CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for steroid-dependent Crohn's disease: a randomized, double-blind, placebo-controlled trial

Background More than 50% of patients with Crohn's disease become either steroid resistant or dependent. Accordingly, development of new treatments for steroid-dependent Crohn's disease is a research priority. Aim To evaluate CDP571, a humanized antibody to tumour necrosis factor-α, for the treatment of steroid-dependent Crohn's disease. Methods Patients with steroid-dependent Crohn's disease (n = 271) were enrolled in a 36-week, double-blind, placebo-controlled trial. Steroid dependence was defined as use of prednisolone or prednisone (15–40 mg/day) or budesonide (9 mg/day) for ≥8 weeks, a previous failed attempt to decrease or discontinue steroids within 8 weeks of screening, and a Crohn's Disease Activity Index score of ≤150 points. Patients were randomized to receive intravenous CDP571 10 mg/kg or placebo 8-weekly through to week 32. Steroids were then tapered using a defined schedule. The primary efficacy endpoint was the percentage of patients with steroid sparing, defined as discontinuation of steroid therapy without a disease flare (Crohn's Disease Activity Index score ≥220 points) at week 36. Results Steroid sparing occurred in 53 of 181 (29.3%) CDP571 patients and 33 of 90 (36.7%) placebo patients (P = 0.24). Adverse events occurred at similar frequencies in both treatment groups. Conclusions CDP571 was ineffective for sparing steroids in patients with steroid-dependent Crohn's disease. CDP571 was well tolerated.

Efficacy of speech pathology management for chronic cough: a randomised placebo controlled trial of treatment efficacy

Background: Chronic cough that persists despite medical treatment may respond to speech pathology intervention, but the efficacy of such treatment has not been investigated in prospective randomised trials. The aim of this study was to determine the efficacy of a speech pathology intervention programme for chronic cough. Methods: A single blind, randomised, placebo controlled trial was conducted in 87 patients with chronic cough that persisted despite medical treatment. Patients were randomly allocated to receive either a specifically designed speech pathology intervention or a placebo intervention. Participants in both groups attended four intervention sessions with a qualified speech pathologist. Results: Participants in the treatment group had a significant reduction in cough (8.9 to 4.6, p, 0.001), breathing (7.9 to 4.7, p < 0.001), voice (7.3 to 4.6, p < 0.001) upper airway (8.9 to 5.9, p < 0.001) symptom scores and limitation (2.3 to 1.6, p < 0.001) ratings following intervention. There was also a significant reduction in breathing (6.8 to 5.6, p=0.047), cough (7.6 to 6.3, p=0.014), and limitation ( 2.3 to 2.0, p=0.038) scores in the placebo group, but the degree of improvement was significantly less than in the treatment group (p < 0.01). Clinical judgement of outcome indicated successful ratings in 88% of participants in the treatment group compared with 14% in the placebo group ( p, 0.001). Conclusion: Speech pathology is an effective management intervention for chronic cough which may be a viable alternative for patients who do not respond to medical treatment.

A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis

Objectives: The antiinflammatory effect of macrolide antibiotics has been well-established, as has their role in the treatment of certain disorders of chronic airway inflammation. Several studies have suggested that long-term, low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis; however, these studies have lacked a control group. To date, this effect has not been tested in a randomized, placebo-controlled study. Method: The authors conducted a double-blind, randomized, placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis. Subjects received either 150 mg roxithromycin daily for 3 months or placebo. Outcome measures included the Sinonasal Outcome Test-20 (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for interleukin-8, fucose, and a2-macroglobulin. Results. There were statistically significant improvements in SNOT-20 score, nasal endoscopy, saccharine transit time, and IL-8 levels in lavage fluid (P < .05) in the macrolide group. A correlation was noted between improved outcome measures and low IgE levels. No significant improvements were noted for olfactory function, peak nasal inspiratory flow, or lavage levels for fucose and a2-macroglobulin. No improvement in any outcome was noted in the placebo-treated patients. Conclusion: These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with low levels of IgE, and supports the in vitro evidence of their antiinflammatory activity. Additional studies are required to assess their place in clinical practice.

The effect of the dietary supplement, Chitosan, on body weight: a randomised controlled trial in 250 overweight and obese adults

CONTEXT: Chitosan, a deacetylated chitin, is a widely available dietary supplement purported to decrease body weight and serum lipids through gastrointestinal fat binding. Although evaluated in a number of trials, its efficacy remains in dispute. OBJECTIVE: To evaluate the efficacy of chitosan for weight loss in overweight and obese adults. DESIGN AND SETTING: A 24-week randomised, double-blind, placebo-controlled trial, conducted at the University of Auckland between November 2001 and December 2002. PARTICIPANTS: A total of 250 participants (82% women; mean (s.d.) body mass index, 35.5 (5.1) kg/m(2); mean age, 48 (12) y). INTERVENTIONS: Participants were randomly assigned to receive 3 g chitosan/day (n = 125) or placebo (n = 125). All participants received standardised dietary and lifestyle advice for weight loss. Adherence was monitored by capsule counts. MAIN OUTCOME MEASURES: The primary outcome measure was change in body weight. Secondary outcomes included changes in body mass index, waist circumference, body fat percentage, blood pressure, serum lipids, plasma glucose, fat-soluble vitamins, faecal fat, and health-related quality of life. RESULTS: In an intention-to-treat analysis with the last observation carried forward, the chitosan group lost more body weight than the placebo group (mean (s.e.), -0.4 (0.2) kg (0.4% loss) vs +0.2 (0.2) kg (0.2% gain), P = 0.03) during the 24-week intervention, but effects were small. Similar small changes occurred in circulating total and LDL cholesterol, and glucose (P < 0.01). There were no significant differences between groups for any of the other measured outcomes. CONCLUSION: In this 24-week trial, chitosan treatment did not result in a clinically significant loss of body weight compared with placebo.

A multicentre, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis

Background The treatment of infants with bronchiolitis is largely supportive. The role of bronchodilators is controversial. Most studies of the use of bronchodilators have enrolled small numbers of subjects and have examined only short-term outcomes, such as clinical scores. Methods We conducted a randomized, double-blind, controlled trial comparing nebulized single-isomer epinephrine with placebo in 194 infants admitted to four hospitals in Queens-land, Australia, with a clinical diagnosis of bronchiolitis. Three 4-ml doses of 1 percent nebulized epinephrine or three 4-ml doses of normal saline were administered at four-hour intervals after hospital admission. Observations were made at admission and just before, 30 minutes after, and 60 minutes after each dose. The primary outcome measures were the length of the hospital stay and the time until the infant was ready for discharge. The secondary outcome measures were the degree of change in the respiratory rate, the heart rate, and the respiratory-effort score and the time that supplemental oxygen was required. Results There were no significant overall differences between the groups in the length of the hospital stay (P=0.16) or the time until the infant was ready for discharge (P=0.86). Among infants who required supplemental oxygen and intravenous fluids, the time until the infant was ready for discharge was significantly longer in the epinephrine group than in the placebo group (P=0.02). The need for supplemental oxygen at admission had the greatest influence on the score for severity of illness and strongly predicted the length of the hospital stay and the time until the infant was ready for discharge (P

A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses

Background: Solar keratoses (SKs) are among the strongest determinants of skin cancer, but little is known about the success of measures to control these common skin tumors. Objective: To determine whether daily sunscreen application and/or beta carotene supplementation retards the rate of occurrence of SKs in adults in the medium term. Design: Randomized controlled trial conducted between February 1992 and August 1996. Setting: General community of the subtropical township of Nambour, Australia (latitude, 26degrees south). Participants: A total of 1621 adults aged 25 to 74 years. Interventions: Participants were randomized to daily use of sunscreen (application of a high-protection sunscreen to their head, neck, arms, and hands every morning) or application of sunscreen at their usual discretionary rate. They were also randomly assigned to take either one 30-mg tablet of beta carotene or one placebo tablet each day. Main Outcome Measure: Change in the prevalent number of SKs in the intervention group relative to change in the control group. Results: The ratio of SK counts in 1994 relative to 1992 was lower in people randomized to daily sunscreen use (1.20; 95% confidence interval, 1.04-1.39) than in those randomized to discretionary sunscreen use (1.57; 95% confidence interval, 1.35-1.84). This 24% reduction is equivalent to the prevention of an average of I additional SK per person over that time. A reduction in the rate of change of SK prevalence was also seen in the sunscreen intervention group relative to the discretionary sunscreen group between 1994 and 1996, but it was not significant. No effect on the rate of change of prevalent SK counts was seen among those taking beta carotene supplements relative. to those taking placebo tablets. Conclusions: Daily application of sunscreen retarded the rate of SK acquisition among adults in a subtropical environment, while a beta carotene supplementation of 30 mg/d had no influence on the occurrence of SKs.

Zinc and vitamin A supplementation in Indigenous Australian children hospitalised with lower respiratory tract infection: a randomised controlled trial

Objective: To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection (ALRI). Design: Randomised controlled, 2-by-2 factorial trial of supplementation with zinc and vitamin A. Setting and participants: 187 Indigenous children aged < 11 years hospitalised with 215 ALRI episodes at Alice Springs Hospital (April 2001 to July 2002). Interventions: Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU (infants under 12 months), or 100 000 IU; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg (infants under 12 months) or 40 mg. Main outcome measure: Time to clinical recovery from fever and tachypnoea, duration of hospitalisation, and readmission for ALRI within 120 days. Results: There was no clinical benefit of supplementation with vitamin A, zinc or the two combined, with no significant difference between zinc and no-zinc, vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea, or duration of hospitalisation. Instead, we found increased morbidity; children given zinc had increased risk of readmission for ALRI within 120 days (relative risk, 2.4; 95% CI, 1.003–6.1). Conclusion: This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas. Even in populations with high rates of ALRI and poor living conditions, vitamin A and zinc therapy may not be useful. The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population.

Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial

Background The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. Methods In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. Findings 1383 participants underwent full shin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new shin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100 000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100 000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100 000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100 000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100 000; 0.61 [0.46-0.81]). Interpretation There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.