Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients

Fludarabine plus cytarabine (Ara-C) and idarubicin (FLAI) is an effective and well-tolerated induction regimen for the treatment of acute myeloid leukaemia (AML). This phase III trial compared the efficacy and toxicity of FLAI versus idarubicin plus Ara-C and etoposide (ICE) in 112 newly diagnosed AML patients <60 years. Fifty-seven patients received FLAI, as the first induction-remission course, and 55 patients received ICE. Post-induction treatment consisted of high-dose Ara-C (HDAC). After HDAC, patients in complete remission (CR) received a second consolidation course (mitoxantrone, etoposide, Ara-C) and autologous stem cell transplantation (auto-SCT) or allogeneic (allo)-SCT, according to the age, disease risk and donor availability. After a single induction course, CR rate was 74% in the FLAI arm and 51% in the ICE arm (P = 0.01), while death during induction was 2% and 9% respectively. Both haematological (P = 0.002) and non-haematological (P = 0.0001) toxicities, especially gastrointestinal (i.e. nausea, vomiting, mucositis and diarrhoea), were significantly lower in FLAI arm. In both arms, relapses were more frequent in patients who were not submitted to allo-SCT. After a median follow-up of 17 months, 30% and 38% of the patients are in continuous CR in FLAI and ICE arm respectively. Our prospective randomised study confirmed the anti-leukaemic effect and the low toxic profile of FLAI as induction treatment for newly diagnosed AML patients.     

Growth-related oncogene alpha induction of apoptosis in osteoarthritis chondrocytes

OBJECTIVE: To evaluate the apoptotic effect of the chemokine growth-related oncogene alpha (GROalpha), which we recently reported to be up-regulated in osteoarthritis (OA) chondrocytes. Chondrocyte apoptosis is considered to be a major determinant of cartilage damage in OA, a disease resulting from the aberrant production of inflammatory mediators (cytokines and chemokines) and effectors (matrix metalloproteinases and reactive oxygen and nitrogen species) by chondrocytes. METHODS: We investigated the apoptotic effect of GROalpha on isolated human cells and on in vitro-cultured cartilage explants by conventional methods (morphology, detection of DNA fragmentation in situ and in solution, exposure of phosphatidylserine) and by analysis of "early" biochemical events (plasma membrane depolarization, activation of caspase 3, and phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase). RESULTS: We clearly demonstrated that GROalpha was able to initiate a series of morphologic, biochemical, and molecular changes that led to chondrocyte apoptosis. Moreover, we found that additional signals delivered from the extracellular matrix (ECM) were essential in the control of chondrocyte susceptibility to GROalpha-induced apoptosis, since cell death was detected only when cells were stimulated after reestablishment of their proper interactions with the ECM, or in cartilage explant samples with reduced ECM, as indicated by decreased Safranin O staining. CONCLUSION: GROalpha can induce apoptosis in articular chondrocytes, and the induction is dependent upon additional signals from the ECM. These findings are relevant to understanding the pathogenesis of OA, in view of the availability of the GROalpha chemokine in the joint space in the course of this rheumatic disease.     

Prediction of Falls in Subjects Suffering From Parkinson Disease,Multiple Sclerosis,and Stroke

Objective

To compare the risk of falls and fall predictors in patients with Parkinson disease (PD), multiple sclerosis (MS), and stroke using the same study design.

What do people appreciate in physicians' communication? An international study with focus groups using videotaped medical consultations

Background

The literature shows that the quality of communication is usually determined from a professional perspective. Patients or lay people are seldom involved in the development of quality indicators or communication.

Objective

To give voice to the lay people perspective on what constitutes ‘good communication’ by evoking their reactions to variations in physician communication.

Design

Lay people from four different countries watched the same videotaped standardized medical encounters and discussed their preferences in gender‐specific focus groups who were balanced in age groups.

Setting and participants

Two hundred and fifty‐nine lay people (64 NL, 72 IT, 75 UK and 48 BE) distributed over 35 focus groups of 6–8 persons each.

Main variables studied

Comments on doctors'' behaviours were classified by the GULiVer framework in terms of contents and preferences.

Results

Participants prevalently discussed ‘task‐oriented expressions’ (39%: competency, self‐confident, providing solutions), ‘affective oriented/emotional expressions'' (25%: empathy, listening, reassuring) and ‘process‐oriented expressions'' (23%: flexibility, summarizing, verifying). ‘Showing an affective attitude’ was most appreciated (positive percentage within category: 93%, particularly facilitations and inviting attitude), followed by ‘providing solution’ (85%). Among disfavoured behaviour, repetitions (88%), ‘writing and reading’ (54%) and asking permission (42%) were found.

Conclusions

Although an affective attitude is appreciated by nearly everybody, people may vary widely in their communication needs and preferences: what is ‘good communication’ for one person may be disliked or even a source of irritation for another. A physician should be flexible and capable of adapting the consultation to the different needs of different patients. This challenges the idea of general communication guidelines.