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P Mismetti

Publications and source records attributed to P Mismetti.

47 records · Page 3Linked to original sources
PubMedDate not supplied

Influence of confounding factors on designs for dose-effect relationship estimates.

Three types of designs can be used to estimate the drug dose-effect relationship during phase II clinical trials: parallel-dose designs (parallel); cross-over designs (X), and dose-escalation designs ([symbol: see text]). Despite the use of non-linear mixed effect models, the potential influence of confounding factors on [symbol: see text] designs has not been previously fully elucidated; we undertook simulations to investigate this for all three experimental designs. We found that: (i) monotonic spontaneous evolution of the effect (EV) did not affect the maximum effect estimation (Emax) and the dose giving 50 per cent of this (ED50); (ii) EV similar to a regression to the mean gave rise to biases for [symbol: see text] designs; (iii) the introduction of a pharmacodynamic carry-over generates important biases and imprecision for [symbol: see text] designs, even when the carry-over is adjusted for; (iv) the introduction of non-responders resulted in bias and imprecision for both Emax and ED50 in all three designs.

Antihypertensive Agents↗
PubMedDate not supplied

A chronopharmacodynamic study on standard heparin, a low molecular weight heparin (nadroparin) and danaproid: establishing and comparing the daily variations of these drugs in rats.

The effects of dosing time on the anticoagulant activity of unfractionated heparin, low molecular weight heparin (nadroparin) and danaproid were investigated. The chronopharmacological comparisons of the drugs were done on the anti-Xa, anti-IIa activities and activated partial thromboplastin time assays. Several dosing times were considered and an analysis based on a population approach was adopted. Under unfractionated heparin, the pharmacological activities did not exhibit significant daily variations. In contrast, significant daily profiles were observed in all the biological assays performed with low molecular weight heparin. Anti-Xa and anti-IIa activities showed some fluctuations over a 24-hour period with a peak at noon. As for the variations of the activated partial thromboplastin time, two peaks were noted early in the morning and at the beginning of nightfall. As for danaproid, only a daytime maximum of anti-Xa activity could be found.

Animals↗
PubMedDate not supplied

[Evaluation of the risk of venous thromboembolism in the medical patients].

The venous thromboembolic risk seems to be demonstrated in medical patients since the incidence of symptomatic and asymptomatic deep vein thrombosis (DVT) without any prophylactic methods is respectively about 50 per cent in stroke, 25 per cent in acute myocardial infarction (AMI) and 15 per cent in internal medicine. A synthesis of clinical trials performed in medical patients shows that prophylactic doses of heparins (unfractionated heparin or low molecular weight heparins) reduce the incidence of DVT by 40 to 60 per cent compared with the lack of any antithrombotic agents but without any significant effect on total mortality. Other antithrombotic agents such as antiplatelet agents seem to reduce the incidence of DVT by about 40 per cent associated with a significant decrease in total mortality of stroke or AMI. But the recommendations made on the basis of these results have to be extremely cautious since the number of medical patients included in clinical trials is quite limited compared with the surgical area. Moreover, each of these recommendations is not sufficiently proven. Thus more clinical trials have to be carried out with a placebo control group in internal medicine and an aspirin control group for stroke and AMI.

Anticoagulants↗
PubMedDate not supplied

[Prevention of thrombosis during pregnancy: from recommendations to practice from 26 cases].

Recommendations have recently been published regarding the prescription of low-molecular-weight heparin (LMWH) during pregnancy in women at risk of thromboembolism. To assess how well these recommendations are followed, we retrospectively recorded all pregnancy consultations in a thrombosis unit for two years. Of the 26 women included (mean age 30 +/- 4.8 years), 81% presented with a history of thromboembolism, 35% thrombophilia, and 15% a history of pregnancy termination for medical reasons. Clinical follow-up concerned 17% of the women; 8% were given aspirin, 63% LMWH at prophylactic dosages, 4% combination of aspirin and prophylactic LMWH, and 8% were on curative LMWH. Neither thromboembolic nor neonatal events were observed. One case of termination of pregnancy for medical reasons was observed at the 5th month. Although we also took into account the gravity of previous thromboembolism, our prescriptions were globally in compliance with the recommendations. This approach has still to be validated with a decision-making tree.

Adult↗
PubMedDate not supplied

Thrombotic thrombocytopenic purpura: MR findings.

Neurologic manifestations occur in over 90% of patients with thrombotic thrombocytopenic purpura. Neuropathologically, thrombi produce occlusion of terminal arterioles and capillaries resulting in diffuse small infarcts. In the great majority of surviving patients, brain CT does not disclose any abnormalities. The authors report a case of thrombotic thrombocytopenic purpura in which brain MR examination showed multiple punctate lesions in the white matter.

Adult↗
PubMedDate not supplied

[Thrombopenia induced by heparin: treatment with Org 10172. Tolerability and efficacy].

OBJECTIVES: Heparin-induced thrombocytopenia is a relatively common and potentially serious adverse complication of heparin treatment. After heparin withdrawal initiation of an alternative anticoagulant is often indicated. Org 10172 or Orgaran is a mixture of several non-heparin low molecular weight glycosaminoglycans with proven antithrombotic efficacy. Unlike low molecular weight heparins, Org 10172 has a low cross reaction rate (about 10%) with the heparin-dependent antibody. METHODS: We present nine patients with heparin induced thrombocytopenia. Org 10172 was prescribed to treat or to prevent a thromboembolic event. RESULTS: Seven patients required further parenteral anticoagulant at diagnosis of heparin-induced thrombocytopenia. Org 10172 was given at prophylactic doses for three patients with a high thrombosis risk and at therapeutic doses for four patients who presented either a venous or an arterial thrombosis related to thrombocytopenia. Two patients presented heparin-induced thrombocytopenia four to six years earlier and needed a parenteral anticoagulation treatment in a post-operative period. CONCLUSION: For the nine patients, Org 10172 was a safe and effective antithrombotic treatment. However, strict monotoring of the platelet count is absolutely mandatory during Org 10172 therapy.

Adult↗
PubMedDate not supplied

[Heparins and curative treatment of venous thromboembolic disease: meta-analysis].

Heparin treatment of venous thromboembolic disease has been validated since 1960. Nevertheless no study was sufficient to determine an optimal therapeutic schedule between sub-cutaneous (SC) unfractionated heparin (UFH), intravenous (IV) UFH and low molecular weight heparin (LMWH). One meta-analysis showed a significant risk reduction of recurrent thromboembolic events (OR = 0.58, CI 95 per cent [0.34-0.99]) and a non-significant risk reduction of haemorrhagic events (OR = 0.78 [0.40-1.52]) with UFH SC compared to UFH IV, but homogeneity testing was significant (p < 0.001). Some discrepancy was shown between the results of the three metaanalyses which compared LMWH to UFH according to the selection criteria of clinical trials used. With an exhaustive selection, LMWH involved a non-significant risk reduction of recurrent thromboembolic events (OR = 0.66 [0.41-1.07], p = 0.09), and a non-significant risk reduction of haemorrhagic events (OR = 0.65 [0.36-1.16], p = 0.15). So no definitive conclusion could be drawn but it seems that UFH can be recommended whatever the administration route or LMWH for deep vein thrombosis treatment.

Anticoagulants↗
PubMedDate not supplied

[Clinical evaluation: from intermediate to surrogate criteria].

The development and evaluation of new drugs often rely on surrogacy. An intermediate outcome becomes a surrogate outcome if it fulfils certain criteria, it should be easier to measure compared with the clinical outcome, a statistical relationship should exist between the clinical outcome and the surrogate outcome, a relation should exist allowing prediction of the degree of clinical effect based on the measured effect on the surrogate outcome. Development and authorization of drugs today often rely on so-called surrogate outcomes. Is this use sound? The validity of such outcomes has been reviewed in different therapeutic areas: hypertension, venous thromboembolism, AIDS, osteoporosis, hepatitis C. Based on this review, a pragmatic strategy is proposed which allows for the validation and proper use of surrogate outcomes.

Acquired Immunodeficiency Syndrome↗