Training in flexible intensive insulin therapy improves quality of life, decreases the risk of hypoglycaemia and ameliorates poor metabolic control in patients with type 1 diabetes.

AIM: Intensified insulin therapy has evolved to be the standard treatment of type 1 diabetes. However, it has been reported to increase significantly the risk of hypoglycaemia. We studied the effect of structured group teaching courses in flexible insulin therapy (FIT) on psychological and metabolic parameters in patients with type 1 diabetes. METHODS: We prospectively followed 45 type 1 diabetic patients of our outpatient clinic participating in 5 consecutive FIT teaching courses at the University Hospital of Basel. These courses consist of 7 weekly ambulatory evening group sessions. Patients were studied before and 1, 6, and 18 months after the course. Main outcome measures were glycated haemoglobin (HbA1c), severe hypoglycaemic events, quality of life (DQoL), diabetes self-control (IPC-9) and diabetes knowledge (DWT). RESULTS: Quality of life, self-control and diabetes knowledge improved after the FIT courses (all p<0.001). The frequency of severe hypoglycaemic events decreased ten-fold from 0.33 episodes/6 months at baseline to 0.03 episodes/6 months after 18 months (p<0.05). Baseline HbA1c was 7.2+/-1.1% and decreased in the subgroup with HbA1c > or = 8% from 8.4% to 7.8% (p<0.05). CONCLUSIONS: In an unselected, but relatively well-controlled population of type 1 diabetes, a structured, but not very time consuming FIT teaching programme in the outpatient setting improves psychological well-being and metabolic parameters.

Epigenetic deregulation of DNA repair and its potential for therapy.

Epigenetic silencing of essential components of DNA repair pathways is a common event in many tumor types, and comprise O6-methylguanine-DNA methyltransferase (MGMT), human mut L homolog 1 (hMLH1), Werner syndrome gene (WRN), breast cancer susceptibility gene 1 (BRCA1), and genes of the Fanconi anemia pathway. Most interestingly, some of these alterations become the Achilles heel of the affected tumors upon treatment with certain classes of anticancer agents. That is, patients whose tumors carry such defects can be stratified for respective therapy rendering some classic DNA damaging agents, such as alkylators or DNA crosslinking agents, into "targeted therapies." Here we review some of the affected repair pathways that, when inactivated, sensitize the tumors to specific drugs and are thus exploitable for individualized therapy.

Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells.

Engineering of fetal tissue has a high potential for the treatment of acute and chronic wounds of the skin in humans as these cells have high expansion capacity under simple culture conditions and one organ donation can produce Master Cell Banks which can fabricate over 900 million biological bandages (9 x 12cm). In a Phase 1 clinical safety study, cases are presented for the treatment of therapy resistant leg ulcers. All eight patients, representing 13 ulcers, tolerated multiple treatments with fetal biological bandages showing no negative secondary effects and repair processes similar to that seen in 3rd degree burns. Differential gene profiling using Affymetrix gene chips (analyzing 12,500 genes) were accomplished on these banked fetal dermal skin cells compared to banked dermal skin cells of an aged donor in order to point to potential indicators of wound healing. Families of genes involved in cell adhesion and extracellular matrix, cell cycle, cellular signaling, development and immune response show significant differences in regulation between banked fetal and those from banked old skin cells: with approximately 47.0% of genes over-expressed in fetal fibroblasts. It is perhaps these differences which contribute to efficient tissue repair seen in the clinic with fetal cell therapy.

LAPATAX: A randomized phase II trial of FEC-docetaxel combined with lapatinib and/or trastuzumab as neoadjuvant therapy of HER2- positive breast cancer-EORTC 10054 trial.

Background: Patients with HER2 +ve breast cancer suitable for neoadjuvant chemotherapy (NAC) have been shown in a series of clinical trials to have the best outcome when treated with anthracyclines (A), taxanes (T), and trastuzumab (Tz). Recent evidence confirms that adjuvant Tz is more effective when given concomitantly rather than sequentially with T (Perez SABCS 2009). Whilst there remains uncertainty as to the most efficacious A-T regimen and duration of Tz, there is widespread use in Europe of FEC-D [3 cycles of 5-FU 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 (FEC100) followed by 3 cycles of docetaxel 100 mg/m2 (D) q3w] following the results of PACS-01. The advent of TKI anti-HER2 agents such as L could offer superior outcomes if combined with NAC. However, a phase I study in heavily pre-treated advanced breast cancer reported difficulties in combining lapatinib (L) with D 100 mg/m2 (LoRusso JCO 2008). Methods: EORTC 10054 is designed as a two-part study to compare FEC-D with either Tz, L or their combination as NAC for patients with HER2 +ve large operable or locally advanced breast cancer. Before and on-treatment frozen tumor and blood samples will be taken to better define which tumours are particularly sensitive to either Tz and/or L. Stage 1: (complete) a dose- finding study has confirmed that with primary prophylactic G-CSF, D 100 mg/m2 can be safely and effectively given with L 1,250 mg daily continuously. The dose-limiting toxicity was myelosuppression, and there was no significant diarrhoea or cardiac toxicity (ESMO 2009 abstr P- 5073). Stage 2: (opening Q1 2010) will enroll 150 patients from European centres into a 3-arm randomized trial whose primary endpoint is pathological complete response. All patients will receive FEC-D before primary surgery: 3 cycles of FEC (without anti-HER2 therapy) followed by 3 cycles of D plus either Tz (conventional weekly schedule), monotherapy L, or the combination of Tz and L, using doses based on the EGF100161 dose-finding study in 1st line metastatic therapy of D+L+Tz. After surgery all patients will receive standard 3-weekly Tz, radiotherapy and endocrine therapy as per local guidelines.

Antibiothérapie empirique lors de neutropénie fébrile [Empirical antibiotic therapy for febrile neutropenia]

Immediate broad-spectrum empirical antibacterial therapy is the key of management in febrile neutropenic patients. These patients can be stratified according to the risk of complications with the clinical MASCC score. Patients at low risk of complications can be efficaciously treated with oral antibiotics (e.g. fluoroquinolone and beta-lactam), provided that compliance and drug absorption are adequate. Early discharge is possible if clinical, logistic, and social criteria are fulfilled. Intravenous antibiotic therapy with broad-spectrum beta-lactam antibiotics in the hospital remains the standard in high-risk patients. The empirical addition of an aminoglycoside and/or a glycopeptide is recommended if the local incidence of infections due to beta-lactam resistant pathogens is high or in critically ill septic patients.

Major bleeding risk in anticoagulated patients receiving concomitant antiplatelet therapy: A prospective study.

INTRODUCTION: Current literature suggesting a higher bleeding risk during combination therapy compared to oral anticoagulation alone is primarily based on retrospective studies or specific populations. We aimed to prospectively evaluate whether unselected medical patients on oral anticoagulation have an increased risk of bleeding when on concomitant antiplatelet therapy. MATERIAL AND METHODS: We prospectively studied consecutive adult medical patients who were discharged on oral anticoagulants between 01/2008 and 03/2009 from a Swiss university hospital. The primary outcome was the time to a first major bleed on oral anticoagulation within 12months, adjusted for age, international normalized ratio target, number of medications, and history of myocardial infarction and major bleeding. RESULTS: Among the 515 included anticoagulated patients, the incidence rate of a first major bleed was 8.2 per 100 patient-years. Overall, 161 patients (31.3%) were on both anticoagulant and antiplatelet therapy, and these patients had a similar incidence rate of major bleeding compared to patients on oral anticoagulation alone (7.6 vs. 8.4 per 100 patient-years, P=0.81). In a multivariate analysis, the association of concomitant antiplatelet therapy with the risk of major bleeding was not statistically significant (hazard ratio 0.89, 95% confidence interval, 0.37-2.10). CONCLUSIONS: The risk of bleeding in patients receiving oral anticoagulants combined with antiplatelet therapy was similar to patients receiving oral anticoagulants alone, suggesting that the incremental bleeding risk of combination therapy might not be clinically significant.

Therapist interventions using the Psychodynamic Interventions Rating Scale (PIRS) in dynamic therapy, psychoanalysis and CBT.

Abstract One requirement for psychotherapy research is an accurate assessment of therapeutic interventions across studies. This study compared frequency and depth of therapist interventions from a dynamic perspective across four studies, conducted in four countries, including three treatment arms of psychodynamic psychotherapy, and one each of psychoanalysis and CBT. All studies used the Psychodynamic Intervention Rating Scales (PIRS) to identify 10 interventions from transcribed whole sessions early and later in treatment. The PIRS adequately categorized all interventions, except in CBT (only 91-93% categorized). As hypothesized, interpretations were present in all dynamic therapies and relatively absent in CBT. Proportions of interpretations increased over time. Defense interpretations were more common than transference interpretations, which were most prevalent in psychoanalysis. Depth of interpretations also increased over time. These data can serve as norms for measuring where on the supportive-interpretive continuum a dynamic treatment lies, as well as identify potentially mutative interventions for further process and outcome study.

Mirror therapy in children with hemiplegia: a pilot study.

Mirror therapy, which provides the visual illusion of a functional paretic limb by using the mirror reflection of the non-paretic arm, is used in the rehabilitation of hemiparesis after stroke in adults. We tested the effectiveness and feasibility of mirror therapy in children with hemiplegia by performing a pilot crossover study in ten participants (aged 6-14 y; five males, five females; Manual Ability Classification System levels: one at level I, two at level II, four at level III, three at level IV) randomly assigned to 15 minutes of daily bimanual training with and without a mirror for 3 weeks. Assessments of maximal grasp and pinch strengths, and upper limb function measured by the Shriner's Hospital Upper Extremity Evaluation were performed at weeks 0 (baseline), 3, 6 (intervention), and 9 (wash-out). Testing of grasp strength behind the mirror improved performance by 15% (p=0.004). Training with the mirror significantly improved grasp strength (with mirror +20.4%, p=0.033; without +5.9%, p>0.1) and upper limb dynamic position (with mirror +4.6%, p=0.044; without +1.2%, p>0.1), while training without a mirror significantly improved pinch strength (with mirror +6.9%, p>0.1; without +21.9%, p=0.026). This preliminary study demonstrates the feasibility of mirror therapy in children with hemiplegia and that it may improve strength and dynamic function of the paretic arm.