Treatment with metformin of non-diabetic men with hypertension, hypertriglyceridaemia and central fat distribution: the BIGPRO 1.2 trial.

BACKGROUND: In the BIGPRO 1 trial, one year of treatment with metformin in non-diabetic obese subjects with a central fat distribution had no significant effect on fasting plasma triglyceride concentration or on blood pressure despite a decrease in weight, fasting plasma insulin and glucose concentrations. To re-evaluate the effect of metformin on fasting triglyceride concentration and on blood pressure, the BIGPRO 1.2 trial included non-diabetic men (n=168) with a fasting plasma triglyceride concentration > or =1.7 and < or =6.5 mmol/l, high blood pressure (systolic > or =140 and < or =180 and/or diastolic > or =90 and < or =105 mmHg, or treatment for hypertension) and a waist-to-hip ratio > or =0.95. METHODS: A randomised double-blind trial comparing metformin treatment (850 mg bid) with placebo. RESULTS: Metformin had no significant effect either on blood pressure or plasma triglyceride concentration. In comparison with the placebo group, fasting plasma insulin (p<0.04), total cholesterol (p<0.05) and Apo B (p<0.008) concentrations decreased more in the metformin group in the BIGPRO 1. 2 trial, confirming most of the previous results of the BIGPRO 1 trial. Tissue plasminogen activator antigen concentration decreased significantly (p<0.01) only in the metformin group, but this was not significantly different from the placebo group (p<0.12); further, there were no significant differences in the change in plasminogen activator inhibitor 1. CONCLUSIONS: The consistency of the two BIGPRO trials supports the conclusion that metformin affects several cardiovascular risk factors favourably in non-diabetic subjects with a central fat distribution.

[Prevention of avoidable iatrogenic effects: the obligation for vigilance]. / Prévention de la iatrogénie évitable: le devoir de vigilance.

PREVALENCE: Latrogenic-related morbidity and mortality rates are difficult to determine. Certain estimations in France and other countries have suggested that drug-related accidents alone could account for 5 to 10% of all acute hospitalizations. This would mean that in France, several thousand deaths are caused annuallty by drugs. COST CONSIDERATIONS: Independent of the human aspect, health care expenditures related to iatrogenic accidents are substantial. In France, the cost would be several ten billion francs. Although the cost/benefit ratio remains highly positive, statistically speaking one cannot ignore the high cost of severe accidents. THE NOTION OF RISK: There is an urgent need to persuade the public opinion that all effective medicines, like all surgical procedures, carry a risk. Zero risk does not exist. Patients, and the public in general, should come to realize that the objective is to minimize risk inherent in all therapies. PREVENTION: It is the duty of the entire health care team to calculate the level of acceptable risk and take all the necessary preventive measures. One of the objectives of the French National Educational Association for Training in Therapeutics (APNET) is to define means of reducing latrogenic effects.

[Initial and continuous education. Entreaty for better education of physicians in therapeutics]. / Formation initiale et continue. Plaidoyer pour une meilleure formation des médecins en Thérapeutique.

Concrete education on therapeutical decision must constitute a major institutional objective during the higher academic period of the medical students. The current therapeutics constitutes a branch of instruction based on the up-to-date of the "medical science" and on the evidence evaluation. However, such evidence-based medicine still biased, evolutionary and thus provisory valid; whereas at the same time it must be appropriate and suitable for the patients benefit. Data issued from medical science are on the basis of the interactive and pragmatic apprenticeship of the therapeutical decision and prescription with a personalized approach of patient and at each step of its disease. The continuous postgraduate education programs following the initial Academic instruction contributes to up date the knowledges and moreover the professional experience and practice. This evolution is performed with respect of both the individual ethic-related to the patient and the collective ethics in terms of public health.

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

[An epidemiological survey on iatrogenic disease in hospitals]. / Enquête épidémiologique sur la iatrogénie en milieu hospitalier.

In a "on a given day" study, we analysed the prevalence and causes of drug-related and non-drug, related iatrogenic illnesses. The human and financial costs of iatrogenic illnesses show that risk-prevention measures are required.

[Iatrogenic disease observed in a hospital setting. II. Analysis of causes and suggestions for novel preventive measures]. / Iatrogénie observée en milieu hospitalier. II--Analyse des causes et propositions pour de nouvelles mesures préventives.

In a previous article, we reported the results of a survey of iatrogenic illness in teaching hospitals. In the second part of this study, we shall consider the origins of the 109 adverse events which occurred in a 24-hour period among 1733 hospital patients in a total of 43 units (mean prevalence, 6.28%). In a total of 89 cases (83 of which were drug-related and 6 of which were of various non-instrumental causes), self-treatment and/or poor patient compliance appeared to be the main cause in 16 (18%); negligence or erroneous prescription (non-respect of a contraindication, wrong indication or dosage, excessive duration of treatment, inadequate monitoring, etc...) appeared to be responsible in 27 cases (30.3%). It may be that at least some of these cases of iatrogenic illness due to errors or negligence on the part of the patient and/or physician (48.3%) could be avoided in future by better training of health personnel and improved public health education. The human and financial costs of iatrogenic illness show that risk-prevention measures are required; we propose a number of strategies concerning both initial training in medical school and ongoing education in therapeutics, together with ways of improving the behaviour of both physicians and the pharmaceutical industry. The latter suggestions are addressed at the media and the health authorities; some concern legislation, while others are aimed at improving early public health education, an essential element in this setting.

[Iatrogenic illness observed in the hospital environment. I. A report of 109 cases collected in a cross-sectional APNET study]. / Iatrogénie observée en milieu hospitalier. I--A propos de 109 cas colligés à partir d'une enquête transversale de I'APNET.

In an "on a given day" study, we analysed the prevalence and causes of drug-related and non-drug-related iatrogenic illnesses for educational and preventive purposes. Forty-three hospital departments of various specialties and involving 62 APNET members participated in the study. From a total of 112 cases reported, 109 were considered iatrogenic illnesses on the basis of the French criteria for adverse effects. Four major types of iatrogenic illness were defined, as follows: I--drug-related cases (n = 83); II--miscellaneous cases (n = 6); III--cases due to therapeutic instrumentation (n = 16); IV--cases due to diagnostic instrumentation (n = 4). Overall, 6.28% of the patients admitted presented an iatrogenic illness; 67 (61.46%) of the 109 cases concerned women and 66 (60.55%) concerned patients aged 65 years or more. The types of illness in the "drug-induced" and "miscellaneous" categories were endocrine and metabolic disturbances (n = 14), gastrointestinal conditions (n = 13) and hematological disorders (11 cases of bone marrow aplasia). Instrument-related iatrogenic illnesses comprised cardiovascular conditions (n = 6), locoregional anatomic lesions (n = 5), infectious complications (n = 3), bleeding (n = 3) and others (n = 3). Seventeen incidents were benign, 38 dangerous and 51 serious; there were three deaths. The main drug categories concerned in the 89 cases of "drug-related" and "miscellaneous" iatrogenic illnesses were as follows: cardiovascular agents (n = 20), antiinflammatory and analgesic drugs (n = 18), hormone and nutritional treatments (n = 11) and neuropsychiatric drugs (n = 11). Instrument-related iatrogenic illnesses chiefly involved venous approaches (n = 8), surgery (n = 4), intensive care procedures (n = 2), renal dialysis (n = 2) and radiation therapy (n = 2). The main causes of drug-related iatrogenic illnesses were self-treatment (n = 8), poor compliance (n = 8), and therapeutic errors (n = 27) [non-respect of a contraindication (n = 2), wrong indication (n = 6), excessive dose (n = 13), over-prolonged treatment (n = 2) and other errors (n = 4). A cost-analysis of 74 of the 109 cases gave a minimum figure of 2 million French francs. The human and financial costs of iatrogenic illnesses show that risk-prevention measures are required; these will be dealt with in a later paper, but should be based on stricter regulations and educational programmes aimed at doctors, patients, the general public, the pharmaceutical industry and the health authorities.

[Education of hypertensive patients (from the experience with diabetic patients)]. / L'enseignement des malades hypertendus (à partir de l'expérience chez les diabétiques).

The education of patients with arterial hypertension is a prerequisite to their co-operation in the daily management of their disease. It probably improves their compliance with the treatment prescribed and the quality of the results obtained in terms of blood pressure levels. The experience acquired in the education of diabetic patients supports this view. It started in Europe more than 10 years ago and its results begin to be evaluated. Its principles, means and objectives are summarized and illustrated here. Based on their experience but avoiding undue assimilation, the authors, who are diabetologists, are offering a first list of objectives in the education of hypertensive patients. This list is certainly not imperative or exhaustive; it should be regarded, at best, as incentive.

[Hyperlipidemia aggravated or induced by combined oral contraceptives: preliminary results of a decision-making scheme for the prevention of cardiovascular episodes]. / Hyperlipidemies revelees ou induites par les contraceptifs estroprogestatifs. Attitudes adoptees--resultats preliminaires.

PIP: This article outlines a systematic treatment for patients on combined oral contraceptives (OCs) in whom hyperlipidism is induced or aggravated by the OCs. 36 women aged 20-40 years who used OCs containing 50 mcg of ethinyl estradiol (EE) and Norgestrel were treated by the same team of physicians with an identical protocol. 9 of the 36 women had elevated triglyceride (TG) levels, 5 had elevated total cholesterol (TC) levels, and 22 had both. The average level of TG was 1.56 and of TC 2.88 g/l. When the EE dosage of the 1st group was reduced to 30 mcg, the average TG level fell from 1.44 to l g/l. In a 2nd group, in which either lipid levels were very high or predisposing factors were present, the use of combined OCs was discontinued; the average level of TG declined from 1.64 to .95. Some patients were treated successively in both groups. In patients receiving reduced dosages of EE, the average TC level declined from 2.80 to 2.22. The average TC level for those discontinuing OC therapy declined form 2.89 to 2.40. Despite high initial values in those for whom OC therapy was stopped, most cases were normalized with these procedures. In 2 cases of elevated TG, 5 of TC, and 5 of both, the levels were not normalized within 3 months of discontinuing OC therapy. In 9 of 10 cases of elevated TC or TC and TG, predisposing factors were present. The experience suggests the existence of 2 categories of lipid anomales, those induced by the OCs, which tend to be moderate and subject to improvement or disappearance with reduced dosage of EE or discontinuation of OCs, and probably preexisting cases which are aggravated by the OCs. Such cases are of greater significance and are likely to persist longer. In cases of preexisting lipid anomalies when genetic factors are involved, OCs should be stopped to avoid the risk of vascular accidents.^ieng

[Congenital diverticuli of the common bile duct. Review of the literature]. / Diverticules congénitaux de la voie biliaire principale. Revue de la littérature

Among congenital dilatations of the common bile duct, a congenital diverticulum of the common bile duct may remain clinically latent for a long period. One case is reported in a 77 year old subject. Precise diagnosis of the disease is often made at operation and on pathological examination. The diverticulum is cured in most cases after surgery which consists of simple removal, but which may sometimes require reconstruction of the common bile duct.