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Biomedical subjects

J Benichou

Publications and source records attributed to J Benichou.

At least 19 recordsLinked to original sources

Occupational and nonoccupational factors associated with high grade bronchial pre-invasive lesions.

Besides tobacco exposure, factors associated with the development of pre-invasive bronchial lesions are not known. Autofluorescence bronchoscopy was used to assess the prevalence of severe dysplasia and carcinoma in situ (SD/CIS) of the proximal bronchial tree in relation to occupational or nonoccupational carcinogen exposure. Among the 241 individuals in this study, the overall prevalence of at least one SD/CIS was 9% (21 subjects). Multivariable analysis revealed significant and independent associations between presence of SD/CIS and: 1) active smoking, relative to former smokers; 2) presence of synchronous invasive lung cancer; 3) duration of asbestos exposure and; 4) exposure to other occupational carcinogens. The independent associations of synchronous lung cancer with severe dysplasia and carcinoma, after adjusting for both occupational and nonoccupational carcinogen exposures, suggest other mechanisms than a field cancerisation may be involved in the carcinogenesis of these pre-invasive lesions. Moreover, active smokers, patients with recently resected invasive lung cancer and workers occupationally exposed to bronchial carcinogens may represent a population of choice for early cancer endoscopic detection programmes in view of their high severe dysplasia and carcinoma prevalence.

Asbestos↗

[VENISE: Non-invasive ventilation during mechanical ventilation weaning in chronic respiratory failure patients. A prospective randomised controlled and multicenter trial].

INTRODUCTION: The clinical efficacy of non-invasive ventilation (NIV) has now been demonstrated in the management of acute-on-chronic respiratory failure (ACRF) in various etiologies. Endotracheal mechanical ventilation (ETMV) can lead to numerous complications and weaning difficulties increasing the risk of prolonged ETMV, morbidity and mortality as well as excess cost of intensive care. Therefore, it could be useful to consider NIV for delivering effective ventilatory support to reduce the length of ETMV in ACRF patients who are still not capable of maintaining spontaneous breathing. From the interesting but discordant results of two recent randomised controlled trials, a working group from the Société de Réanimation de Langue Française (SRLF) decided to perform a new prospective randomised controlled multicenter trial. The aim of the study will be to assess the usefulness of NIV as an extubation and weaning technique in ventilated ACRF patients. METHODS: The methodology used will compare three parallel weaning strategies in ACRF patients considered difficult to wean: invasive conventional weaning (group A), extubation relayed by nasal oxygentherapy (group B), and extubation relayed by NIV (group C). Based on the main end-point defined as the weaning success rate, 208 patients from 17 investigator centers are planned to be included. Results of the study will also allow to assess the respective impact of the three weaning strategies on the length of ETMV and weaning, the mechanical ventilation-related morbidity, the patients lengths of stay and mortality. EXPECTED RESULTS: Results of the VENISE trial should permit to improve the management of the difficult to wean ACRF patients and thus contribute to more precisely define the place of NIV in the weaning and prevention of re-intubation strategies in these patients.

Chronic Disease↗

An assessment of the visibility of MeSH-indexed medical web catalogs through search engines.

Manually indexed Internet health catalogs such as CliniWeb or CISMeF provide resources for retrieving high-quality health information. Users of these quality-controlled subject gateways are most often referred to them by general search engines such as Google, AltaVista, etc. This raises several questions, among which the following: what is the relative visibility of medical Internet catalogs through search engines? This study addresses this issue by measuring and comparing the visibility of six major, MeSH-indexed health catalogs through four different search engines (AltaVista, Google, Lycos, Northern Light) in two languages (English and French). Over half a million queries were sent to the search engines; for most of these search engines, according to our measures at the time the queries were sent, the most visible catalog for English MeSH terms was CliniWeb and the most visible one for French MeSH terms was CISMeF.

Abstracting and Indexing↗

A comparison of several methods to test for the existence of a monotonic dose-response relationship in clinical and epidemiological studies.

The Mantel-extension chi-square test for overall trend and an asymptotically equivalent test based on logistic regression are commonly used to test for a monotonic dose-response relationship between exposure and disease in epidemiological and clinical studies. However, these tests present two important disadvantages, as they (i) make the restrictive assumption of a parametric model of linear form on the logit scale and (ii) impose the a priori choice of scores to code for the exposure categories. Indeed, the linear assumption, if made incorrectly, can lead to an invalid conclusion, and the choice of scores lends arbitrariness to the test results. Some alternative tests have been proposed in the literature. We have considered several of these tests, namely one based on isotonic regression, the T-test based on contrasts and a recently published test based on adjacent contrasts (Dosemeci-Benichou test). The aim of our study was to compare the statistical properties (type I error and power) of these tests and of the commonly used Mantel-extension test for overall trend. We generated cohort and case-control data and considered one- and two-sided versions of the tests. Moreover, we studied the tests under the null hypothesis of no relationship between exposure and disease and under various alternative patterns of monotonic or non-monotonic dose-response relationships. This study confirms that the commonly used trend tests can lead to erroneous conclusion of a monotonic dose-response relationship. The test based on isotonic regression does not represent a favourable alternative, as it tends to be too powerful in case of non-monotonic dose-response relationship patterns. The tests based on contrasts seem to possess more favourable properties by combining close to nominal type I error, high power for monotonic alternatives and low power for non-monotonic alternatives.

Case-Control Studies↗

Does age play a role in mylohyoideus muscle function?

Because swallowing disorders are frequent in the elderly, we assessed the relationship between age and mylohyoideus muscle contraction, which is an important component of the initial step in swallowing. In a prospective study, 120 subjects without any personal history of diseases associated with swallowing disorders underwent electromyographic recording (EMG) of mylohyoideus muscle activity. Four groups of equal size (n = 30) were defined according to age (< or = 50, 51-70, 71-85, >85 years). The frequency and duration of mylohyoideus muscle asynchronisms were compared among the four groups. The comparison of mylohyoideus muscle EMG among groups did not show a significant difference in the mean number of asynchronisms, in duration per subject or in the frequency of long-lasting asynchronisms. Asynchronisms were a very frequent event, observed in 98% of subjects, and were mostly short, lasting less than 0.1 s in 90% of subjects. In healthy elderly patients, there was no linear relationship between the mean duration of asynchronisms and ageing. The occurrence of one or more long-lasting asynchronisms or of at least six asynchronisms during a sequence of 10 successive swallows should be considered to be abnormal.

Aged↗

Carcinoembryonic gene member 2 mRNA expression as a marker to detect circulating enterocytes in the blood of colorectal cancer patients.

BACKGROUND: The aim of this study was to report our experience with a new molecular tool to detect circulating enterocytes in the blood of patients with colorectal cancer. METHODS: The study included 193 individuals: 78 patients with colorectal cancer and 115 controls composed of patients with benign colorectal diseases (n = 16), patients with noncolorectal cancer (n = 31), healthy individuals (n = 62), and healthy bone marrow transplantation donors (n = 6). A nested reverse transcriptase-polymerase chain reaction with specific primers for the carcinoembryonic gene member 2 (CGM2) was used to detect circulating enterocytes in the peripheral blood of 78 patients with colorectal cancer. The blood (n = 109) or the bone marrow (n = 6) of the 115 controls was studied to test the absence of CGM2 illegitimate transcription in nucleated blood cells and nucleated blood cell progenitors. The assay sensitivity was effective in detecting 1 CGM2-positive cell per 10(6) nucleated blood cells. RESULTS: Fifty-nine percent (46/78) of patients with colorectal cancer were found positive whereas all negative controls remained negative. Positivity rates were 38% (3/8) in Dukes' A classification, 43% (9/21) in Dukes' B, 77% (23/30) in Dukes' C, and 58% (11/19) in Dukes' D. CONCLUSIONS: The clinical significance of enterocyte detection in the blood of colorectal cancer patients by means of this CGM2 messenger RNA assay needs further evaluation.

Adult↗

Gastric involvement in systemic sclerosis: a prospective study.

OBJECTIVES: This study aims to assess the prevalence of gastric electrical activity dysfunction with cutaneous electrogastrography (EGG), disturbances of gastric emptying function using radiopaque pellets, and gastric endoscopic abnormalities in patients with systemic sclerosis (SSc). We also investigate for an association between EGG and gastric-emptying data with clinical manifestations and esophageal motor disturbances. METHODS: Fasting and postprandial gastric electrical activity was studied in 22 consecutive patients with SSc (17 with and 5 without clinical gastric manifestations) and 22 age- and sex-matched healthy subjects. Gastric emptying of radiopaque pellets and gastroscopy were also performed in SSc patients. RESULTS: The prevalence of EGG disturbances was as high as 81.82% in SSc patients. SSc patients exhibited, compared with controls, higher median percentage of dominant frequency in bradygastria during the fasting period and lower median values for postprandial electrical power and postprandial to fasting ratio for electrical power. Gastric emptying of radiopaque pellets was delayed in 11 SSc patients, and gastroscopy demonstrated "watermelon stomach" in 3 SSc patients. No correlation was found between the severity of gastric impairment and clinical presentation, SSc duration and subsets, and esophageal manometric impairment. CONCLUSIONS: Our study underlines the high frequency of gastric dysfunction in SSc patients. It suggests the usefulness of EGG in SSc in noninvasively detecting disorders of gastric electrical activity at an early stage and symptomatic patients with gastroparesis (because there was a correlation between values of postprandial to fasting ratio for electrical power of < 1 on EGG and delayed gastric emptying). Gastric-emptying evaluation of radiopaque pellets may further be a helpful method to depict symptomatic SSc patients with gastroparesis. Finally, our series confirms that watermelon stomach diagnosis should be excluded in SSc patients presenting with gastrointestinal hemorrhage or with anemia related to iron deficiency.

Adult↗

A review of adjusted estimators of attributable risk.

This paper reviews adjusted methods of estimation of attributable risk (AR), that is methods that allow one to obtain estimates of AR while controlling for other factors. Estimability and basic principles of AR estimation are first considered and the rationale for adjusted AR estimators is discussed. Then, adjusted AR estimators are reviewed focusing on cross-sectional, cohort and case-control studies. Two inconsistent adjusted estimators are briefly commented upon. Next, adjusted estimators based on stratification, namely the weighted-sum and Mantel-Haenszel (MH) approaches, are reviewed and contrasted. It appears that the weighted-sum approach, which allows for full interaction between exposure and adjustment factors, can be affected by small-sample bias. By contrast, the MH approach, which rests on the assumption of no interaction between exposure and adjustment factors may be misleading if interaction between exposure and adjustment factors is present. Model-based adjusted estimators represent a more general and flexible approach that includes both stratification approaches as special cases and offers intermediate options. Bruzzi et al.'s and Greenland and Drescher's estimators are reviewed and contrasted. Finally, special problems of adjusted estimation are considered, namely estimation from case-cohort data, estimation for risk factors with multiple levels, for multiple risk factors, for recurrent events, estimation of the prevented and preventable fractions, and estimation of the generalized impact fraction. Comments on future directions are presented.

Algorithms↗

Reading factor: a bibliometric tool to manage a virtual library.

UNLABELLED: Among the many bibliometric criteria used to evaluate biomedical journals, the impact factor is the most commonly used. Despite its limitations, it quantifies the influence of a journal on secondary publications. It does not however evaluate the practical usefulness of primary documents. Usefulness is field-related and varies greatly among specialities. We introduce a new bibliographic criterion, the "reading factor", and define it as the ratio between the number of electronic consultations of a particular journal (i.e., number of clicks on a hyper-link) and the mean number of electronic consultations of all the journals studied (itself calculated by dividing the total number of electronic accesses by the number of journals in the database). We describe its observed distribution, relative to that of the impact factor, based on electronic consultation records from our University Hospital medical digital library, where full-text electronic versions of 45 major biomedical journals have been available since December 1997. From this analysis we found no correlation between the 1999 reading factor and the 1998 impact factor of these 45 journals, and we observed a dramatic change in the hierarchy of journals upon using the reading factor as the yardstick rather than the impact factor. Moreover, we describe how using the reading factor has helped in managing the collection of our University Hospital's virtual library. The selection of journals to be discarded from the virtual library for the year 2001 was based on journals' RF values and this process will repeated over the coming years. The reading factor also permits a cost-analysis of a virtual library. CONCLUSION: The measurement of the reading factor is highly automated, practical and efficient. It appears as a new tool for electronic collection management by librarians, well fitting with economical data.

Bibliometrics↗

Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China.

The length of the polymorphic CAG trinucleotide repeat in the polyglutamine region of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Because increased androgenic activity has been linked to prostate cancer and because an ethnic variation exists in the CAG repeat length, this polymorphism has been suggested to explain part of the substantial racial difference in prostate cancer risk. We conducted a population-based case-control study in China to investigate whether CAG and other polymorphisms of the AR gene are associated with clinically significant prostate cancer in this low-risk population. Genomic DNA from 190 prostate cancer patients and 304 healthy controls was used for direct sequencing to evaluate the relationship of CAG and GGN (polyglycine) repeat length in the AR gene. Relative to western men, our study subjects had a longer CAG repeat length, with a median of 23 and only 10% of the subjects having a CAG repeat length shorter than 20. Men with a CAG repeat length shorter than 23 (median length) had a 65% increased risk of prostate cancer (odds ratio, 1.65; 95% confidence interval, 1.14-2.39), compared with men with a CAG repeat length of 23 or longer. For the GGN tract (GGT3GGG1GGT2GGCn), based on the sequencing results from 481 samples, we are the first to show that although GGC regions in the polyglycine tract are highly variable, there are no mutations or polymorphisms in the GGT and GGG regions. More than 72% of the subjects had a GGN repeat length of 23, and those with a GGN repeat length shorter than 23 had a 12% increased risk of prostate cancer (95% confidence interval, 0.71-1.78), compared with those with > or = 23 GGN repeats. Our study not only confirms that Chinese men do have a longer CAG repeat length than western men but also represents the first population-based study to show that even in a very low-risk population, a shorter CAG repeat length confers a higher risk of clinically significant prostate cancer. These results imply that CAG repeat length can potentially serve as a useful marker to identify a subset of individuals at higher risk of developing clinically significant prostate cancer. Larger studies are needed to evaluate the combined effect of CAG and GGN repeats. Because of the significance of AR in prostate cancer, investigation of factors that interact with the polyglutamine region of the AR gene to alter AR function and modulate prostate cancer risk is an important area for future research.

Aged↗

Score tests for familial correlation in genotyped-proband designs.

In the genotyped-proband design, a proband is selected based on an observed phenotype, the genotype of the proband is observed, and then the phenotypes of all first-degree relatives are obtained. The genotypes of these first-degree relatives are not observed. Gail et al. [(1999) Genet Epidemiol] discuss likelihood analysis of this design under the assumption that the phenotypes are conditionally independent of one another given the observed and unobserved genotypes. Li and Thompson [(1997) Biometrics 53:282-293] give an example where this assumption is suspect, thus suggesting that it is important to develop tests for conditional independence. In this paper, we develop a score test for the conditional independence assumption in models that might include covariates or observation of genotypes for some of the first degree relatives. The problem can be cast more generally as one of score testing in the presence of missing covariates. A standard analysis would require specifying a distribution for the covariates, which is not convenient and could lead to a lack of model-robustness. We show that by considering a natural conditional likelihood, and basing the score test on it, a simple analysis results. The methods are applied to a study of the penetrance for breast cancer of BRCA1 and BRCA2 mutations among Ashkenazi Jews.

Alleles↗

A study comparing centralized CD-ROM and decentralized intranet access to MEDLINE.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of a decentralized intranet access in each medical department as opposed to centralized unique MEDLINE access in the medical library. DESIGN: A two-phase questionnaire to evaluate MEDLINE use was given to junior and senior physicians at Rouen University Hospital (RUH). Phase I (August-October 1996) corresponded to a time period when centralized access was the only means of access available and phase II (August-October 1997) to a time period following the introduction of decentralized intranet access. RESULTS: A total of 168 physicians filled out at least one phase of the questionnaire, among whom 123 (73%) filled out both phases. Use of MEDLINE significantly increased in 1997 (average of 10.2+/-1.1 searches in three months) versus 1996 (average of 4.9+/-0.7 searches in three months, P<0.0001). The aim of searches changed, becoming significantly more care oriented in phase II (P<0.0001). The number of searches performed by the physicians alone increased (P<0.0001) and searches performed by the librarian decreased (P<0.0001) in phase II. The method of searches also changed, as searches by author (P< 0.0001), by journal (P = 0.0042), and by free word (P = 0.0027) increased in phase II. Knowledge of the following concepts of MEDLINE significantly increased: explosion (P<0.0001), scope note (P<0.0001), Abridged Index Medicus (AIM) journals (P<0.0001), Medical Subject Headings (MeSH) qualifier (P<0.0001), and focus (P<0.0001). CONCLUSION: A decentralized intranet access to MEDLINE increased the number of searches and knowledge of this bibliographic database. MEDLINE intranet access modified the purpose and the methods of searching.

CD-ROM↗

Body size and prostate cancer: a population-based case-control study in China.

We conducted a population-based case-control study in China to investigate whether body size plays a role in prostate cancer etiology and whether it can explain the rapid increase in prostate cancer incidence rates in China. A total of 238 cases newly diagnosed with primary prostate cancer in Shanghai, China, during 1993-1995 were included in the study. Four hundred and seventy-one healthy control subjects were randomly selected from among residents of Shanghai and frequency-matched to cases on the basis of age. In-person interviews were conducted to elicit information on height, weight history, and other lifestyle factors. Waist and hip circumferences were measured at interview. Odds ratios (ORs) were used to measure the association between prostate cancer and anthropometric variables including height, weight, body mass index (BMI), waist, hip, and right upper arm circumferences, and waist-to-hip ratio (WHR; an indicator of abdominal adiposity). High levels of WHR were related to an excess risk, with men in the highest quartile (WHR > 0.92) having an almost 3-fold risk (OR, 2.71; 95% CI = 1.66-4.41; Ptrend = 0.0001) compared with men in the lowest quartile (WHR < 0.86). In contrast, men in the highest quartile of hip circumference (>97.4 cm) had a reduced risk (OR, 0.46; 95% CI = 0.29-0.74; Ptrend = 0.0002) relative to men in the lowest quartile (<86 cm). No association was found for height, usual adult weight, or preadult and usual adult BMI. Our results suggest that even in a very lean population (average BMI = 21.9), abdominal adiposity may be associated with an increased risk of clinical prostate cancer, pointing to a role of hormones in prostate cancer etiology. Additional research is needed to confirm these findings in prospective studies, especially in Western populations where abdominal obesity is much more common, and to clarify the underlying hormonal mechanisms involved.

Abdomen↗

Validation studies for models projecting the risk of invasive and total breast cancer incidence.

BACKGROUND: In 1989, Gail and colleagues developed a model for estimating the risk of breast cancer in women participating in a program of annual mammographic screening (designated herein as model 1). A modification of this model to project the absolute risk of developing only invasive breast cancer is referred to herein as model 2. We assessed the validity of both models by employing data from women enrolled in the Breast Cancer Prevention Trial. METHODS: We used data from 5969 white women who were at least 35 years of age and without a history of breast cancer. These women were in the placebo arm of the trial and were screened annually. The average follow-up period was 48.4 months. We compared the observed number of breast cancers with the predicted numbers from the models. RESULTS: In terms of absolute risk, the ratios of total expected to observed numbers of cancers (95% confidence intervals [CIs]) were 0.84 (0. 73-0.97) for model 1 and 1.03 (0.88-1.21) for model 2, respectively. Within the age groups of 49 years or less, 50-59 years, and 60 years or more, the ratios of expected to observed numbers of breast cancers (95% CIs) for model 1 were 0.91 (0.73-1.14), 0.96 (0.73-1. 28), and 0.66 (0.52-0.86), respectively. Thus, model 1 underestimated breast cancer risk in women more than 59 years of age. For model 2, the risk ratios (95% CIs) were 0.93 (0.72-1.22), 1.13 (0.83-1.55), and 1.05 (0.80-1.41), respectively. Both models exhibited a tendency to overestimate risk for women classified in the higher quintiles of predicted 5-year risk and to underestimate risk for those in the lower quintiles of the same. CONCLUSION: Despite some limitations, these methods provide useful information on breast cancer risk for women who plan to participate in an annual mammographic screening program.

Age Factors↗

Percutaneous mechanical mitral commissurotomy with a newly designed metallic valvulotome: immediate results of the initial experience in 153 patients.

BACKGROUND: Percutaneous balloon valvotomy has become a common treatment of mitral stenosis, but the cost of the procedure remains a limitation in countries with restricted financial resources, leading to a frequent reuse of the disposable catheters. To overcome this limitation, a reusable metallic valvotomy device has been developed with the goals of both improving the mitral valvotomy results and decreasing the cost of the procedure. METHODS AND RESULTS: The device consists of a detachable metallic cylinder with 2 articulated bars screwed onto the distal end of a disposable catheter whose proximal end is connected to an activating pliers. By the transseptal route, the device is advanced across the valve over a traction guidewire. Squeezing the pliers opens the bars up to a maximum extent of 40 mm. The clinical experience consisted of 153 patients with a broad spectrum of mitral valve deformities. The procedure was successful in 92% of cases and resulted in a significant increase in mitral valve area, from 0.95+/-0.2 to 2. 16+/-0.4 cm2. No increase in mitral regurgitation was noted in 80% of cases. Bilateral splitting of the commissures was observed in 87%. Complications were 2 cases of severe mitral regurgitation (1 requiring surgery), 1 pericardial tamponade, and 1 transient cerebrovascular embolic event. In this series, the maximum number of consecutive patients treated with the same device was 35. CONCLUSIONS: The results obtained with this new device are encouraging and at least comparable to those of current balloon techniques. Multiple uses after sterilization should markedly decrease the procedural cost, a major advantage in countries with limited resources and high incidence of mitral stenosis.

Adolescent↗

Designing studies to estimate the penetrance of an identified autosomal dominant mutation: cohort, case-control, and genotyped-proband designs.

One can obtain population-based estimates of the penetrance of a measurable mutation from cohort studies, from population-based case-control studies, and from genotyped-proband designs (GPD). In a GPD, we assume that representative individuals (probands) agree to be genotyped, and one then obtains information on the phenotypes of first-degree relatives. We also consider an extension of the GPD in which a relative is genotyped (GPDR design). In this paper, we give methods and tables for determining sample sizes needed to achieve desired precision for penetrance estimates from such studies. We emphasize dichotomous phenotypes, but methods for survival data are also given. In an example based on the BRCA1 gene and parameters given by Claus et al. [(1991) Am J Hum Genet 48:232-242], we find that similar large numbers of families need to be studied using the cohort, case-control, and GPD designs if the allele frequency is known, though the GPDR design requires fewer families, and, if one can study mainly probands with disease, the GPD design also requires fewer families. If the allele frequency is not known, somewhat larger sample sizes are required. Surprisingly, studies with mixtures of families of affected and non-affected probands can sometimes be more efficient than studies based exclusively on affected probands when the allele frequency is unknown. We discuss the feasibility and validity of these designs and point out that GPD and GPDR designs are more susceptible to a bias that results when the tendency for an individual to volunteer to be a proband or to be a subject in a cohort or case-control study depends on the phenotypes of his or her relatives.

Bias↗

[Interpretation of standard chest x-rays in thoracic trauma: influence of the experience of the interpreter].

OBJECTIVE: To compare the quality of interpretation of chest radiographs (CRs) by physicians of different levels of experience, with reference to data obtained from helicoidal computed tomography (HCT). STUDY DESIGN: Prospective observational study. MATERIAL: CRs of 50 thorax trauma patients as recent to HCTs as possible obtained within the 48 h following admission to the intensive therapy unit. METHOD: CRs were analyzed according to a grid by observers included in one of the four groups: residents in anaesthesiology (n = 6), residents in radiology (n = 3), senior anaesthesiologists (n = 5), and senior radiologists (n = 3). The inter-observer agreements, the specificity and sensibility of each group with reference to HCT, and their global performances were assessed. RESULTS: Inter-observer agreements were poor and sensitivities low in comparison to specificities. No group of observers performed better than another one. These data substantiate the low sensitivity of CRs in comparison to HCT and show that the quality of interpretation of CRs of thorax trauma patients is not influenced by physicians' experience.

Adult↗