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Biomedical subjects

B Falissard

Publications and source records attributed to B Falissard.

At least 19 recordsLinked to original sources

Immunohistochemical variability of epidermal growth factor receptor (EGFR) in liver metastases from colonic carcinomas.

AIMS: To follow and compare immunohistochemical expression of epidermal growth factor receptor (EGFR) in tumour cells during the entire natural history of colonic carcinoma, from primary tumour to paired lymph node and sequentially resected liver metastases; and to test interobserver reproducibility of EGFR analysis. METHODS AND RESULTS: Forty patients had resection of colonic adenocarcinoma (27 with metastatic lymph nodes) and at least one partial hepatectomy (PH) for liver metastases; a second and a third PH were performed, respectively, in 14 and three patients; seven patients had tumour liver biopsy. EGFR immunohistochemistry (n = 130) was analysed independently by two pathologists. EGFR expression (membranous staining detected in > or = 1% of tumour cells) was detected in 38/40 colonic carcinomas, 23/26 lymph nodes and 51/64 liver metastases. Both primary tumours and related metastases were EGFR+ in 28 patients (73%). Discrepancies were found in EGFR status between liver and lymph node (23%) and among the different liver samples (31%). Interobserver agreement was very good (intraclass correlation coefficients of 0.81, 0.91 and 0.85, respectively, for interpretation of staining in colon, lymph node and liver metastases). CONCLUSIONS: Since immunohistochemical detection of EGFR remains a prerequisite for EGFR-targeted therapy eligibility, different tumour samples should be tested to allow every patient a chance to take advantage of this treatment.

Carcinoma↗

Association between symptoms of attention-deficit/hyperactivity disorder and bulimic behaviors in a clinical sample of severely obese adolescents.

OBJECTIVE: Preliminary evidence suggests a comorbidity between attention-deficit/hyperactivity disorder (ADHD) and obesity. This study was carried out to identify the clinical characteristics of obese adolescents with a higher probability of ADHD and advance the understanding of the potential factors underlying the comorbidity between obesity and ADHD. We evaluated the association between ADHD symptoms and bulimic behaviors, depressive and anxiety symptoms, degree of obesity, pubertal stage, age and gender in a clinical sample of obese adolescents. DESIGN: Cross-sectional study. SUBJECTS: Ninety-nine severely obese adolescents aged 12-17 years. MEASUREMENTS: Subjects filled out the Bulimic Investigatory Test, Edinburgh, the Beck Depression Inventory and the State-Trait Anxiety Inventory for Children. Their parents completed the Conners Parent Rating Scale, which assesses ADHD symptoms. The degree of overweight was expressed as body mass index-z score. Puberty development was clinically assessed on the basis of Tanner stages. RESULTS: Bulimic behaviors were significantly associated with ADHD symptoms after controlling for depressive and anxiety symptoms. The degree of overweight, pubertal stage, age and gender were not significantly associated with ADHD symptoms. CONCLUSION: Obese adolescents with bulimic behaviors may have a higher probability to present with ADHD symptoms independently from associated depressive or anxiety symptoms. The degree of overweight, pubertal stage, age and gender might not be useful for detecting obese adolescents with ADHD symptoms. Therefore, we suggest systematic screening for ADHD in obese adolescents with bulimic behaviors. Further studies are needed to understand which specific dimension of ADHD primarily accounts for the association with bulimic behaviors. Future research should also investigate the causal link between bulimic behaviors and ADHD and explore potential common neurobiological alterations. This may lead to a better understanding of the effectiveness of stimulants for the treatment of bulimic behaviors in obese subjects.

Adolescent↗

Psychotropic combination in schizophrenia.

OBJECTIVE: To study adjunctive medications used with antipsychotic agents in schizophrenia via comparisons of antidepressant, anxiolytic and antiparkinsonian co-prescribing. METHOD: In the context of a national naturalistic prospective observational study, a database containing all the prescriptions from 100 French psychiatrists during the year 2002 was analysed. The inclusion criteria were a diagnosis of schizophrenia or schizoaffective disorder and age over 18. A log-linear model and generalised linear mixed models were used. RESULTS: In all 5,257 prescriptions for 922 patients were analysed. The proportion of patients who were prescribed an antiparkinsonian drug was 32.9%. Amisulpride, haloperidol, phenothiazines with a sedative action and depot typical antipsychotics proved more likely to be prescribed with antiparkinsonians. The frequency of antidepressant and anxiolytic prescriptions was 51.2% and 52.3%, respectively. Associations between atypical antipsychotics (except clozapine) and antidepressants were positive while associations between typical antipsychotics and antidepressants were not. There were no differences among antipsychotics for the prescription of anxiolytics. CONCLUSIONS: Atypical antipsychotics can be expected to be less likely associated with antiparkinsonians. This result is indeed found for olanzapine, clozapine and to a limited extent for risperidone. Furthermore, a trend towards a positive association between atypical antipsychotics and antidepressants appears. In view of the antidepressive action of certain atypical antipsychotics, this result is surprising. The increase in the prescriptions of anxiolytics concerns all types of antipsychotics. In view of the increase in associated medications in schizophrenia and the difficulty of estimating it in randomised trials, this study underlines the contribution of naturalistic studies on this score.

Adult↗

Differing mental health practice among general practitioners, private psychiatrists and public psychiatrists.

BACKGROUND: Providing care for mental health problems concerns General Practitioners (GPs), Private Psychiatrists (PrPs) and Public Psychiatrists (PuPs). As patient distribution and patterns of practice among these professionals are not well known, a survey was planned prior to a re-organisation of mental health services in an area close to Paris METHODS: All GPs (n = 492), PrPs (n = 82) and PuPs (n = 78) in the South-Yvelines area in France were informed of the implementation of a local mental health program. Practitioners interested in taking part were invited to include prospectively all patients with mental health problem they saw over an 8-day period and to complete a 6-month retrospective questionnaire on their mental health practice. 180 GPs (36.6%), 45 PrPs (54.9%) and 63 PuPs (84.0%) responded. RESULTS: GPs and PrPs were very similar but very different from PuPs for the proportion of patients with anxious or depressive disorders (70% v. 65% v. 38%, p < .001), psychotic disorders (5% v. 7% v. 30%, p < .001), previous psychiatric hospitalization (22% v. 26 v. 61%, p < .001) and receiving disability allowance (16% v. 18% v. 52%, p < .001). GPs had fewer patients with long-standing psychiatric disorders than PrPs and PuPs (52%, 64% v. 63%, p < .001). Time-lapse between consultations was longest for GPs, intermediate for PuPs and shortest for PrPs (36 days v. 26 v. 18, p < .001). Access to care had been delayed longer for Psychiatrists (PrPs, PuPs) than for GPs (61% v. 53% v. 25%, p < .001). GPs and PuPs frequently felt a need for collaboration for their patients, PrPs rarely (42% v. 61%. v. 10%, p < .001). Satisfaction with mental health practice was low for all categories of physicians (42.6% encountered difficulties hospitalizing patients and 61.4% had patients they would prefer not to cater for). GPs more often reported unsatisfactory relationships with mental health professionals than did PrPs and PuPs (54% v. 15% v. 8%, p < .001). CONCLUSION: GP patients with mental health problems are very similar to patients of private psychiatrists; there is a lack of the collaboration felt to be necessary, because of psychiatrists' workload, and because GPs have specific needs in this respect. The "Yvelines-Sud Mental Health Network" has been created to enhance collaboration.

Adult↗

An in vivo study of the relationship between craving and reaction time during alcohol detoxification using the ecological momentary assessment.

BACKGROUND: To study cognitive interference associated with craving for alcohol, the Ecological Momentary Assessment (EMA) method was used to measure the relationship between craving and reaction time. A secondary aim was the study of the predictive factors for craving during alcohol detoxification. The EMA enables both repeated measures of craving in a natural setting and the recording of reaction time without the patient being aware of this. METHODS: Craving for alcohol, reaction time, sadness and anxiety were recorded 8 to 12 times a day, over three weeks of detoxification in 14 alcoholics (n=1767 measures), on an electronic diary issuing random prompts. Mixed models were used for statistical analysis (alpha=5%, 1-beta=88%). RESULTS: Reaction time was significantly increased in univariate analysis when a craving episode occurred but this difference did not persist after multivariate analysis. Craving episodes were more frequent and intense than previously reported. Predictive factors of craving during detoxification were: age, gender, sadness, anxiety and the number of previous detoxifications. Antidepressants, anti-craving medications but not benzodiazepines were negatively associated to craving.

Adolescent↗

Using patients' and rheumatologists' opinions to specify a short form of the WOMAC function subscale.

BACKGROUND: The WOMAC (Western Ontario and McMaster Universities) function subscale is widely used in clinical trials of hip and knee osteoarthritis. Reducing the number of items of the subscale would enhance efficiency and compliance, particularly for use in clinical practice applications. OBJECTIVE: To develop a short form of the WOMAC function subscale based on patients' and experts' opinions (WOMAC function short form). METHODS: WOMAC function subscale data (Likert version) were obtained from 1218 outpatients with painful hip or knee osteoarthritis. These patients and their rheumatologists selected the five items that they considered most in need of improvement. The rheumatologists were asked to select the five items for which patients in general are the most impaired. Items that were least important to patients and experts, those with a high proportion of missing data, and those with a response distribution showing a floor or ceiling response were excluded, along with one of a pair of items with a correlation coefficient >0.75. RESULTS: The WOMAC function short form included items 1, 2, 3, 6, 7, 8, 9, and 15 of the long form. The short form did not differ substantially from the long form in responsiveness (standardised response mean of 0.84 v 0.80). CONCLUSIONS: A short form of the WOMAC function subscale was developed according to the views of patients and rheumatologists, based on the responses of 1218 patients and 399 rheumatologists. The clinical relevance and applicability of this WOMAC function subscale short form require further evaluation.

Activities of Daily Living↗

Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement.

BACKGROUND: In clinical trials, at the group level, results are usually reported as mean and standard deviation of the change in score, which is not meaningful for most readers. OBJECTIVE: To determine the minimal clinically important improvement (MCII) of pain, patient's global assessment of disease activity, and functional impairment in patients with knee and hip osteoarthritis (OA). METHODS: A prospective multicentre 4 week cohort study involving 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. Patients assessed their response to treatment on a five point Likert scale at the final visit. An anchoring method based on the patient's opinion was used. The MCII was estimated in a subgroup of 814 patients (603 with knee OA, 211 with hip OA). RESULTS: For knee and hip OA, MCII for absolute (and relative) changes were, respectively, (a) -19.9 mm (-40.8%) and -15.3 mm (-32.0%) for pain; (b) -18.3 mm (-39.0%) and -15.2 mm (-32.6%) for patient's global assessment; (c) -9.1 (-26.0%) and -7.9 (-21.1%) for WOMAC function subscale score. The MCII is affected by the initial degree of severity of the symptoms but not by age, disease duration, or sex. CONCLUSION: Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients.

Adult↗

Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state.

BACKGROUND: The patient acceptable symptom state (PASS) is the value beyond which patients can consider themselves well. This concept can help in interpreting results of clinical trials. OBJECTIVE: To determine the PASS estimate for patients with knee and hip osteoarthritis (OA) by assessing pain, patient's global assessment of disease activity, and functional impairment. METHODS: A 4 week prospective multicentre cohort study of 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment of disease, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. The patients assessed their satisfaction with their current state at the final visit. An anchoring method based on the patient's opinion was used. RESULTS: For patients with knee and hip OA, the estimates of PASS were, respectively, 32.3 and 35.0 mm for pain, 32.0 and 34.6 mm for patient global assessment of disease activity, and 31.0 and 34.4 points for WOMAC function score. The PASS varied moderately across the tertiles of baseline scores but not across age, disease duration, or sex. CONCLUSION: The use of PASS in clinical trials would provide more meaningful results expressed as a proportion of patients in an acceptable symptom state.

Adult↗

Evaluation of the nutritional and inflammatory status in cancer patients for the risk assessment of severe haematological toxicity following chemotherapy.

BACKGROUND: The toxicity outcome of cancer patients receiving chemotherapy is difficult to predict. In this study the influence of malnutrition and inflammation on acute haematological toxicity was investigated. PATIENTS AND METHODS: Between January 1999 and January 2000, 48 consecutive cancer patients experienced severe haematological toxicity (SHT), either neutropenic fever or severe thrombocytopenia, following various chemotherapy regimens. Their baseline characteristics were compared with those of 59 control patients. Previous chemotherapy regimens, type of chemotherapy, performance status (PS), calculated creatinine clearance, bilirubin, C-reactive protein (1), alpha-1 acid glycoprotein (2), albumin (3), pre-albumin (4) and the nutritional and inflammatory status (NIS) ratio [NIS = (1 x 2)/(3 x 4)] were studied. Statistical analysis was carried out using either a t-test or a chi-square test. A receiver operating characteristic (ROC) curve determined the cut-off value for NIS. RESULTS: Patients experiencing SHT had a higher PS (P <0.001), inflammatory serum protein levels (P <0.001) and NIS ratio (P <0.0001), but lower haemoglobin (P <0.05) and serum-albumin levels (P <0.0001). Using a cut-off of 0 or 1 for PS and 1 for NIS, sensitivity was 98%, 43% and 89%; specificity was 38%, 90% and 66%, respectively. In 37 patients treated with topotecan as single agent, the determinants for SHT were PS (P <0.0001) and NIS (P <0.0001). CONCLUSIONS: Altered nutritional and inflammatory status correlates with increased risk of severe haematological toxicity following anticancer chemotherapy.

Adult↗

[Cultural adaptation and validation of questionnaires measuring satisfaction with the French health system].

Two questionnaires measuring satisfaction of the population with regard to health care offer were constructed from measures validated in the USA (the Consumer Satisfaction Survey Questionnaire or CSS, and the Visit-Specific Satisfaction questionnaire, the VSQ). This work was comprised two stages: i) translation and cultural adaptation of the American instrument to the French health care context, implicating 6 translators, users and experts; and ii) a telephone survey in the general population (n = 706) to test the psychometric qualities of the French instrument (content and internal validity). The French version, the CSS-VF comprises 9 scales: access to primary care, access to secondary care, scope for choice, health cover, communication with and competence of GPs, communication with specialists, competence of specialists, human qualities of practitioners and overall satisfaction. The VSQ-VF, which measures satisfaction with the last medical consultation is unidimensional. The results of the psychometric analyses are good overall, and endorse the use of these scales in assessment studies.

Consumer Behavior↗

Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid.

Potentiation of the cytotoxic activity of 5-fluorouracil (FUra) by folinic acid (5-HCO-H4folate) is due to elevation of the methylene tetrahydrofolate (CH2-H4folate) level, which increases the stability of the ternary complex of thymidylate synthase (TS), fluorodeoxyuridine monophosphate, and CH2-H4folate that inactivates the TS. Methionine deprivation results in the production of tetrahydrofolate (H4folate) and, subsequently, CH2-H4folate from methyl tetrahydrofolate, as a consequence of the induction of methionine synthesis. We hypothesized that the efficacy of FUra could be augmented by the combination of high-concentration 5-HCO-H4folate and recombinant methioninase (rMETase), a methionine-cleaving enzyme. Studies in vitro were performed with the cell line CCRF-CEM. Cytotoxic synergism of FUra + rMETase and FUra + 5-HCO-H4folate + rMETase was demonstrated with the combination index throughout a broad concentration range of FUra and rMETase. A subcytotoxic concentration of rMETase reduced the IC50 of FUra by a factor of 3.6, and by a factor of 7.5, in the absence and in the presence of 5-HCO-H4folate, respectively. 5-HCO-H4folate increased the intracellular concentrations of CH2-H4folate and H4folate from their baseline levels. Concentrations of folates were not changed by exposure to rMETase. Levels of free TS in cells treated with FUra + 5-HCO-H4folate and with FUra + rMETase were lower than those in cells exposed to FUra alone. The decrease of TS was still more pronounced in cells treated with FUra + 5-HCO-H4folate + rMETase. The synergism described in this study will be a basis for further exploration of combinations of fluoropyrimidines, folates, and rMETase.

Antimetabolites, Antineoplastic↗

Impact of reminders and method of questionnaire distribution on patient response to mail-back satisfaction survey.

Nonresponse and methods of data collection could affect satisfaction measurement. The goal of this study was to estimate the impact of (1) nonresponse and (2) distribution method on evaluation of patient satisfaction in a mail-back study measuring patient opinion of medical and nursing care. The study was conducted in an adult hospital. Patients were pseudo-randomized according to the initial mode of questionnaire distribution (given at hospital or sent by mail). Three reminders were made at 1-week intervals to nonrespondents, regardless of the method of initial questionnaire distribution. Groups were distinguished according to the delay of response: initial (before any reminder), middle (after one or two mailed reminders), and late respondents (after mailed reminders plus telephone contact). The study included consecutively discharged patients to obtain 300 patients per arm. 482 patients returned the questionnaire (248 in the group receiving the questionnaire at the hospital and 234 in the other group). Groups were compared for satisfaction scores and delay of response. Early respondents were compared with middle and late respondents for patient characteristics, modality of hospital care, and satisfaction scores. Multivariate analyses were performed. Participation rate before any reminder was higher when the questionnaire was mailed than when it was given at the hospital (45% versus 39.7%, p = 0.03). The initial method of distribution did not influence patient satisfaction level. Satisfaction did not differ between respondents with or without reminders. Distributing questionnaires by mail may be preferred to distribution at discharge to optimize response rate. Reminders do not seem necessary to estimate satisfaction of overall potential respondents.

Adult↗

Genetic clustering of hepatitis C virus strains and severity of recurrent hepatitis after liver transplantation.

The influence of viral factors on the severity of hepatitis C virus (HCV)-related liver disease is controversial. We studied 68 liver transplant patients with recurrent hepatitis C, of whom 53 were infected by genotype 1 strains. Relationships between core sequences, serum HCV RNA levels, and fibrosis scores for each patient were analyzed in pairwise fashion 5 years after transplantation. We used Mantel's test, a matrix correlation method, to evaluate the correspondence between measured genetic distances and observed phenotypic differences. No clear relationship was found when all 68 patients were analyzed. In contrast, when the 53 patients infected by genotype 1 strains were analyzed, a strong positive relationship was found between genetic distance and differences in 5-year fibrosis scores (P = 0.001) and differences in virus load (P = 0.009). In other words, the smaller the genetic distance between two patients' viral core sequences, the smaller the difference between the two patients' fibrosis scores and viral replication levels. No relationship was found between genetic distance and differences in age, sex, or immunosuppression. In multivariate analysis, the degree of fibrosis was negatively related to the virus load (r = -0.68; P = 0.003). In the particular setting of liver transplantation, and among strains with closely related phylogenetic backgrounds (genotype 1), this study points to a correlation between the HCV genetic sequence and the variability of disease expression.

Genotype↗

Use of hormone replacement therapy: women's representations of menopause and beauty care practices.

OBJECTIVES: Hormone replacement therapy (HRT) during menopause has been shown to have beneficial effects on women's health, including preventing osteoporosis and probably reducing cardiovascular mortality and morbidity. However, these effects appear only after long use. Knowledge of factors influencing HRT use is a prerequisite for developing and assessing preventive actions. Most studies of user characteristics have focused on medical knowledge and socioeconomic characteristics, although social and cultural models of menopause may also play a role. Therefore, our study of the determinants of HRT use focused on representations of menopause and on beauty care. METHODS: Two scores, one concerning the level of beauty care and the other the representations of menopause, were calculated. In our population of 561 postmenopausal women from the GAZEL cohort in France, 409 (72.9%) had been using HRT for more than one year, and 152 (27.1%) had used it for less than three months, if ever. Associations between the study variables and HRT use were then analysed. RESULTS: No association was found between representations of menopause and HRT use. Beauty care and some beliefs about HRT (i. e. that it is useful for osteoporosis prevention, causes resumption of menstruation, and has anti-aging effects) were independently associated with HRT use. Moreover, the proportion of HRT users increased with socioeconomic status, with vasomotor symptoms in early menopause, and among hysterectomised women. CONCLUSIONS: The results suggest that the amount of attention women pay to beauty care plays a role, in determining HRT use.

Beauty↗

Performance of an automated system for quantification of hepatitis C virus RNA.

The Amplicor HCV Monitor test for quantitative determination of serum or plasma hepatitis C virus (HCV) RNA was modified recently and introduced onto the Cobas Amplicor instrument to automate fully amplification, detection and calculation of results. This new version (v2.0) was evaluated in a routine diagnostic laboratory. The sensitivity and reproducibility were assessed on well-characterized panels (Eurohep) and clinical samples. HCV RNA levels measured by the v2.0 Monitor test were about 1log(10) higher than those detected by the previous version test, and genotypes 1 and 3 were quantified with equal sensitivity. Within the linear dynamic range of 10(3) to 10(6) copies/ml, the coefficients of variation for both intra- and inter-assay reproducibility ranged from 1.9 to 2.95%. This test system was found to be a reliable and labor saving assay for the quantification of HCV RNA.

Automation↗

Hepatocellular carcinoma with lymphoid stroma: a tumour with good prognosis after liver transplantation.

AIMS: Carcinomas with lymphoid stroma arising in non-liver-organs have a better prognosis than other carcinomas and may be associated with Epstein-Barr virus. We determined the frequency, characteristics and prognosis of hepatocellular carcinomas with lymphoid stroma. METHODS AND RESULTS: Histology of the livers of 162 patients with hepatocellular carcinoma, who underwent an orthotopic liver transplantation, was reviewed independently by three pathologists. Hepatocellular carcinoma with lymphoid stroma was diagnosed when all tumour samples contained more lymphocytes than tumour cells. Epstein-Barr virus was detected by in-situ hybridization and by polymerase chain reaction. Five patients (3.6%) were classified as hepatocellular carcinomas with lymphoid stroma. All patients were males. Cirrhosis was present in four/five patients. Serum alpha-fetoprotein levels were normal. Inter-observer histological reproducibility was good. Tumour cells did not contain Epstein-Barr virus. The five patients were alive without tumour at three years, although two of them had adverse prognostic factors at the time of transplantation (more than one tumour with a diameter > or = 40 mm). Only one patient had tumour recurrence, but he survived 7.6 years post-transplantation. The 5-year survival of patients with hepatocellular carcinoma with lymphoid stroma was better than that of the patients with other types of hepatocellular carcinomas (P = 0.04). CONCLUSIONS: Hepatocellular carcinoma with lymphoid stroma should be considered as a distinct clinicopathological and prognostic entity.

Carcinoma, Hepatocellular↗