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Biomedical subjects

J P Daurès

Publications and source records attributed to J P Daurès.

At least 19 recordsLinked to original sources

[Evaluation of the relation between consumption of fluoroquinolones and emergence of resistance among Escherichia coli: contribution of observational and quasi-experimental studies].

The emergence of Escherichia coli (E. coli) resistance to fluoroquinolones (FQs) increased and spread gradually worldwide since the early 1990s. The selective pressure of FQs is the main mechanism responsible for the emergence of FQ resistance as shown by in vitro studies. Clinical trials are required to prove the causality between exposure to FQs and emergence of resistance. But this would not be ethical in humans. Non experimental studies must answer several principles to establish causality: association, anteriority, and directional change. We described and compared the contribution of observational and quasi-experimental studies implemented to answer several of these principles. Quasi-experimental studies using interventional models (ARIMA models with transfer function), can answer several of these principles, unlike observational studies. Thus, in addition to assessment of the association, they were able to show that the exposure to FQs precedes the emergence of FQ resistance to E. coli. They were also able to estimate the time necessary for the emergence of resistance and the dose effect, and to show if this association was reversible.

Case-Control Studies↗

[Ovarian cancer: incidence and mortality in France].

OBJECTIVES: To describe the ovarian cancer incidence and mortality trends in France from 1980 to 2000. MATERIALS AND METHODS: Incidence data were obtained from 9 French departments covered by cancer registries which systematically record all cancers, of which those of the ovary. Mortality data has been provided by INSERM bureau in charge of the analysis of death certificates. RESULTS: With 4500 incident cases and 3500 deaths for the year 2000 in France, ovarian cancer still shows a poor prognosis. Age adjusted incidence and mortality rates are almost stable over the study period at an annual rate of 9 by 100000 for incidence and 5.5 by 100000 for mortality. However the risk of developing this cancer and the risk of dying from it, steadily decreased for the cohort born in 1930 to 1950, and the beginning of this reduction corresponds exactly to the beginning of oral contraception. We present comparisons between departments and analyze the border-line tumors in parallel with invasive cancers. CONCLUSION: The cancer of the ovary represents only a small part of female cancers (3.8%) in France and its incidence is stable over time, but its prognosis is very bad.

Adolescent↗

Evolution of fluoroquinolone resistance among Escherichia coli urinary tract isolates from a French university hospital: application of the dynamic regression model.

Escherichia coli urinary tract isolates were collected in 1997-2003 from Nimes University Hospital in order to investigate long-term trends in antibiotic resistance and to explore the relationship between antibiotic use and the emergence of resistance. Time-series analysis (ARIMA models) and dynamic regression models were used to investigate relationships between antibiotic use and resistance to ofloxacin and ciprofloxacin. Significant increases were seen in the frequency of ofloxacin (8.9 to 16.7%) and ciprofloxacin resistance (6.2 to 10.1%) (p < 0.001). Using multivariate dynamic regression analysis, it was found that an increased use of one defined daily dose (DDD)/1000 patient-days for ofloxacin, ciprofloxacin and norfloxacin induced average increases of 0.81%, 0.65% and 0.53% in E. coli ofloxacin resistance (p < 0.01), with average delays of 4, 4 and 6 months, respectively. An increase of 1 DDD/1000 patient-days of ciprofloxacin, ofloxacin and norfloxacin use induced increases of 0.73%, 0.82% and 0.63% in E. coli ciprofloxacin resistance (p < 0.01), with average delays of 4, 4 and 5 months, respectively. The use of nalidixic acid was not associated significantly with an increase in resistance to fluoroquinolones by multivariate analysis.

Anti-Infective Agents↗

Economics of the clinical management of lung cancer in France: an analysis using a Markov model.

To evaluate, according to the histologic type and initial stage, the mean cost (MC) of managing patients with lung cancer and the costs of the different management phases. A Markov approach was used to model these costs, based on the management of a representative nation-wide sample of 428 patients with newly diagnosed lung cancer. The 18-month MC ranged from US$ 20 691 (95% CI: 5777-50 380 for diffuse non-small-cell lung cancer (NSCLC) to US$ 31 833 (95% CI: 15 866-64 455) for localised small-cell lung cancer (SCLC); first-line treatment costs ranged from 33.8% of MC for medically inoperable localised NSCLC to 74.6% for diffuse SCLC; second- or third-line treatment costs ranged from 7.8% of MC for surgically treated localised NSCLC to 32% for locally advanced NSCLC; and the cost of palliative care ranged from 9.1% of MC for locally advanced NSCLC to 39.9% for medically inoperable localised NSCLC. The cost of first-line chemotherapy and the percentage of actively treated patients impacted more on MC than did the cost of second- or third-line chemotherapy regimens or the cost of palliative care. In conclusion, this model provides a robust economic analysis of the cost of lung cancer management, and will be useful for assessing the economic consequences of future changes in patient management.

Aged↗

Risk factors for multidrug-resistant Pseudomonas aeruginosa nosocomial infection.

A case-control study was conducted in a university hospital to determine the risk factors for nosocomial infection with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) among all hospitalized patients and among those with a nosocomial infection due to P. aeruginosa. Eighty patients infected with MDR-PA, 75 infected with a non-MDR phenotype and 240 random controls were included in the 12-month study. Among all hospitalized patients, age, severity index, having a bedridden condition, transfer from other units, nasogastric feeding, urinary catheterization and exposure to beta-lactams (OR=2.5) or fluoroquinolones (OR=4.1) in the seven days before infection were linked to nosocomial infection due to MDR-PA. Among patients infected by P. aeruginosa, exposure to fluoroquinolones (OR=4.7) or surgery (OR=0.5) were linked to the isolation of MDR-PA. This study showed that, in addition to urinary catheterization, nasogastric feeding is an important risk factor in MDR-PA infection. Indeed, an imbalance in gut flora, modifications to the mucous membranes due to the use of nasogastric feeding and the selection pressures exerted by antibiotics were implicated in the occurrence of this infection.

Adult↗

Characteristics of patients with rheumatoid arthritis in France: a study of 1109 patients managed by hospital based rheumatologists.

OBJECTIVE: To describe the characteristics of rheumatoid arthritis in patients managed by hospital based rheumatologists in France. METHODS: All public and non-profit private hospitals in France were invited to participate in a cross sectional study. Clinical data on the day of inclusion and health resources used for rheumatoid arthritis over the previous 12 months (treatments, medical devices, physician visits, examinations, hospital admissions, and other health professional care) were recorded. RESULTS: 1109 patients from 75 centres located throughout the country were included (846 female; mean disease duration, 10.6 years; mean age, 56.7 years). Active disease (swollen joint count > or =6, tender joint count > or =6, and two of: morning stiffness > or =45 min, C reactive protein > or =20 mg/l, erythrocyte sedimentation rate >28 mm/h) was observed in 146 patients (13.2%). Mean (SD) DAS(28) was 4.51 (1.55). Severe extra-articular manifestations were reported in 8.4%. ACR functional status was: class I, 19%; class II, 28%; class III, 31%; class IV, 22%. Comorbidity was observed in 44.9% of cases, particularly chronic pulmonary disease and coronary or peripheral vascular disease. Average AIMS2-SF dimension scores were between 4.56 and 6.18, and mean HAQ was 1.32 (0.77). Disease modifying antirheumatic drugs (DMARDs) were prescribed for 82.1% of the patients. During the previous four weeks, one DMARD was used in 62.5%, and two or more in 19.5%. Corticosteroids were prescribed in 72%. CONCLUSIONS: In a rheumatoid arthritis population managed by hospital based rheumatologists, the disease was active in 13% and severe in more than one third of cases.

Adult↗

The analysis of asthma control under a Markov assumption with use of covariates.

In studies of disease states and their relation to evolution, data on the state are usually obtained at in frequent time points during follow-up. Moreover in many applications, there are measured covariates on each individual under study and interest centres on the relationship between these covariates and the disease evolution. We developed a continuous-time Markov model with use of time-dependent covariates and a Markov model with piecewise constant intensities to model asthma evolution. Methods to estimate the effect of covariates on transition intensities, to test the assumption of time homogeneity and to assess goodness-of-fit are proposed. We apply these methods to asthma control. We consider a three-state model and we discuss in detail the analysis of asthma control evolution.

Asthma↗

Lower respiratory tract infections in adults: non-antibiotic prescriptions by GPs.

BACKGROUND: The AIR II study is a prospective multicentre assessing management of lower respiratory tract infections (LRTIs) in adults by general practitioners (GPs). Epidemiological studies generally address the prescriptions of antibiotics. To our knowledge, little is known about the real impact of non-antibiotic therapeutic prescriptions (defined here as co-prescriptions) in LRTI. Therefore, the aim of the study was to evaluate non-antibiotic prescriptions in LRTIs. METHODS: Two thousand general practitioners (GPs) were randomly selected and asked to participate in each of 30 predefined areas covering mainland France. The patient's sociomedical record was completed by the GP during the consultation and sent to the data processing centre at the same time as an anonymous copy of his prescription. The GP also had to report the inclusion by telephone and agree to a telephone appointment with an interviewer. RESULTS: GPs (n = 3144) reported 5469 evaluable cases. Pneumonia accounted for 9.6% of diagnoses, acute exacerbations of chronic bronchitis 14.9% and acute bronchitis 72.5%. Antibiotics were prescribed to 96.5% of patients. In addition to the 5270 prescriptions of antibiotics, co-prescriptions proved to be twice as numerous as prescriptions of antibiotics (10,027 prescriptions for 5115 patients). Mucomodifiers, steroidal anti-inflammatory drugs and bronchodilators were significantly more prescribed in AECB than others. Non-steroidal anti-inflammatory drugs and antitussives were significantly more prescribed in acute bronchitis than AECB or CAP. CONCLUSIONS: Our results suggest that recommendations of management in LRTIs need to take into account co-prescriptions.

Adolescent↗

Financial costs of alcoholism treatment programs: a longitudinal and comparative evaluation among four specialized centers.

BACKGROUND: Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow-up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification. METHODS: We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service. RESULTS: The mean cost of hospitalization ranged from 1326 euros to 1917 euros(p = 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow-up per patient ranged from 419 euros to 1704 euros (p = 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately 500 euros/month in three centers and 658 euros in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p = 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost. CONCLUSIONS: This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost-efficient, and beneficial for patients and the public health office economy.

Adult↗

Assessment of variations in control of asthma over time.

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.

Adolescent↗

[Review of quality of life instruments used in end-stage renal disease].

Health related quality of life (HRQOL) indicators take into account the personal perception of health, and are proposed as an alternative for efficacy indicators in medical and therapeutic decision making. They provide, due to elaboration and validation of a questionnaire, a standardised assessment of the health status perception. This paper provides a review of a variety of HRQOL instruments developed for patients suffering end-stage renal disease (ESRD). Generic instruments are designed to be applicable in general population and disease-targeted instrument are potentially more sensitive to the characteristics of a specific population. Among HRQOL instruments, we found 4 generic questionnaires (the Sickness Impact Profile, the SF 36, the Nottingham Health Profile and the EQ-5D), 3 disease-targeted questionnaires developed for ESRD patient undergoing dialysis (the Kidney Disease Quality of Life instrument, the Kidney Disease Questionnaire and the Choice Health Experience Questionnaire), 1 questionnaire specific for ESRD patients (the HRQOL questionnaire), and 2 specific disease-targeted instruments for renal transplant (the Kidney Transplant Questionnaire and the ESRD Symptom Checklist-Transplantation Module). In France, very few studies on the quality of life of ESRD patients were published; no specific questionnaire validated in French is yet published.

Humans↗

[Influence of general practitioners' personal knowledge on migraine in medical attitudes towards their patients suffering from migraine].

The subjective aspects of the doctor-patient relationship may impact disease management methods applied to migraine patients. This prospective study compared the medical attitudes of doctors towards migraine headache in relationship to their personal sensitivity to this disease. The study concerned data on the health care management of migraine headache by 711 general practitioners, 325 of whom suffer from migraine headache themselves, 227 who do not suffer from migraines, but who have a close family member that does, and 159 who neither suffer from migraine headache, nor have anyone close who does. Each doctor filled out a medical practice questionnaire concerning this pathology and included one migraine patient in the survey. Each patient answered a specific quality of life questionnaire. It was shown that doctors suffering from migraine headache themselves declared having more migraine patients in their practices than the other doctors. Nonetheless, the doctor's sensitivity to migraine headache does not seem to have an impact on the diagnosis and therapeutic care of patients; diagnosis criteria are the same within the three groups and correspond to international headache society criteria. Furthermore, the therapeutic means applied, whether acute first or second intention treatment, or long-term treatment, do not differ amongst the three groups. Quality of life and patients' feelings about medical support were significantly related to the doctor's level of sensitivity towards the disease: they were highest amongst patients treated by doctors suffering from migraines themselves, and lowest amongst patients treated by doctors with no close family members suffering from migraines. Although therapeutical attitudes do not vary, the quality of life perceived by patients is better when the doctors themselves are concerned by the disease.

Adult↗

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data.

In lung cancer, DNA content abnormalities have been described as a heterogeneous spectrum of impaired tumour cell DNA histogram patterns. They are merged into the common term of aneuploidy and probably reflect a high genotypic instability. In non-small-cell lung cancer, the negative effect of aneuploidy has been a subject of controversy inasmuch as studies aimed at determining the survival-DNA content relationship have reported conflicting results. We made a meta-analysis of published studies aimed at determining the prognostic effect of aneuploidy in surgically resected non-small-cell lung cancer. 35 trials have been identified in the literature. A comprehensive collection of data has been constructed taking into account the following parameters: quality of specimen, DNA content assessment method, aneuploidy definition, histology and stage grouping, quality of surgical resection and demographic characteristics of the analysed population. Among the 4033 assessable patients, 2626 suffered from non-small-cell lung cancer with aneuploid DNA content (overall frequency of aneuploidy: 0.65; 95% CI: (0.64-0.67)). The DerSimonian and Laird method was used to estimate the size effects and the Peto and Yusuf method was used in order to generate the odds ratios (OR) of reduction in risk of death for patients affected by a nearly diploid (non-aneuploid) non-small-cell lung cancer. Survivals following surgical resection, from 1 to 5 years, were chosen as the end-points of our meta-analysis. Patients suffering from a nearly diploid tumour benefited from a significant reduction in risk of death at 1, 2, 3 and 4 years with respective OR: 0.51, 0.51, 0.45 and 0.67 (P< 10(-4)for each end-point). 5 years after resection, the reduction of death was of lesser magnitude: OR: 0.87 (P = 0.08). The test for overall statistical heterogeneity was conventionally significant (P< 0.01) for all 5 end-points, however. None of the recorded characteristics of the studies could explain this phenomenon precluding a subset analysis. Therefore, the DerSimonian and Laird method was applied inasmuch as this method allows a correction for heterogeneity. This method demonstrated an increase in survival at 1, 2, 3, 4 and 5 years for patients with diploid tumours with respective size effects of 0.11, 0.15, 0.20, 0.20 and 0.21 (value taking into account the correction for heterogeneity;P< 10(-4)for each end-point). Patients who benefit from a surgical resection for non-small-cell lung cancer with aneuploid DNA content prove to have a higher risk of death. This negative prognostic factor decreases the probability of survival by 11% at one year, a negative effect deteriorating up to 21% at 5 years following surgery.

Aged↗

Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study.

BACKGROUND: The combination of etoposide plus cisplatin (EP) is considered to be standard therapy for small-cell lung cancer (SCLC). To determine whether drug intensification improves survival of patients with extensive SCLC, we compared this treatment with a four-drug regimen containing EP plus cyclophosphamide and 4'-epidoxorubicin (PCDE). METHODS: In a phase III clinical trial organized by the French Federation of Cancer Institutes, patients were randomly assigned to receive either EP (n = 109; etoposide at a dose of 100 mg/m(2) on days 1-3 plus cisplatin at 100 mg/m(2) on day 2) or PCDE (n = 117; etoposide and cisplatin given as in EP plus cyclophosphamide at 400 mg/m(2) on days 1-3 and 4'-epidoxorubicin at 40 mg/m(2) on day 1) every 4 weeks. Both groups received a total of six cycles. Survival differences were analyzed by Wilcoxon and log-rank tests. Associations of treatment group and putative prognostic variables with survival were tested in the Cox proportional hazards model. Quality of life was assessed from the responses to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (C30, health status and lung cancer module 13). All statistical tests were two-sided. RESULTS: Patients in the PCDE arm had a statistically significant higher frequency of combined complete plus partial responses compared with those in the EP arm (21% plus 55% versus 13% plus 48%, respectively; P =.02 for difference in combined objective responses). Patients in the PCDE arm survived longer than those in the EP arm (1-year survival rate: 40% and 29%, respectively; median survival: 10.5 and 9.3 months, respectively; log-rank P =.0067). In the Cox model, the relative risk of death for patients in the PCDE arm compared with those in the EP arm was 0.70 (95% confidence interval = 0.51 to 0.95); the disease also progressed more slowly in patients in the PCDE arm. Hematologic toxicity was higher in the PCDE arm (22% with documented infections compared with 8% in the EP arm; P =.0038), and the toxicity-related death rate was 9% in the PCDE arm versus 5.5% in the EP arm (P =.22). The global health status showed similar improvement in both arms during treatment. CONCLUSION: Compared with the EP regimen, the PCDE regimen yielded higher response rates and better survival rates in patients with extensive SCLC without affecting the quality of life of the patients during chemotherapy.

Adult↗

Regression splines for threshold selection in survival data analysis.

The Cox proportional hazards model restricts the hazard ratio to be linear in the covariates. A survival model based on data from a clinical trial is developed using spline functions with variable knots to estimate the log hazard function. Moreover, the main point of the method is that a knot, seen as free parameters for a piecewise linear spline, represents a break point in the log hazard function which may be interpreted as a threshold value. The likelihood ratio test is used to select the final model and to determine the threshold number for a covariate. Confidence intervals for these threshold values are computed by bootstrapping the data. Two examples illustrate the method.

Carcinoma, Small Cell↗

Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study.

OBJECTIVE: To determine prognostic factors of radiologic damage and radiologic progression in early rheumatoid arthritis (RA). METHODS: A cohort of 191 patients with RA whose disease duration was shorter than 1 year were prospectively followed up for 3 years. Radiologic scores (as determined by Sharp's method, modified by van der Heijde) and radiologic progression were used as outcome measures. Numerous baseline clinical, laboratory, genetic, and radiographic data were obtained. RESULTS: The change in the total radiologic score for the patients followed up over 3 years was a mean +/- SD increase of 6.1 +/- 6.2. Radiologic progression was observed in 71 of the 172 patients for whom there were data at the end of the study. By univariate analysis with Fisher's exact test, radiologic scores and progression at followup were closely correlated with the baseline values of the erythrocyte sedimentation rate (ESR), C-reactive protein level, IgM and IgA rheumatoid factor positivity, antiperinuclear antibody positivity, radiologic scores, duration of morning stiffness, and RA-associated HLA-DRB1*04 genes. No correlation was demonstrated with sex, age, Disease Activity Score, swollen or tender joint counts, extraarticular manifestations, Health Assessment Questionnaire score, Ritchie Articular Index, patient's assessment of pain, positivity for anti-heat-shock protein 90-kd antibodies, anticalpastatin antibodies, anti-RA33 antibodies, antinuclear antibodies, YKL-40, or antikeratin antibodies, and HLA-DRB1*01 genes. The logistic regression analysis revealed that the only baseline values that were predictive of the 3-year radiologic scores were IgM rheumatoid factor positivity, DRB1*04 genes, pain score, and total radiologic score. Progression of joint damage was predicted by the ESR, IgM rheumatoid factor positivity, DRB1*04 genes, and erosions score at baseline. CONCLUSION: Prognostic factors for radiographic damage in early RA were identified. A combination of these baseline values allowed us to draw up a predictive arithmetic score that could be used to predict radiologic damage at 3 years and radiologic progression in individual patients.

Arthritis, Rheumatoid↗