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Multicentre
Terms modified by Multicentre Selected AbstractsReview article: drug-induced liver injury in clinical practiceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010E. Björnsson Aliment Pharmacol Ther 2010; 32: 3,13 Summary Background, Drug-induced liver injury (DILI) is an important differential diagnosis in many patients in clinical hepatology. DILI is the leading cause of acute liver failure and is an important safety issue when new drugs are developed. Aims, To provide a review of the recent data on DILI with particular focus on the most common and relevant issues seen in clinical practice. Methods, A Medline search was undertaken to identify relevant literature using search terms including ,drug-induced liver injury' and ,hepatotoxicity'. Results, The true incidence of DILI remains unknown but incidence up to 14 cases per 100 000 inhabitants and year has been reported. Antibiotics, analgesics and NSAIDs are the most common drugs causing liver injury. Idiosyncratic DILI has been shown to have a dose-dependent component and drugs without significant hepatic metabolism rarely cause DILI. Chronic elevation in liver enzymes can develop after DILI but this is rarely associated with clinical morbidity or mortality. Conclusions, Drug-induced liver injury remains a diagnostic challenge. Multicentre studies and international collaborative work with well-characterized patients will increase our understanding of liver injury associated with drugs. New therapies for acute liver failure resulting from drugs are needed. [source] Previous induced abortions and the risk of very preterm delivery: results of the EPIPAGE studyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 4 2005Caroline Moreau Objectives To evaluate the risk of very preterm birth (22,32 weeks of gestation) associated with previous induced abortion according to the complications leading to very preterm delivery in singletons. Design Multicentre, case-control study (the French EPIPAGE study). Setting Regionally defined population of births in France. Sample The sample consisted of 1943 very preterm live-born singletons (<33 weeks of gestation), 276 moderate preterm live-born singletons (33,34 weeks) and 618 unmatched full-term controls (39,40 weeks). Methods Data from the EPIPAGE study were analysed using polytomous logistic regression models to control for social and demographic characteristics, lifestyle habits during pregnancy and obstetric history. The main mechanisms of preterm delivery were classified as gestational hypertension, antepartum haemorrhage, fetal growth restriction, premature rupture of membranes, idiopathic preterm labor and other causes. Main outcome measures Odds ratios for very preterm birth by gestational age and by pregnancy complications leading to preterm delivery associated with a history of induced abortion. Results Women with a history of induced abortion were at higher risk of very preterm delivery than those with no such history (OR + 1.5, 95% CI 1.1,2.0); the risk was even higher for extremely preterm deliveries (<28 weeks). The association between previous induced abortion and very preterm delivery varied according to the main complications leading to very preterm delivery. A history of induced abortion was associated with an increased risk of premature rupture of the membranes, antepartum haemorrhage (not in association with hypertension) and idiopathic spontaneous preterm labour that occur at very small gestational ages (<28 weeks). Conversely, no association was found between induced abortion and very preterm delivery due to hypertension. Conclusion Previous induced abortion was associated with an increased risk of very preterm delivery. The strength of the association increased with decreasing gestational age. [source] Aspirin (100 mg) used for prevention of pre-eclampsia in nulliparous women: the Essai Régional Aspirine Mère,Enfant study (Part 1)BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 5 2003Damien Subtil Objective To reduce the incidence of pre-eclampsia in nulliparous women, in accordance with the suggestion of a recent meta-analysis that low dose aspirin might decrease this incidence by more than half if used early enough in and at a sufficient dose during pregnancy (more than 75 mg). Design Multicentre randomised double-blinded placebo-controlled trial. Setting Twenty eight centres in Northern of France and one in Belgium. Population Three thousand and two hundred ninety-four nulliparous women recruited between 14 and 20 weeks. Methods Randomisation to either 100 mg aspirin or placebo daily from inclusion through 34 weeks. Main outcome measures Preeclampsia was defined as hypertension (,140 and or 90 mmHg) associated with proteinuria (,0.5 g/L). Results The aspirin (n= 1644) and placebo (n= 1650) groups did not differ significantly in the mothers' incidence of pre-eclampsia (28 of 1632 [1.7%] vs 26 of 1637 [1.6%]; relative risk, RR, 1.08, 95% CI 0.64,1.83), hypertension, HELLP syndrome or placental abruption, or in the children's incidence of perinatal deaths or birthweight below the 10th centile. The incidence of babies with birthweight below the third centile was significantly higher in the aspirin group, with no explanation. The incidence of maternal side effects was higher in the aspirin group, principally because of a significantly higher rate of haemorrhage. Conclusions Aspirin at a dose of 100 mg does not reduce the incidence of pre-eclampsia in nulliparous women. Aspirin (100 mg) is associated with an increase in bleeding complications. [source] Randomised comparison of uterine artery Doppler and aspirin (100 mg) with placebo in nulliparous women: the Essai Régional Aspirine Mère,Enfant study (Part 2)BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 5 2003Damien Subtil Objective To assess the effectiveness of a pre-eclampsia prevention strategy based on routine uterine artery Doppler flow velocity waveform examination during the second trimester of pregnancy, followed by a prescription for 100 mg aspirin in the case of abnormal Doppler findings. Design Multicentre randomised controlled trial. Setting Eleven centres in the north of France and one in Belgium. Population One thousand and eight hundred and fifty-three nulliparous women recruited between 14 and 20 weeks of gestation. Methods Randomisation either to undergo a uterine Doppler examination between 22 and 24 week of gestation or to take a placebo. Women with abnormal Doppler waveforms received 100 mg of aspirin daily from Doppler examination through 36 weeks. Main outcome measures Pre-eclampsia was defined as hypertension (, 140 and/or 90 mmHg) associated with proteinuria (, 0.5 g/L). Results One thousand two hundred and fifty-three women (67%) were randomised into the systematic Doppler group and 617 (33%) into the placebo group. Of the 1175 patients in the Doppler group who underwent this examination, 239 (20.3%) had abnormal uterine artery Doppler and received a prescription for aspirin. Despite the aspirin prescription, the frequency of pre-eclampsia did not differ between the systematic Doppler group and the placebo group (28 of 1237 [2.3%] vs 9 of 616 [1.5%]; RR = 1.55, 95% CI 0.7,3.3). Furthermore, the groups did not differ in the frequency of children who were very small for their gestational age (,3rd centile) or for perinatal deaths. Compared with patients with normal Doppler findings, those with abnormal Doppler were at high risk of pre-eclampsia (RR = 5.5, 95% CI 2.5,12.2) and of giving birth to a small-for-gestational-age child (RR = 3.6, 95% CI 1.6,8.1). Conclusion Despite its sensitivity in screening for pre-eclampsia, routine uterine Doppler in the second trimester cannot be recommended for nulliparous patients. [source] Iron plus folate is more effective than iron alone in the treatment of iron deficiency anaemia in pregnancy: a randomised, double blind clinical trialBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 9 2002Jorge Juarez-Vazquez Objective To evaluate whether folate supplementation to iron is able to accelerate solving of iron deficiency anaemia in pregnancy. Design Multicentre, double blind, randomised clinical trial. Setting Nine hospital gynaecologic units located in Mexico. Population Three hundred seventy-one women with iron deficiency anaemia between 14 and 27 weeks of pregnancy. Methods Random allocation of the study population to receive 80 mg iron proteinsuccinylate, with or without 0.370 mg folinic acid daily for 60 days. Main outcome measure Haemoglobin concentration increase. Results Combined iron and folate therapy showed a better therapeutic response: the increase in haemoglobin levels from baseline was 1.42 (0.14) g/dL for women treated with both compounds vs 0.80 (0.125) g/dL for those given iron only (P < 0.001). A multivariable regression analysis showed that this effect was independent of basal levels of blood iron, ferritine and serum folate and was more evident in women with more severe anaemia. In the 64 women belonging to the subgroup defined by the per-protocol (PP) population and the lowest quartile of baseline haemoglobin values (mean 8.96, range 5.9,9.8 g/dL), the increase at day 60 was estimated 2.3 (0.53) g/dL for the combined therapy vs 0.5 (0.5) g/dL for iron only (P= 0.07). No significant differences in tolerability were observed between the two groups. Conclusion Folate supplementation is recommended in pregnant women with iron deficiency anaemia irrespective of the serum levels of folate. [source] Multicentre randomized clinical trial of mechanical bowel preparation in elective colonic resection (Br J Surg 2007; 94: 689,695)BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2007E. J. Noble The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and,if approved,appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Management of bronchiolitis without antibiotics: a multicentre randomized control trial in BangladeshACTA PAEDIATRICA, Issue 10 2009ARML Kabir Abstract Objective:, To ascertain that antibiotics have no role in the management of bronchiolitis. Design:, Multicentre randomized control trial (RCT). Setting:, Five purposively selected teaching hospitals in Bangladesh. Patient:, Children under 24 months old with bronchiolitis. Interventions:, Children were randomized into three groups of therapeutic interventions: parenteral ampicillin (P-Ab), oral erythromycin (O-Ab) and no antibiotic (N-Ab) in adjunct to supportive measures. Main outcome measures:, Clinical improvement was assessed using 18 symptoms/signs which were graded on a two-point recovery scale of ,rapid' and ,gradual', indicating improvement within ,four days' and ,beyond four days', respectively. Results:, Each intervention group consisted of 98 ± 1 children having comparable clinico-epidemiological characteristics at the baseline. The trial revealed that most chesty features (features appearing to arise from chest, i.e. cough, breathing difficulty, wheeze, chest indrawing, tachypnoea, tachycardia, rhonchi and crepitation) demonstrated a gradual recovery, beyond 4th admission day and, not differing among the three intervention groups (p > 0.23, p < 0.62, p = 0.54, p < 0.27, p = 0.75, p = 0.76, p = 0.81, p > 0.98, respectively). Most non-chesty features (features appearing to arise away from chest, i.e. feeding/sleeping difficulties, social smile, restlessness, inconsolable crying, nasal flaring, fever and hypoxaemia) demonstrated a rapid recovery, within 4 days, remaining comparable among the three intervention groups (p < 0.07, p = 0.65, p = 0.24, p < 0.61, p = 0.22, p = 0.84, p = 0.29 and p = 0.96, respectively). However, nasal symptoms (runny nose and nasal blockage) also showed no difference among groups (p = 0.36 and p = 0.66, respectively). Thus, the dynamics of clinical outcome obviates that children not receiving antibiotics had similar clinical outcome than those who did. Conclusion:, In hospital settings, managing bronchiolitis with only supportive measures but without antibiotics remains preferable. [source] Addition of insulin lispro protamine suspension or insulin glargine to oral type 2 diabetes regimens: a randomized trialDIABETES OBESITY & METABOLISM, Issue 10 2010K. Strojek Aims: The addition of basal insulin to existing oral therapy can help patients with type 2 diabetes (T2D) achieve glycaemic targets. This study compares the efficacy and safety of insulin lispro protamine suspension (ILPS) and insulin glargine in insulin-naive patients with T2D and inadequate control on oral antihyperglycaemic medication (OAM). Materials and Methods: An open-label, randomized, multicentre, multinational 24-week study of 471 patients receiving ,2 OAMs for ,3 months with a body mass index between 25 and 45 kg/m2 and HbA1c 7.5,10.0% was conducted. ILPS was injected once or twice daily vs. glargine injected once daily plus prestudy OAMs. Primary objective compared the HbA1c change from baseline. Results: HbA1c change from baseline to endpoint was similar in both groups [,1.46% (ILPS) and ,1.41% (glargine)]. Least-squares mean difference (95% CI) for HbA1c (,0.05 [,0.21, 0.11]%), glycaemic variability (0.06 [,0.06, 0.19] mmol/l) and weight change (,0.01 [,0.61, 0.59] kg) showed non-inferiority (margins of 0.4%, 0.8 mmol/l and 1.5 kg, respectively). Percentages of patients achieving HbA1c <7.0% were 43.8% ILPS and 41.2% glargine. Mean daily insulin dose was 0.39 vs. 0.35 U/kg (p = 0.02) and weight gain was 1.04 vs. 1.07 kg for ILPS vs. glargine (p = 0.98). Overall hypoglycaemia (episodes/patient/year) was similar for ILPS and glargine (24.2 ± 28.8 vs. 23.0 ± 30.9); nocturnal (6.1 ± 10.6 vs. 4.1 ± 9.4, p < 0.001) rates were higher for ILPS. Severe hypoglycaemia was higher for ILPS vs. glargine (n = 9 vs. n = 2; p = 0.04). Conclusions: At endpoint, ILPS was non-inferior to glargine in HbA1c change from baseline, but associated with increased risk of hypoglycaemia. [source] Safety of pramlintide added to mealtime insulin in patients with type 1 or type 2 diabetes: a large observational studyDIABETES OBESITY & METABOLISM, Issue 6 2010R. Pencek The objective of this Phase 4, open-label, multicentre, observational study was to fulfil food and drug administration (FDA) postapproval requirement to evaluate in healthcare practices the risk of insulin-induced severe hypoglycaemia following initiation of pramlintide therapy in N = 1297 patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) with inadequate glycaemic control. The duration of the study was approximately 6 months. During the adjustment period (0,3 months), the incidence and event rate of patient-ascertained severe hypoglycaemia (PASH) were 4.8% and 0.33 events/patient-year in patients with T1DM and 2.8% and 0.19 events/patient-year in patients with T2DM. During the maintenance period (>3,6 months), the incidence and event rate of PASH declined in patients with T1DM or T2DM. This study confirms that in healthcare practices, the risk of insulin-induced severe hypoglycaemia following the initiation of pramlintide is low in patients with T1DM or T2DM. [source] Earlier triple therapy with pioglitazone in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 9 2009G. Charpentier Aims: This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. Methods: This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA1c) ,6.5%] or titrated up to 45 mg (if HbA1c >6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA1c (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ,-cell function (HOMA-B) were calculated. Results: Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA1c and ,2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA1c level of <8.5% achieved the HbA1c target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA1c level was , 8.5%, 13% achieved the HbA1c target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. Conclusions: In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA1c, FPG and surrogate measures of ,-cell function. Patients were more likely to reach target HbA1c levels (< 7.0%) with pioglitazone treatment if their baseline HbA1c levels were < 8.5%, highlighting the importance of early triple therapy. [source] Orlistat 120 mg improves glycaemic control in type 2 diabetic patients with or without concurrent weight lossDIABETES OBESITY & METABOLISM, Issue 4 2009S. Jacob Background:, Both obesity and type 2 diabetes are associated with increased morbidity and mortality. Published data suggest that orlistat 120 mg, a lipase inhibitor used to treat obesity, may improve glycaemic parameters through weight loss,independent effects. Aim:, To investigate the effect of orlistat 120 mg on weight loss, and assess whether changes in glycaemic parameters [fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c)] are independent of weight loss. Methods:, This retrospective analysis of pooled data from seven multicentre, double-blind, placebo-controlled studies involved overweight or obese patients with type 2 diabetes (aged 18,70 years). Patients were required to have a body mass index of 27,43 kg/m2, HbA1c of 6.5 to <13%, and stable weight for ,3 months. Subjects received orlistat 120 mg tid or placebo for 6 or 12 months. Results:, A total of 2550 overweight or obese patients with type 2 diabetes were enrolled and randomized to treatment with orlistat 120 mg tid (n = 1279) or placebo (n = 1271). For the whole population, patients treated with orlistat 120 mg had significantly greater mean decreases in FPG compared with placebo-treated patients (,1.39 mmol/l vs. ,0.47 mmol/l; p < 0.0001). In addition, orlistat 120 mg provided significantly larger mean decreases in HbA1c compared with placebo (,0.74% vs. ,0.31%; p < 0.0001). For patients with minimal weight loss (,1% of baseline body weight), orlistat 120 mg still provided a significantly greater decrease in the least squares mean value for both FPG (,0.83 mmol/l vs. ±0.02 mmol/l; p = 0.0052) and HbA1c,0.29% vs. ±0.14%; p = 0.0008). This suggested that the improvement of glycaemic control with orlistat 120 mg was independent of weight loss. Using linear regression analysis, improvement in glycaemic control (FPG and HbA1c) with orlistat 120 mg was less strongly correlated with weight loss than for placebo. Conclusion:, Orlistat 120 mg appears to improve glycaemic control more than would be predicted by weight loss alone in overweight or obese patients with type 2 diabetes. Postulated mechanisms underlying this effect include an improvement of insulin sensitivity, a slower and incomplete digestion of dietary fat, reduction of postprandial plasma non-esterified fatty acids, decreased visceral adipose tissue, and stimulation of glucagon-like peptide-1 secretion in the lower small intestine. [source] Robust improvements in fasting and prandial measures of ,-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy databaseDIABETES OBESITY & METABOLISM, Issue 10 2008R. E. Pratley Aim:, To assess the effects of 24-week treatment with vildagliptin on measures of ,-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM). Methods:, Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of ,-cell function [homeostasis model assessment of ,-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test,derived) measures of ,-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29). Results:, In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AM,) = 10.3 ± 1.5] and vs. placebo (between-treatment difference in AM, = 11.5 ± 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AM, = ,0.05 ± 0.01) and vs. placebo (between-treatment difference in AM, = ,0.09 ± 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test,derived parameters, and ISR/G (between-treatment difference in AM, = 9.8 ± 2.8 pmol/min/m2/mM, p < 0.001) and the insulinogenic index0,peak glucose (between-treatment difference in AM, = 0.24 ± 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo. Conclusions:, Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test,derived measures of ,-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov. [source] Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metforminDIABETES OBESITY & METABOLISM, Issue 4 2006Irina Chazova Aim:, To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. Methods:, A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients ,40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. Results:, With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1,35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. Conclusions:, Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease. [source] Comparison of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) in paediatric Type 1 diabetes: a multicentre matched-pair cohort analysis over 3 yearsDIABETIC MEDICINE, Issue 1 2008B. I. Jakisch Abstract Aims To conduct a multicentre, matched-pair cohort analysis comparing glycaemic control and adverse events of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) in paediatric patients. Methods Using standardized computer-based prospective documentation, HbA1c, insulin dose, body mass index,standard deviation score (BMI,SDS), rate of hypoglycaemia, rate of diabetic ketoacidosis (DKA) and intensity of care were analysed in 434 matched pairs during a follow-up period of 3 years after initiation of MDI or CSII. Results HbA1c was significantly lower in the CSII group during the first year of new regimen (CSII 7.5 ± 0.05 vs. MDI 7.7 ± 0.06; P < 0.05), but rose to the same level as in the MDI group during year 3. Insulin requirement remained significantly lower in the CSII group. The BMI,SDS increased in both study groups, with no significant difference. The rate of severe hypoglycaemia decreased significantly after the change of regimen (CSII 17.87 ± 2.85 vs. MDI 25.14 ± 3.79; P < 0.05) and during year 3 of the regimen, particularly when compared with baseline (,21% vs. ,16%). The rate of DKA was lower at baseline in the CSII group and remained significantly lower over all 3 years. Intensity of care was the same in both subsets. Conclusions Employing a large cohort, this matched-pair analysis has demonstrated over a 3-year study period that CSII is a safe form of intensive insulin therapy with similar glycaemic effects, but with significantly reduced rates of hypoglycaemia and DKA and a lower insulin requirement when compared with MDI. [source] Rosiglitazone RECORD study: glucose control outcomes at 18 monthsDIABETIC MEDICINE, Issue 6 2007P. D. Home Abstract Aims To compare glucose control over 18 months between rosiglitazone oral combination therapy and combination metformin and sulphonylurea in people with Type 2 diabetes. Methods RECORD, a multicentre, parallel-group study of cardiovascular outcomes, enrolled people with an HbA1c of 7.1,9.0% on maximum doses of metformin or sulphonylurea. If on metformin they were randomized to add-on rosiglitazone or sulphonylurea (open label) and if on sulphonylurea to rosiglitazone or metformin. HbA1c was managed to , 7.0% by dose titration. A prospectively defined analysis of glycaemic control on the first 1122 participants is reported here, with a primary outcome assessed against a non-inferiority margin for HbA1c of 0.4%. Results At 18 months, HbA1c reduction on background metformin was similar with rosiglitazone and sulphonylurea [difference 0.07 (95% CI ,0.09, 0.23)%], as was the change when rosiglitazone or metformin was added to sulphonylurea [0.06 (,0.09, 0.20)%]. At 6 months, the effect on HbA1c was greater with add-on sulphonylurea, but was similar whether sulphonylurea was added to rosiglitazone or metformin. Differences in fasting plasma glucose were not statistically significant at 18 months [rosiglitazone vs. sulphonylurea ,0.36 (,0.74, 0.02) mmol/l, rosiglitazone vs. metformin ,0.34 (,0.73, 0.05) mmol/l]. Increased homeostasis model assessment insulin sensitivity and reduced C-reactive protein were greater with rosiglitazone than metformin or sulphonylurea (all P , 0.001). Body weight was significantly increased with rosiglitazone compared with sulphonylurea [difference 1.2 (0.4, 2.0) kg, P = 0.003] and metformin [difference 4.3 (3.6, 5.1) kg, P < 0.001]. Conclusions In people with diabetes, rosiglitazone in combination with metformin or sulphonylurea was demonstrated to be non-inferior to the standard combination of metformin + sulphonylurea in lowering HbA1c over 18 months, and produces greater improvements in C-reactive protein and basal insulin sensitivity but is also associated with greater weight gain. [source] Comparison of insulin detemir and insulin glargine in subjects with Type 1 diabetes using intensive insulin therapyDIABETIC MEDICINE, Issue 6 2007T. R. Pieber Abstract Aims To compare glycaemic control and risk of hypoglycaemia of twice-daily insulin detemir with once-daily insulin glargine in subjects with Type 1 diabetes. Methods In this 26-week, multicentre, open-label, parallel-group trial, 320 subjects with Type 1 diabetes received either insulin detemir twice daily or insulin glargine once daily. each in combination with premeal insulin aspart. Results After 26 weeks, HbA1c had decreased from 8.8 to 8.2% in the insulin detemir group and from 8.7 to 8.2% in the insulin glargine group. Home-measured fasting plasma glucose (PG) was lower with insulin glargine than with insulin detemir (7.0 vs. 7.7 mmol/l, P < 0.001). The overall shape of the home-measured nine-point PG profiles was comparable between treatments (P = 0.125). Overall, there was no significant difference in within-subject variation in PG (P = 0.437). Within-subject variation in predinner PG was lower with insulin detemir than with insulin glargine (P < 0.05). The overall risk of hypoglycaemia was similar with no differences in confirmed hypoglycaemia. However, the risk of severe and nocturnal hypoglycaemia was 72% and 32%, respectively, lower with insulin detemir than with insulin glargine (P < 0.05). Body weight gain was not significantly different comparing insulin detemir and insulin glargine (0.52 kg vs. 0.96 kg, P = 0.193). Conclusions Treatment with twice-daily insulin detemir or once-daily insulin glargine, each in combination with insulin aspart, resulted in similar glycaemic control. The overall risk of hypoglycaemia was comparable, whereas the risks of both severe and nocturnal hypoglycaemia were significantly lower with insulin detemir. [source] Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetesDIABETIC MEDICINE, Issue 3 2006S. G. Ashwell Abstract Aims To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen. Methods In this 32-week, five-centre, two-way cross-over study, people with Type 1 diabetes (n = 56, baseline HbA1c 8.0 ± 0.8%) were randomized to evening insulin glargine + mealtime insulin lispro or to NPH insulin (once- or twice-daily) + mealtime unmodified human insulin. Each 16-week period concluded with a 24-h inpatient plasma glucose profile. Results HbA1c was lower with glargine + lispro than with NPH + human insulin [7.5 vs. 8.0%, difference ,0.5 (95% CI ,0.7, ,0.3) %, P < 0.001]. This was confirmed by an 8% lower 24-h plasma glucose area under the curve (AUC) (187 vs. 203 mmol l,1 h,1, P = 0.037), a 24% reduction in plasma glucose AUC > 7.0 mmol/l1 (47 vs. 62 mmol l,1 h,1, P = 0.017) and a 15% lower post-prandial plasma glucose AUC (75 vs. 88 mmol l,1 h,1, P = 0.002). There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l. Monthly rate of nocturnal hypoglycaemia was reduced by 44% with glargine + lispro (0.66 vs. 1.18 episodes/month, P < 0.001). Conclusions Compared with NPH insulin + unmodified human insulin, the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinically significant degree, together with a reduction in nocturnal hypoglycaemia. [source] Improved glycaemic control with metformin,glibenclamide combined tablet therapy (Glucovance®) in Type 2 diabetic patients inadequately controlled on metforminDIABETIC MEDICINE, Issue 8 2002M. Marre Abstract Aims To evaluate the efficacy and safety of two dosage strengths of a single-tablet metformin,glibenclamide (glyburide) combination, compared with the respective monotherapies, in patients with Type 2 diabetes mellitus (DM) inadequately controlled by metformin monotherapy. Methods In this 16-week, double-blind, multicentre, parallel-group trial, 411 patients were randomized to receive metformin 500 mg, glibenclamide 5 mg, metformin,glibenclamide 500 mg/2.5 mg or metformin,glibenclamide 500 mg/5 mg, titrated with the intention to achieve fasting plasma glucose (FPG) , 7 mmol/l. Results Decreases in glycated haemoglobin (HbA1c) and FPG were greater (P < 0.05) for metformin,glibenclamide 500 mg/2.5 mg (,1.20% and ,2.62 mmol/l) and 500 mg/5 mg (,0.91% and ,2.34 mmol/l), compared with metformin (,0.19% and ,0.57 mmol/l) or glibenclamide (,0.33% and ,0.73 mmol/l). HbA1c < 7% was achieved by 75% and 64% of patients receiving metformin,glibenclamide 500 mg/2.5 mg and 500 mg/5 mg, respectively, compared with 42% for glibenclamide and 38% for metformin (P = 0.001). These benefits were achieved at lower mean doses of metformin or glibenclamide with metformin,glibenclamide 500 mg/2.5 mg and 500 mg/5 mg (1225 mg/6.1 mg and 1170 mg/11.7 mg) than with glibenclamide (13.4 mg) or metformin (1660 mg). Treatment-related serious adverse events occurred in two patients receiving glibenclamide. Plasma lipid profiles were unaffected and mean changes in body weight were , 1.0 kg. Conclusions Intensive management of Type 2 DM with a new metformin,glibenclamide combination tablet improved glycaemic control and facilitated the attainment of glycaemic targets at lower doses of metformin or glibenclamide compared with the respective monotherapies, without compromising tolerability. Diabet. Med. 19, 673,680 (2002) [source] Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre studyDIABETIC MEDICINE, Issue 5 2001S. Madsbad Abstract Aims To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. Methods Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40,75 years, body mass index (BMI) 20,35 kg/m2, HbA1c 4.2,12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1,4 mg at mealtimes, or glipizide, 5,15 mg daily. Results Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively). Conclusions Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients. Diabet. Med. 18, 395,401 (2001) [source] Pericranial injection of botulinum toxin type A (Dysport®) for tension-type headache , A multicentre, double-blind, randomized, placebo-controlled studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2008A. Straube Increasingly, botulinum type A toxin is used to influence pathologically increased muscle activity in conditions such as dystonia and spasticity. Studies have also assessed its efficacy in tension-type headache, where muscle tenderness may be increased. We undertook a prospective, multicentre, randomized, double-blind, placebo-controlled trial. Patients received injections of Dysport® (total dose of 420 or 210 units) or saline placebo in 18 sites on the head and neck. Of 125 patients treated, 118 were included in the intention-to-treat dataset. No significant differences between each verum group and placebo were seen for the primary efficacy parameter , change in the number of headache-free days at 4,8 weeks after injection compared with 4 weeks before injection. The groups receiving 420 or 210 units of Dysport experienced 2.60 and 2.87 more headache-free days respectively, compared with 1.93 more headache-free days for the placebo group (P = 0.66 versus 420 units; P = 0.52 versus 210 units). Treatment with 420 units of Dysport was associated with significant improvements compared with placebo for two secondary efficacy parameters: mean change in headache duration from baseline to weeks 8,12 (P < 0.05) and improved global physician and patient assessment scores (P < 0.05). Further studies should address the possible value of multiple injections with extended observation periods, dose optimization, and whether duration of headache history and number of previous treatments are predictors of patient response. [source] Clinical safety surveillance study of the safety and efficacy of long-term home treatment with ReFacto® utilizing a computer-aided diary: a Nordic multicentre studyHAEMOPHILIA, Issue 1 2009P. PETRINI Summary., A Nordic multicentre, open-label, non-interventional postmarketing surveillance study was carried out during a period of 24 months evaluating safety and efficacy of ReFacto as prophylactic or on-demand replacement therapy in patients with haemophilia A treated by self-medication. Fifty-seven patients were enrolled and studied for safety; efficacy was evaluated in 39 patients who received ReFacto for 24 months and recorded sufficient diary data on a hand-held computer. The compliance of using the device was good in small children, variable in adults and poor in teenagers. The fact that the overall compliance was low constituted a limitation of the number of patients with reliable diary data. Overall safety was rated as excellent or good by the clinicians for all patients at all visits and overall efficacy at 24 months evaluated to be excellent (74%) or good (26%). It was noticed that ,50% of patients/parents reported no absences from school or work owing to bleeding episodes during the study period. Among patients on regular prophylaxis, 6 of the 30 patients (20%) receiving ReFacto experienced no bleeding episodes. A median of four bleeding episodes occurred during the 24-month study period, and 93% of the episodes were resolved with ,2 ReFacto infusions. In the 7 on-demand patients, there was a median of 18 bleeding episodes, 87% of which resolved with ,2 ReFacto infusions. Interestingly, 42% of the ReFacto infusions taken by the patients classified to the on-demand group were registered as prophylactic treatment. In conclusion, ReFacto demonstrated good safety and efficacy in prophylaxis as well as treatment of bleeding episodes. [source] Evaluation of pharmacokinetics, efficacy and safety of Immunate® solvent detergent in previously treated patients with severe haemophilia AHAEMOPHILIA, Issue 1 2007L. NEMES Summary., Immunate® Solvent Detergent (S/D) is a plasma derived, purified, human factor VIII (FVIII) , von Willebrand factor (VWF) complex subjected to two virus inactivation/removal processes: S/D and vapor heat treatment. This prospective, multicentre, three-part clinical study evaluated the pharmacokinetics (in comparison to the predecessor product Immunate®), efficacy and safety of Immunate® S/D in 56 previously treated patients with severe haemophilia A. Subjects received Immunate® S/D on-demand, as a prophylactic regimen or both. The results of the pharmacokinetic population demonstrate that Immunate® and Immunate® S/D were equivalent with respect to the FVIII , and to the retrospectively VWF , parameters assessed. A total of 623 bleeding episodes were reported in 47/56 subjects. The duration of prophylaxis ranged from 0.1--5.2 months with a total of 175.6 months. The median number of bleeds per month in subjects on prophylaxis was 0 (range 0--10). Ninety-six percent of bleeding episodes were rated as having an excellent or good response. For most bleeding episodes (89%), subjects required only one infusion with a mean dose of 29.6 IU kg,1. No FVIII inhibitory antibodies were observed in any subject. No related serious adverse events were reported. Thus, the introduction of S/D treatment did not alter the PK characteristics and function of VWF and FVIII molecules of Immunate® S/D which is effective and safe for treatment of bleeding episodes, management of surgical procedures, and prophylaxis. [source] Viral safety of a pasteurized, monoclonal antibody-purified factor VIII concentrate in previously untreated haemophilia A patientsHAEMOPHILIA, Issue 2 2001C. S. Philipp The efficacy and viral safety of a pasteurized, immunoaffinity-purified procoagulant factor VIII protein (FVIII:C; Monoclate-P) was studied in two multicentre, prospective, open-label trials in 30 previously untreated patients, 18 with severe (< 1% FVIII:C activity), and 12 with moderate (1% to 5% FVIII:C activity) haemophilia A. Clinical assessments, performed at screening and regularly thereafter for 6 to > 24 months (maximum 34 months), showed that none of 24 assessable patients acquired illnesses consistent with monitored transfusion-transmissible diseases. No patients acquired hepatitis B surface antigen, or antibodies against hepatitis B core antigen, hepatitis C, or human immunodeficiency virus. Likewise, no patients acquired treatment-related hepatitis A antibodies or sustained elevations of alanine aminotransferase levels. The safety profile for Monoclate-P is brought about by a multi-step safety system that incorporates viral inactivation (through a combination of immunoaffinity chromatography and pasteurization) plus donor screening, plasma testing, and quality assurance. The inhibitor development rate (13% low titre, 10% high titre) was similar to that reported in the literature for other FVIII concentrates (24% to 52%). The most frequently reported adverse events were related to typical infant and childhood diseases. Monoclate-P was effective in all patients treated according to protocol, except in two, who developed inhibitors. [source] Effect of simplification from protease inhibitors to boosted atazanavir-based regimens in real-life conditionsHIV MEDICINE, Issue 9 2010R Rubio Background Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well-tolerated, once-daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs. Objective The aim of the study was to determine the effectiveness and safety of ATV-containing regimens in patients who have simplified their antiretroviral treatment. Methods SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI-containing therapy and who were switched to an ATV/r-based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction. Results A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/,L. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low-density lipoprotein cholesterol were ,13 mg/dL (,7%; P<0.0001), ,19 mg/dL (,13%; P<0.0001) and ,7 mg/dL (,6%; P=0.021), respectively. Conclusions In a real-world setting, switching from other PIs to ATV/r is a well-tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients. [source] TRIZAL study: switching from successful HAART to TrizivirTM (abacavir-lamivudine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence resultsHIV MEDICINE, Issue 2 2003C Katlama Objective To assess the antiviral efficacy, safety, and adherence in subjects who switched to TrizivirÔ following long-term HIV-1 RNA suppression. Study design A randomized, open-label, multicentre, 48-week comparative study in subjects who have received two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or an nonnucleoside reverse transcriptase inhibitor or three nucleoside reverse transcriptase inhibitors for at least 6 months, with a history of undetectable plasma HIV-1 RNA since initiation of therapy and plasma viral load of < 50 HIV-1 RNA copies/mL at screening. Methods Subjects were randomized 1:1 to continue their current treatment or to switch to a simplified treatment with TrizivirÔ administered twice daily. Assessments included plasma HIV-1 RNA, lymphocyte counts, clinical laboratory evaluations, adverse events, and adherence to treatment (obtained via subject self-report). Treatment failure was defined as a plasma viral load of , 400 HIV-1 RNA copies/mL on two consecutive occasions or premature discontinuation of randomized treatment. Results At week 48, the proportion of treatment failures in TrizivirÔ arm (23/106, 22%) was noninferior to that observed in continued arm (23/103, 22%) with a treatment difference stratified by prior ART of 1.2%[-10.1; 12.5]. Incidence of adverse events was similar in both treatment groups. The incidence of possible hypersensitivity reaction in the TrizivirÔ arm was 10%. Significant reductions in cholesterol and triglyceride plasma levels were observed in the TrizivirÔ arm (P < 0.001 and P = 0.006, respectively). Conclusion Switching to TrizivirÔ offers a potent and simplified regimen with equivalent efficacy and significant improvement in lipid abnormalities compared to continued triple therapy. [source] Managing obstruction of the central airwaysINTERNAL MEDICINE JOURNAL, Issue 6 2010J. P. Williamson Abstract Lung cancer is the most common cause of cancer death in Australia, Europe and the USA. Up to 20,30% of these cancers eventually affect the central airways and result in reduced quality of life, dyspnoea, haemoptysis, post-obstructive pneumonia and ultimately death. Non-malignant processes may also lead to central airway obstruction and can have similar symptoms. With the development of newer technologies, the last 20 years have seen the emergence of the field of interventional pulmonology to deal specifically with the diagnosis and management of thoracic malignancy, including obstruction of the central airways. This review discusses the pathology, pre-procedure work-up and management options for obstructing central airway lesions. Several treatment modalities exist for dealing with endobronchial pathology with local availability and expertise guiding choice of treatment. While the literature lacks large, multicentre, randomized studies defining the optimal management strategy for a given problem, there is growing evidence from numerous case studies of improved physiology, of quality of life and possibly of survival with modern interventional techniques. [source] Could exercise be a new strategy to revert some patients with atrial fibrillation?INTERNAL MEDICINE JOURNAL, Issue 1 2010P. Gates Abstract Background: This study is the result of the anecdotal observation that a number of patients with atrial fibrillation (AF) had noted reversion to sinus rhythm (SR) with exercise. We aimed to evaluate the potential role of exercise stress test (EST) for the reversion of AF. Methods: Patients with AF who were scheduled to undergo electrical cardioversion (DCR) underwent EST using a modified Bruce protocol. Results: Eighteen patients (16 male); aged 36,74 years (mean 58 years) were studied. Five patients (27.7%) had successful reversion with exercise (group 1). Thirteen patients remained in AF (group 2). No patient who failed to revert with exercise did so spontaneously before DCR 3 h to 7 months later (median 20 days). Comparison between group 1 and group 2 did not reveal any significant difference Conclusion: This small preliminary study suggests that in some patients it may be possible to revert AF to SR with exercise and avoid DCR and concomitant general anaesthesia. The authors suggest that a larger multicentre randomized trial is warranted to confirm or refute these initial results and if correct identify those who might benefit. [source] Present and future therapeutic strategies for idiopathic oligozoospermiaINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2000Dimitrios A. Adamopoulos The effectiveness of medical treatment for idiopathic oligozoospermia (IO) has been at best doubtful until now and a logical consequence of this unsatisfactory situation has been the partial displacement of this approach by assisted reproduction techniques. This state of affairs has resulted from insufficient investigation, inappropriately designed clinical trials and consistent disregard for the principles of evidence-based medicine. Protocol-related shortcomings and wrong interpretation of the data available have also been some of the all too frequent problems encountered in this therapeutic approach. In this rather misty situation, it appears that, of the therapeutic agents used so far, follicle stimulating hormone (FSH) (mainly FSH-secretagogues) may exert some beneficial effects on a number of biological endpoints related to spermatogenesis and sperm maturation. The short and medium term prospects of medical treatment for IO rest mainly with improvement of investigative procedures to a higher degree of sophistication, with emphasis placed on identifying the causes rather than the results of dysfunction so that a better selection of candidates can be made. Moreover, the introduction of prognostic indices for evaluation of the beneficial effects of a therapeutic agent may be of paramount importance. Finally, a better assessment of the preparations available and, possibly, the introduction of new more specific agents may also be an important step forward in this field. This type of large-scale effort should not be left to individual investigators or special centres working independently, but it may come under the auspices of a central regulating agency so that undisputed results from large, multicentre and uniform studies might be obtained, if medical treatment is to remain a good option. In this context, it may also be emphasized that andrology's main task should always be to treat the male with the problem rather than his healthy female partner, whenever this is possible. [source] Irbesartan has no short-term effect on insulin resistance in hypertensive patients with additional cardiometabolic risk factors (i-RESPOND)INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2010K. G. Parhofer Summary Aims:, Intervention studies have shown that angiotensin receptor blockers (ARB) may reduce the incidence of type 2 diabetes mellitus. It is currently unclear whether short-term therapy with ARBs affects metabolic parameters. Methods:, i-RESPOND, a randomised, controlled, multicentre, double-blind study evaluated the effect of 16 weeks of irbesartan vs. hydrochlorothiazide (HCTZ) on insulin resistance as well as on lipid and inflammatory parameters in hypertensive subjects with metabolic syndrome. Patients received irbesartan (150 mg/d; n = 211) or HCTZ (12.5 mg/d; n = 215), titrated to 300 mg/day and 25 mg/day respectively. In a second part of the study (weeks 16,28), patients initially randomised to irbesartan received additional HCTZ and vice versa. Results:, At week 16 both irbesartan and HCTZ had no effect on insulin resistance measured by the Matzuda index and beta-cell function. Similarly, in the second part of the study (week 16,28) no differences between irbesartan and HCTZ with respect to glucose metabolism were observed. However, irbesartan induced beneficial changes in high-sensitivity-C-reactive protein (hs-CRP) (irbesartan: ,5.5 ± 5.2%; HCTZ + 19.9 ± 6.5%, p = 0.0024) and in urinary albumin/creatinine ratio (ACR) (irbesartan: ,13%; HCTZ + 9%; p = 0.0041) compared with HCTZ despite a similar decrease in blood pressure in both treatment groups. Irbesartan and HCTZ were well tolerated and adverse events were comparable. Conclusion:, Irbesartan did not show significant favourable effects on insulin resistance compared with HCTZ in this study; however, may have beneficial effects on inflammation and microalbuminuria in hypertensive patients with metabolic syndrome. [source] Trospium chloride once-daily extended release is effective and well tolerated for the treatment of overactive bladder syndrome: an integrated analysis of two randomised, phase III trialsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2009D. R. Staskin Summary Background:, Trospium chloride is an antimuscarinic agent with a hydrophilic polar quaternary amine structure that is minimally metabolised by hepatic cytochrome P450 and is actively excreted in the urine, each of which confers a potential benefit with regard to efficacy and tolerability. Purpose:, We analysed pooled data from two identically designed phase III trials of a once-daily, extended-release (XR) formulation of trospium chloride (trospium XR 60-mg capsules) in subjects with overactive bladder syndrome (OAB). Methods:, Adults with OAB of , 6 months' duration with urinary urgency, frequency and , 1 urge urinary incontinence (UUI) episode/day were enrolled in these multicentre, parallel-group, double-blind trials. Participants were randomised (1 : 1) to receive trospium XR 60 mg or placebo for 12 weeks. Primary efficacy variables were changes in urinary frequency and the number of UUI episodes/day. Adverse events (AEs) were recorded throughout. Results:, In total, 1165 subjects were randomised (trospium XR, 578; placebo, 587). At baseline, subjects averaged 12.8 toilet voids/day and 4.1 UUI episodes/day. Compared with placebo, subjects treated with trospium XR had significantly greater reductions from baseline in the mean number of toilet voids/day (,1.9 vs. ,2.7; p < 0.001) and UUI episodes/day (,1.8 vs. ,2.4; p < 0.001) at week 12. The most frequent AEs considered possibly related to study treatment were dry mouth (trospium XR, 10.7%; placebo, 3.7%) and constipation (trospium XR, 8.5%; placebo, 1.5%). Notably, rates of central nervous system (CNS) AEs were lower with trospium XR vs. placebo (dizziness: 0.2% vs. 1.0%; headache: 1.4% vs. 2.4%). Conclusions:, Treatment with trospium XR resulted in statistically significant improvements in both of the dual primary and all of the secondary outcome variables. Trospium XR demonstrated favourable rates of AEs, particularly CNS AEs (numerically lower than with placebo) and dry mouth (lower than previously reported with trospium immediate-release, although not compared in a head-to-head study). [source] | |||||||||||||||||||||||||||||||||||||