A systematic review and meta-analysis of clinical trials on physical interventions for lateral epicondylalgia

A systematic review of the literature on the effectiveness of physical interventions for lateral epicondylalgia ( tennis elbow) was carried out. Seventy six randomised controlled trials were identified, 28 of which satisfied the minimum criteria for meta-analysis. The evidence suggests that extracorporeal shock wave therapy is not beneficial in the treatment of tennis elbow. There is a lack of evidence for the long term benefit of physical interventions in general. However, further research with long term follow up into manipulation and exercise as treatments is indicated.

Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial

Background Resection remains the best treatment for carcinoma of the oesophagus in terms of local control, but local recurrence and distant metastasis remain an issue after surgery. We aimed to assess whether a short preoperative chemoradiotherapy regimen improves outcomes for patients with resectable oesophageal cancer. Methods 128 patients were randomly assigned to surgery alone and 128 patients to surgery after 80 mg/m(2) cisplatin on day 1, 800 mg/m(2) fluorouracil on days 1-4, with concurrent radiotherapy of 35 Gy given in 15 fractions. The primary endpoint was progression-free survival. Secondary endpoints were overall survival, tumour response, toxic effects, patterns of failure, and quality of life. Analysis was done by intention to treat. Findings Neither progression-free survival nor overall survival differed between groups (hazard ratio [HR] 0.82 [95% CI 0.61-1.101 and 0.89 [0.67-1.19], respectively). The chemoradiotherapy-and-surgery group had more complete resections with clear margins than did the surgery-alone group (103 of 128 [80%] vs 76 of 128 [59%], p=0.0002), and had fewer positive lymph nodes (44 of 103 [43%] vs 69 of 103 [67%], p=0.003). Subgroup analysis showed that patients with squamous-cell tumours had better progression-free survival with chemoradiotherapy than did those with non-squamous tumours (HR 0.47 [0.25-0.86] vs 1.02 [0.72-1.44]). However, the trial was underpowered to determine the real magnitude of benefit in this subgroup. Interpretation Preoperative chemoradiotherapy with cisplatin and fluorouracil does not significantly improve progression-free or overall survival for patients with resectable oesophageal cancer compared with surgery alone. However, further assessment is warranted of the role of chemoradiotherapy in patients with squamouscell tumours.

Pubovaginal sling versus transurethral Macroplastique for stress urinary incontinence and intrinsic sphincter deficiency: a prospective randomised controlled trial

Objective To compare the pubovaginal sling and transurethral Macroplastique in the treatment of female stress urinary incontinence (SUI) and intrinsic sphincter deficiency (ISD). Design A prospective randomised controlled trial comparing two surgical treatments for SUI and ISD. Setting Tertiary referral urogynaecology unit in Australia. Population Women with SUI and ISD who were suitable for either surgical technique. Methods Forty-five women with SUI and ISD were randomly allocated the pubovaginal sling (n = 22) or transurethral Macroplastique (n = 23). Subjective and objective success rates, patient satisfaction and cost measurements at six months and one year following surgery were the primary outcome measures. A telephone questionnaire survey was performed at a mean follow up period of 62 months (43-71). Main outcome measure Comparison of success rates, complications and costs. Results The symptomatic and patient satisfaction success rates were similar following the sling and Macroplastique with the objective success rate being significantly greater (P < 0.001) following the sling (81% vs 9%). Macroplastique had significantly lower morbidity but was more expensive than the sling (P < 0.001). Response rate at 62 months follow up was 60% in both groups with the sling group reporting better continence success (69% vs 21%) and satisfaction rates (69% vs 29%, P = 0.057). Conclusions The pubovaginal sling was more effective and economical than transurethral Macroplastique for the treatment of SUI and ISD. However, transurethral Macroplastique remains an appropriate treatment in selected cases of SUI and ISD.

Appraising the quality of randomized controlled trials: inter-rater reliability for the OTseeker evidence database

Rationale and aims 'OTseeker' is an online database of randomized controlled trials (RCTs) and systematic reviews relevant to occupational therapy. RCTs are critically appraised and rated for quality using the 'PEDro' scale. We aimed to investigate the inter-rater reliability of the PEDro scale before and after revising rating guidelines. Methods In study 1, five raters scored 100 RCTs using the original PEDro scale guidelines. In study 2, two raters scored 40 different RCTs using revised guidelines. All RCTs were randomly selected from the OTseeker database. Reliability was calculated using Kappa and intraclass correlation coefficients [ICC (model 2,1)]. Results Inter-rater reliability was 'good to excellent' in the first study (Kappas >= 0.53; ICCs >= 0.71). After revising the rating guidelines, the reliability levels were equivalent or higher to those previously obtained (Kappas >= 0.53; ICCs >= 0.89), except for the item, 'groups similar at baseline', which still had moderate reliability (Kappa = 0.53). In study 2, two PEDro scale items, which had their definitions revised, 'less than 15% dropout' and 'point measures and variability', showed higher reliability. In both studies, the PEDro items with the lowest reliability were 'groups similar at baseline' (Kappas = 0.53), 'less than 15% dropout' (Kappas

A Comparison of Methodologies from Two Longitudinal Community-Based Randomized Controlled Trials of Similar Interventions in Palliative Care: What Worked and What Did Not

Background: Methodological challenges such as recruitment problems and participant burden make clinical trials in palliative care difficult. In 2001-2004, two community-based randomized controlled trials (RCTs) of case conferences in palliative care settings were independently conducted in Australia-the Queensland Case Conferences trial (QCC) and the Palliative Care Trial (PCT). Design: A structured comparative study of the QCC and PCT was conducted, organized by known practical and organizational barriers to clinical trials in palliative care. Results: Differences in funding dictated study designs and recruitment success; PCT had 6 times the budget of QCC. Sample size attainment. Only PCT achieved the sample size goal. QCC focused on reducing attrition through gatekeeping while PCT maximized participation through detailed recruitment strategies and planned for significant attrition. Testing sustainable interventions. QCC achieved a higher percentage of planned case conferences; the QCC strategy required minimal extra work for clinicians while PCT superimposed conferences on normal work schedules. Minimizing participant burden. Differing strategies of data collection were implemented to reduce participant burden. QCC had short survey instruments. PCT incorporated all data collection into normal clinical nursing encounters. Other. Both studies had acceptable withdrawal rates. Intention-to-treat analyses are planned. Both studies included substudies to validate new outcome measures. Conclusions: Health service interventions in palliative care can be studied using RCTs. Detailed comparative information of strategies, successes and challenges can inform the design of future trials. Key lessons include adequate funding, recruitment focus, sustainable interventions, and mechanisms to minimize participant burden.

A randomised controlled trial of a CBT intervention for anxiety in children with Asperger syndrome

Background: The aim of the study was to evaluate the effectiveness of a brief CBT intervention for anxiety with children diagnosed with Asperger syndrome (AS). A second interest was to evaluate whether more intensive parent involvement would increase the child's ability to manage anxiety outside of the clinic setting. Methods: Seventy-one children aged ten to twelve years were recruited to participate in the anxiety programme. All children were diagnosed with AS and the presence of anxiety symptoms was accepted on parent report via brief interview. Children were randomly assigned to one of three conditions: intervention for child only, intervention for child and parent, wait-list control. Results: The two intervention groups demonstrated significant decreases in parent-reported anxiety symptoms at follow-up and a significant increase in the child's ability to generate positive strategies in an anxiety-provoking situation. There were a number of significant differences between the two interventions to suggest parent involvement as beneficial. Conclusions: The sample of children with AS in this study presented with a profile of anxiety similar to a sample of clinically diagnosed anxious children. The intervention was endorsed by parents as a useful programme for children diagnosed with Asperger syndrome and exhibiting anxiety symptoms, and active parent involvement enhanced the usefulness of the programme. Limitations of the study and future research are discussed.

An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the kneel

Objective: Five double-blind, randomized, saline-controlled trials (RCTs) were included in the United States marketing application for an intra-articular hyaluronan (IA-HA) product for the treatment of osteoarthritis (OA) of the knee. We report an integrated analysis of the primary Case Report Form (CRF) data from these trials. Method. Trials were similar in design, patient population and outcome measures - all included the Lequesne Algofunctional Index (LI), a validated composite index of pain and function, evaluating treatment over 3 months. Individual patient data were pooled; a repeated measures analysis of covariance was performed in the intent-to-treat (ITT) population. Analyses utilized both fixed and random effects models. Safety data from the five RCTs were summarized. Results: A total of 1155 patients with radiologically confirmed knee OA were enrolled: 619 received three or five IA-HA injections; 536 received. placebo saline injections. In the active and control groups, mean ages were 61.8 and 61.4 years; 62.4% and 58.8% were women; baseline total Lequesne scores 11.03 and 11.30, respectively. Integrated analysis of the pooled data set found a statistically significant reduction (P < 0.001) in total Lequesne score with hyaluronan (HA) (-2.68) vs placebo (-2.00); estimated difference -0.68 (95% CI: -0.56 to -0.79), effect size 0.20. Additional modeling approaches confirmed robustness of the analyses. Conclusions: This integrated analysis demonstrates that multiple design factors influence the results of RCTs assessing efficacy of intra-articular (IA) therapies, and that integrated analyses based on primary data differ from meta-analyses using transformed data. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Small-scale randomized controlled trials need more powerful methods of mediational analysis than the Baron-Kenny method

Objective: To devise more-effective physical activity interventions, the mediating mechanisms yielding behavioral change need to be identified. The Baron-Kenny method is most commonly used. but has low statistical power and May not identify mechanisms of behavioral change in small-to-medium size Studies. More powerful statistical tests are available, Study Design and Setting: Inactive adults (N = 52) were randomized to either a print or a print-plus-telephone intervention. Walking and exercise-related social support Were assessed at baseline, after file intervention, and 4 weeks later. The Baron-Kenny and three alternative methods of mediational analysis (Freedman-Schatzkin; MacKinnon et al.: bootstrap method) were used to examine the effects of social support on initial behavior change and maintenance. Results: A significant mediational effect of social support on initial behavior change was indicated by the MacKinnon et al., bootstrap. and. marginally. Freedman-Schatzkin methods, but not by the Baron-Kenny method. No significant mediational effecl of social support on maintenance of walking was found. Conclusions: Methodologically rigorous intervention studies to identify mediators of change in physical activity are costly and labor intensive, and may not be feasible with large samples. The Use of statistically powerful tests of mediational effects in small-scale studies can inform the development of more effective interventions. (C) 2006 Elsevier Inc. All rights reserved.

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.