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Biomedical subjects

François Gueyffier

Publications and source records attributed to François Gueyffier.

At least 19 recordsLinked to original sources
PubMed2006

Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock.

OBJECTIVE: The immediate overwhelming release of inflammatory mediators in septic shock is rapidly followed by strong anti-inflammatory responses inducing a state of immunosuppression. The patients who survive the initial hyper-inflammatory step of septic shock but subsequently die may be those who do not recover from immunosuppression. We assessed whether a low monocyte human leukocyte antigen-DR (mHLA-DR) expression, proposed as a marker of immunosuppression, is an independent predictor of mortality in patients who survived the initial 48 h of septic shock. DESIGN AND SETTING: Prospective observational study performed in two adult intensive care units at a university hospital. PATIENTS: 93 consecutive patients with septic shock. MEASUREMENTS AND RESULTS: At days 1-2, mHLA-DR values (determined by flow cytometry) were not significantly different between survivors and non-survivors. A sharp difference became highly significant at days 3-4 when survivors had increased their values, while non-survivors had not (43% vs. 18%, percentage of HLA-DR positive monocyte, p < 0.001). Multivariate logistic regression analysis revealed that low mHLA-DR (< 30%) at days 3-4 remained independently associated with mortality after adjustment for usual clinical confounders, adjusted odds ratio (CI): 6.48 (95% CI: 1.62-25.93). CONCLUSION: The present preliminary results show that mHLA-DR is an independent predictor of mortality in septic shock patients. Being a marker of immune failure, low mHLA-DR may provide a rationale for initiating therapy to reverse immunosuppression. After validation of the current results in multicenter studies, mHLA-DR may help to stratify patients when designing a mediator-directed therapy in a time-dependent manner.

Aged↗
PubMed2006

[Smoking cessation counseling center in a French hospital: Effectiveness at one year and predictors of outcome].

OBJECTIVE: To assess the effectiveness at 1 year of a hospital clinic providing individual management of persons seeking to stop smoking and the factors predictive of failure. METHODS: This prospective descriptive study included smokers seeking assistance at this hospital clinic over a 1-year period. This analysis excludes persons with schizophrenia and those who came only to a first consultation. Treatment methods were those recommended by the 1998 consensus conference: nicotine substitutes or slow-release bupropion, depending on the level of nicotine dependence, cognitive-behavioral therapy appropriate for smoking in all cases, and the prescription before cessation of a selective serotonin re-uptake inhibitor (SSRI) for patients with anxiety or depressive disorders. Assessment was based on patients' self-report at 3 months, 6 months and 1 year. RESULTS: Of 99 smokers who came for at least one consultation, 38 were excluded and 61 were considered in the analysis. At one year, 18 patients (29.5%) were still not smoking. Of the 43 patients who resumed smoking, 27 (63%) did so during the first three months after cessation. According to the multivariate analysis, only female sex (p = 0.0173) and early end to follow-up (p = 0.0023) were significantly associated with the risk of relapse at 1 year. CONCLUSION: The study confirmed the usefulness of specialized medical support over a one-year period and highlighted the difficulties of smoking cessation for women, who appear to need a new not yet invented approach. The other standard factors predictive of failure were not observed, possibly because of either the broad prescription of SSRIs in cases of anxiety- or depression-related comorbidity or the statistical limitations associated with the population size.

Adult↗
PubMed2005

[Cardiovascular prevention and large clinical trials].

Large clinical trials of the three last decades have transformed the therapeutic landscape in depth. After putting into question the multi-factorial approach and simplistic models such as that of isotropy, clinical trials have shown to which extent some drugs are an efficacious way of reducing the burden of premature cardiovascular events and of prolonging life. The optimal use of the results from large clinical trials requires a permanent updating process, which is not realistic for the non-specialist physician: dedicated and fitted interfacing tools have to be developed. Practitioners must be trained to use these new concepts and tools.

Cardiovascular Diseases↗
PubMed2005

Systolic and diastolic blood pressure lowering as determinants of cardiovascular outcome.

Based on individual patient data, we performed a quantitative overview of trials in hypertension to investigate to what extent lowering of systolic blood pressure (SBP) and diastolic blood pressure (DBP) contributed to cardiovascular prevention. We selected trials that tested active antihypertensive drugs against placebo or no treatment. Our analyses included 12,903 young (30 to 49 years of age) patients randomized in 3 trials and 14,324 old (60 to 79 years of age) and 1209 very old (> or =80 years of age) patients enrolled in 8 trials. Antihypertensive treatment reduced SBP/DBP by 8.3/4.6 mm Hg in young patients, by 10.7/4.2 mm Hg in old patients, and by 9.4/3.2 mm Hg in very old patients, respectively, resulting in ratios of DBP to SBP lowering of 0.55, 0.39, and 0.32, respectively (P=0.004 for trend with age). In spite of the differential lowering of SBP and DBP, antihypertensive treatment reduced the risk of all cardiovascular events, stroke and myocardial infarction in the 3 age strata to a similar extent. Absolute benefit increased with age and with lower ratio of DBP to SBP lowering. Furthermore, in patients with a larger-than-median reduction in SBP, active treatment consistently reduced the risk of all outcomes irrespective of the decrease in DBP or the achieved DBP. These findings remained consistent if the achieved DBP averaged <70 mm Hg. In conclusion, our overview suggests that antihypertensive drug treatment improves outcome mainly through lowering of SBP.

Antihypertensive Agents↗
PubMed2005

[Hormonal treatment for menopause and arterial risk].

Is hormonal atmosphere before menopause the cause of the lower risk of coronary heart disease in women? Big clinical trials do not validate this hypothesis, however simple and attractive: in 5 primary or secondary prevention trials, estrogens alone or in association with progestatives to near 32000 women after menopause, do not leave hope for a significant reduction of coronary risk, and show in contrast an 30% increase of stroke risk. These results highlight the crucial importance of clinical trials to validate therapeutic models. The remaining hypotheses on the nature of hormonal treatments and the administration route must follow the same validation process. The prescription of hormonal treatment for menopause illustrates the importance of informed decision including individualised estimate of the risk to benefit ratio.

Aged↗
PubMed2005

Apparent effect on blood pressure is only partly responsible for the risk reduction due to antihypertensive treatments.

The mechanism of risk reduction obtained by blood pressure-lowering pharmacological treatment remains unclear. We explored the amount of risk reduction attributable to the apparent effect of antihypertensive medicines on blood pressure by using the capture approach. Five randomized, placebo or nil controlled trials with a total of 28,997 subjects and 1,935 cardiovascular fatal or non-fatal events from the INDANA database met the eligibility criteria. Computations were performed on the original individual records using multiple Cox's proportional hazard regression models designed for meeting the assumed treatment mode of action and comparing relevant assumptions. For coronary event, the results are inconclusive essentially because the risk reduction is mild. However, for stroke the risk reduction adjusted for baseline risk factors is 34% (P<0.0001). The part explained by the effect of treatment on systolic blood pressure is 49% of this reduction, with 95% confidence interval not including 100%. This result suggests that the apparent effect on blood pressure is not the only cause of stroke risk reduction in hypertensive subjects submitted to an antihypertensive medicine.

Antihypertensive Agents↗
PubMed2003

Absolute benefit, number needed to treat and gain in life expectancy: which efficacy indices for measuring the treatment benefit?

The absolute benefit (AB) is extensively used to summarize the results of clinical trials. As the AB depends directly on the patient's baseline risk, therapeutic decisions based on AB tend to favor patients at high risk. To evaluate the consequences of this decision's procedure for life-long therapy, we compare the AB with the gain in event-free life expectancy in a simulated hypertensive population. Our results show that the AB goes through a maximum and then declines as the duration of treatment increases. The amplitude of the variation of AB is independent of the baseline risks but the maximum is reached more quickly in the high-risk patients. Considering the gain in event-free life expectancy, low-risk patients benefit more than high-risk patients do, at the expense of a longer treatment exposure. The interpretation of the AB changes depending on follow-up.

Adult↗
PubMed2003

How should therapeutic information be transferred to users?

Without an efficient solution to the problems that prevent prescribers and consumers having easy access to published and unpublished evidence, Evidence-Based Medicine will never become a reality. Among the problems, dissemination of the summarized evidence is a major one. It involves representing the summarized evidence in a format that corresponds to the users' needs and knowledge, interpreting it within the context of other related evidence, putting it in perspective, and then delivering it physically to the users at the appropriate time. The current formats, vehicles and representation models, e.g. those for guidelines or textbooks, do not seem efficient enough to fill in the gap of knowledge. We suggest that a new approach is possible by reducing the transferred information to its core and integrating it through appropriate representation models into the doctor's decision-making process.

Decision Making↗
PubMed2003

Pharmacogenetics and responders to a therapy: theoretical background and practical problems.

In a narrow meaning, responders to a therapy are all those who will react as expected following the administration of this therapy. However, a wider definition is worth considering: all those for whom the administration of the therapy will be beneficial. Innovative therapies are increasingly expensive and hazardous, and limiting prescriptions to responders is both economically and ethically compulsory. The theoretical basis for such an approach exists. The process of defining the profile of responders consists of identifying the characteristics of the patients that interact with the size of the effect and integrating them quantitatively in a predictive model. The effect model, which is the relation between the risks of the event with and without the treatment, can be used for the prediction. It can integrate interactions of the efficacy with risk factors and/or genes. The data to be used to achieve both the identification of the interactions and the building of the predictive model are those from the studied population, the set of patients enrolled in clinical trials. Hence, the process of defining the therapy is an extrapolation from the studied population. To carry out the extrapolation process one can use various available techniques, of which none fully fits the purpose. No method is currently both fully adequate and validated. Finally, the predictive models, which we need to identify responders, do not exist in practice. Fortunately, new research approaches have been developed recently.

Humans↗
PubMed2002

J-shaped relationship between blood pressure and mortality in hypertensive patients: new insights from a meta-analysis of individual-patient data.

BACKGROUND: Population-based longitudinal studies of hypertension have usually shown a continuous and positive relationship between blood pressure and mortality. However, several studies in hypertensive patients receiving treatment have described this relationship as J-shaped, with an increased risk for events in patients with low blood pressure. OBJECTIVE: To assess the evidence for a J-shaped relationship between blood pressure and mortality and its relation to treatment. DESIGN: Meta-analysis of individual-patient data. SETTING: Seven randomized clinical trials from the INDANA (INdividual Data ANalysis of Antihypertensive intervention) database. PATIENTS: 40 233 persons with hypertension (mean follow-up, 3.9 years). INTERVENTION: Primarily beta-blockers or thiazide diuretics versus placebo or no treatment. MEASUREMENTS: Diastolic and systolic blood pressure and number of cardiovascular, noncardiovascular, and all-cause deaths in yearly periods of follow-up. RESULTS: The analysis included data on 1655 deaths (56% cardiovascular). A J-shaped relationship between diastolic blood pressure and risk for death was observed for total and cardiovascular mortality in treated patients (nadir, 84 and 80 mm Hg, respectively) and untreated patients (nadir, 90 and 85 mm Hg, respectively). For noncardiovascular deaths, the relationship was J-shaped in the treated group (nadir, 84 mm Hg) and negative in the control group. Similar results were observed for systolic blood pressure. The presence of patients with wide pulse pressure did not explain these findings. CONCLUSIONS: The increased risk for events observed in patients with low blood pressure was not related to antihypertensive treatment and was not specific to blood pressure-related events. Poor health conditions leading to low blood pressure and an increased risk for death probably explain the J-shaped curve.

Antihypertensive Agents↗
PubMed2002

Pulsatile blood pressure component as predictor of mortality in hypertension: a meta-analysis of clinical trial control groups.

OBJECTIVE: Although current guidelines rest exclusively on the measurement of systolic and diastolic blood pressures, the arterial pressure wave is more precisely described as consisting of a pulsatile (pulse pressure) and a steady (mean pressure) component. This study explored the independent roles of pulse pressure and mean pressure as predictors of mortality in a wide range of patients with hypertension. DESIGN AND METHODS: This meta-analysis, based on individual patient data, has combined results from the control groups of seven randomized clinical trials conducted in patients with systolo-diastolic or isolated systolic hypertension. The relative hazard rates associated with pulse pressure and mean pressure were calculated using Cox's proportional hazard regression models with stratification for the seven trials and with adjustment for sex, age, smoking and the other pressure. RESULTS: A 10 mmHg wider pulse pressure at baseline, which corresponds to approximately one-half of its standard deviation, was independently associated with an increase in risk by 6% for total mortality (P = 0.001), 7% for cardiovascular mortality (P = 0.01), and 7% for fatal coronary accidents (P = 0.03). The corresponding increase in risk of fatal stroke was similar (+6%, P = 0.27) but there were too few strokes to reach statistical significance. In similar analyses, mean pressure was not identified as an independent predictor of these outcomes. Significant interactions of pulse pressure or mean pressure with age suggested that the prognostic power of pulse pressure for fatal stroke was more important at higher age (P = 0.04), whereas the prognostic power of mean pressure for coronary mortality was greatest in the young (P = 0.01). CONCLUSIONS: In hypertensive patients pulse pressure, not mean pressure, is associated with an increased risk of fatal events. This appears to be true in a broad range of patients with hypertension.

Age Factors↗