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Biomedical subjects

A J Scheen

Publications and source records attributed to A J Scheen.

At least 109 records · Page 6Linked to original sources
PubMed2002

[Clinical study of the month. The MRC/BHF Heart Protection Study].

20,536 adults (15,454 men and 5,082 women, aged 40-80 years) with coronary heart disease, other occlusive arterial disease or diabetes mellitus were randomly allocated to receive 40 mg simvastatin daily or matching placebo. In addition to being randomized to compare simvastatin vs placebo, all patients were also randomized to compare antioxidant vitamin supplementation (vitamin E 600 mg/day, vitamin C 250 mg/day and betacarotene 20 mg/day) vs placebo in a "2 x 2 factorial" design. Duration of the study was 5 years. All-cause mortality was significantly reduced among patients allocated to simvastatin (-12.3%) due to a highly significant (-18%) reduction in the coronary death rate, a marginally significant reduction in other vascular deaths and a non-significant reduction in non-vascular deaths. There were highly significant reductions (of about one-quarter) in the first event rate for non-fatal myocardial infarction and coronary death (combined), for non-fatal and fatal stroke and for coronary or non-coronary revascularization. The beneficial effect of simvastatin was seen in all sub-categories which were studied and, particularly: women vs men; patients aged > 70 years vs those aged < 70 years; patients with LDL cholesterol < vs > 116 mg/dl, or total cholesterol < vs > 193 mg/dl. The treatment was well tolerated and the annual risk of myopathy was 0.01%. All comparisons between antioxidant vitamin supplementation and placebo failed to reveal any difference in favour or against the supplementation which was otherwise well tolerated. These important results and their implications will be briefly discussed.

Adult↗
PubMed2002

[Info-congress. Prevention of type 2 diabetes in obese patients: first results with orlistat in the XENDOS study].

The results of the XENDOS study were presented by Professor Lars Sjöström (Gothenburg, Sweden), on August 26, 2002, at the 9th International Congress on Obesity in Sao Paulo, Brazil. XENDOS (XENical in the prevention of Diabetes in Obese Subjects) is a multicentre, randomised, double-blind, placebo-controlled, parallel-group prospective study performed in Sweden over a period of 4 years. The aim of XENDOS was to investigate the use of a weight loss agent (orlistat, Xenical) compared with lifestyle changes for the prevention of type 2 diabetes in obese patients (body mass index > or = 30 kg/m2). Weight loss was greater in the orlistat group (-6.9 kg; n = 1.640) than in the placebo group (-4.1 kg; n = 1.637; p < 0.001). Such a difference in weight reduction was sufficient to significantly reduce the cumulative incidence of type 2 diabetes (6.2% versus 9.0%; p = 0.0032; relative risk reduction of 37.3%). The difference was especially remarkable in obese patients with impaired glucose tolerance (21% of the cohort), with a reduction of conversion to diabetes from 28.8% in the placebo group to 18.8% in the orlistat group (p < 0.005) and a number needed to treat to avoid one event of 11 only. Significant and sustained reductions in cardiovascular risk factors such as arterial blood pressure and lipid levels were also observed in the orlistat group as compared to the placebo group. XENDOS is the first study demonstrating that an antiobesity agent, like orlistat, is able to reduce the progression to diabetes in obese subjects as compared with lifestyle changes alone.

Adult↗
PubMed2002

[Info-congress. Study of the prevention of type 1 diabetes with nicotinamide: positive lessons of a negative clinical trial (ENDIT)].

ENDIT ("European Nicotinamide Diabetes Intervention Trial") is a large placebo-controlled randomised clinical trial that aimed at studying the efficacy of nicotinamide in the prevention of type 1 diabetes mellitus among first-degree relatives of type 1 diabetic patients with positive islet cell antibodies (ICA). The results presented at the last congress of the European Association for the Study of Diabetes (EASD) in Budapest do not evidence any significant difference in the risk of developing overt diabetes mellitus in the patients treated with nicotinamide (n = 274) as compared to those receiving placebo (n = 275) after 5 years of follow-up. Despite these negative results, positive lessons could be drawn from ENDIT: 1) the feasibility of a large long-standing multicentre European trial in a difficult research area; 2) the importance of large randomised controlled clinical trials to bring the evidence requested by "Evidence-Based Medicine"; 3) the predictive value of various risk markers to progress toward type 1 diabetes in first-degree relatives, especially the number of positive auto-antibodies; and 4) the urgent need to continue intensive research in this important field of preventive medicine.

Diabetes Mellitus, Type 1↗
PubMed2002

New antiobesity agents in type 2 diabetes: overview of clinical trials with sibutramine and orlistat.

Besides genetic predisposition, obesity is the most important risk factor for the development of type 2 diabetes mellitus. Even modest weight reduction can improve blood glucose control in overweight subjects. After failure of lifestyle modifications, antiobesity drugs such as orlistat, a potent and selective inhibitor of gastric and pancreatic lipases that reduces lipid intestinal absorption, or sibutramine, a noradrenaline and 5-hydroxytryptamine reuptake inhibitor that regulates food intake, may be considered to favour weight loss and/or weight maintenance. Several placebo-controlled studies have recently demonstrated that both drugs are able to promote weight loss in obese type 2 diabetic patients treated with diet alone, sulphonylureas, metformin or insulin. The greater weight reduction as compared to placebo was associated with a significant reduction of glycated haemoglobin levels and/or of the doses of classical antihyperglycaemic agents, especially in good responders who lost at least 10% of initial body weight. In addition, vascular risk factors associated to insulin resistance were also reduced after weight loss. These antiobesity agents may also contribute to delay or prevent the progression from impaired glucose tolerance to overt type 2 diabetes in at risk obese individuals ("Xenical in the prevention of diabetes in obese subjects" trial). Large long-term prospective studies, such as the "Sibutramine cardiovascular and diabetes outcome study" should better determine the place of pharmacological anti-obesity strategy in the overall management of obese patients with impaired glucose tolerance or type 2 diabetes.

Anti-Obesity Agents↗
PubMed2002

[Therapeutic advances in 2002 (1)].

The most important drugs registered and/or launched in Belgium during the last year in the various disciplines of internal medicine will be briefly described. The main characteristics of each molecule and its modalities of appropriate use in clinical practice will be emphasized. For all these molecules, both the efficacy and tolerance have been proven in randomised clinical trials according to the rules of Evidence-Based Medicine.

Belgium↗
PubMed2002

[The PROSPER Study (PROspective study of pravastatin in the elderly at risk)].

Statins reduce coronary and cerebrovascular mortality and morbidity in middle-aged individuals. Until recently, their efficacy and safety in elderly people had not yet been firmly established. PROSPER was a controlled, randomised study involving 2,804 men and 3,000 women aged 70-82, with a history of, or risk factors for cardiovascular disease. Their baseline cholesterol level was 135-350 mg/dl; they were randomised to either 40 mg pravastatin per day, or matching placebo. Average follow-up was 3.2 years. The primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Pravastatin lowered LDL-cholesterol (-34%), and reduced the incidence of the primary endpoint (-15%; CI 95%: 3-26%; p = 0.014). Coronary death and non-fatal myocardial infarction risk was also reduced (-19%; p = 0.006), and mortality from coronary disease fell by 24% (p = 0.043). The risk for stroke, however, was unaffected (p = 0.8), whereas the incidence of transient ischemic attacks was reduced by 25%, which was (marginally) insignificant (p = 0.051). Pravastatin had no effect on cognitive functions or incapacity. New cancers were more frequent amongst pravastatin-treated individuals (+25%; p = 0.020). However incorporation of this new data in a meta-analysis of all pravastatin and all statin trials revealed no overall increase of cancer risk.

Aged↗
PubMed2001

Obesity: causes and new treatments.

The prevalence of obesity increases rapidly in developed and developing countries. Obesity results from a cumulative positive energy balance and is favoured by both genetic and environmental factors. Preventing obesity requires a major investment in nutritional and lifestyle education, particularly in children and adolescents.--The pharmacological approach to obesity includes drugs that reduce food intake (noradrenergic and serotoninergic agents), drugs that increase energy expenditure and compounds that affect nutrient partitioning. In all instances, the benefit-to-risk ratio needs to be carefully assessed. In some patients (severe obesity or obesity accompanied by serious high-risk comorbid conditions), gastric surgery (gastric restriction or gastric bypass) should be considered. In our own experience, it is safe and effective.

Energy Metabolism↗
PubMed2001

Hepatotoxicity with thiazolidinediones: is it a class effect?

Decreased insulin sensitivity plays a major role in various human diseases. particularly type 2 diabetes mellitus, and is associated with a higher risk of atherosclerosis and cardiovascular complications. Thiazolidinediones, more commonly termed glitazones, are the first drugs to specifically target muscular insulin resistance. They have proven efficacy for reducing plasma glucose levels in patients with type 2 diabetes mellitus treated with diet alone, sulphonylureas, metformin or insulin. In addition, they are associated with some improvement of the cardiovascular risk profile. However, troglitazone, the first compound approved by the Food and Drug Administration in the US, proved to be hepatotoxic and was withdrawn from the market after the report of several dozen deaths or cases of severe hepatic failure requiring liver transplantation. It remains unclear whether or not hepatotoxicity is a class effect or is related to unique properties of troglitazone. Rosiglitazone and pioglitazone, two other glitazones, appear to have similar efficacy with regard to blood glucose control in patients with type 2 diabetes mellitus as compared with troglitazone. In controlled clinical trials, the incidence of significant (> or =3 x upper limit of normal) increases in liver enzyme levels (ALT in particular) was similar with rosiglitazone or pioglitazone as compared with placebo, whereas troglitazone was associated with a 3-fold greater incidence. In contrast to the numerous case reports of acute liver failure in patients receiving troglitzone, only a few case reports of hepatotoxicity have been reported in patients treated with rosiglitazone until now, with a causal relationship remaining uncertain. Furthermore, no single case of severe hepatotoxicity has been reported yet with pioglitazone. It should be mentioned that troglitazone, unlike pioglitazone and rosiglitazone, induces the cytochrome P450 isoform 3A4, which is partly responsible for its metabolism, and may be prone to drug interactions. Importantly enough, obesity, insulin resistance and type 2 diabetes mellitus are associated with liver abnormalities, especially non-alcoholic steatohepatitis, independent of any pharmacological treatment. This association obviously complicates the selection of patients who are good candidates for a treatment with glitazones as well as the monitoring of liver tests after initiation of therapy with any thiazolidinedione compound. While regular monitoring of liver enzymes is still recommended and more long term data are desirable, current evidence from clinical trials and postmarketing experience in the US supports the conclusion that rosiglitazone and pioglitazone do not share the hepatotoxic profile of troglitazone.

Aged↗
PubMed2001

[Pharma-clinics. The drug of the month. Celecoxib (Celebrex)].

Celecoxib (Celebrex, Pharmacia) is a potent and selective inhibitor of the COX-2 isoform of cyclooxygenase which is used as nonsteroidal anti-inflammatory drug (NSAID). Its current indications are osteoarthritis and rheumatoid arthritis. The usual recommended daily dosage of celecoxib is 200 mg (in one or two intakes per day), to be increased up to 400 mg (two intakes per day) if necessary. Its clinical efficacy seems to be similar to that of other NSAIDs. However, its safety profile, especially gastro-intestinal tolerance and perhaps renal safety, is much better because of the COX-2 selectivity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

[Clinical study of the month. After the storm over central anorectic agents, the "STORM" study of sibutramine].

The results of the "Sibutramine Trial of Obesity Reduction and Maintenance" (STORM) published in the last issue of December 2000 of the Lancet are summarized. This clinical trial (open label for the first 6 months and double blind versus placebo for a further 18 months) demonstrates the positive effect of sibutramine, a new anorectic drug, on long-term weight maintenance after weight loss in obese subjects. The benefit of sibutramine on the cardiovascular risk profile of the obese patient is more particularly discussed.

Appetite Depressants↗
PubMed2001

[Clinical study of the month. The CALM study assessing the combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist in the treatment of diabetic nephropathy].

The main objective of the CALM (Candesartan And Lisinopril Microalbuminuria) study is to assess the effect of a dual blockade of the renin-angiotensin system--using both an angiotensin converting enzyme inhibitor (ACE-I) and an angiotensin II type 1 receptor blocker--in patients with type 2 diabetes, high blood pressure and microalbuminuria. The study included 200 patients randomized to receive candesartan 16 mg or lisinopril 20 mg for 12 weeks, followed by 12 weeks of the same monotherapy or a combination treatment. Main outcomes are the reduction of microalbuminuria and blood pressure. All three of the treatments are effective, but the dual blockade is respectively 18%, 8 mmHg and 5 mmHg more effective in reducing microalbuminuria, systolic and diastolic blood pressure. No comparison is made between this "new" association and the more frequently used biotherapy (i.e. ACE-I plus thiazidic diuretic) and therefore its usefulness in regular practice is still to be determined.

Adult↗
PubMed2001

[Pharmacy clinics. Medication of the month. Clopidogrel (Plavix)].

Clopidogrel is launched in Belgium by Sanofi-Synthelabo and Bristol-Myers Squibb under the trade name of Plavix. It is a potent and irreversible ADP receptor antagonist that proved to be more effective than aspirin as antiplatelet agent in the multicentre, randomised double-blind CAPRIE study. It is indicated, at a dosage of 75 mg/day, for the reduction of atherosclerotic events including myocardial infarction, ischaemic stroke and vascular death in patients with atherosclerosis manifested by recent stroke, myocardial infarction or established peripheral vascular disease. Furthermore, recent studies demonstrated that the combination of clopidogrel with aspirin is more effective than aspirin alone and better tolerated than the combination ticlopidine-aspirin for the prevention of atherothrombosis after placement of intravascular stents. Ongoing trials are evaluating the efficacy and safety of such clopidogrel-aspirin combination after acute ischaemic coronary events or in patients at very high risk of stroke. Thus the indications of clopidogrel may become even larger in a next future.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

[Hormonal-metabolic adaptations to muscular exercise].

Physical exercise induces numerous metabolic and hormonal changes that may be influenced by various factors, among which the intensity and the duration of the exertion seem to play a major role besides the possible influence of the intake of exogenous substrates. Such modifications are necessary to satisfy the marked increase in energy demand by exercising muscles, while maintaining plasma glucose concentrations within physiological range. The purpose of the present concise review is to analyse the most important fuel-hormonal adaptations observed during short heavy muscular exercise or during prolonged exercise of moderate intensity as well as those observed after physical training in normal subjects.

Adaptation, Physiological↗
PubMed2001

[Beneficial effects of physical activity on cardiovascular risk factors].

Numerous observational (epidemiological surveys) or interventional (controlled trials) studies demonstrated that regular physical activity increases insulin sensitivity in normal subjects and decreases insulin resistance in patients with obesity and/or type 2 diabetes. These favourable effects are at least partially linked to a reduction in abdominal fat mass. This results in a significant improvement of lipid profile, with a decrease in the concentrations of total cholesterol, LDL cholesterol and triglycerides, associated with an increase of HDL cholesterol level. Such favourable metabolic effects related to regular physical activity probably explain the better cardiovascular prognosis observed in regularly exercising subjects as compared to sedentary individuals. These observations should motivate any practitioner to promote endurance physical exercise in every subject, especially in individuals at high cardiovascular risk.

Cardiovascular Diseases↗
PubMed2001

[Physical exercise for preventing obesity, promoting weight loss and maintaining weight management].

Obesity is a multifactorial disease making difficult the determination of the precise role of one specific factor such as physical activity or sedentary. Nevertheless, numerous arguments, derived from epidemiological observational studies or from randomized controlled interventional trials, support a favourable role of regular physical activity in the control of body weight. Physical activity contributes to prevent the occurrence of weight excess, especially in children or adolescents, to obtain a satisfactory weight loss, in general in combination with reduced-energy diets, and to maintain long-term weight loss. In addition, physical activity improves both the metabolic profile and health of obese subjects.

Clinical Trials as Topic↗
PubMed2001

Thiazolidinediones and liver toxicity.

Thiazolidinediones or glitazones specifically target insulin resistance. They have proven efficacy for reducing plasma glucose levels of type 2 diabetic patients treated with diet alone, sulphonylureas, metformin or insulin. In addition, they may be associated to some improvement of cardiovascular risk profile. However, troglitazone, the first compound approved by the FDA in the US, proved to be hepatotoxic and was withdrawn from the market after the report of several dozens of deaths or cases of severe hepatic failure requiring liver transplantation. It remains unclear whether or not hepatotoxicity is a class effect or is related to the unique tocopherol side chain of troglitazone. Rosiglitazone and pioglitazone, two other glitazones, appear to have similar efficacy on blood glucose control of type 2 diabetic patients as compared to troglitazone. In controlled clinical trials, the incidence of significant increases in liver enzyme levels (ALT) was similar with rosiglitazone or pioglitazone as compared to placebo, whereas troglitazone was associated with a threefold greater incidence. In contrast to the numerous case reports of acute liver failure in patients receiving troglitzone, only two cases of severe reversible liver failure have been reported in patients treated with rosiglitazone, with a causal relationship remaining uncertain. Furthermore, no single case of severe hepatotoxicity has been reported yet with pioglitazone. While regular monitoring of liver enzymes is still recommended and more long-term data are desirable, current clinical evidence supports the conclusion that rosiglitazone and pioglitazone do not share the hepatotoxic profile of troglitazone.

Blood Glucose↗