Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide : Phase I clinical trial of three dosing schedules in patients with solid malignancies

Thalidomide is an anti-angiogenic agent currently used to treat patients with malignant cachexia or multiple myeloma. Lenalidomide (CC-5013) is an immunomodulatory thalidomide analogue licensed in the United States of America (USA) for the treatment of a subtype of myelodysplastic syndrome. This two-centre, open-label phase I study evaluated dose-limiting toxicities in 55 patients with malignant solid tumours refractory to standard chemotherapies. Lenalidomide capsules were consumed once daily for 12 weeks according to one of the following three schedules: (I) 25 mg daily for the first 7 d, the daily dose increased by 25 mg each week up to a maximum daily dose of 150 mg; (II) 25 mg daily for 21 d followed by a 7-d rest period, the 4-week cycle repeated for 3 cycles; (III) 10 mg daily continuously. Twenty-six patients completed the study period. Two patients experienced a grade 3 hypersensitivity rash. Four patients in cohort I and 4 patients in cohort II suffered grade 3 or 4 neutropaenia. In 2 patients with predisposing medical factors, grade 3 cardiac dysrhythmia was recorded. Grade 1 neurotoxicity was detected in 6 patients. One complete and two partial radiological responses were measured by computed tomography scanning; 8 patients had stable disease after 12 weeks of treatment. Fifteen patients remained on treatment as named patients; 1 with metastatic melanoma remains in clinical remission 3.5 years from trial entry. This study indicates the tolerability and potential clinical efficacy of lenalidomide in patients with advanced solid tumours who have previously received multi-modality treatment. Depending on the extent of myelosuppressive pre-treatment, dose schedules (II) or (III) are advocated for large-scale trials of long-term administration. © 2006 Elsevier Ltd. All rights reserved.

Randomised clinical trial of a family-based lifestyle intervention for childhood obesity involving parents as the exclusive agents of change

Parent-centred interventions for childhood obesity aim to improve parents' skills and confidence in managing children's dietary and activity patterns, and in promoting a healthy lifestyle in their family. However, few studies assess changes in parenting over the course of treatment. This study describes the evaluation of a lifestyle-specific parenting program (Group Lifestyle Triple P) on multiple child and parent outcomes. One-hundred-and-one families with overweight and obese 4- to 11-year-old children participated in an intervention or waitlist control condition. The 12-week intervention was associated with significant reductions in child BMI z score and weight-related problem behaviour. At the end of the intervention, parents reported increased confidence in managing children's weight-related behaviour, and less frequent use of inconsistent or coercive parenting practices. All short-term intervention effects were maintained at one-year follow-up assessment, with additional improvements in child body size. The results support the efficacy of Group Lifestyle Triple P and suggest that parenting influences treatment outcomes. Further research is needed to evaluate the long-term effectiveness of the intervention and to elucidate the mechanisms of change. © 2010 Elsevier Ltd.

Randomized, double-blind, placebo-controled clinical trial of sublingual immunotherapy in natural rubber latex allergic patients

Trial registration number: CTRN12611000543987

Secondary Outcomes in a Clinical Trial of Carotenoids with Coantioxidants versus Placebo in Early Age-Related Macular Degeneration

Purpose: To report the secondary outcomes in the Carotenoids with Coantioxidants in Age-Related Maculopathy trial.

Design: Randomized double-masked placebo-controlled clinical trial (registered as ISRCTN 94557601).

Participants: Participants included 433 adults 55 years of age or older with early age-related macular degeneration (AMD) in 1 eye and late-stage disease in the fellow eye (group 1) or early AMD in both eyes (group 2).

Intervention: An oral preparation containing lutein (L), zeaxanthin (Z), vitamin C, vitamin E, copper, and zinc or placebo. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), Raman spectroscopy, stereoscopic colour fundus photography, and serum sampling were performed every 6 months with a minimum follow-up time of 12 months.

Main Outcome Measures: Secondary outcomes included differences in BCVA (at 24 and 36 months), CS, Raman counts, serum antioxidant levels, and progression along the AMD severity scale (at 12, 24, and 36 months).

Results: The differential between active and placebo groups increased steadily, with average BCVA in the former being approximately 4.8 letters better than the latter for those who had 36 months of follow-up, and this difference was statistically significant (P = 0.04). In the longitudinal analysis, for a 1-log-unit increase in serum L, visual acuity was better by 1.4 letters (95% confidence interval, 0.3-2.5; P = 0.01), and a slower progression along a morphologic severity scale (P = 0.014) was observed.

Conclusions: Functional and morphologic benefits were observed in key secondary outcomes after supplementation with L, Z, and coantioxidants in persons with early AMD.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.

Efficacy and safety of adjunctive mitomycin C during Ahmed Glaucoma Valve implantation:A prospective randomized clinical trial

Purpose To evaluate the efficacy and safety of intraoperative mitomycin C (MMC) in eyes undergoing Ahmed Glaucoma Valve implantation. Design Randomized controlled clinical trial. Participants Sixty patients with refractory glaucoma. Intervention Sixty eyes of 60 patients with refractory glaucoma were randomized to receive intraoperative MMC (0.5 mg/ml for 5 minutes) (n = 34) or balanced salt solution (n = 26) during Ahmed Glaucoma Valve implantation. Main outcome measures Surgical success was defined according to 2 different criteria: (1) postoperative intraocular pressure (IOP) between 6 and 21 mmHg, with or without antiglaucoma medications, and (2) IOP reduction of at least 30% relative to preoperative values. Eyes requiring additional glaucoma surgery, developing phthisis, or showing loss of light perception were classified as failures. Success rates in both groups were compared using Kaplan-Meier survival curves and the log rank test. Other outcome measures were mean IOP, number of glaucoma medications, and complications. Results After a mean follow-up of 12.3 months, Kaplan-Meier survival analysis showed a probability of success of 59% at 18 months for the MMC group and 61% for the control group when the first criterion for success was used (IOP between 6 and 21 mmHg). When an IOP reduction of at least 30% was used as the criterion to define success, the Kaplan-Meier survival analysis demonstrated a probability of success at 18 months of 62% for the MMC group and 67% for the control group. There were no significant differences in survival rates between the 2 groups with either criterion (P = 0.75 and P = 0.37, respectively). After 15 days postoperatively, the mean IOP did not significantly differ for both MMC and control eyes. Mean numbers of postoperative antiglaucoma medications were similar in MMC-treated eyes and controls. There was no significant difference between the incidences of postoperative complications in both groups. Conclusion Mitomycin C did not increase the short- or intermediate-term success rates of Ahmed Glaucoma Valve implantation. © 2004 by the American Academy of Ophthalmology.

Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome

Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. In all, 44 patients with Rome II positive IBS completed a 12-week single centre parallel crossover controlled clinical trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored. The prebiotic significantly enhanced faecal bifidobacteria (3.5 g/d P < 0.005; 7 g/d P < 0.001). Placebo was without effect on the clinical parameters monitored, while the prebiotic at 3.5 g/d significantly changed stool consistency (P < 0.05), improved flatulence (P < 0.05) bloating (P < 0.05), composite score of symptoms (P < 0.05) and SGA (P < 0.05). The prebiotic at 7 g/d significantly improved SGA (P < 0.05) and anxiety scores (P < 0.05). The galactooligosaccharide acted as a prebiotic in specifically stimulating gut bifidobacteria in IBS patients and is effective in alleviating symptoms. These findings suggest that the prebiotic has potential as a therapeutic agent in IBS.

The validity and internal structure of the bipolar depression rating scale (BDRS): data from a clinical trial of N-acetylcysteine as adjunctive therapy in bipolar disorder

Background: The phenomenology of unipolar and bipolar disorders differ in a number of ways, such as the presence of mixed states and atypical features. Conventional depression rating instruments are designed to capture the characteristics of unipolar depression and have limitations in capturing the breadth of bipolar disorder.

Method: The Bipolar Depression Rating Scale (BDRS) was administered together with the Montgomery Asberg Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) in a double-blind randomised placebo-controlled clinical trial of N-acetyl cysteine for bipolar disorder (N = 75).

Results: A factor analysis showed a two-factor solution: depression and mixed symptom clusters. The BDRS has strong internal consistency (Cronbach's alpha = 0.917), the depression cluster showed robust correlation with the MADRS (r = 0.865) and the mixed subscale correlated with the YMRS (r = 0.750).

Conclusion: The BDRS has good internal validity and inter-rater reliability and is sensitive to change in the context of a clinical trial.

Therapeutic Effects of Low-Level Laser Therapy After Premolar Extraction in Adolescents: A Randomized Double-Blind Clinical Trial

Objective: The purpose of this study was to evaluate the effect of low-level laser therapy (LLLT) on wound healing process and pain levels after premolar extraction in adolescents. Background data: The advantage of using LLLT in oral surgeries is the reduction of inflammation and postoperative discomfort; however, the optimal dosing parameters and treatment effects in surgical procedures are inconclusive. Methods: A double-blind, randomized, controlled clinical trial was conducted with 14 patients who were to undergo surgical removal of premolars. Patients were randomly allocated to the LLLT (test) group and placebo (control) group. Patients in the test group received 5.1 J (60 J/cm(2)) of energy density of a gallium-aluminum-arsenide (GaAlAs) diode laser (wavelength, 830 nm; output power, 0.1 W) at three different points intraorally, 1 cm from the target tissue immediately and at 48 and 72 h after the surgical procedure. For patients in the placebo group, the laser device was applied to the same points without activating the hand piece. The wound healing process was evaluated by an independent examiner by visual inspection with the support of digital photographs at baseline and 2, 7, and 15 days postoperatively. Patients recorded the degree of pain using the visual analogue scale (VAS). Results: Compared with the placebo group, the test group showed a lower intensity of pain, but this difference was not statistically significant at any time point. The wound healing process was similar in both groups. Conclusions: Within the limitations of this study, the LLLT parameters used neither increased the wound healing process nor significantly decreased pain intensity after premolar extraction in adolescents.

Low-level laser therapy for pain relief after episiotomy: a double-blind randomised clinical trial

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A randomised clinical trial of the effect of low-level laser therapy for perineal pain and healing after episiotomy: A pilot study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dentin hypersensitivity after teeth bleaching with in-office systems. randomized clinical trial

Purpose: To comparatively and prospectively compare in a randomized clinical trial, dentin hypersensitivity after treatment with three in-office bleaching systems, based on hydrogen peroxide at different concentrations, with and without light source activation. Methods: 88 individuals were included according to inclusion and exclusion criteria. Subjects were randomly divided into the following three treatment groups: Group 1 was treated with three 15-minute applications of hydrogen peroxide at 15% with titanium dioxide (Lase Peroxide Lite) that was light-activated (Light Plus Whitening Lase) with five cycles of 1 minute and 30 seconds each cycle, giving a total treatment time of 45 minutes; Group 2 was treated with three 10-minute applications of hydrogen peroxide at 35% (Lase Peroxide Sensy), activated by light (LPWL) same activation cycles than Group 1, with a total treatment time of 30 minutes; Group 3 was treated with only one application for 45 minutes of hydrogen peroxide at 35% (Whitegold Office) without light activation. Each subject underwent one session of bleaching on the anterior teeth according to the manufacturers' instructions. Dentin sensitivity was recorded with a visual analogue scale (VAS) at baseline, immediately after, and at 7 and 30 days after treatment using a stimulus of an evaporative blowing triple syringe for 3 seconds on the upper central incisors from a distance of 1 cm. A Kruskal-Wallis test followed by Mann-Whitney test was performed for statistical analysis. Results: All groups showed increased sensitivity immediately after treatment. Group 1 displayed less changes relative to baseline with no significant differences (P= 0.104). At 7 and 30 days after treatment, a comparison of VAS values indicated no significant differences between all groups (P= 0.598 and 0.489, respectively).

A randomised clinical trial of the effect of low-level laser therapy for perineal pain and healing after episiotomy: A pilot study

Objective: to evaluate the effects of low-level laser therapy for perineal pain and healing after episiotomy. Design: a double-blind, randomised, controlled clinical trial comparing perineal pain scores and episiotomy healing in women treated with low-level laser therapy (LLLT) and with the simulation of the treatment. Setting: the study was conducted in the Birth Centre and rooming-in units of Amparo Maternal, a maternity service located in the city of Sao Paulo, Brazil. Participants: fifty-two postpartum women who had had mediolateral episiotomies during their first normal delivery were randomly divided into two groups of 26: an experimental group and a control group. Intervention: in the experimental group, the women were treated with LLLT. Irradiation was applied at three points directly on the episiotomy after the suture and in three postpartum sessions: up to 2 hrs postpartum, between 20 and 24 hrs postpartum and between 40 and 48 hrs postpartum. The LLLT was performed with diode laser, with a wavelength of 660 nm (red light), spot size of 0.04 cm(2), energy density of 3.8 J/cm(2), radiant power of 15 mW and 10 s per point, which resulted in an energy of 0.15 J per point and a total energy of 0.45 J per session. The control group participants also underwent three treatment sessions, but without the emission of radiation (simulation group), to assess the possible effects of placebo treatment. Main outcomes: perineal pain scores, rated on a scale from 0 to 10, were evaluated before and immediately after the irradiation in the three sessions. The healing process was assessed using the REEDA scale (Redness, Edema, Echymosis, Discharge Aproximation) before each laser therapy session and 15 and 20 days after the women's discharge. Findings: comparing the pain scores before and after the LLLT sessions, the experimental group presented a significant within-group reduction in mean pain scores after the second and third sessions (p=0.003 and p<0.001, respectively), and the control group showed a significant reduction after the first treatment simulation (p=0.043). However, the comparison of the perineal pain scores between the experimental and control groups indicated no statistical difference at any of the evaluated time points. There was no significant difference in perineal healing scores between the groups. All postpartum women approved of the low-level laser therapy. Conclusions: this pilot study showed that LLLT did not accelerate episiotomy healing. Although there was a reduction in perineal pain mean scores in the experimental group, we cannot conclude that the laser relieved perineal pain. This study led to the suggestion of a new research proposal involving another irradiation protocol to evaluate LLLT's effect on perineal pain relief. (C) 2011 Elsevier Ltd. All rights reserved.

Low-level laser therapy for pain relief after episiotomy: a double-blind randomised clinical trial

Aims and objectives. To evaluate the effectiveness of a low-level laser therapy for pain relief in the perineum following episiotomy during childbirth. Background. Laser irradiation is a painless and non-invasive therapy for perineal pain treatment and its effects have been investigated in several studies, with no clear conclusion on its effectiveness. Design. A double-blind randomised controlled clinical trial. Method. One hundred and fourteen women who underwent right mediolateral episiotomies during vaginal birth in an in-hospital birthing centre in Sao Paulo, Brazil and reported pain =3 on a numeric scale (010) were randomised into three groups of 38 women each: two experimental groups (treated with red and infrared laser) and a control group. The experimental groups were treated with laser applied at three points directly on the episiotomy after suturing in a single session between 656 hours postpartum. We used a diode laser with wavelengths of 660 nm (red laser) and 780 nm (infrared laser). The control group participants underwent all laser procedures, excluding the emission of irradiation. The participants and the pain scores evaluator were blinded to the type of intervention. The perineal pain scores were assessed at three time points: before, immediately after and 30 minutes after low-level laser therapy. Results. The comparison of perineal pain between the three groups showed no significant differences in the three evaluations (p = 0.445), indicating that the results obtained in the groups treated with low-level laser therapy were equivalent to the control group. Conclusions. Low-level laser therapy did not decrease the intensity of perineal pain reported by women who underwent right mediolateral episiotomy. Relevance to clinical practice. The effect of laser in perineal pain relief was not demonstrated in this study. The dosage may not have been sufficient to provide relief from perineal pain after episiotomy during a vaginal birth.

The short-term treatment effects on the microbiota at the dorsum of the tongue in intra-oral halitosis patients-a randomized clinical trial

OBJECTIVES This study aims to assess the effects of rinsing with zinc- and chlorhexidine-containing mouth rinse with or without adjunct tongue scraping on volatile sulfur compounds (VSCs) in breath air, and the microbiota at the dorsum of the tongue. MATERIAL AND METHODS A randomized single-masked controlled clinical trial with a cross-over study design over 14 days including 21 subjects was performed. Bacterial samples from the dorsum of the tongue were assayed by checkerboard DNA-DNA hybridization. RESULTS No halitosis (identified by VSC assessments) at day 14 was identified in 12/21 subjects with active rinse alone, in 10/21 with adjunct use of tongue scraper, in 1/21 for negative control rinse alone, and in 3/21 in the control and tongue scraping sequence. At day 14, significantly lower counts were identified only in the active rinse sequence (p < 0.001) for 15/78 species including, Fusobacterium sp., Porphyromonas gingivalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Tannerella forsythia. A decrease in bacteria from baseline to day 14 was found in successfully treated subjects for 9/74 species including: P. gingivalis, Prevotella melaninogenica, S. aureus, and Treponema denticola. Baseline VSC scores were correlated with several bacterial species. The use of a tongue scraper combined with active rinse did not change the levels of VSC compared to rinsing alone. CONCLUSIONS VSC scores were not associated with bacterial counts in samples taken from the dorsum of the tongue. The active rinse alone containing zinc and chlorhexidine had effects on intra-oral halitosis and reduced bacterial counts of species associated with malodor. Tongue scraping provided no beneficial effects on the microbiota studied. CLINICAL RELEVANCE Periodontally healthy subjects with intra-oral halitosis benefit from daily rinsing with zinc- and chlorhexidine-containing mouth rinse.