ between groups, resulting in a higher (P less than 0.001) insulin to C-peptide ratio in the peripheral group. This indicated that the hyperinsulinemia in the peripheral group was due to decreased insulin clearance rather than increased insulin secretion. Isotopically determined splanchnic uptake of ingested glucose, postprandial suppression of hepatic glucose release, incorporation of CO2 into glucose (a qualitative measure of gluconeogenesis), and total-body glucose uptake were virtually identical in all groups. Similarly, plasma lipid, beta-hydroxybutyrate, and lactate concentrations did not differ between groups. Our data indicate that, despite differences in systemic insulin concentration, portal and peripheral insulin delivery comparably regulate hepatic and extrahepatic carbohydrate metabolism after meal ingestion.