[Efficiency of a four-day course of pristinamycin compared to a five-day course of cefuroxime axetil for acute bacterial maxillary sinusitis in adult outpatients]. / Efficacité comparée de la pristinamycine en quatre jours et du céfuroxime axétil en cinq jours dans le traitement des sinusites maxillaires aiguës bactériennes de l'adulte.

OBJECTIVE: The aim of this multicentric, randomized, double blind study was to demonstrate that a 4-day treatment with pristinamycin 1 g bid was as efficient as a 5-day treatment with cefuroxime axetil 250 mg bid in adults presenting with an acute maxillary sinusitis. DESIGN: The clinical diagnosis was based on the association of sub-orbital pain, purulent rhinorrhea and purulent discharge on the middle nasal meatus and was confirmed radiologically. A rhinoscopic bacteriologic sampling was made on the middle nasal meatus. RESULTS: Four hundred and eighty five patients were included in the study: in France (n = 301), Tunisia (n = 48), Poland (n = 69) and Argentina (n = 67) between January 2001 and February 2002. Cultures were positive in 199/434 patients (46%), mainly S. pneumoniae (34.2%), H. influenzae (21.5%), S. aureus (15.4%), and M. catharralis (7.9%). The clinical cure rate at day 12-19 in the per protocol population, the main study criterion, was equal to 91.4% (201/220) and 91.1% (195/214) respectively in the pristinamycin and cefuroxime axetil groups; delta = 0.14%; 95%CI: [-5.1%; 5.3%]. The non-inferiority of 4-day pristinamycin versus 5-day cefuroxime axetil was demonstrated. The efficacy at follow up after treatment (day 26-31) was 88.6% and 85.8% respectively, confirming the non-inferiority. The bacteriological cure rate at day 12-19 was 87% (87/100) and 87.9% (87/99) respectively. Both treatments were well tolerated. CONCLUSION: A 4-day course with pristinamycin 1 g bid is as effective as a 5-day course of cefuroxime axetil 250 mg bid in the treatment of acute maxillary sinusitis in adults.

Predictors of response to glimepiride in patients with type 2 diabetes mellitus.

OBJECTIVE: The purpose of DIAMETRE (DIabète et Amarel en Monothérapie. Etude de Titration pour la définition des Répondeurs) was to identify factors predictive of response to glimepiride monotherapy in type 2 diabetic patients in the setting of a prospective multicentre open study. MATERIAL AND METHODS: Patients aged 35-70 years with poorly controlled diabetes [fasting plasma glucose (FPG) > or =1,40 g/l and < 3 g/l at baseline] were treated with glimepiride for 6 months, with dosage titrated from 1-6 mg daily, depending on the monthly FPG measurement. Responders were defined as patients with a) FPG < 7.78 mmol/l (1.40 g/l) and HbA(1c) < 7.5% at endpoint, or b) decrease in FPG > or = 20% and/or HbA1c > or = 10%. Stepwise logistic regression analysis was used to identify factors predictive of response. RESULTS: Of 849 patients evaluable for efficacy, 483 (56.9%) were responders. The response was independently influenced by prior treatment with OADs [OR: 0.399 (0.290-0.549), p=0.0001] and diabetes duration [OR: 0.912 (0.877-0.948), p=0.0001]. Ninety patients (9.2%) experienced 124 episodes of symptomatic hypoglycaemia. Multivariate analysis revealed that a high level of HbA(1c) decreased the risk of symptomatic hypoglycaemia [OR: 0.734 (0.628; 0.858), p=0.0001] whereas a family history of type 2 diabetes doubled this risk [OR: 1.956 (1.246; 3.072), p=0.003]. CONCLUSION: This large-scale study, conducted under conditions approximating to current medical practice, confirms that glimepiride has a favourable risk-benefit ratio in type 2 diabetes mellitus. Diabetes duration and previous treatment with OADs reduced the likelihood of being a responder to treatment.

Efficacy and safety of HOE 901 versus NPH insulin in patients with type 1 diabetes. The European Study Group of HOE 901 in type 1 diabetes.

OBJECTIVE: HOE 901 (Hoechst Marion Roussel, Frankfurt, Germany) is a biosynthetic insulin with a prolonged action. The aim of this study was to compare the effect of the long-acting insulin analog HOE 901 with NPH insulin regarding glycemic control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 333 type 1 diabetic patients were enrolled in this multinational parallel group trial. Subjects were randomized either to two different formulations of HOE 901 (the formulations differed only in zinc content) or to NPH insulin. The study was only partially blinded because patients can distinguish HOE 901 (a clear solution) from NPH (a cloudy suspension). In addition to premeal injections of regular insulin, patients received HOE 901 at bedtime or NPH once daily at bedtime or twice daily in the morning and at bedtime. RESULTS: Fasting plasma glucose levels were significantly lower with HOE 901 (-1.88 mmol/l. P = 0.0005) as were fasting self-monitored blood glucose levels (-0.80 mmol/l, P = 0.0020). HbA1c levels also showed a significant reduction with HOE 901 (-0.14%) versus NPH (P = 0.030). The overall frequency of hypoglycemia did not differ, but the frequency of nocturnal hypoglycemia was significantly (P = 0.0037) lower with HOE 901 (36 vs. 55%). However, this effect on nocturnal hypoglycemia was significant only versus NPH once daily not NPH twice daily. The pattern of adverse events and injection site reactions with HOE 901 was similar to that with NPH. CONCLUSIONS: This study indicates that HOE 901 achieves better control of fasting glucose and HbA1c levels over 4 weeks, and HOE 901 has a possible safety benefit in terms of nocturnal hypoglycemia.

The Eurevie Study: contrasting effect of piretanide and thiazides in mild to moderate hypertension.

UNLABELLED: This study compares the loop diuretic piretanide 6 mg in a slow-release formulation (PIR) with hydrochlorothiazide 25 mg (HCT) and the fixed combination altizide 15 mg-spironolactone 25 mg (ALT-SP) in hypertension. 1105 mild to moderate hypertensive patients entered a three-week placebo wash-out period; 899 were randomized in a 6-month, double-blind, parallel group treatment phase; 800 completed the study. Primary end-points; serum potassium concentration and quality of life at one month; secondary end-points: ionic, renal and metabolic variables; blood pressure (BP) measurements. HCT and ALT-SP were compared only to PIR using Dunnett's or chi 2 tests. RESULTS: No difference was found for the overall quality of life. No change of serum potassium concentration at one month was found in PIR while small decreases were detected with ALT-SP (-0.1 mM) and HCT (-0.26 mM). Serum creatinine concentration increased significantly in ALT-SP when compared to PIR. All the drugs were effective in reducing BP: HCT had a higher rate of responders than PIR with similar mean BP falls and ALT-SP induced greater falls in blood pressure. CONCLUSION: PIR proves to be a potent antihypertensive drug without significant effect on serum electrolytes, plasma glucose and lipids. HCT was slightly more potent but induced a fall in serum potassium concentration with a significant risk of hypokalaemia. The addition of SP to ALT led to a more potent diuretic with a higher level of serum potassium and plasma creatinine disturbances.

Effect of ramipril on insulin sensitivity in obese patients. Time-course study of glucose infusion rate during euglycaemic hyperinsulinaemic clamp.

To assess the effects of angiotensin converting enzyme (ACE) inhibitor on insulin action in obesity, five normotensive non-diabetic obese women were examined on two occasions as part of a double-blind, randomized, cross-over study involving ten days of treatment with either 1.25 mg ramipril or placebo. The study consisted of a euglycaemic hyperinsulinaemic clamp (two periods of insulin infusion at rates of 0.4 and 1 mU/kg/min, 2 h for each step) combined with indirect calorimetry. The most notable results involved a significantly faster time-course of glucose infusion rates during the first 30 min of each insulin infusion period [analysed by calculating slopes (S1 and S2)] after ramipril than placebo administration. The mean glucose infusion rates reached during the last 30 min of each insulin infusion period (G1 and G2), as well as the increases in carbohydrate oxidation rates during the clamp (C1-C0 and C2-C0) and the decreases in plasma nonesterified fatty acids (A0-A1 and A0-A2), were not significantly different after ramipril and placebo. According to robust principal component analysis of S1, S2, G1, G2, C1, C2, A1 and A2 (orthogonally to C0 and A0), insulin sensitivity was improved with ramipril as compared to placebo (p = 0.013). This study strongly suggests that a low dose of an ACE inhibitor increases the activation phase of insulin action in normotensive nondiabetic obese patients and may accelerate insulin action.

[Comparative study, using a placebo, of the frequency of micturition after repeated administration of piretanide SR 6 mg/day (Eurelix) to healthy volunteers]. / Etude comparative au placebo de l'évolution de la fréquence des mictions sous pirétanide 6 mg L.P. (Eurélix) en administration réiterée chez le volontaire sain.

Thirty healthy volunteers received piretanide SR 6 mg/day (n = 15) or placebo (n = 15) in a 10-day double-blind parallel-group comparative trial. 24-h urine output was significantly greater with piretanide than with placebo on D1 (1919 +/- 434 ml and 1160 +/- 335 ml respectively, p = 0.001 one-sided) as on D10 (1563 +/- 538 ml and 1236 +/- 435 ml respectively, p = 0.04 one-sided). Nevertheless the evolution of urinary output from D1 to D10 was significantly different (p = 0.008): it remained stable with placebo but diminished with piretanide. The diuretic effect of piretanide was apparent with a supplementary miction between 8 a.m. and 4 p.m. both on D1 and D10. Between 4 p.m. and 8 a.m., the number of mictions was the same in both groups. Thus piretanide SR 6 mg has a mild effect on the number of mictions; it should not alter patients' well-being.