PROactive 07: pioglitazone in the treatment of type 2 diabetes: results of the PROactive study

Patients with type 2 diabetes face an increased risk of macrovascular disease compared to those without. Significant reductions in the risk of major cardiovascular events can be achieved with appropriate drug therapy, although patients with type 2 diabetes remain at increased risk compared with non-diabetics. The thiazolidinedione, pioglitazone, is known to offer multiple, potentially antiatherogenic, effects that may have a beneficial impact on macrovascular outcomes, including long-term improvements in insulin resistance (associated with an increased rate of atherosclerosis) and improvement in the atherogenic lipid triad (low HDL-cholesterol, raised triglycerides, and a preponderance of small, dense LDL particles) that is observed in patients with type 2 diabetes. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) study showed that pioglitazone can reduce the risk of secondary macrovascular events in a high-risk patient population with type 2 diabetes and established macrovascular disease. Here, we summarize the key results from the PROactive study and place them in context with other recent outcome trials in type 2 diabetes.     

Small Scale Preparation and Clinical Use of Factor IX-Prothrombin Complex

Abstract. A. procedure is described for the preparation of a concentrate of factors II, VII, IX and X, using a modification of the method of Bruning and Loelioer, involving aluminium hydroxide adsorption of ACD plasma followed by phosphate elution and dialysis.
The concentrate produced had an average factor IX activity of 7.4 U/ml with a yield of 61% and a purification of 34.5.
Clinical trials in patients with either a congenital deficiency of factor IX or liver disease showed that the concentrate was well tolerated and was an effective haemostatic agent. The average factor IX response was 1.09% for each U/kg injected, giving a recovery of 48%.     

Discrepant results between pyrazinamide susceptibility testing by the reference BACTEC 460TB method and pncA DNA sequencing in patients infected with multidrug-resistant W-Beijing Mycobacterium tuberculosis strains

BACKGROUND: Mycobacterium tuberculosis strains belonging to the W-Beijing family have received broad clinical and public health attention because of their rapid worldwide spread and their frequent association with outbreaks, multidrug resistance, and treatment failures and relapses. METHODS: The present study examined a large number of multidrug-resistant strain-W isolates (isolates of 29 patients) by susceptibility testing for pyrazinamide (PZA) using the reference BACTEC 460TB method (Becton Dickinson Diagnostic Instrument Systems; Sparks, MD) and also by DNA sequencing of the pncA gene. RESULTS: We found that despite of the presence of a strain W-specific Thr47Ala in the pncA gene, all strains showed susceptibility to PZA in the reference BACTEC 460TB system due to their higher minimum inhibitory concentrations (relative to BACTEC 460TB PZA-susceptible strains). CONCLUSIONS: Our results suggest that the current radiometric reference method cannot reproducibly detect PZA resistance in patients infected with W-Beijing strains. Therefore, PZA susceptibility testing should instead be based on analysis of the pncA gene for resistance-associated mutations.     

Adjunctive parenteral therapy with lipo-ecraprost, a prostaglandin E1 analog, in patients with critical limb ischemia undergoing distal revascularization does not improve 6-month outcomes

PURPOSE: In patients with critical limb ischemia (CLI), distal revascularization remains the procedure of choice for preventing limb loss, but long-term outcomes for pain relief, wound healing, and prevention of amputation remain suboptimal. Prostaglandin drug therapy as an adjuvant to revascularization may improve these outcomes. The current trial was designed to test the hypothesis that the use of lipo-ecraprost, a lipid encapsulated prostaglandin E(1) prodrug, as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI. METHODS: The study was randomized, multicenter, double blind, and placebo controlled. Patients meeting clinical and hemodynamic criteria for CLI who were undergoing either bypass or endovascular revascularization of the below knee popliteal or more distal arteries were randomized to receive placebo or a 60-microg dose of lipo-ecraprost administered intravenously starting 相似文献   

Predicting which patients will develop chronic critical leg ischemia

Although numerically far less than claudicants, patients with critical leg ischemia (CLI) demand a disproportionately large commitment both in medical effort and economically and represent the major workload for vascular surgical units. The incidence and prevalence of CLI is approximately 500 to 1,000/million/year. The risk factors for the development of CLI are largely the same as those for the progression of local disease in IC, the most important, apart from age, being smoking and diabetes. Major amputation is more common amongst claudicants who are heavy smokers and who continue to smoke, and although stopping smoking slows down the vascular changes and reduces the likelihood of symptomatic progression, it does not reduce the risk of major amputation over the following 2 to 3 years. Diabetic PAOD patients are about 10 times more likely to come to amputation than nondiabetic PAOD patients, and the prevalence of gangrene is 20 to 30 times higher in individuals with diabetes and PAOD compared with nondiabetics with PAOD. There is some evidence that most of these effects of risk factors are additive.     

Intermittent claudication: a condition with underrated risks

Intermittent claudication (IC) is a symptom of peripheral arterial occlusive disease (PAOD); it is subjective and therefore difficult to measure reliably. Both the WHO/Rose Questionnaire and the Edinburgh Questionnaire have been used widely, but they have a low sensitivity and therefore underestimate the true prevalence of IC. The addition of a clinical examination does not necessarily eliminate errors found on questionnaires alone. The single most important part of the physical examination to confirm a diagnosis of IC is the palpation of the patient's peripheral pulses, which alone appears to be more sensitive, but less specific, than the questionnaires. The most useful noninvasive test is the ankle-brachial pressure index (ABPI), and it has been suggested that a resting ABPI of 0.9 is up to 95% sensitive in detecting angiogram-positive disease, and almost 100% specific in identifying apparently healthy individuals. An ABPI of 0.9 or less is believed to be associated with 50% or greater vessel stenosis. The incidence of IC varies depending on the methodology used to define it, but there is a general pattern of a gradual increase in incidence up to the age of at least 70 years. For a chronic disease, the prevalence is a more relevant indicator of how common it is. The prevalence of IC is 3% to 6% in men aged 60 years and increases with age. The prevalence of asymptomatic PAOD may be as high as 20% in the adult population, using noninvasive testing. This is important because, as will be seen in later articles, PAOD, whether symptomatic or asymptomatic, is a serious risk factor for cardiovascular morbidity and mortality.     

What colour are the alligators? A critical look at methods used to assess communication skills in adults with learning difficulties

This paper describes the assessment of communication skills in 120 adults with severe to moderate learning difficulties. Each subject was assessed on the Communication Assessment Profile (CASP), a new communication assessment procedure for use with this client group. Qualitative and quantitative comparisons were made between three different methods of assessment used in CASP. These included observational assessment, elicited conversation and a structured language task. The relative usefulness of each method was evaluated, and the implications for communication assessment outlined.     

Improvement in experimental vascular graft patency by controlled defibrinogenation.

A sensitive animal model was used to investigate treatment designed to improve vascular graft patency. A Dacron graft was inserted into the infrarenal vena cava of 30 rabbits. Half were treated with subcutaneous Arvin for 28 days after operation. This produced a significant lowering of the post operative plasma fibrinogen. The patency rate of the grafts in the treated rabbits was significantly greater than in the control rabbits.     

Immune complexes and abnormal liver function in haemophilia.

Abnormal 125I-Clq-binding activity was found in the sera of 94% of 55 haemophiliacs. Sera from 66% of these patients inhibited macrophage uptake of labelled aggregated human IgG in a competitive radiobioassay. These results suggest that large molecular weight immune complexes are present in these sera. Analysis of the precipitates obtained directly from the sera by addition of 4% polyethylene glycol showed either a mixture of IgG and IgM or IgM alone. There was poor correlation between the radiobioassay results and the Clq-binding activities in the whole group of 55 patients, suggesting a heterogeneous population of complexes. Nevertheless, a significant correlation was found between Clq-binding activities and the radiobioassay results in seven patients with antibodies to factor VIII, suggesting a homogeneous population of complexes. There was poor correlation between the level of immune complexes and the amount of replacement therapy the patient had received in the previous six months. Abnormal liver function tests were found in 55% of the patients studied but there was poor correlation between these abnormal levels and the Clq binding activities and radiobioassay results. Only two patients had clinical evidence of liver disease.