Prostate irradiation with focal dose escalation to the intraprostatic dominant nodule: a systematic review.

Radiation therapy (RT) is a curative treatment option for localized prostate cancer. Prostate irradiation with focal dose escalation to the intraprostatic dominant nodule (IDN) is an emerging treatment option that involves the prophylactic irradiation of the whole prostate while increasing RT doses to the visible prostatic tumor. Because of the lack of large multicentre trials, a systematic review was performed in an attempt to get an overview on the feasibility and efficacy of focal dose escalation to the IDN. A bibliographic search for articles in English, which were listed in MEDLINE from 2000 to 2016 to identify publications on RT with focal directed boost to the IDN, was performed. The review was completed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-two articles describing 1,378 patients treated with RT using focal boost were identified and fulfilled the selection criteria. Intensity-modulated radiation therapy (IMRT) was used in 720 patients (52.3%), volumetric modulated arc therapy was used in 45 patients (3.3%), stereotactic body radiation therapy (SBRT) in 113 patients (8.2%), and low-dose rate and high-dose rate brachytherapy (BT) were used in 305 patients (22.1%) and 195 patients (14.1%), respectively. Use of androgen deprivation therapy varied substantially among series. Biochemical disease-free survival at 5 years was reported for a cohort of 812 (58.9%) patients. The combined median biochemical disease-free survival for this group of patients was 85% (range: 78.8-100%; 95% confidence interval: 77.1-82.7%). The average occurrence of grade III or worse gastrointestinal and genitourinary late toxicity was, respectively, 2.5% and 3.1% for intensity-modulated RT boost, 10% and 6% for stereotactic body RT, 6% and 2% for low-dose rate BT, and 4% and 4.3% for high-dose rate BT. This review shows encouraging results for focal dose escalation to the IDN with acceptable short- to medium-term side effects and biochemical disease control rates. However, owing to the heterogeneity of patient population and the short follow-up, the results should be interpreted with caution. Considering that the clinical endpoint in the studies was biochemical recurrence, the use and duration of androgen deprivation therapy administration should be carefully considered before driving definitive conclusions. Randomized trials with long-term follow-up are needed before this technique can be generally recommended

Cyclosporin A treatment in severe childhood psoriasis

Though used occasionally, systemic therapies in severe childhood psoriasis have not been systematically investigated. Cyclosporin A (CysA) is effective in adults with severe psoriasis but there are no extensive data regarding the efficacy and safety of its use in childhood psoriasis. In this paper, we describe six children aged between 11 months and 13 years (average: 7.6 years) treated with CysA microemulsion formulation for severe psoriasis, who had been unresponsive to other treatments. The CysA dose ranged from 2 to 4 mg/kg/day, for periods varying from 8 to 105 weeks (mean: 54 weeks). Dose tapering was gradual after lesion improvement and adjusted according to clinical response. Adjuvant therapy with topical steroids, vitamin D3 ointments, coal tar preparations or anthralin was used in all children. Acitretin was used in three patients for short periods. The children were regularly monitored for serum renal and liver function and blood pressure. Improvement of skin lesions was achieved after between 4 and 30 (mean: 12) weeks of treatment, with complete remission in three children. Relapse of lesions occurred in the other children during CysA reduction, but they responded to a dose increase. The treatment was found to be well tolerated and with no significant side-effects. CysA can be used in carefully selected and monitored patients and may represent an alternative tool for severe episodes of psoriasis in children, when other therapies are unsuccessful

Recommendations for ICT use in Alzheimer's Disease assessment: Monaco CTAD expert meeting

International audienceAlzheimer disease (AD) and other related dementia represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments for assessing disease severity and disease progression to optimize patient's care and support to care provide rs, and also provide better tools for clinical research. In this area, Information and Communication Technologies (ICT) are of particular interest. Such techniques enable accurate and standardized assessments of patients' performance and actions in real time and real life situations. The aim of this article is to provide basic recommendation concerning the development and the use of ICT for Alzheimer's disease and related disorders. During he ICT and Mental Health workshop (CTAD meeting held in Monaco on the 30th October 2012) an expert panel was set up to prepare the first recommendations for the use of ICT in dementia research. The expert panel included geriatrician, epidemiologist, neurologist, psychiatrist, psychologist, ICT engineers, representatives from the industry and patient association. The recommendations are divided into three sections corresponding to 1/ the clinical targets of interest for the use of ICT, 2/ the cond itions, the type of sensors and the outputs (scores) that could be used and obtained, 3/ finally the last section concerns specifically the use of ICT within clinical trials

Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial

BackgroundType 1 diabetes results from T-cell-mediated destruction of β cells. Findings from preclinical studies and pilot clinical trials suggest that antithymocyte globulin (ATG) might be effective for reducing this autoimmune response. We assessed the safety and efficacy of rabbit ATG in preserving islet function in participants with recent-onset type 1 diabetes, and report here our 12-month results.MethodsFor this phase 2, randomised, placebo-controlled, clinical trial, we enrolled patients with recent-onset type 1 diabetes, aged 12-35 years, and with a peak C-peptide of 0.4 nM or greater on mixed meal tolerance test from 11 sites in the USA. We used a computer generated randomisation sequence to randomly assign patients (2:1, with permuted-blocks of size three or six and stratified by study site) to receive either 6.5 mg/kg ATG or placebo over a course of four days. All participants were masked and initially managed by an unmasked drug management team, which managed all aspects of the study until month 3. Thereafter, to maintain masking for diabetes management throughout the remainder of the study, participants received diabetes management from an independent, masked study physician and nurse educator. The primary endpoint was the baseline-adjusted change in 2-h area under the curve C-peptide response to mixed meal tolerance test from baseline to 12 months. Analyses were by intention to treat. This is a planned interim analysis of an on-going trial that will run for 24 months of follow-up. This study is registered with ClinicalTrials.gov, number NCT00515099.FindingsBetween Sept 10, 2007, and June 1, 2011, we screened 154 individuals, randomly allocating 38 to ATG and 20 to placebo. We recorded no between-group difference in the primary endpoint: participants in the ATG group had a mean change in C-peptide area under the curve of -0.195 pmol/mL (95% CI -0.292 to -0.098) and those in the placebo group had a mean change of -0.239 pmol/mL (-0.361 to -0.118) in the placebo group (p=0.591). All except one participant in the ATG group had both cytokine release syndrome and serum sickness, which was associated with a transient rise in interleukin-6 and acute-phase proteins. Acute T cell depletion occurred in the ATG group, with slow reconstitution over 12 months. However, effector memory T cells were not depleted, and the ratio of regulatory to effector memory T cells declined in the first 6 months and stabilised thereafter. ATG-treated patients had 159 grade 3-4 adverse events, many associated with T-cell depletion, compared with 13 in the placebo group, but we detected no between-group difference in incidence of infectious diseases.InterpretationOur findings suggest that a brief course of ATG does not result in preservation of β-cell function 12 months later in patients with new-onset type 1 diabetes. Generalised T-cell depletion in the absence of specific depletion of effector memory T cells and preservation of regulatory T cells seems to be an ineffective treatment for type 1 diabetes

Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients

BACKGROUND. Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining β cells in patients with newly diagnosed T1D

Mortalité par accidents de la vie courante à l île de la Réunion de 2000 à 2004

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF