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Background: Achieving recommended glycated haemoglobin (HbA1c ) targets in patients with type 2 diabetes mellitus (T2DM) requires effective control of fasting and post-prandial plasma glucose. As T2DM progresses, oral anti-diabetics are no longer sufficient to maintain glycaemic control. Five phase III studies in the GetGoal clinical trial programme assessed the efficacy of lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, in combination with oral anti-diabetics in patients with T2DM insufficiently controlled using oral anti-diabetics., Methods: A meta-analysis was performed of the results of five 24-week clinical trials (comprising 2760 patients) concerning lixisenatide or placebo plus oral anti-diabetic therapy. The primary endpoint of these studies was change in HbA1c at week 24. Changes in fasting and post-prandial plasma glucose, and weight were also established as were the odds ratios for hypoglycaemia and composite safety and efficacy endpoints. Meta-analysis outcomes were assessed using a random effects model. All meta-analyses were performed using RevMan, version 5.1., Results: Lixisenatide was significantly better than placebo in terms of achieving all endpoints in this meta-analysis, including the primary endpoint change in HbA1c at week 24, with p < 0.0001 for all endpoints. The mean number of symptomatic hypoglycaemic events per patient year was increased for patients in the lixisenatide versus placebo groups (p = 0.04). However, compared with patients in the placebo group, patients treated with lixisenatide were more likely to achieve composite efficacy and safety endpoints., Conclusions: This meta-analysis demonstrates that lixisenatide in combination with oral anti-diabetic therapy significantly improves outcomes combining efficacy and safety parameters in patients with T2DM., (© 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd.)

Background: A high frequency of asymptomatic pulmonary embolism (PE) has been reported in patients with deep venous thrombosis (DVT) in studies of a limited number of patients using varying criteria for lung scan assessment., Objectives: To estimate the frequency of PE using systematic lung scans in a large group of outpatients with DVT and to compare the results using varying lung scan assessment criteria., Methods: An international multicenter study comparing 2 different regimens of low-molecular-weight heparin nadroparin in DVT: perfusion lung scans were performed in 622 outpatients with no clinical indication of PE and with proximal DVT confirmed by venography. Three hundred seventy-nine of these patients underwent ventilation lung scans. High-probability (HP) scans for PE were assessed separately using either ventilation scans or chest radiographs to define mismatched perfusion defects., Results: Perfusion scans showed abnormalities in 82% of the patients; 59% had segmental defects and 30% had normal scans or scans with a very low probability of PE. Depending on the criteria used, 32% to 45% had HP scans for PE; these percentages were higher in young patients. No relationship was found between extent of thrombosis and HP scans. The estimated frequency of silent PE was 39.5% to 49.5%. During a 3-month follow-up period during which the patients received therapy, the rate of PE recurrence was low (1.3%) and did not differ between patients with baseline HP scans and those with normal scans., Conclusions: Regardless of what interpretative criteria are used for assessing lung scans in PE, the frequency of silent PE is 40% to 50% in patients with DVT. A baseline lung scan may easily detect PE in these patients but is not useful for predicting early thromboembolic recurrences that may occur during therapy.

Background: Although the association of ticlopidine and aspirin has been shown to be superior to anti-vitamin K agents and aspirin after coronary stent implantation in low-risk patients, the latter combination has remained an unproven reference regimen for high-risk patients until recently., Methods and Results: We randomized 350 high-risk patients within 6 hours after stent implantation to receive during 30 days either aspirin 250 mg and ticlopidine 500 mg/d (A+T group) or aspirin 250 mg/d and oral anticoagulation (A+OAC group) targeted at an international normalized ratio of 2.5 to 3. The primary composite end point was defined as the occurrence of cardiovascular death, myocardial infarction, or repeated revascularization at 30 days. Patients were eligible if (1) the stent(s) were implanted to treat abrupt closure after PTCA; (2) the angiographic result after implantation was suboptimal; (3) a long segment was stented (>45 mm and/or >/=3 stents); or (4) the largest balloon inflated in the stent had a nominal diameter of

No randomized study comparing the effect of combined ticlopidine and aspirin therapy versus each drug alone in reducing poststenting thrombotic complications has been performed. To compare these three antiplatelet regimens versus placebo, we conducted a double-blind randomized study using an ex vivo model of thrombosis. Sixteen healthy male volunteers were assigned to receive for 8 days the following four regimens separated by a 1-month period: aspirin 325 mg/d, ticlopidine 500 mg/d, aspirin 325 mg/d + ticlopidine 500 mg/d, and placebo. At the end of each treatment period, native nonanticoagulated blood was drawn directly from an antecubital vein over collagen- or tissue factor (TF)-coated coverslips positioned in a parallel-plate perfusion chamber at an arterial wall shear rate (2, 600 s-1 ) for 3 minutes. Thrombus, which formed on collagen in volunteers treated by placebo, were rich in platelets and poor in fibrin. As compared with placebo, aspirin and ticlopidine alone reduced platelet thrombus formation by only 29% and 15%, respectively (P > .2). In contrast, platelet thrombus formation was blocked by more than 90% in volunteers treated by aspirin + ticlopidine (P < .01 v placebo or each treatment alone). Furthermore, the effect of the drug combination therapy was significantly larger than the sum of the two active treatments (P < .05). Thrombus, which formed on TF-coated coverslips in volunteers treated by placebo, were rich in fibrin and platelets. Neither of the three antiplatelet treatments significantly inhibited fibrin deposition and platelet thrombus formation on this surface (P > .2). Thus, the present study shows that combined aspirin and ticlopidine therapy dramatically potentiates the antithrombotic effect of each drug alone, but that the antithrombotic effect of the combined treatment depends on the nature of the thrombogenic surface., (Copyright 1998 by The American Society of Hematology.)

Background: Clinical trials have been performed to compare with standard heparin a once or a twice daily regimen of low-molecular-weight heparin but no direct comparison has been done between these two low-molecular-weight heparin regimens in terms of efficacy and safety with a long-term clinical evaluation., Methods: Patients with proximal deep vein thrombosis, confirmed by venography were randomly assigned to either nadroparin (10,250 AXa IU/ml) twice daily or nadroparin (20,500 AXa IU/ml) once daily for at least 5 days. Regimens were adjusted to bodyweight. Oral anticoagulants were started on day 1 or 2 and continued for 3 months. Patients were followed up for 3 months. The composite outcome of venous thromboembolism and death possibly related to pulmonary embolism was the primary measure of efficacy. Major bleeding was the principal measure of safety. The study was designed to show equivalence between the two regimens., Results: Recurrent thromboembolic events or death possibly related to pulmonary embolism were reported in 13 patients in the once daily group (4.1%) and in 24 patients of the twice daily group (7.2%): (absolute difference 3.1% in favor of the once daily regimen; 95% confidence interval -6.6%, +0.5%). Major bleeding episodes during nadroparin treatment occurred in 4 (1.3%) and 4 patients (1.2%) in the once and twice daily groups, respectively., Conclusions: A nadroparin regimen of one injection per day is at least as effective and safe as the same total daily dose divided over two injections for the treatment of acute deep vein thrombosis.

This study reports the results of a 2-yr clinical trial with GH in 95 short prepubertal children with non-GH-deficient intrauterine growth retardation. This randomized, double blind, controlled study compared the effects of placebo (restricted to the first 6 months) and two doses of GH (0.4 and 1.2 IU/kg.week) given sc 6 days/week for 2 yr. A significant GH dose-dependent growth acceleration was observed. Mean height gain (SDS/CA) was 0.66 +/- 0.07 in group I (low dose, 0.4 IU/kg.week) compared to 1.25 +/- 0.07 in group II (high dose, 1.2 IU/kg.week). Mean bone maturation progression (expressed in months) was 26.2 +/- 1.7 and 30.2 +/- 1.5 over 24 months in groups I and II, respectively. Onset of puberty was observed in some patients of both groups. Whether chronic use of a high GH dose will advance the onset of puberty remains to be established. A great variability of growth acceleration was seen among GH dose groups, suggesting that factors in addition to GH dose might modulate individual responses to treatment. In conclusion, it is suggested that in these patients, dose-dependent catch-up growth could be induced by GH treatment.

The release of growth hormone (GH) during the 120 min following a bolus venous injection of 1-44 GH-releasing hormone (GHRH) 2 micrograms/kg was studied in 52 prepubertal children aged 8.4 +/- 2.1 years, having a nonfamilial growth deficiency of prenatal onset (-3.26 +/- 1.13 SDS at birth, -3.22 +/- 0.88 SDS at the time of study) and a normal response to conventional GH stimulation tests. GH release reached a peak level of 96.1 +/- 60.2 microU/ml, being significantly higher than that found in 68 non-GH-deficient very short children whose growth failure had a postnatal onset, and not significantly correlated with the response to conventional tests. 26 of the 52 intrauterine growth retardation (IUGR) patients were re-tested with GHRH in similar conditions after 6-12 months of daily subcutaneous injections of GH and 2 days without. They reached at the second test a peak plasma GH level of 91.7 +/- 56.1 microU/ml, not different from their response to the first test. These data could be taken into consideration for long-term studies of the clinical effects of GH in IUGR children with persisting severe growth deficiency.