Pandemic A/H1N1 influenza vaccination during pregnancy: a comparative study using the EFEMERIS database.

OBJECTIVE: To evaluate the risk of adverse pregnancy outcomes following A/H1N1 vaccination in pregnant women. METHODS: This observational cohort study compared vaccinated and non-vaccinated pregnant women in EFEMERIS, a French prescription database including pregnant women. Women who ended their pregnancy in South Western France between October 21, 2009 and November 30, 2010 (the period of the French vaccination campaign) were included. Two non-vaccinated women were individually matched to each vaccinated woman by month and year of pregnancy onset. Conditional logistic regression and Cox proportional hazards regression were used to evaluate associations between each outcome (all-cause pregnancy loss, preterm delivery, small for gestational age (SGA) and neonatal pathology) and A/H1N1 vaccination during pregnancy. RESULTS: 1645 women of the 12,120 (13.6%) in the database who were administered A/H1N1 vaccine during pregnancy were compared to 3290 non-vaccinated women. Most were vaccinated in December 2009 (61%) with a non-adjuvanted vaccine (93%). The risks of pregnancy loss (adjusted HR=0.56; 95% CI=0.31-1.01), of preterm birth (adjusted HR=0.82; 95% CI=0.64-1.06), and of neonatal pathology (adjusted OR=0.70; 95% CI=0.49-1.02) did not differ between the vaccinated and the non-vaccinated groups. The rate of SGA was lower in the vaccinated group than in the non-vaccinated group (0.5% vs. 1.4%; adjusted OR=0.36; 95% CI=0.17-0.78). CONCLUSION: There was no significant association between adverse pregnancy outcomes and vaccination with a non-adjuvanted A/H1N1 vaccine during pregnancy.

[Prevalence of overweight preschool-age children: medical examination data of schoolchildren in southwestern France]. / Prévalence du surpoids chez le jeune enfant : analyse des données des bilans de santé à 3-4ans en Haute-Garonne.

OBJECTIVE: To analyze anthropometric data in a sample of 3- to 4-year-old children examined by Mother and Infant Welfare in preschools in the Haute-Garonne area of France. PATIENTS AND METHODS: Two consecutive school years (2007-2008 and 2008-2009) were analyzed. The samples studied included 5470 children the first year (mean age ± standard deviation : 3.9±0.4 years) and 4088 children the second year (4.0±0.4 years). Prevalence of overweight (defined according to International Obesity Task Force references) and its association with various factors (sex, age, and school location) were studied. RESULTS: Prevalence of overweight (including obesity) was 8.4% for the 2 years, with a prevalence of obesity of 1.8% in 2007-2008 and of 1.6% in 2008-2009. Overweight was significantly more frequent in girls than in boys (10.2% vs. 6.8% in 2007-2008 and 9.7% vs. 7.2% in 2008-2009) and in schools located in Priority Education Zones (ZEP) compared to schools in non-ZEP schools (17.9% vs. 7.1% in 2007-2008 and 15.7% vs. 7.2% in 2008-2009). CONCLUSION: This analysis will be repeated to follow the prevalence of overweight in children. These preliminary results confirm the need to focus on preventive actions, screening and care for overweight and obesity in underprivileged populations.

[First epidemiologic data about phloroglucinol exposure during first trimester of pregnancy]. / Premières données épidémiologiques sur le phloroglucinol et exposition au cours du premier trimestre de grossesse.

OBJECTIVE: Phloroglucinol is used to prevent gastric, intestine or urogenital spasms. In France, many pregnant women are exposed to phloroglucinol for which no data are available about its use in pregnancy. The present study, using EFEMERIS database, investigates potential teratogenic risk of phloroglucinol in pregnancy. MATERIALS AND METHODS: EFEMERIS is a database including prescribed and delivered drugs during pregnancy (data from Caisse Primaire d'Assurance Maladie of Haute-Garonne) and outcomes (data from Maternal and Infant Protection Service and from Antenatal diagnostic Centre). Women delivered from July 1st 2004 to June 30th 2008 in Haute-Garonne and registered in the French Health Insurance Service were included into EFEMERIS database. We compared pregnancy outcomes and newborn health between women exposed to phloroglucinol during organogenesis and non-exposed women. Malformations were classified according to Eurocat classification. RESULTS: Five thousand one hundred and thirty-two newborns (12.7%) exposed during organogenesis to phloroglucinol were compared to 35,223 controls (non exposed newborns). The mean number of different drugs prescribed during the first trimester of pregnancy per woman was higher in women exposed to phloroglucinol than in non-exposed women (6.4 ± 4.3 versus 2.4 ± 3.3, P < 10(-4)). Among newborns, 126 (2.5%) had a malformation versus 804 (2.3%) in control newborns (OR=1.1, [0.9-1.3]). The present study was powered to find a 1.3 fold increase in the overall rate of major anomalies. DISCUSSION AND CONCLUSION: This first epidemiologic study about phloroglucinol in pregnancy does not support evidence of a teratogenic risk for phloroglucinol in humans.

Prescription of drugs during pregnancy: a study using EFEMERIS, the new French database.

BACKGROUND: Because of the limited data concerning drug risks in pregnancy, health professionals are often deprived of relevant and sufficient information related to prescribing or dispensing during pregnancy. However, previous studies have emphasised the widespread French prescription of several drugs (sometimes "typically French") which have not been assessed in pregnant women. OBJECTIVES: The aim of the present study was to create the first French database of drugs prescribed and dispensed during pregnancy and the outcome of these pregnancies. METHODS: This feasibility study concerns pregnant women who gave birth to a baby between 1 July 2004 to 30 June 2005 in Haute-Garonne and who are registered in the French Health Insurance Service. Data sources include (1) the French Health Insurance Database (drugs prescribed during pregnancy), (2) the Mother and Child Protection Centre Database (newborn health at birth and 9 months after) and (3) the Antenatal Diagnostic Centre Database (medical pregnancy interruptions). RESULTS: The database is composed of 10,174 "mother-outcome" pairs. The prevalence rate of congenital anomalies was 2.2%. Pregnant women were prescribed 11.3 +/- 8.2 different drugs. Among the 20 most frequently prescribed drugs, around half of them have not been evaluated in pregnant women. CONCLUSIONS: The first results of this study show that implementation of a French database on prescription of drugs and pregnancy outcomes is feasible. Compared with several databases available in other countries, EFEMERIS provides exact data on period of exposure to drugs, pregnancy terminations, and follow up of the baby 9 months after birth. Recording these data would make it possible to assess the risk of malformations due to a greater number of drugs and would contribute to international drug evaluation studies.

Nateglinide improves glycaemic control when added to metformin monotherapy: results of a randomized trial with type 2 diabetes patients.

AIMS/HYPOTHESIS: This study evaluated the addition of nateglinide, a d-phenylalanine derivative that restores early phase insulin release, to metformin in type 2 diabetes patients stabilized on high-dose metformin. METHODS: This multicentre, double-blind, parallel group trial included 467 metformin-treated patients with glycosylated haemoglobin (HbA1c) between 6.8% and 11%. Patients were randomized to add nateglinide 60 mg, 120 mg or placebo before three meals to metformin 1000 mg b.i.d. for 24 weeks. RESULTS: HbA1c was significantly reduced with nateglinide 60 mg and 120 mg plus metformin compared with metformin control (-0.36%, p = 0.003; -0.59%, p < 0.001 respectively). Greater benefits occurred if patients had elevated HbA1c at baseline (-1.38% with nateglinide 120 mg in patients with HbA1c > 9.5%). A modest fasting plasma glucose reduction was observed. Most symptoms suggestive of hypoglycaemia occurred in patients with low HbA1c levels (

Rapid and short-acting mealtime insulin secretion with nateglinide controls both prandial and mean glycemia.

OBJECTIVE: The objective of the study was to assess the efficacy and safety of four fixed doses of nateglinide compared with placebo in the treatment of patients with type 2 diabetes with focus on the prandial state. RESEARCH DESIGN AND METHODS: This randomized double-blind placebo-controlled multicenter study was conducted in 289 patients who received either nateglinide at doses of 30 mg (n = 51), 60 mg (n = 58), 120 mg (n = 63), or 180 mg (n = 57) or placebo (n = 60) before three main meals for 12 weeks. Levels of HbA1c, fasting plasma glucose (FPG), fructosamine, and plasma lipids were measured at predetermined intervals, and the effects of nateglinide on prandial glucose insulin, C-peptide, and triglyceride levels were measured after a liquid standard meal (Sustacal; Mead Johnson, Evansville, IN). Adverse events and hypoglycemic episodes were recorded. RESULTS: After a liquid meal challenge, nateglinide rapidly increased mealtime insulin levels within 30 min of drug intake and reduced mealtime glucose excursions without affecting triglyceride levels. At study end point, reduction of HbA1c levels was statistically significantly greater with nateglinide at doses of 60, 120, and 180 mg than placebo (-0.45, -0.62, and -0.64%, respectively; P<0.05). The mean level of FPG was significantly reduced versus placebo in the nateglinide 120-mg group only (-1.14 mmol/l P<0.01). Overall, nateglinide was well tolerated. CONCLUSIONS: This study demonstrated that nateglinide improves mealtime and mean glycemic control in a dose-dependent manner by restoring early insulin secretion phase. Nateglinide was well tolerated and is suitable for the treatment of patients with type 2 diabetes.

Comparison of efficacy of spirapril and enalapril in control of mild-to-moderate hypertension.

The efficacy of spirapril, 6 mg once daily, was compared with enalapril, 5-20 mg once daily, in the control of mild-to-moderate hypertension in a placebo-controlled, parallel-group study. A total of 251 patients participated in the study, all of whom underwent a 4-week washout period on placebo. Thereafter, 100 patients were randomized to spirapril, 6 mg once daily, 101 patients to enalapril, 5-20 mg once daily, and 50 patients remained on placebo. Sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were measured at 2-weekly clinic visits. Blood pressure profiles during peak and trough plasma drug concentrations (2-4 hours and 24-26 hours postdose, respectively) were determined at baseline and 4 and 8 weeks after starting the double-blind phase. Compared with placebo, treatment with both spirapril and enalapril resulted in significant reductions (p < 0.001) in DBP and SBP. DBP was reduced to a greater extent with spirapril than with enalapril both at peak (-17.4 mmHg vs. -14.8 mmHg) and trough (-14.7 mmHg vs. -12.4 mmHg). Thus, although the trough/peak DBP ratios for spirapril and enalapril were very similar (84% vs. 82%), actual reductions in DBP were different. Spirapril and enalapril treatment resulted in similar reductions in SBP at both peak and trough levels. Both drugs were well tolerated, and there were very few adverse events or changes in hematological or biochemical parameters during the study. In conclusion, spirapril, 6 mg once daily, as the initial and maintenance dose, is at least as effective and well tolerated as enalapril individually titrated.

Pharmacokinetics of spirapril in renal impairment.

The pharmacokinetics of spirapril and its active diacid metabolite spiraprilat were characterized in four groups of patients categorized on the basis of their renal function. No statistically significant effects of renal impairment upon the disposition of spirapril were detected. In contrast, there were significant perturbations in the pharmacokinetics of spiraprilat: The maximum plasma concentration (Cmax) values in the severely renally impaired group were 2-3 times those in the group of patients with normal renal function whereas the corresponding area under the curve (AUC) values were 5-6 times higher. However, there was no evidence of accumulation of spiraprilat in any of the groups as determined by the pharmacokinetic parameters derived after single and multiple doses. Thus, despite the evidence of a significant influence of renal impairment upon the disposition of spiraprilat, the lack of accumulation during the translation from single to multiple doses indicates that there is a considerable margin of safety for spirapril in renal impairment.

24-hour ambulatory blood pressure monitoring and spirapril in mild to severe essential hypertension: a randomized dose comparison.

This was a multicentre randomized, double-blind, parallel-group study to compare the antihypertensive efficacy of spirapril at 3 mg with 12 mg once daily, as determined by 24-hour ambulatory blood pressure monitoring (ABPM), in patients with mild to severe essential hypertension. Following a 4-week placebo run-in phase, 52 male and female outpatients, aged 23-67 years with mild to severe essential hypertension [diastolic blood pressure (DBP) > or = 100 mmHg and < 120 mmHg] were randomized to receive spirapril at either 3 mg or 12 mg once daily for 8 weeks. At the end of active treatment and using the standard mercury sphygmomanometer, the number of responders (sitting DBP < 90 mmHg, but decrease > or = 10 mmHg) was the same in both groups (32% and 37%). There were mean decrease in both systolic blood pressure (SBP) and DBP at trough with both 3 mg and 12 mg doses: -9/-7 mmHg and -12/-7 mmHg, respectively. The rate of normalization (trough DBP < or = 90 mmHg) was 12% and 30% with the 3 mg and 12 mg doses, respectively. Of the 44 patients whose daytime ABPM could be compared, one of 20 patients taking 3 mg of spirapril, and 9 of 24 taking 12 mg of spirapril achieved a DBP < or = 90 mmHg for all time intervals while awake. The differences in blood pressure-lowering were significant with both SBP and DBP during the day and at the end of the dosing interval (p < 0.001 and p < 0.01, respectively). The changes from baseline at 24 hours postdose for SBP/DBP were -3/-6 mmHg with 3 mg and -14/-12 mmHg with 12 mg of spirapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Placebo-controlled crossover comparison of spirapril at 3, 6, 12 and 24 mg once daily in mild to severe essential hypertension.

In a randomized, double-blind, crossover study, 20 patients with mild to severe essential hypertension received 3 weeks of treatment with each of four dosages of spirapril (3, 6, 12 and 24 mg once daily) or placebo. Standing and supine blood pressures were measured by use of both an automatic oscillometric instrument (Dinamap) and a mercury sphygmomanometer over a 24-hour period. Spirapril at 6, 12 and 24 mg once daily produced similar reductions in systolic and diastolic blood pressure. At most time points, there was a statistically significant difference between the reductions with spirapril compared with placebo. Spirapril at 3 mg once daily was less effective than the higher dosages, producing a lower mean blood pressure reduction and a shorter duration of antihypertensive action, mainly as regards systolic pressure. Spirapril was well tolerated and no patients withdrew from the study because of adverse effects. These data suggest that, although all four evaluated spirapril dosages effectively lowered supine and standing blood pressure in patients with mild to severe hypertension, the blood pressure-lowering effect of the 3 mg/day regimen was less than optimal. There were only minor variations in efficacy between dosages > or = to 6 mg/day, which may be attributable to the variability of blood pressure. Further investigations of larger numbers of patients are required to verify these results.

Placebo-controlled comparison of spirapril at 6, 12 and 24 mg/day in mild to severe essential hypertension.

In a double-blind, parallel-group study, 260 patients with mild to severe essential hypertension were randomized to treatment with placebo or spirapril at 6, 12 or 24 mg once daily for 6 weeks. When blood pressures were measured at the end of the dosing interval (trough), all spirapril regimens had produced similar reductions in sitting systolic and diastolic blood pressures (siSBP/siDBP) which were significantly greater than those observed in placebo-treated patients. There were no relevant changes in resting heart rate in any of the study groups. At the study endpoint, the mean reductions in siSBP/siDBP were 14.9/11.5 mmHg with spirapril at 6 mg, 15.4/12.0 mmHg with spirapril at 12 mg and 17.8/12.4 mmHg with spirapril at 24 mg/day vs. 3.1/3.6 mmHg with placebo. In a subgroup of 122 patients, blood pressure was recorded at the end of the dosing interval and during the 8 hours immediately postdose to monitor the peak effects on blood pressure. All spirapril dosages produced similar reductions at peak with a mean decrease of siDBP of approximately 20 mmHg in comparison to baseline values vs 6-7 mmHg with placebo. The trough:peak ratios for 6, 12 and 24 mg all lay between 60% and 90% for siSBP and siDBP, indicating that most of the peak effect was maintained at trough. Spirapril was well tolerated; the adverse event profile was not different from that with placebo, and no dose-related adverse events were observed.(ABSTRACT TRUNCATED AT 250 WORDS)