Prevalence and epitope specificity of non-neutralising antibodies in a large cohort of haemophilia A patients without inhibitors.

Antibodies (inhibitors and non-neutralising antibodies [NNA]) directed against factor VIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Inhibitors reduce FVIII pro-coagulant properties, whereas NNA are directed against non-functional epitopes. NNA are poorly studied and their prevalence, epitope specificity and physiopathology inadequately defined. The aim of this study was first to evaluate NNA prevalence in a French retrospective multicentric series of 210 patients without inhibitors, then to determine their epitope specificity (against the heavy chain [HC] or the light chain [LC] of FVIII) and particularly to assess the prevalence of anti-B domain NNA using specifically designed x-MAP assays. NNA occurred in 18.1% of patients (38/210) and their prevalence was not influenced by the severity of the disease. Among the 38 patients with NNA, 73.7% had anti-FVIII Abs against the HC, 13.2% against the LC and 13.2% had anti-FVIII Abs against both chains. There is thus a clear immuno-dominance of the HC of FVIII in the epitope profile of NNA, whatever the severity of HA. The proportion of NNA that recognised the B domain was 18.4% (n=7/38). A multivariate analysis did not highlight differences in NNA occurrence between patients treated with recombinant FVIII or with plasma- derived FVIII (19.6% vs. 14.9%, p=0.53).

Expressed emotion measure adaptation into a foreign language.

Expressed emotion (EE) measures have been created in English; adaptation into a foreign language is difficult. The aim of this study was to adapt the five minutes speech sample (FMSS), with a designed procedure ensuring optimum quality of the adaptation, and thus better trans-cultural validity. A strategy for improving inter-rater agreement comprised three phases: (1) phase of initial ratings (70 French samples), (2) experimental phase in two steps: ratings of 40 other samples in French, followed by analysis of differences between the French-language ratings and English-language ratings and (3) final rating phase of the initial 70 samples. For each phase, the κ coefficients measuring inter-rater agreement were calculated and compared using a bootstrap procedure. The improvements between these scorings were significant at p < 0.05 (phase 2 initial versus phase 2 final and phases 1 versus 3). The French inter-rater agreement significantly improved after this procedure.

Lack of validity of a French adaptation of a scale measuring attitudes towards clinical practice guidelines.

BACKGROUND: Valid instruments to measure practitioners' attitudes towards clinical practice guidelines need to be developed. However, few of the available instruments have been thoroughly validated. OBJECTIVE: To adapt into French and to test the reliability and validity of a scale for measurement of attitudes towards guidelines developed by Elovainio et al. METHODS: A 27-item scale (divided into six dimensions) measuring attitudes towards guidelines was translated into French by two English native translators, reviewed and finalized by expert committee and administered to 314 practitioners who agreed to participate. Main practitioners' characteristics were collected. Item and dimension reproducibility were assessed for 62 practitioners by calculation of intraclass correlation coefficients. Internal construct validity was assessed by principal components analyses. Convergent and discriminant validity were analysed. RESULTS: Item response rates ranged from 82 to 100%. In the test-retest procedure, intraclass correlation coefficients for separate items ranged from 0.1 to 0.7 and those for dimensions were 0.7 [95% confidence interval (CI): 0.5-0.8] for usefulness, 0.5 (0.3-0.6) for reliability, 0.4 (0.2-0.5) for individual competence, 0.5 (0.3-0.6) for organizational competence, 0.7 (0.5-0.8) for impracticality and 0.4 (0.3-0.6) for availability. The factorial structure after Varimax rotation showed that none of the different solutions obtained had a strictly comparable structure to that of the original scale. External construct validity was satisfactory. CONCLUSION: This scale does not have satisfactory psychometric properties and therefore cannot confidently be used in future research assessing whether attitudes towards guidelines are a determining factor in physicians' compliance with guidelines. More research is needed to develop valid scales in a more rigorous procedure, involving qualitative and quantitative steps.

Impact of choice of treatment for bleeding episodes on inhibitor outcome in patients with mild/moderate hemophilia a and inhibitors.

Patients with mild/moderate hemophilia A (MHA) may develop inhibitors to factor VIII (FVIII). In this condition, FVIII clotting activity (FVIII:C) baseline levels may remain stable for some patients, but may be reduced to less than 0.01 U/mL for others. Several risk factors for the development of inhibitors in MHA have been proposed. Genetic factors, such as mutations in the FVIII gene, may play a central role; however, other influences, such as intensive treatment with FVIII products, may also be important. Optimal treatment regimens have yet to be determined, not only for the eradication of inhibitors, but also for the management or surgical prophylaxis of hemorrhages associated with this condition. Several treatment options for the control of bleeding in patients with MHA and inhibitors (MHAI) are currently available, and the choice of therapeutic strategy should be given careful consideration; some treatments may produce an anamnestic response, thus delaying the return to FVIII:C baseline levels and adversely affecting the duration of the severe bleeding phenotype. To increase our knowledge of MHAI, a retrospective collection of data is currently being performed among hemophilia centers in France and Belgium. Based on five examples of patients with MHAI collated from preliminary study data, we illustrate the impact on inhibitor outcome of the therapeutic choices used to treat bleeding episodes in these patients.

A correlation method for weight loss after gastroplasty.

BACKGROUND: Prevalence of morbid obesity is increasing in western countries. As a consequence, bariatric surgery has intensively developed in the last decades. Someone facing the need for comparison between gastric restrictive procedures could find it useful to have a general expression for weight loss after surgery. METHODS: A first approach of this issue can be made, taking into account two simple hypotheses: linear dependencies of weight variation versus sum of energy transfer, and of loss of energy versus weight. With the additional assumption of a constant energy income (the goal of surgery), one can obtain for the weight loss DeltaP=P(0)-P=(P(0)-B)(1-e(-betat)), where P and P(0) are the weight at time t and t(0), B and beta being adjustable constants. RESULTS: A preliminary study has shown us that most of our weight loss data could be fitted using such an expression. The model was successfully tested on gastric banding and calibrated vertical banded gastroplasty data, but with greater emphasis on laparoscopic vertical banded gastroplasty. CONCLUSION: We introduce a simple, exponential growth-like function that can be used for the fit of weight loss data of patients who underwent bariatric surgery in our surgical unit. Such a function could also be of practical interest for the survey of weight loss.

[Cultural adaptation and validation of questionnaires measuring satisfaction with the French health system]. / Adaptation culturelle et validation de questionnaires de satisfaction à l'égard du système de santé français.

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.

The LM Proring Band and left approach in laparoscopic vertical banded gastroplasty: preliminary results in 44 cases.

BACKGROUND: Morbid obesity is one of the most important social and medical issues in Western countries. Many authors have adopted a minimally invasive approach to reproduce current bariatric operations. The aim of this study is to present a personal technique for laparoscopic vertical banded gastroplasty (LVBG) and the preliminary results of 44 patients. METHODS: Patients fulfilled the indications for bariatric surgery and were followed prospectively. LVBG was performed in patients who refused laparoscopic banding because of port placement and adjustment, or in patients with hiatus hernia, with or without gastroesophageal reflux disease. The technique performed consisted of a laparoscopic Mason modified-MacLean gastroplasty using only 4 ports. The circular stapler was introduced in the left anterior axillary line subcostally using the same working port as the Endo-GIA stapler. A new device, a non-adjustable silicone ring, was placed as the collar around the lower end of the gastric pouch. RESULTS: The 44 patients underwent a satisfactory LVBG with no conversions to open surgery. Mean operative time was 80 minutes (range 45-180), hospital stay was 4 days, and all 44 operations had an uneventful postoperative course. There were 40 women and 4 men, with mean age 42.5 years (24-59). Preoperative mean weight was 118.7 kg (84.5-184), with mean BMI 44.5 (35.6-60.1). 27 of the 44 patients were selected for analysis of weight loss, selection criteria being a sufficient amount of data (> 2 weight losses separated by at least 2 months). For these 27 patients, mean age 41.9 (26-59), preoperative weight 119.3 kg (95-145) and mean BMI 44.6 (38.3-53.6), weight loss data were fitted with an exponential growth function, using a quasi-Newton fit algorithm. The fitted coefficient was used to calculate % excess weight loss and BMI. Mean weight loss at 1, 3, 6 and 12 months was 9.2 kg (4.4-17.2), 24.5 kg (11.0-35.9), 29 kg (12.6-53.6), and 36.5 kg (12.8-66.5) respectively. CONCLUSION: LVBG has given good results thus far and may be selected as a restrictive procedure. Weight loss and resolution of comorbidities occurred, and a considerable increase in self-confidence and quality of life were reported.

Cost related to replacement therapy during hospitalization in haemophiliacs with or without inhibitors: experience of six French haemophilia centres.

Replacement therapy in haemophiliacs has a major economic impact on health establishments. We assessed in this prospective study the cost of clotting factor concentrate therapy for haemophilia A or B patients. We compared the overall costs of treated patients with or without inhibitors. In six French haemophilia centres, 278 consecutive hospitalizations were collected and analysed between June 97 and June 99. Haemophilia must be considered as the main cost factor during hospitalization. The severity of bleeds and surgical procedures increase the total cost. Furthermore, the daily and total costs are closely linked to the presence or the absence of inhibitors. This study should enable the hospital administration to evaluate the necessary resources to the clotting factor therapy in haemophiliacs with or without inhibitors during hospitalization.

Use of recombinant factor VIIa (NovoSeven) in patients with Glanzmann thrombasthenia.

Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) appears effective and relatively safe for the treatment of bleeding and for surgical prophylaxis in patients with Glanzmann thrombasthenia as reported to the International Registry on rFVIIa and Congenital Platelet Disorders. One of the shortcomings of the Registry data is the heterogeneity of treatment protocol, including dosage, number of doses used, duration of treatment before declaration of failure, and mode of rFVIIa administration (bolus v continuous infusion). The data are not yet sufficient to define optimal regimens for various indications such as the type of bleeding or the type of procedures. The place of this drug compared to platelet transfusion in the overall management of patients with Glanzmann thrombasthenia will need to be determined in relationship to a number of challenges and unresolved issues in the clinical care of these patients. These issues include: how to improve local measures for patients with mucosal bleeds, optimal management of young women during menarche, optimal platelet transfusion regimens for various indications, the relationship between antiplatelet antibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and effectiveness of platelet transfusion, whether there are other biological tests that may correlate with effectiveness of platelet transfusion, and management of pregnancy and delivery regarding antiplatelet immunization.

[Evaluation of somatostatin or octreotide efficacy in the treatment of external pancreatic fistulas]. / Evaluation de l'efficacité de la somatostatine ou de l'octréotide dans le traitement des fistules pancréatiques externes.

AIM OF THE STUDY: To evaluate the prevalence of pancreatic pseudocyst after persistent fistula closure with somatostatin or octreotide. To compare the patient characteristics according to the subsequent presence or absence of pseudocyst. PATIENTS AND METHODS: This retrospective study from January 1994 to August 1999 included 15 patients with an external pancreatic fistula. Fistula closure was observed for all patients with somatostatin or octreotide. CT scan was performed 66 +/- 34 days after the end of this treatment. RESULTS: CT scan was normal in 9 patients (favorable group) and showed pancreatic pseudocyst (failure group) in 6 patients. Pancreatic fistula etiologies were different between the two groups. The 5 patients presenting pancreatic fistula after duodenopancreatectomy belonged to the favorable group. Six of the 10 patients presenting pancreatic fistula after pseudocyst drainage belonged to the failure group. There were no other differences between the two groups. CONCLUSION: Persistent pancreatic fistula can be cured with somatostatin or octreotide. However, fistulas occurring after duodenopancreatectomy are more easily cured with somatostatin or octreotide than fistulas occurring after external pseudocyst drainage. Somatostatin or octreotide cannot be considered to be an effective treatment for pancreatic fistula occurring after pseudocyst drainage, despite the fact that 40% of them were permanently cured.

Attempt to modify the immune response developed against FIV gp120 protein by preliminary FIV DNA injection.

Following inactivated virus vaccination trials, the surface glycoprotein gp120 (SU) of the feline immunodeficiency virus (FIV) was considered as one of the determinants for protection. However, several vaccination trials using recombinant Env protein or some Env-derived peptides failed to induce protection. To study the influence of the environment in which the surface protein (SU) is injected. we analyzed the impact of a nucleocapsid (NC) DNA immunization on the presentation of the recSU protein to the immune system. Cats were vaccinated either with the recSU protein alone or with NC DNA followed by the recSU protein. Two routes of nucleocapsid DNA vaccination were tested: intramuscular and mucosal injections. Cats immunized with the recSU protein showed a facilitation of infection, since they presented the earliest and the highest humoral response correlating with the highest proviral load. They also showed an acceleration of the appearance of IL4 mRNA signal. Preliminary injection of the DNA coding for NC protein, regardless the route of inoculation, seemed to inhibit the facilitation induced by vaccination with the recSU protein alone. The previously nucleocapsid DNA immunized cats had infectious status similar to those of the control cats, but with lower proviral load and less developed anti-FIV humoral response. Cat No. 2, belonging to the group vaccinated with NC protein by the mucosal route, had a protected-like status which did not correlate with the humoral response. This cat was the only one to have a persisting IFN mRNA signal after challenge specific for the p10 nucleocapsid and recSU proteins. However, no NC specific cytotoxic cells were observed throughout the experiment in this cat. The role of nucleocapsid DNA vaccination is still unknown nevertheless we did demonstrate that the facilitation observed in vaccination trial with recombinant proteins could be modified and that recombinant proteins could be a component of an effective vaccine.

The French SF-36 Health Survey: translation, cultural adaptation and preliminary psychometric evaluation.

This article reports on the main developmental stages and on the preliminary psychometric assessment of the final French version of the SF-36. A standard forward/backward translation procedure was followed. When translating survey items, the emphasis was placed on conceptual equivalence. When translating response choices, we attempted to select a set of response choices that replicate the U.S. version. The distance between the response choices was checked using visual analogue scales (N = 30). The adaptation procedure also included formal ratings of the difficulty of the translation, of the quality of the translation, and of the equivalence between the American source version and the French target version. The face validity was checked during lay panel sessions at which the translated questionnaire was administered to subjects from the general public, hospital employees, and subjects with a low level of education. Standard psychometric techniques were used to evaluate the cultural adaptation of the SF-36, using data from a general population survey. The main objective of this analysis was to determine how well the scaling assumptions (summated rating or Likert-type scaling construction) of the SF-36 were satisfied. The results support the claim that the scaling properties of the French version of the SF-36 are adequate and that health outcomes may be reliably assessed using this version of the instrument.

Chromosomal mapping of two novel human FGF genes, FGF11 and FGF12.

The fibroblast growth factor (FGF) family comprises to date 12 members, which are involved in various physiological processes throughout embryogenesis and adult life. Two novel members of the family have been identified recently (FGF11 and FGF12). Using in situ hybridization on metaphasic chromosomes, we have been able to assign FGF11 to band p12-p13 of human chromosome 17 and FGF12 to band q28 of human chromosome 3.

An international questionnaire to explore neurotoxic symptoms.

EURONEST (European Neurotoxic Solvents Toxicity) is a concerted action within the European Communities to use standardized methods available in all countries. The product of this effort is a new symptom questionnaire, EUROQUEST (European Questionnaire). The original version was developed in English. To obtain transcultural reliability, the translation of questionnaires into other languages must be validated. We adopted a procedure with translation, back translation, and agreement between translators. Ten other European countries also followed the same translation procedure for EUROQUEST.

[Comparative study of actual costs of radiotherapy and its value]. / Etude comparative des coûts réels des actes de radiothérapie et de leur valorisation par lettre clef.

PURPOSE: Financial costs from "Z" procedures were evaluated and compared with the amount of direct costs that are needed for the annual activity of a radiation oncology department. MATERIALS AND METHODS: The various components, particularly staff earnings that are estimated for each procedure according to their category and working time, were cumulated for calculation of direct loads. RESULTS: Comparisons between direct expenses and the total amount of Z procedures led to the following results: the global cost is the same; at analysis of therapeutic procedures, however, this apparent similarity masks some very significant gaps; valorization of Z procedures is much lower than that of the corresponding real loads, especially when therapeutic procedures are quite different from techniques that are considered as "standard"; these differences do not apply to all the components of radiation therapy procedures. In particular, medical steps would be uniformly underestimated, while irradiation per se is overestimated. CONCLUSION: The authors suggest modifications of the general objectives and items of the nomenclature of radiotherapy and brachytherapy procedures.

[The cost of radiotherapy. Evaluation of the real cost of treatments performed in a radiotherapy service of a center for fight against cancer]. / Le coût de la radiothérapie. Evaluation du coût réel des traitements réalisés dans un service de radiothérapie d'un centre de lutte contre le cancer.

The authors present a retrospective analysis dealing with the cost of therapeutic procedures achieved in the department of radiotherapy of the Centre Claudius-Regaud. This analysis was performed according to the actual cost of the different components of each treatment including the human costs. For this last purpose, serial countings of time spent by each category of employees were performed and then translated into financial terms. Results show a large discrepancy between the costs of therapeutic procedures. These differences are mainly related to the purpose of therapeutic plan, dealing with the most expensive procedures dealing with the developmental treatments. This study provides a tool that can be used by medical and/or administrative managers of radiation oncology departments when changes or innovations in therapeutic procedures. This cost accounting analysis is compared to the French administrative procedures used to pay the health care services and to determine the level of hospital resources.

[Kinetics of erythropoietin blood levels from D-1 to D-29 in kidney transplantation]. / Cinétique de l'érythropoïétinémie de J-1 à J29 en transplantation rénale.

This study of serum erythropoietin levels and reticulocytes counts in the first month after kidney transplantation shows that the erythropoietin peak is efficient only when serum creatinine level at the time of the peak is under 200 mumol/l.