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Biomedical subjects

Jacques Benichou

Publications and source records attributed to Jacques Benichou.

16 recordsLinked to original sources
PubMed2006

Stressful life events as a risk factor for inflammatory bowel disease onset: A population-based case-control study.

BACKGROUND AND AIMS: Stress is often perceived by patients with inflammatory bowel disease (IBD) as the leading cause of their disease. The aim of this study was to assess whether stress, evaluated through life event (LE) occurrence, is associated with IBD onset. METHODS: Incident cases of IBD, including 167 patients with Crohn's disease (CD) and 74 with ulcerative colitis (UC), were compared with two control groups, one of 69 patients with acute self-limited colitis (ASLC) and another of 255 blood donors (BDs). Stress was assessed using Paykel's self-questionnaire of LEs. Only LEs occurring within 6 months before the onset of symptoms in IBD cases and ASLC controls and before blood donation in BD controls were registered. Anxiety and depression were assessed using Bate's and Beck's questionnaires, respectively. RESULTS: In univariate analysis, occurrence of LEs was more frequent in the 6-month period prior to diagnosis in CD cases than in UC cases or either control group. After adjustment for depression and anxiety scores as well as other characteristics such as smoking status and sociodemographic features, this association appeared no longer significant. No associations were noted between occurrence of LEs and onset of UC relative to controls. CONCLUSIONS: Despite its separate association with CD, LE occurrence does not appear to be an independent risk factor for IBD onset.

Adult↗
PubMed2006

Estimates of the cancer burden in Europe from radioactive fallout from the Chernobyl accident.

The Chernobyl accident, which occurred April 26, 1986, resulted in a large release of radionuclides, which were deposited over a very wide area, particularly in Europe. Although an increased risk of thyroid cancer in exposed children has been clearly demonstrated in the most contaminated regions, the impact of the accident on the risk of other cancers as well as elsewhere in Europe is less clear. The objective of the present study was to evaluate the human cancer burden in Europe as a whole from radioactive fallout from the accident. Average country- and region-specific whole-body and thyroid doses from Chernobyl were estimated using new dosimetric models and radiological data. Numbers of cancer cases and deaths possibly attributable to radiation from Chernobyl were estimated, applying state-of-the-art risk models derived from studies of other irradiated populations. Simultaneously, trends in cancer incidence and mortality were examined over time and by dose level. The risk projections suggest that by now Chernobyl may have caused about 1,000 cases of thyroid cancer and 4,000 cases of other cancers in Europe, representing about 0.01% of all incident cancers since the accident. Models predict that by 2065 about 16,000 (95% UI 3,400-72,000) cases of thyroid cancer and 25,000 (95% UI 11,000-59,000) cases of other cancers may be expected due to radiation from the accident, whereas several hundred million cancer cases are expected from other causes. Although these estimates are subject to considerable uncertainty, they provide an indication of the order of magnitude of the possible impact of the Chernobyl accident. It is unlikely that the cancer burden from the largest radiological accident to date could be detected by monitoring national cancer statistics. Indeed, results of analyses of time trends in cancer incidence and mortality in Europe do not, at present, indicate any increase in cancer rates -- other than of thyroid cancer in the most contaminated regions -- that can be clearly attributed to radiation from the Chernobyl accident.

Adolescent↗
PubMed2006

Projecting absolute invasive breast cancer risk in white women with a model that includes mammographic density.

BACKGROUND: To improve the discriminatory power of the Gail model for predicting absolute risk of invasive breast cancer, we previously developed a relative risk model that incorporated mammographic density (DENSITY) from data on white women in the Breast Cancer Detection Demonstration Project (BCDDP). That model also included the variables age at birth of first live child (AGEFLB), number of affected mother or sisters (NUMREL), number of previous benign breast biopsy examinations (NBIOPS), and weight (WEIGHT). In this study, we developed the corresponding model for absolute risk. METHODS: We combined the relative risk model with data on the distribution of the variables AGEFLB, NUMREL, NBIOPS, and WEIGHT from the 2000 National Health Interview Survey, with data on the conditional distribution of DENSITY given other risk factors in BCDDP, with breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, and with national mortality rates. Confidence intervals (CIs) accounted for variability of estimates of relative risks and of risk factor distributions. We compared the absolute 5-year risk projections from the new model with those from the Gail model on 1744 white women. RESULTS: Attributable risks of breast cancer associated with DENSITY, AGEFLB, NUMREL, NBIOPS, and WEIGHT were 0.779 (95% CI = 0.733 to 0.819) and 0.747 (95% CI = 0.702 to 0.788) for women younger than 50 years and 50 years or older, respectively. The model predicted higher risks than the Gail model for women with a high percentage of dense breast area. However, the average risk projections from the new model in various age groups were similar to those from the Gail model, suggesting that the new model is well calibrated. CONCLUSIONS: This new model for absolute invasive breast cancer risk in white women promises modest improvements in discriminatory power compared with the Gail model but needs to be validated with independent data.

Adult↗
PubMed2006

A comparison of stratified and adjusted trend tests for binomial proportions.

For the problem of testing for a monotonic trend between an ordinal exposure and a binary response while controlling for categorical cofactors, we derived stratified and adjusted versions of two single contrast tests. Using simulations, we compared their statistical properties to those of the commonly used stratified Mantel-extension trend (MET) test. All tests had high power in case of monotonic relationships between exposure and response. In case of non-monotonic relationships, the stratified and adjusted contrast tests were markedly less powerful than the stratified MET-test particularly for five exposure levels, a favourable feature when the aim is to test for the existence of a monotonic dose-response relationship. These results are illustrated by an example.

Clinical Trials as Topic↗
PubMed2006

A keratitis rat model for evaluation of anti-Acanthamoeba polyphaga agents.

PURPOSE: To develop a rat model of chronic Acanthamoeba polyphaga keratitis suitable for pharmacologic assessment of therapeutic agents. METHODS: An A. polyphaga isolate (ATCC #50495) was grown in peptone-yeast extract-glucose medium. Five-weeks-old, Sprague-Dawley male rats were injected with 10(3) or 10(4) trophozoites in the left cornea stromal layer. A subconjunctival injection of 0.14, 0.28, or 0.57 mg long-acting betamethasone was performed weekly. At the end of experiments, rats were killed; the superficial corneal epithelium gently scraped and cultured; and globes histologically examined. Topical polyhexamethylene biguanide (PHMB), hexamidine diisethionate, and miltefosine (hexadecylphosphocholine) were administered topically as eye drops 3 times a day at concentrations of 0.02%, 0.1%, and 0.01% respectively. In vitro minimal inhibitory concentration (MIC) and fractional inhibitory concentration values were measured in A. polyphaga cultures. RESULTS: In infected eyes, lesions consisted of the sequential appearance within 2 weeks of edema, infiltrates, and/or abscesses. On day 35 postinfection, a combination of 10(4) parasites with a regimen of 0.28 mg/week betamethasone resulted in the highest ratio of rats with abscesses. Presence of A. polyphaga was confirmed histologically and inconsistently in cultures. In rats optimally prepared as said earlier, agents were administered on day 6 postinfection. A combination of PHMB and hexamidine diisethionate exerted a synergistic effect and was more effective than PHMB, hexamidine diisethionate, or miltefosine alone. In vitro, PHMB (MIC = 14.6 microM) and hexamidine diisethionate (MIC = 555 microM) exerted a synergistic effect (fractional inhibitory concentration = 0.06), and miltefosine exhibited antiamoebal activity (MIC = 27.4 microM). CONCLUSIONS: In this study, a rat model of chronic A. polyphaga keratitis was obtained and found suitable for assessment of pharmacologic agents. It provides an in vivo approach of drug resistance, pathogenicity, and physiopathologic mechanisms of chronic amoebic keratitis.

Acanthamoeba↗
PubMed2005

Prediction of survival for patients with bullous pemphigoid: a prospective study.

OBJECTIVE: To identify the prognostic factors of bullous pemphigoid (BP). DESIGN: Prospective study of patients with BP included in a randomized, controlled trial. SETTING: Twenty dermatology departments in France. Patients One hundred seventy patients with BP initially treated with a 40-g/d dosage of clobetasol propionate cream (testing sample) and 171 patients initially treated with oral corticosteroids at a dosage of 0.5 or of 1.0 mg/kg per day, depending on the extent of BP (validation samples). MAIN OUTCOME MEASURES: The end point was overall survival during the first year after BP diagnosis. From the testing sample, associations of clinical and biological variables with overall survival were assessed using univariate and multivariate analyses. Selected predictors were included in a prognostic model. To verify that these predictors were not dependent on the treatment used, the model was then validated independently on the 2 series of BP patients treated with oral corticosteroids. RESULTS: Median age of the BP patients included in the testing sample was 83 years. The 1-year Kaplan-Meier survival rate was 74%. From univariate analysis, the main deleterious predictors were demographic factors (ie, older age and female sex), associated medical conditions (ie, cardiac insufficiency, history of stroke, and dementia), and low Karnofsky score, which is a measure of the patient's general condition. No factors directly related to BP, in particular extent of cutaneous lesions, were shown to be related to the patients' prognosis. From multivariate analysis, only older age (P = .02) and low Karnofsky score (P<.001) appeared independently predictive of death. From the Cox model including these 2 predictors, the predicted 1-year survival rates were 90% (95% confidence interval [CI], 85%-96%) for patients 83 years or younger with Karnofsky score greater than 40, 79% (95% CI, 69%-90%) for patients older than 83 years with Karnofsky score greater than 40, 65% (95% CI, 50%-86%) for patients 83 years or younger with Karnofsky score of 40 or less, and 38% (95% CI, 26%-57%) for patients older than 83 years with Karnofsky score of 40 or less. Kaplan-Meier survival distributions of patients from the validation samples appeared clearly separated according to these 4 categories and were in close agreement with corresponding predicted 1-year survival rates obtained from the testing sample. CONCLUSIONS: The prognosis of patients with BP is influenced by age and Karnofsky score. These predictors are easy to use and should facilitate the management of BP.

Administration, Oral↗
PubMed2005

Usefulness of cutaneous T-cell clonality analysis for the diagnosis of cutaneous T-cell lymphoma in patients with erythroderma.

CONTEXT: Demonstration of a dominant T-cell clone in skin biopsy specimens by a molecular assay constitutes an additional diagnostic criterion to differentiate cutaneous T-cell lymphomas (CTCLs) from inflammatory dermatoses. OBJECTIVE: To determine which patients, depending on their clinical presentations, could most benefit from a cutaneous T-cell clonality analysis in addition to histopathologic analysis for the diagnosis of CTCL. DESIGN: Comparison of sensitivity and specificity of histopathologic analysis and a combination of this method and the detection of a T-cell receptor gamma chain gene rearrangement by polymerase chain reaction denaturing gradient gel electrophoresis performed on skin biopsy specimens obtained at initial presentation. PATIENTS: One hundred forty consecutive patients were classified into 4 groups, depending on their clinical presentation: (1) eczematous patches suggestive of early-stage mycosis fungoides (MF) (IA and IB of the TNM classification) (n = 42); (2) plaques, nodules, or tumors that arise on or are associated with plaques suggestive of late-stage MF (IIB and III of the TNM classification) (n = 16); (3) erythroderma (n = 50); and (4) nodules or tumors that arise in normal skin, suggestive of non-MF CTCL (n = 32). RESULTS: When compared with histopathologic examination, the addition of clonality analysis increased the sensitivity of CTCL diagnosis in all groups of patients except those with cutaneous lesions suggestive of late-stage MF, because the diagnosis was made based on histopathologic analysis alone in 100% of these cases. The main increase in sensitivity of CTCL diagnosis was observed in patients with erythroderma: 62% with histopathologic analysis alone to 87% with the combination of both methods (P = .04). Diagnostic specificity of molecular assays decreased from 100% to 76% (P = .01) in patients with patch lesions and from 100% to 70% (P = .04) in patients with nodules that occurred in normal skin due to the detection of a T-cell clone in 6 patients with follicular mucinosis without a histologic pattern of MF and in 5 of 20 cases of T-cell pseudolymphoma (25%), respectively. In contrast, a T-cell clone was not detected in the 34 patients with erythroderma of inflammatory origin. CONCLUSION: Polymerase chain reaction analysis of cutaneous T-cell clonality could be useful for the diagnosis of CTCL in patients who present with erythroderma.

Clone Cells↗
PubMed2004

Factors associated with early-stage pulmonary fibrosis as determined by high-resolution computed tomography among persons occupationally exposed to asbestos.

OBJECTIVES: Asbestosis remains difficult to diagnose, particularly in its early stages. The aim of this study was to determine criteria for independently associated features of pulmonary fibrosis in high-resolution computed tomograms among persons occupationally exposed to asbestos. METHODS: Retired persons with documented occupational asbestos exposure and no known asbestos-related diseases were assessed for occupational, clinical, functional respiratory, and chest X-ray criteria. In addition, they all underwent high-resolution computed tomography (HRCT) in the prone position. RESULTS: Altogether 51 (7.2%) of the 706 enrolled participants had features of pulmonary fibrosis consistent with asbestosis in the HRCT. Among those with small irregular opacities of <1/0 according to the 1980 International Labour Office Classification (ILO-C) in their X-rays, 5% had asbestosis in the HRCT. In a multivariate analysis, only age [odds ratio (OR) per year 1.08, 95% confidence interval (95% CI) 1.02-1.14], cumulative-exposure index (CEI) for asbestos (OR 6.4, 95% CI 1.5-28.4 for a CEI of > or =100 fibers/ml x years), and the presence of small irregular X-ray opacities of > or =1/0 ILO-C (OR 3.0, 95% CI 1.6-6.0) were independently associated with HRCT asbestosis. No combinations of these criteria simultaneously yielded high sensitivity and specificity for the diagnosis of early-stage HRCT asbestosis. Moreover, only 2% of the persons with a CEI of <25 fibers/ml x years had HRCT asbestosis, the finding confirming the low incidence of asbestosis for such low exposure, as previously reported on the basis of X-ray data. CONCLUSIONS: Additional research is needed to better identify the persons most likely to benefit from HRCT screening for asbestosis.

Aged↗
PubMed2003

HIV and HCV co-infection: situation at six French university hospitals in the year 2000.

The aims of this study were to assess the sociodemographic, epidemiological, clinical, and biological characteristics of French patients co-infected with human immunodeficiency virus-hepatitis C virus (HIV-HCV), as well as the management of their HCV infection. Data on 509 HIV-HCV co-infected patients, followed up at six French University Hospitals, were collected using a questionnaire. Student's t-test, Pearson's chi-square, Fisher's exact, and Fisher-Freeman-Halton's exact tests were used. The mean age of the patients was 38.3 years, and the male to female sex ratio 2.08; 88% of patients were born in Metropolitan France, and 20% were dependent on health benefits; 74% were intravenous drug users and 14% blood or blood product recipients. Forty-seven percent were in CDC classification stage A, 18% had a CD4+ count of <200, and 79% were undergoing current antiretroviral treatment. HCV RNA was positive in 84% (50% type 1, 13% untypable). Forty-four percent had normal alanine aminotransferase (ALT) levels, 24% alcohol consumption >15 g/day, and 51% had undergone liver biopsy (10% of which had cirrhosis). Histological grade was not related to ALT level or CD4+ count. Overall, 40% of patients had been treated for HCV infection. HCV treatment was significantly associated with performance of liver biopsy, histological grade, ALT level, CD4+ count, Centers for Disease Control (CDC) classification, but not with age or alcohol consumption. Rate of early response to treatment was fifty percent among patients treated with bitherapy. Eighty-nine percent of all patients with previous or current anti-HCV treatment had undergone liver biopsy. In conclusion, despite the difficulties in managing hepatitis C in HIV-infected patients, almost one-half of all patients in this study had received anti-HCV treatment.

Adult↗
PubMed2003

Smoking status, occupational asbestos exposure and bronchial location of lung cancer.

The objective of this study was to determine the factors associated with central airway versus peripheral bronchial location of lung cancer. All patients diagnosed with lung cancer from 1997 through 2000 in the Respiratory Disease Department of Rouen University Hospital were prospectively interviewed about their smoking and occupational history using a standardized questionnaire. All patients underwent white-light bronchial endoscopy using a 4.5 mm flexible endoscope. Tumors were classified as central when they were accessible and visible using this technique. Out of 217 cases of lung cancer included in this study, 155 (71%) were central. Histological type of lung cancer was strongly associated with bronchial location as central location was observed in 48, 82 and 92% of Adenocarcinoma (AC), Squamous Cell (SqC), and Small Cell Carcinoma (SCC), respectively (P<0.0001). Among non asbestos-exposed patients, location varied little with smoking status, with central location frequency ranging from 74 to 80%. In contrast, lung cancer was recorded central in 41% of long-term (> or =10 years) ex-smokers, 67% of short-term (<10 years) ex-smokers and 75% of current smokers (P=0.04) among patients exposed to asbestos, suggesting an interaction between duration of smoking cessation and occupational asbestos exposure with respect to lung cancer location. These findings were confirmed after adjustment for sex, age and histologic type in multivariate analysis. These results suggest that individually-tailored multimodality screening strategies relying on various combinations of low-dose CT scan, sputum analysis and fluorescence endoscopy according to each patient's profile may be more effective than standard strategies based on a single approach for all patients.

Adenocarcinoma↗
PubMed2003

Secular stability and reliability of measurements of the percentage of dense tissue on mammograms.

Elevated mammographic density is associated with increased risk of breast cancer. We conducted a reliability study on mammographic density assessments to determine their potential usefulness for projecting individual breast cancer risk. We used baseline screening mammograms from 7251 women in the Breast Cancer Detection Demonstration Project (BCDDP). Repeated measurements from the same images were used to assess measurement variability by an experienced evaluator. Intraclass correlations of assessments over time usually exceeded 0.9, indicating usefulness for prospective applications. Data also indicated it may be reasonable to include cases identified in the first year of screening together with other cases in developing a risk model. Older ages and increased weight were associated with decreased mammographic density. The density of the right breast slightly exceeded that of the left. Among women who developed breast cancer, the baseline mammographic density of the ipsilateral (diseased) breast was 0.53 (95% confidence interval (CI) 0.20-0.86) percentage units higher than in the contralateral breast.

Adult↗
PubMed2003

Boussignac continuous positive airway pressure device in the emergency care of acute cardiogenic pulmonary oedema: a randomized pilot study.

This study aimed to assess the short-term respiratory effects of a new portable device that delivers a continuous positive airway pressure via a face mask (Boussignac-CPAP) in patients with severe acute cardiogenic pulmonary oedema, and the feasibility of using this technique in an emergency department. We prospectively studied 30 consecutive patients with acute cardiogenic pulmonary oedema. They were randomly assigned either to the Boussignac-CPAP valve, which delivered oxygen, or to standard oxygen delivery for a duration of 30 min. The end-expiratory pressure reached 9.3+/-0.3 cm H2O with the Boussignac-CPAP valve. At the end of the 30 min period, the decreases in respiratory rate and muscular activity were significantly greater among patients assigned to the Boussignac-CPAP valve compared with those on standard oxygen delivery [24+/-1.6 breaths/min, median 24 (15-37) versus 28.5+/-1.9, median 27 (16-38) and 1.3+/-0.2, median 1 (0-4) versus 2.7+/-0.3, median 2 (0-4), respectively]. Moreover, the arterial oxygen tension to inspired oxygen concentration ratio and tidal volume were improved at the end of the 30 min Boussignac-CPAP period compared with baseline. Boussignac-CPAP was easily implemented and no side-effects were reported. Continuous positive pressure delivered using the Boussignac-CPAP device is feasible in an emergency care setting. It can quickly improve respiratory distress in acute cardiogenic pulmonary oedema patients. A larger trial should be initiated in such an emergency care setting to demonstrate the effectiveness of the Boussignac-CPAP device.

Acute Disease↗
PubMed2002

A comparison of oral and topical corticosteroids in patients with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is the most common autoimmune blistering skin disease of the elderly. Because elderly people have low tolerance for standard regimens of oral corticosteroids, we studied whether highly potent topical corticosteroids could decrease mortality while controlling disease. METHODS: A total of 341 patients with bullous pemphigoid were enrolled in a randomized, multicenter trial and stratified according to the severity of their disease (moderate or extensive). Patients were randomly assigned to receive either topical clobetasol propionate cream (40 g per day) or oral prednisone (0.5 mg per kilogram of body weight per day for those with moderate disease and 1 mg per kilogram per day for those with extensive disease). The primary end point was overall survival. RESULTS: Among the 188 patients with extensive bullous pemphigoid, topical corticosteroids were superior to oral prednisone (P=0.02). The one-year survival rate was 76 percent in the topical-corticosteroid group and 58 percent in the oral-prednisone group. Disease was controlled at three weeks in 92 of the 93 patients in the topical-corticosteroid group (99 percent) and 86 of the 95 patients in the oral-prednisone group (91 percent, P=0.02). Severe complications occurred in 27 of the 93 patients in the topical-corticosteroid group (29 percent) and in 51 of the 95 patients in the oral-prednisone group (54 percent, P=0.006). Among the 153 patients with moderate bullous pemphigoid, there were no significant differences between the topical-corticosteroid group and the oral-prednisone group in terms of overall survival, the rate of control at three weeks, or the incidence of severe complications. CONCLUSIONS: Topical corticosteroid therapy is effective for both moderate and severe bullous pemphigoid and is superior to oral corticosteroid therapy for extensive disease.

Administration, Oral↗