[Quality of life of living kidney donor: a national report]. / Rapport qualité de vie des donneurs vivants de rein. Étude QV DVR transversale.

The renal transplantation is nowadays the reference treatment of ESRD. Living donor kidney transplantation is less often performed in France than in other countries. Nevertheless, numerous French and international surveys have evidenced that it provides the recipients a longer life expectancy and a better quality of life. Donors themselves, what do they become? How are they? For the first time in France, a survey has been implemented to investigate the quality of life of living kidney donor to one of their close relations. This study has been undertaken by the Agency of the biomedecine and the service Clinical Epidemiology and Evaluation (EEC), of the University teaching hospital of Nancy. The main objective was to describe the quality of life of the living donors having given a kidney for more than a year and less than 5 years. The secondary objective was to contribute to the knowledge of the main factors associated to the living kidney donor quality of life, one year after the donation. Participants had to be living in France at the time of the donation which had taken place between June 30(th), 2005 and March 1(st), 2009. A folder gathering various self-administrated questionnaires was sent to the place of residence of the donor between March and April, 2010. These data were completed by medical data collected near the transplantation centres by the Agency of biomedecine within the framework of the register CRISTAL. They included the characteristics of the donation and of the donor at the very time of the donation, 3 months after the donation and at the last annual assessment. Three living donors in four, that is 501 persons, agreed to fully participate. They constituted a representative national sample of all the living donors of this period. The non participants were younger (4.5 years on average) and had a less adequate annual follow-up. The women were more represented (61 %) than men. The median age was 53 years. More of 2/3 were employed at the time of the survey. The three main categories of donors were ascendants (36 %), collateral (33 %) and spouses (26%). The donation decision was taken without hesitation (94 %) and at an early stage of the evolution of the recipient renal disease (64 %). The delivered information was considered globally satisfactory except for the painful consequences and for the scar. The living donors were, long after their donation, in an excellent physical health state according to the SF36 summarized physical score and this especially when they were old as compared to the same age and sex general population. This phenomenon highlights the drastic selection of the potential donors. The only factor influencing the level of long term physical health was the surgical technique: the 261 subjects having undergone a coelioscopy had less often presented post operative pain (OR=0.5; 0.3-0.8; P<0.002) and had more often recovered completely without any residual pain (OR=1.7; 1.2-2.5; P<0.004). The quality of life mental dimension according to the SF36 summarized mental score was very close to that of the same age and sex of the general population although a slightly lower. It is influenced by characteristics related to the way the donation had been lived, particularly the understanding of their donation by their circle of acquaintances (average score 74.2/100), the perception of a feeling of owing on behalf of the recipient (46.5 %) and the fact of having lived a competition to be retained as the donor (for 266 cases another potential donor did exist and 21 lived the donation as a strong competition). More than 84 % of the donors was still followed by a healthcare professional at the time of the survey. The main expressed complaints concern the quality of the medical follow-up (70 donors expressed themselves openly on this topic) and the pain and scar after effects of the intervention. In spite of the surgical complications, of the dissatisfactions regarding their medical follow-up, of dismissals or of necessary adjustments of their professional life (13 %), of their difficulties to carry heavy loads, of sometimes complex relations with the recipient (23 % positive, 10 % negative) or their circle of acquaintances, of expenses non reimbursement and of losses of salary (12 %), they would be 95 % to recommend the donation and if it was to be redone 98 % would do it again! Benefits brought to the recipient won largely over the encountered difficulties. This retrospective and cross-sectional study allows to state recommendations which have to be confirmed by the 2009-2012 longitudinal study: to favour the coelioscopy which offers an advantage in terms of less frequent pain and a better post operative recovery, to better understand the phenomena of competition between potential and donors recipients, to improve the information about the potential consequences of the donation on the pain and on the scar, to inform the donor about the importance to associate the proxies with the decisionmaking or at least with the discussion and finally to improve the society recognition of the donation.

[Effect of smoking on the effectiveness of antimalarial drugs for cutaneous lesions of patients with lupus: assessment in a prospective study]. / Influence du tabagisme sur l'efficacité des antipaludéens de synthèse (APS) sur les lésions cutanées de sujets atteints de lupus: évaluation à travers une étude prospective.

PURPOSE: Smoking has been involved in the failure of antimalarial therapy in patient with chronic or subacute erythematosus lupus. METHODS: We report a prospective study of 26 patients with chronic, subacute or systemic erythematosus lupus who were treated with antimalarials. Several variables including smoking are compared in responders and non-responders. RESULTS: Despite the reduced number of patients study that does not permit to allow significative results, it seems that among responders and non-responders, in other respects comparables, there is no difference in the presence of smoking, its quantity or its duration. CONCLUSION: The significance of molecular interactions between some components of tobacco and antimalarials have still to be established.

Postoperative analgesia after total knee replacement: the effect of an obturator nerve block added to the femoral 3-in-1 nerve block.

Femoral nerve block (FNB) does not consistently produce anesthesia of the obturator nerve. In this single-blind, randomized, controlled study we added a selective obturator nerve block (ONB) to FNB to analyze its influence on postoperative analgesia after total knee replacement (TKR). Before general anesthesia, 90 patients undergoing TKR received FNB (Group 1), FNB and selective ONB (Group 2), or placebo FNB (Group 3). Postoperative analgesia was further provided by morphine IV via patient-controlled analgesia. Analgesic efficacy and side effects were recorded in the first 6 h after surgery. Adductor strength decreased by 18% +/- 9% in Group 1 and by 78% +/- 22% in Group 2 (P < 0.0001). Total morphine consumption was reduced in Group 2 compared with Groups 1 and 3 (P < or = 0.0001). Patients in Group 2 reported lower pain scores than those in Groups 1 and 3 (P = 0.0003). The incidence of nausea was more frequent in Groups 1 and 3 (P = 0.01). We conclude that FNB does not produce complete anesthesia of the obturator nerve. Single-shot FNB does not provide additional benefits on pain at rest over opioids alone in the early postoperative period. The addition of an ONB to FNB improves postoperative analgesia after TKR.

Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab.

BACKGROUND: The incidence of secondary central nervous system (CNS) occurrences in diffuse large-B-cell lymphoma is not sufficiently high to warrant the use of CNS prophylaxis in all patients. The addition of rituximab increases the complete response rate and prolongs event-free and overall survival in elderly patients with such lymphoma. PATIENTS AND METHODS: We analyzed a cohort of 399 elderly patients with lymphoma prospectively treated with eight cycles of CHOP with or without rituximab in order to assess if rituximab decreases the risk of CNS localization. Prophylaxis of CNS disease was not part of the treatment protocol. RESULTS: We observed 20 CNS occurrences: 12 on therapy, four after partial remission and four following complete remission. In three patients, the CNS was the only site of relapse. In a multivariate analysis, increased age-adjusted International Prognostic Index (IPI) was the only independent predictive factor of CNS recurrence. Only three of 20 patients are alive with a follow-up of 24 months. CONCLUSIONS: Rituximab did not influence the risk of CNS occurrence, possibly because of low rituximab diffusion. Direct intrathecal administration of rituximab could overcome this problem. We also confirmed that CNS occurrence is related to IPI as well as very poor prognosis of relapses occurring on therapy.

Marital status and sleep-disordered breathing in a sample of middle-aged French men.

The aim of the present study was to test the hypothesis that unmarried (single) men have more sleep-disordered breathing symptoms due to a higher prevalence of obesity and a less healthy lifestyle than men living with a partner. Men (499) aged 23-66 years completed a structured questionnaire, had standard anthropometric measurements and a simple, noninvasive nose-throat examination. Of the 499,496 subjects answered the question concerning their marital status; 86% of them were married or lived with a partner (reference group) and the other 14% had never been married, divorced, or widowed ("single" group, considered at risk). Single subjects were younger, included slightly more smokers (30 vs. 23%) and more subjects with a history of chronic bronchitis, and less frequently had a large soft palate. The prevalence of sleep-disordered symptoms was not significantly different between the two groups. However, a study involving a larger number of subjects with information regarding alcoholic consumption may be needed to further evaluate this question.

Antithrombotic therapy is associated with better survival in patients with severe heart failure and left ventricular systolic dysfunction (EPICAL study).

BACKGROUND: In patients with congestive heart failure (CHF), clinical trials have demonstrated the benefit of a number of drugs on morbidity and mortality. Nevertheless so far, there is no published controlled study of long-term antithrombotic therapy in patients with CHF. The aim of this work was to identify the relationship between cardiovascular drug use, especially antithrombotic therapy, and survival of CHF patients in current clinical practice, using an observational, population-based database. METHODS: The EPICAL study (Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine) has identified prospectively all patients with severe CHF in the community of Lorraine. Inclusion criteria were age 20-80 years in 1994, at least one hospitalisation for cardiac decompensation, NYHA III/IV HF, ventricular ejection fraction < or =30% or cardiothoracic index > or =60% and arterial hypotension or peripheral and/or pulmonary oedema. A total of 417 consecutive patients surviving at hospital discharge were included in the database. The average follow-up period was 5 years. Univariate Cox models were used to test the relationship of baseline biological and clinical factors to survival. Cardiovascular drug prescriptions were tested in a multivariate Cox model adjusted by other known predictive factors. RESULTS: Duration of disease >1 year, renal failure, serum sodium > or =138 mmol/l, old age, serious comorbidity, previous decompensation, high doses of furosemide and vasodilators use were independently associated with poor prognosis at 1 and 5 years. Oral anticoagulants, aspirin, lipid lowering drugs and beta-blockers use were associated with better survival. There was no interaction between aspirin and angiotensin converting enzyme inhibitor use on survival. CONCLUSION: Antithrombotic therapy was associated with a better long-term survival in our study population of severe CHF. These results together with other previously published circumstantial evidence urge for a prospective, controlled and randomised trial specifically designed to evaluate optimal oral anticoagulants and aspirin in patients with congestive heart failure.

[Use of an amino-acid-based formula in the treatment of cow's milk protein allergy and multiple food allergy syndrome]. / Intérêt d'une formule à base d'acide aminés dans le traitement de l'allergie au protéines du lait de vache et du syndrome des allergies alimentaires multiples.

Food allergy to cow's milk proteins (APLV) is frequently found in young infants. Treatment is by starting an elimination diet. Different substitution products have been proposed: soya milk, partial hydrolysate of the proteins of lactoserum, powdered casein hydrolysate, hydrolysed soya and pork collagen. Allergic reactions to soya milk, hydrolysates of lactoserum proteins, powdered casein hydrolysates and hydrolysates of soya have been described. The study that we present evaluates the effect on the natural development of these allergies of a formula based on amino-acids (Neocate) in 26 patients who presented a syndrome of multiple allergies one of which was a food allergy to milk. Twenty-five of them had a severe atopic dermatitis, isolated (14 cases), or associated with gastro-intestinal troubles (6) break in the growth curve (5), anaphylactic reactions (2), one asthma (1). One child had a chronic diarrhoea associated with a weight plateau. Evaluation 2 or 3 months later showed a significant improvement of the atopic dermatitis. Return of the stature-weight growth was noted in 4 children from 5, the check in one was reported as due to a initially unrecognised allergy to gluten. The recovery of the APLV was shown by double-blind oral provocation test in 20/23 children between 11 and 37 months (22 +/- 9). Duration of administration of Neonate was between 6 to 19 months (12 + 5) months. This study confirmed the beneficial effect of the amino-acid formula on weight gain, gastro-intestinal troubles and development of atopic dermatitis. The level of recovery of APLV of 86% at the age of 2 years is better than that reported in the syndrome of multiple food allergies of 22%. The influence of this diet on the development of other food allergies remains to be evaluated.

Occupational status and sleep-disordered breathing in a sample of French males.

Sleep-disordered breathing (SDB) and lower socio-professional status have in common a series of risk factors for ill health such as sedentary lifestyle, weight excess, heavy alcohol and tobacco consumption. We hypothesised that SDB will be more prevalent in lower socio-professional groups. A total of 496 male middle aged subjects (23-66 years) were tested with a protocol including a self-completed structured sleep questionnaire (translation of the Madison sleep cohort study form), anthropometry (including neck, waist and hip girth) and a simple, non-invasive nose-throat examination by a specialist physician. The subjects were classified according to the 10 major groups of the ISCO-88 classification (International Labour Office). Our sampling base did not contain subjects in the major groups 1 (senior officials, legislators), 6 (fishery and agricultural workers), and zero (armed forces), thus these groups were not represented in the analysis. To improve the power of the statistical analysis, groups 3 and 4, 5 and 7, 8 and 9 were merged, the analysis thus including four categories. The differences in demographic data were negligible; as expected, smoking was more prevalent in low socio-occupational groups (difference non-significant). A history of chronic bronchitis was more frequent in low socio-occupational groups, while a low physical job labour was more frequent in higher occupational groups. We did not find any differences in the prevalence of sleep-related respiratory disturbances (snoring, sleep apnoeas). This first study of the possible association between socio-occupational factors and sleep disordered breathing was negative, but we believe further studies, on larger samples, with a more homogeneous distribution of social groups are warranted.

Prevalence of habitual snoring in a sample of French males. Role of "minor" nose-throat abnormalities.

BACKGROUND: No data on snoring prevalence obtained with a standard questionnaire exist for France. Major nose-throat abnormalities have been demonstrated in cases with obstructive sleep apnea; evidence of "minor" abnormalities in community studies is scarce. OBJECTIVES: The first objective of our study was to estimate the prevalence of habitual snoring in a sample of middle-aged active males in France. The second objective was to test the hypothesis that "minor" nose-throat abnormalities could be associated with habitual snoring in a field survey. METHODS: Three hundred thirty-four male employees of a local university volunteered for the study (93.6% of those contacted by mail); 300 returned a sleep questionnaire. The protocol also included anthropometry and a noninvasive nose-throat examination. RESULTS: Complete data were obtained in 299 subjects aged 23-63 years. When "habitual snorers" (= 32%) were compared with never-snorers, significant differences were found for all anthropometric variables, except height. In univariate analysis, habitual snoring was associated with a large number of variables, including a large soft palate, a large uvula, and altered nose patency. A logistic regression model retained 8 factors independently associated with snoring: age, neck circumference, tobacco consumption, breathing pauses during sleep, not feeling rested during the day, need for coffee to stay awake, blocked or running nose at night and a large soft palate. CONCLUSIONS: The prevalence of habitual snoring in this sample of middle-aged French males was 32%. We confirmed the significant association of habitual snoring with age, weight excess, and tobacco smoking, and identified two further factors: blocked nose at night and a large soft palate.

[Determination by flow cytometry of reference values of erythrocyte parameters in aged subjects]. / Détermination par cytométrie de flux des valeurs de référence de la population érythrocytaire chez le sujet âgé.

OBJECTIVES: Normal values for hemoglobin and hematocrit have been established for healthy young adults, but it is unknown whether age-related decline in hematological values occurs in the elderly. We compared normal values of hematological parameters in healthy adults and healthy persons aged 65 years and over using flow cytometry. SUBJECTS AND METHODS: Erythrocyte and reticulocyte parameters were determined in 585 subjects (294 men and 206 women aged 26 to 64 years, and 37 men and 48 women aged 65 years and over), living independently and without medication, symptom and disease, using Technicon H1 (Bayer) and R2000 (Roche) analyzers. Serum erythropoietin levels, red cell folate and creatinine clearance were determined in subjects aged 65 years and over. RESULTS: Irrespective of subject age, hemoglobin (Hb), hematocrit (Hct), red blood cell count (RBC), mean cell volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were higher in males than in females, but sex-related differences tended to decrease with aging. In males, there was a trend toward lower Hb and Hct with aging, due to an increase in RBC, MCV and MCH. In females, Hb and Hct (p < 0.05) increased with aging, due to a trend toward higher values of RBC, MCV and MCH. Red blood cell distribution width and hemoglobin distribution width were not modified by aging. Despite these age-related changes in erythrocyte parameters, values for anemia defined in adults appear appropriate for geriatric subjects (Hb < 130 g/l in males and Hb < 120 g/l in females). Reticulocyte count and creatinine clearance decreased in men and women aged 65 years and over (p < 0.05), whereas erythropoietin levels and red cell folate were not influenced by aging. CONCLUSION: Normal erythrocyte values defined in adults are appropriate for evaluating hematological test results in older individuals. The decrease in reticulocyte count observed in men and women aged 65 years and over does not appear to be linked to a decrease in erythropoietin production with aging.

Breathing pauses during sleep: can a non-invasive ENT examination help identify subjects at risk in epidemiological settings?

In patients with obstructive sleep apnoea (OSA) anatomic and functional upper airway abnormalities are frequent and severe. Invasive methods are used to identify and quantitate the obstruction, to precisely locate its site, etc. as part of pre-treatment or of preoperative evaluations.These methods (lateral skull radiographs, computerized tomography, MRI, fibroscopies, etc) are too expensive and too invasive to be utilized in field surveys. To the classical sleep questionnaires and anthropometric measurements, some simple nose-throat examinations, easily accepted by the volunteers in a population study, could add useful information for the identification of the subjects at risk for sleep-disordered breathing. The present paper is a review of these examinations and of their utility.

[Management, cost and mortality of a cohort of patients with advanced heart failure (the EPICAL study)]. / Prise en charge et coût de l'insuffisance cardiaque sévère dans l'étude EPICAL en Lorraine.

The objectives of this study are to describe the management, outcomes and costs of patients with severe chronic heart failure (CHF) and to identify the associated socio-demographic and clinical determinants. In 1994, the EPICAL study enrolled in a French region a representative cohort of 358 patients presenting for the first time with severe CHF (NYHA class III or IV) requiring hospitalization. The mean annual cost per patient was 125 652 FF, 92.6 per cent of which was associated with in-patient care including the index hospitalization. Ten per cent of patients contributed 33 per cent of the total cumulative costs. The rate of readmission was very high (20 per cent per month of follow-up) and appeared as a major cost driver. Three variables were identified in a multivariate logistic regression as the main contributors to cost: the presence of co-morbidity, renal insufficiency and marital status (living alone versus with spouse). These findings confirmed the major clinical and economic interest of any intervention that could lower the rate of readmissions in this group of patients.

Effect on osteoarthritis of spa therapy at Bourbonne-les-Bains.

OBJECTIVES: Several studies suggest a beneficial overall effect of spa therapy in chronic musculoskeletal diseases. The present open controlled study investigated the effects of spa therapy at Bourbonne-Les-Bains, France, in patients with hip or knee osteoarthritis or low back pain. PATIENTS AND METHODS: In 1998, 102 men and women older than 50 years were included in the study. All had low back pain or lower limb osteoarthritis, and none had contraindications to spa therapy. Quality of life was assessed three times at intervals of 4 weeks, twice before and once immediately after 3 weeks of spa therapy, using the Duke Health Profile (five dimensions and five dysfunctions). RESULTS: Mean age was 66.4 years, and 67% of the patients were women. Quality of life was markedly decreased as compared to the population at large (1996, CFES). The two pretreatment evaluations produced similar quality-of-life scores. Spa therapy was associated with significant improvements in overall quality of life (P=0.004), self-esteem (P=0.009), and pain (P=0.01). CONCLUSION: These findings support those of other studies conducted in France and in other European countries. They indicate that patients report meaningful improvements in their quality of life after spa therapy.

[Use of standard for quantitation of adhesion of polynuclear neutrophils by flow cytometry]. / Utilisation d'un calibrateur pour quantifier les récepteurs d'adhérence du polynucléaire neutrophile par cytométrie en flux.

Adherence receptors are essential for heterotypic (endothelial cell, platelet) polymorphonuclear neutrophil (PMN) interaction. Determination of their expression level give information about activation state and functionality of PMN. Use of flow cytometry associated with an immunolabeling standard, represented by beads coated by a determined amount of immunoglobulins (Qifikit, Dako), allows analysis of specific antibody binding capacity and gives information about antigen density. Using this methodology, the exploration of surface adherence receptors, L-selectin (CD62L) and b2-integrins (CD11a-c/CD18) from PMN unstimulated and incubated with pro-inflammatory stimuli, formyl-methionyl-leucyl-phenylalanine (fMLP) and tumor necrosis factor a (TNFa), allows, on the one hand, the establishment of basal expression values on resting PNN and on the other hand, the study of PNN reactivity. This method of quantification can be applied to clinical studies as adherence receptor deficiency syndromes or inflammatory, infectious and vascular diseases.

Determinants of angiotensin-converting enzyme inhibitor prescription in severe heart failure with left ventricular systolic dysfunction: the EPICAL study.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been demonstrated to reduce morbidity and mortality rates in patients with heart failure with left ventricular systolic dysfunction. Nevertheless, these drugs are underutilized in current practice and prescribed at doses below those usually recommended. The aim of this work was to identify the social, demographic, laboratory, clinical, and therapeutic factors associated with nonprescription of ACE inhibitors and/or their prescription at doses below those recommended in the treatment of severe long-term congestive heart failure (CHF). METHODS AND RESULTS: An epidemiologic observational study, EPICAL (EPidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine), studied 417 patients with severe CHF surviving after the index hospitalization. Multivariate logistic regression determined the factors associated with ACE inhibitor nonprescription and with their prescription at lower-than-recommended doses. ACE inhibitors were taken by 75% of the patients but 38% took lower-than-recommended doses. Factors shown to be associated with nonprescription included patients >65 years of age with renal impairment (odds ratio 19.5, confidence interval [CI] 7.9-48.0), nonsinus cardiac rhythm (odds ratio 2.0, CI 1.2-3.2), and prescription of potassium-sparing diuretics (odds ratio 2.4, CI 1. 2-4.7). Renal impairment was the single most important factor associated with prescription of lower-than-recommended doses, particularly in elderly patients. CONCLUSIONS: Our results underline the need for optimal and better use of ACE inhibitor therapy. CHF treatment guidelines must be more uniformly applied by all physicians caring for patients with heart failure.

Bias and precision in visual analogue scales: a randomized controlled trial.

Various types of visual analogue scales (VAS) are used in epidemiologic and clinical research. This paper reports on a randomized controlled trial to investigate the effects of variations in the orientation and type of scale on bias and precision in cross-sectional and longitudinal analyses. This trial was included in the pilot study of the SU.VI.MAX (supplementation by antioxidant vitamins and minerals) prevention trial in France in 1994. Six types of VAS (simple, middle-marked, graphic rating, graduated, graduated-numbered, and numerical rating) and two orientations (horizontal and vertical) were used to measure three symptoms of ear, nose, and throat infection at 2-month intervals in 870 subjects. Differences between scales were analyzed by comparing variances (Levene's test) and means (variance-covariance analysis for repeated measures). Scale characteristics were shown to influence the proportion of zero and low values (i.e., there was a floor effect), but not mean scores. The precision of measurements varied cross-sectionally according to the type of scale, but no differences were observed in the precision of measurement of change over time. In conclusion, the characteristics of VAS seem to be important in cross-sectional studies, particularly when symptoms of low or high intensity are being measured. Researchers should try to reach a consensus on what type of VAS to use if studies are to be compared.

Effects of medical therapy on outcome assessment using exercise thallium-201 single photon emission computed tomography imaging: evidence of a protective effect of beta-blocking antianginal medications.

OBJECTIVES: The purpose of this study was to determine whether antianginal medications modify the prognostic significance of exercise single photon emission computed tomography (SPECT) ischemia. BACKGROUND: Antianginal medications (especially beta-adrenergic blocking agents) limit exercise SPECT ischemia, but it is not known whether such medications also modify the prognostic effect of exercise SPECT ischemia. METHODS: We included 352 patients with coronary heart disease, who had exercise Tl-201 SPECT and coronary angiography, and who were initially treated medically. Survival Cox models were applied in patients for whom classes of antianginal medications taken at exercise SPECT were the same as those prescribed for follow-up (GI; n = 136), and in patients for whom new classes of antianginal medications, including beta-blockers (GII; n = 79) or not including beta-blockers (GIII; n = 113), were added for follow-up. RESULTS: During a mean 5.3+/-1.6 years of follow-up, 45 patients had cardiac death or myocardial infarction. Variables reflecting necrosis (irreversible defect extent, left ventricular ejection fraction) and those from coronary angiography provided equivalent prognostic information in the three groups. In contrast, the SPECT variable reflecting ischemia (reversible defect extent), which provided comparable prognostic information in GI (p = 0.005) and GIII (p = 0.004), lost its prognostic significance (p = 0.54) in GII, and was associated with a lower relative risk in GII than in GI or GIII (both p < 0.05). CONCLUSIONS: In patients with coronary heart disease, the introduction of antianginal medications, when including beta-blockers, appears to have a favorable effect on the deleterious prognostic effect of exercise ischemia.

Incidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL Study. Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine.

OBJECTIVES: Characterize the incidence, clinical and etiologic features and outcomes of advanced congestive heart failure. BACKGROUND: This condition is frequent, severe and costly, yet no population-based epidemiological data are available that take into account modern advances in diagnosis and therapy. METHODS: The EPICAL (Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine) study was based on a comprehensive registration of patients with ACHF (defined as hospital admission for presence of NYHA class III or IV symptoms, radiological and/or clinical signs of pulmonary congestion and/or signs of peripheral edema, left ventricular ejection fraction <30% or a cardiothoracic ratio >60%) in patients aged 20-80 years during year 1994, in the community of the Lorraine region in France (n = 1,592,263). Average follow-up for readmission to hospital and mortality was 18 months (12-24 months). RESULTS: From 2,576 registered patients, 499 were enrolled into the study among which, 358 were new presentations. This represents a crude incidence rate of 225 per million. 46.3% had a coronary heart disease. One-year mortality rate was 35.4% and the rate of mortality and/or readmission to hospital was 81%. Patients were admitted to hospital 2.05 times per year (64% of these for worsening heart failure), spending 27.6 days per year in hospital. Twenty received a heart transplant (4%). On discharge, 74.8% were using ACE inhibitors and 49.6% digitalis. CONCLUSIONS: Mortality and hospitalization rate of advanced CHF remain very high despite recent therapeutic progress. Major therapeutic and managed-care research is required.

Prevention of EBV-induced B-lymphoproliferative disorder by ex vivo marrow B-cell depletion in HLA-phenoidentical or non-identical T-depleted bone marrow transplantation.

HLA-mismatched bone marrow transplantation (BMT) is hampered by three major complications: graft rejection, acute graft-versus-host disease (aGVHD) and delayed immune reconstitution. Infusion of anti-LFA1 plus anti-CD2 monoclonal antibodies (MAb), combined with ex-vivo T-cell depletion of the graft, was efficient in preventing graft rejection and aGVHD. Nevertheless, disease-free survival was limited by the high frequency of lethal infections, including EBV-induced lymphoproliferative disease (BLPD), which originates mostly from donor B cells, with an incidence of 5-30%. To decrease the rate of this complication, ex-vivo B-cell depletion was attempted. This study compares a group of 19 patients who received a T- and B-cell-depleted marrow from an HLA-mismatched related donor with a retrospective control group of 19 patients, who had received T-cell-depleted marrow by the same method. The level of T-cell depletion was similar in the two groups. For B-cell depletion, two different methods were compared. The median number of B cells infused in the study group was 0.46/kg. Engraftment and aGVHD incidence were similar in the two groups. No EBV donor-derived BPLD occurred in the study group, compared with seven in the control group, four of whom died because of EBV-BPLD. Event-free survival was significantly different between the two groups. We conclude that ex-vivo B-cell depletion of the graft may be a useful means of preventing EBV-BPLD, and warrants further study on a larger group of patients.

[Respiratory evolution of patient with mucoviscidosis treated with mucolytic agents plus dornase alfa]. / Evolution respiratoire de patients atteints de mucoviscidose traités par mucofluidifiants puis par dornase alfa.

AIM: Modifications of bronchial secretions in cystic fibrosis patients account for the long-lasting use of mucolytic agents, despite the lack of adequately controlled clinical studies supporting this approach. Hyperviscosity of bronchial secretions mainly depend on their high DNA content, as a result of degradation of polymorphonuclear neutrophils mobilized by infection and inflammation. This phenomenon has led to the treatment of respiratory complications with human recombinant deoxyribonuclease (dornase alfa). In the present study, we compared the clinical and respiratory outcome in patients receiving mucolytic agents followed by dornase alfa, each for 1 year. POPULATION AND METHODS: Fifty-four patients, aged 5 years or more, have been prospectively followed for 2 years. They received first a 12-month association of mesna (two nebulisations per day) and oral ambroxol (60 mg per day, divided in two doses), followed by a 12-month treatment with one daily aerosol of dornase alfa only (2.5 mg per day). The primary end-points were the results of pulmonary function tests. Secondary end-points were subjective symptoms, bacterial colonization, consumption of antibiotics, and clinical tolerance. RESULTS: At the end of the 12-month mucolytic therapy, a significant decrease of forced expiratory volume/second (FEV1, -10.5% as compared to baseline values) and forced vital capacity (FVC, -12.8%) was observed. At the end of 12-month dornase alfa, FEV1 and FVC had increased by 7.7 and 5.3%, respectively. This change was statistically significant only for FEV1 in most severely disabled patients. However, forced expiratory flow 25-75% (FEF 25-75) decreased during the 2 year period of observation, by 5.6% the first year and 4.9% the second year. The mean number of days with parenteral antibiotics did not statistically differ between both treatments, except for patients more than 15 years of age. In this subgroup, the mean number decreased from 40 days in the first year to 27 in the second year (P < 0.05). Acceptability of treatment by the patients themselves was better with dornase alfa than with mucolytic therapy. However, several episodes of hemoptysis, frequent in only one case, were associated with the treatment by dornase alfa. CONCLUSION: Dornase alfa was associated with a stabilisation, and even a trend to improvement in pulmonary function tests. This stabilisation is by itself a very encouraging result. Long-term comparative studies are needed to evaluate the benefits of dornase alfa in the treatment of respiratory complications of cystic fibrosis and specify the optimal modalities of its use. Synergistic combinations with mucolytic therapy and/or anti-inflammatory drugs could be viewed as a future prospect.