New cutaneous toxicities with generic docetaxel: are the excipients guilty?

PURPOSE: Docetaxel is one of the most widely used anticancer drugs and an ideal candidate for the development of generic formulations to reduce the economic cost. However, the use of generic drugs is an issue of debate because studies of their safety and efficacy in comparison with the original drug are not required for approval. The aim of this study is to determine whether the change in the formulation of the original drug is responsible for the toxicity changes observed. METHODS: A retrospective study contrasts the incidence of acute infusion reactions and skin reactions to four different presentations of docetaxel including the original drug. These drugs differ in the amounts of excipients. RESULTS: 1.031 doses of docetaxel were administered to 268 patients. A total of 26 grade 3/4 infusion reactions were detected. Compared to the original formulation, the relative risk of acute infusion reaction was 3.74 (1.52-9.18, p = 0.002), 0.57 (0.19-1.64, p = 0.288) and 0.37 (0.1-1.34, p = 0.117) for the patients treated with drugs 2, 3 and 4. For the dermal toxicity, 9 % of patients suffered a clinically significant skin reaction. The relative risks of clinically significant dermal toxicity for the different formulations of docetaxel versus the original formulation were as follows: 6.15 (2.78-13.58) and 7.13 (3.24-15.69) for drugs 3 and 4 (p < 0.001). CONCLUSIONS: Our study suggests that some toxic effects of docetaxel may be related to the excipients used in different formulations of the drug.

Study of two MTA cements

To determine and compare the pH, conductivity and calcium release of an experimental Portland cement (PE) consisting of trioxid mineral aggregate and a comercially available modified Portland cement (C.P.M.) after 1, 2, 3, 4, 8, 10, 15 and 30 days. Material and Methods- Cements were mixed following the manufacturer’s instructions, with a powder- liquid ratio of 3-1. Each cement was placed in 12 PVC tubes 1 mm in diameter and 10 mm in length and allowed to set. Four empty tubes were used as negative controls. Tubes were submerged in plastic flasks containing 10 ml deionized water and stored at 37ºC and 100% humidity. After 1, 2, 3, 4, 8, 10, 15 and 30 days tubes were removed from the flasks and these were refilled with deionized water. We measured pH, conductivity and calcium content of the recovered solution. Data were analyzed using repeated measures ANOVA. Results: pH was 0.3 units more alkaline with PE cement (p=0.023). pH experienced a slight decrease with time (p<0.001), independently of the cement type (p>0.05). Conductivity of PE and CPM cements diminished at 4 days and almost recovered at 30 days (p<0.001). PE cement had a higher conductivity (p<0.001). Calcium release diminished from the first day and recovered at 30 days (p<0.001) similarly for both cements (p>0.05). Conclusions: PE cement raised pH slightly more and had higher conductivity than CPM. Calcium release diminished after the first day and recovered at 30 days, similarly for both cements

Study of two MTA cements.

INTRODUCTION: To determine and compare the pH, conductivity and calcium release of an experimental Portland cement (PE) consisting of trioxid mineral aggregate and a comercially available modified Portland cement (C.P.M.) after 1, 2, 3, 4, 8, 10, 15 and 30 days. MATERIAL AND METHODS: Cements were mixed following the manufacturer's instructions, with a powder: liquid ratio of 3:1. Each cement was placed in 12 PVC tubes 1 mm in diameter and 10 mm in length and allowed to set. Four empty tubes were used as negative controls. Tubes were submerged in plastic flasks containing 10 ml deionized water and stored at 37 C and 100% humidity. After 1, 2, 3, 4, 8, 10, 15 and 30 days tubes were removed from the flasks and these were refilled with deionized water. We measured pH, conductivity and calcium content of the recovered solution. Data were analyzed using repeated measures ANOVA. RESULTS: pH was 0.3 units more alkaline with PE cement (p=0.023). pH experienced a slight decrease with time (p<0.001), independently of the cement type (p>0.05). Conductivity of PE and CPM cements diminished at 4 days and almost recovered at 30 days (p<0.001). PE cement had a higher conductivity (p<0.001). Calcium release diminished from the first day and recovered at 30 days (p<0.001) similarly for both cements (p>0.05). CONCLUSIONS: PE cement raised pH slightly more and had higher conductivity than CPM. Calcium release diminished after the first day and recovered at 30 days, similarly for both cements.

New therapeutic approach to Tourette Syndrome in children based on a randomized placebo-controlled double-blind phase IV study of the effectiveness and safety of magnesium and vitamin B6.

BACKGROUND: Tourette Syndrome (TS) is a neurological condition presenting chronic motor and phonic tics, and important degree of comorbidity. Considered an uncommon illness, it first becomes apparent during childhood. Current standard treatment only achieves partial control of the condition, and provokes frequent, and sometimes severe, side effects. METHODS AND DESIGN: Main aim: To show that, with respect to placebo treatment, the combination of 0.5 mEq/Kg magnesium and 2 mg/Kg vitamin B6 reduces motor and phonic tics and incapacity in cases of exacerbated TS among children aged 7-14 years, as measured on the Yale Global Tic Severity Scale (YGTSS). Secondary aims: Assess the safety of the treatment. Describe metabolic changes revealed by PET. Measure the impact of the experimental treatment on family life. METHODOLOGY: Randomized, blinded clinical trials. Phase IV study (new proposal for treatment with magnesium and vitamin B6). SCOPE: children in the geographic area of the study group. Recruitment of subjects: to include patients diagnosed with TS, in accordance with DSM-IV criteria (307.23), during a period of exacerbation, and provided none of the exclusion criteria are met. INSTRUMENTATION: clinical data and the YGTSS score will be obtained at the outset of a period of exacerbation (t0). The examinations will be made after 15 (t1), 30 (t2), 60 (t3) and 90 days (t4). PET will be performed at the t0 and t4. We evaluated decrease in the overall score (t0, t1, t2, t3, t4), PET variations, and impact made by the treatment on the patient's life (Psychological General Well-Being Index). DISCUSSION: Few clinical trials have been carried out on children with TS, but they are necessary, as current treatment possibilities are insufficient and often provoke side effects. The difficulty of dealing with an uncommon illness makes designing such a study all the more complicated. The present study seeks to overcome possible methodological problems by implementing a prior, phase II study, in order to calculate the relevant statistical parameters and to determine the safety of the proposed treatment. Providing a collateral treatment with magnesium and vitamin B6 could improve control of the illness and help reduce side effects. This protocol was approved by the Andalusian Government Committee for Clinical Trials (Spain). This study was funded by the Health Department of the Andalusian Regional Government and by the Healthcare Research Fund of the Carlos III Healthcare Institute (Spanish Ministry of Health). TRIAL REGISTRATION: Current Controlled Trials ISRCTN41082378.

Effectiveness of acupuncture, special dressings and simple, low-adherence dressings for healing venous leg ulcers in primary healthcare: study protocol for a cluster-randomized open-labeled trial.

BACKGROUND: Venous leg ulcers constitute a chronic recurring complaint that affects 1.0-1.3% of the adult population at some time in life, and which corresponds to approximately 75% of all chronic ulcers of the leg. Multilayer compression bandaging is, at present, the only treatment that has been proved to be effective in treating this type of ulcer. There is no consensus, however, about the dressings that may be applied, beneath the compression, to promote the healing of this type of ulcer, as there does not seem to be any added benefit from using special dressings rather than simple, low-adherence ones. As well as analgesia, acupuncture provokes peripheral vasodilation, in skin and muscles - which has been demonstrated both experimentally and in clinical practice - probably due to the axon reflex, among other mechanisms. The aim of the present study is to measure the effectiveness and cost of compression treatment for venous leg ulcers combined with special dressings, in comparison with low-adherence ones and acupuncture. METHODS/DESIGN: Cluster-randomized open-labeled trial, at 15 primary healthcare clinics in the Sevilla-Sur Healthcare District, with a control group treated with compression bandaging and low-adherence dressings; the experiment will consist, on the one hand, of the compression treatment applied in combination with special dressings (Treatment 1), and on the other, the compression treatment applied in association with low-adherence dressings, together with acupuncture (Treatment 2). DISCUSSION: The results will be measured and recorded in terms of the median time elapsed until complete healing of the ulcer, and the rate of complete healing at 3 months after beginning the treatment. An economic analysis will also be made. This study, carried out in the context of real clinical practice, will provide information for decision-taking concerning the effectiveness of special dressings. Moreover, for the first time a high-quality study will evaluate the effectiveness of acupuncture in the process of healing venous leg ulcers. TRIAL REGISTRATION: Current Controlled Trials ISRCTN26438275.

Study protocol for a pragmatic randomised controlled trial in general practice investigating the effectiveness of acupuncture against migraine.

BACKGROUND: Migraine is a chronic neurologic disease that can severely affect the patient's quality of life. Although in recent years many randomised studies have been carried out to investigate the effectiveness of acupuncture as a treatment for migraine, it remains a controversial issue. Our aim is to determine whether acupuncture, applied under real conditions of clinical practice in the area of primary healthcare, is more effective than conventional treatment. METHODS/DESIGN: The design consists of a pragmatic multi-centre, three-armed randomised controlled trial, complemented with an economic evaluation of the results achieved, comparing the effectiveness of verum acupuncture with sham acupuncture, and with a control group receiving normal care only. Patients eligible for inclusion will be those presenting in general practice with migraine and for whom their General Practitioner (GP) is considering referral for acupuncture. Sampling will be by consecutive selection, and by randomised allocation to the three branches of the study, in a centralised way following a 1:1:1 distribution (verum acupuncture; sham acupuncture; conventional treatment). Secondly, one patient in three will be randomly selected from each of the acupuncture (verum or sham) groups for a brain perfusion study (by single photon emission tomography). The treatment with verum acupuncture will consist of 8 treatment sessions, once a week, at points selected individually by the acupuncturist. The sham acupuncture group will receive 8 sessions, one per week, with treatment being applied at non-acupuncture points in the dorsal and lumbar regions, using the minimal puncture technique. The control group will be given conventional treatment, as will the other two groups. DISCUSSION: This trial will contribute to available evidence on acupuncture for the treatment of migraine. The primary endpoint is the difference in the number of days with migraine among the three groups, between the baseline period (the 4 weeks prior to the start of treatment) and the period from weeks 9 to 12. As a secondary aspect, we shall record the index of laterality and the percentage of change in the mean count per pixel in each region of interest measured by the brain perfusion tomography, performed on a subsample of the patients within the real and sham acupuncture groups. TRIAL REGISTRATION: Current Controlled Trials ISRCTN98703707.

Efficacy and safety of acupuncture for the treatment of non-specific acute low back pain: a randomised controlled multicentre trial protocol [ISRCTN65814467].

BACKGROUND: Low back pain and its associated incapacitating effects constitute an important healthcare and socioeconomic problem, as well as being one of the main causes of disability among adults of working age. The prevalence of non-specific low back pain is very high among the general population, and 60-70% of adults are believed to have suffered this problem at some time. Nevertheless, few randomised clinical trials have been made of the efficacy and efficiency of acupuncture with respect to acute low back pain. The present study is intended to assess the efficacy of acupuncture for acute low back pain in terms of the improvement reported on the Roland Morris Questionnaire (RMQ) on low back pain incapacity, to estimate the specific and non-specific effects produced by the technique, and to carry out a cost-effectiveness analysis. METHODS/DESIGN: Randomised four-branch controlled multicentre prospective study made to compare semi-standardised real acupuncture, sham acupuncture (acupuncture at non-specific points), placebo acupuncture and conventional treatment. The patients are blinded to the real, sham and placebo acupuncture treatments. Patients in the sample present symptoms of non specific acute low back pain, with a case history of 2 weeks or less, and will be selected from working-age patients, whether in paid employment or not, referred by General Practitioners from Primary Healthcare Clinics to the four clinics participating in this study. In order to assess the primary and secondary result measures, the patients will be requested to fill in a questionnaire before the randomisation and again at 3, 12 and 48 weeks after starting the treatment. The primary result measure will be the clinical relevant improvement (CRI) at 3 weeks after randomisation. We define CRI as a reduction of 35% or more in the RMQ results. DISCUSSION: This study is intended to obtain further evidence on the effectiveness of acupuncture on acute low back pain and to isolate the specific and non-specific effects of the treatment.