Ablative therapy for people with localised prostate cancer: a systematic review and economic evaluation.

BACKGROUND: For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others. OBJECTIVES: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT. DATA SOURCES: MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources. REVIEW METHODS: Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness. RESULTS: The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research. LIMITATIONS: The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. CONCLUSIONS: The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002461. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial).

BACKGROUND: Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. METHODS: A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. RESULTS: Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. CONCLUSIONS: Cryotherapy is more costly and no more effective than salicylic acid. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246 [controlled-trials.com] and National Research Register N0484189151.

Yoga for chronic low back pain: a randomized trial.

BACKGROUND: Previous studies indicate that yoga may be an effective treatment for chronic or recurrent low back pain. OBJECTIVE: To compare the effectiveness of yoga and usual care for chronic or recurrent low back pain. DESIGN: Parallel-group, randomized, controlled trial using computer-generated randomization conducted from April 2007 to March 2010. Outcomes were assessed by postal questionnaire. (International Standard Randomised Controlled Trial Number Register: ISRCTN 81079604) SETTING: 13 non-National Health Service premises in the United Kingdom. PATIENTS: 313 adults with chronic or recurrent low back pain. INTERVENTION: Yoga (n = 156) or usual care (n = 157). All participants received a back pain education booklet. The intervention group was offered a 12-class, gradually progressing yoga program delivered by 12 teachers over 3 months. MEASUREMENTS: Scores on the Roland-Morris Disability Questionnaire (RMDQ) at 3 (primary outcome), 6, and 12 (secondary outcomes) months; pain, pain self-efficacy, and general health measures at 3, 6, and 12 months (secondary outcomes). RESULTS: 93 (60%) patients offered yoga attended at least 3 of the first 6 sessions and at least 3 other sessions. The yoga group had better back function at 3, 6, and 12 months than the usual care group. The adjusted mean RMDQ score was 2.17 points (95% CI, 1.03 to 3.31 points) lower in the yoga group at 3 months, 1.48 points (CI, 0.33 to 2.62 points) lower at 6 months, and 1.57 points (CI, 0.42 to 2.71 points) lower at 12 months. The yoga and usual care groups had similar back pain and general health scores at 3, 6, and 12 months, and the yoga group had higher pain self-efficacy scores at 3 and 6 months but not at 12 months. Two of the 157 usual care participants and 12 of the 156 yoga participants reported adverse events, mostly increased pain. LIMITATION: There were missing data for the primary outcome (yoga group, n = 21; usual care group, n = 18) and differential missing data (more in the yoga group) for secondary outcomes. CONCLUSION: Offering a 12-week yoga program to adults with chronic or recurrent low back pain led to greater improvements in back function than did usual care. PRIMARY FUNDING SOURCE: Arthritis Research UK.

Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches.

BACKGROUND: Research suggests that food intolerance may be a precipitating factor for migraine like headaches. AIM: To evaluate the effectiveness of the ELISA (Enzyme Linked Immuno-Sorbent Assay) Test and subsequent dietary elimination advice for the prevention of migraine like headaches. DESIGN: Randomised controlled trial. SETTING: Community based volunteers in the UK. PARTICIPANTS: Volunteers who met the inclusion criteria for migraine like headaches and had one or more food intolerance were included in the study. Participants received either a true diet (n = 84) or a sham diet (n = 83) sheet. Participants were advised to remove the intolerant foods from their diet for 12 weeks. MAIN OUTCOME MEASURES: Number of headache days over a 12 week period (item A MIDAS questionnaire). Other measures includes the total MIDAS score and total HIT-6 score. RESULTS: The results indicated a small decrease in the number of migraine like headaches over 12 weeks, although this difference was not statistically significant (IRR 1.15 95% CI 0.94 to 1.41, p = 0.18). At the 4 week assessment, use of the ELISA test with subsequent diet elimination advice significantly reduced the number of migraine like headaches (IRR 1.23 95%CI 1.01 to 1.50, p = 0.04). The disability and impact on daily life of migraines were not significantly different between the true and sham diet groups. CONCLUSIONS: Use of the ELISA test with subsequent diet elimination advice did not reduce the disability or impact on daily life of migraine like headaches or the number of migraine like headaches at 12 weeks but it did significantly reduce the number of migraine like headaches at 4 weeks.

Cryotherapy versus salicylic acid for the treatment of plantar warts (verrucae): a randomised controlled trial.

OBJECTIVE: To compare the clinical effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts. DESIGN: A multicentre, open, two arm randomised controlled trial. SETTING: University podiatry school clinics, NHS podiatry clinics, and primary care in England, Scotland, and Ireland. PARTICIPANTS: 240 patients aged 12 years and over, with a plantar wart that in the opinion of the healthcare professional was suitable for treatment with both cryotherapy and salicylic acid. INTERVENTIONS: Cryotherapy with liquid nitrogen delivered by a healthcare professional, up to four treatments two to three weeks apart. Patient self treatment with 50% salicylic acid (Verrugon) daily up to a maximum of eight weeks. MAIN OUTCOME MEASURES: Complete clearance of all plantar warts at 12 weeks. Secondary outcomes were (a) complete clearance of all plantar warts at 12 weeks controlling for age, whether the wart had been treated previously, and type of wart, (b) patient self reported clearance of plantar warts at six months, (c) time to clearance of plantar wart, (d) number of plantar warts at 12 weeks, and (e) patient satisfaction with the treatment. RESULTS: There was no evidence of a difference between the salicylic acid and cryotherapy groups in the proportions of participants with complete clearance of all plantar warts at 12 weeks (17/119 (14%) v 15/110 (14%), difference 0.65% (95% CI -8.33 to 9.63), P=0.89). The results did not change when the analysis was repeated but with adjustment for age, whether the wart had been treated previously, and type of plantar wart or for patients' preferences at baseline. There was no evidence of a difference between the salicylic acid and cryotherapy groups in self reported clearance of plantar warts at six months (29/95 (31%) v 33/98 (34%), difference -3.15% (-16.31 to 10.02), P=0.64) or in time to clearance (hazard ratio 0.80 (95% CI 0.51 to 1.25), P=0.33). There was also no evidence of a difference in the number of plantar warts at 12 weeks (incident rate ratio 1.08 (0.81 to 1.43), P=0.62). CONCLUSIONS: Salicylic acid and the cryotherapy were equally effective for clearance of plantar warts. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246, National Research Register N0484189151.

Electronic reminders did not improve postal questionnaire response rates or response times: a randomized controlled trial.

OBJECTIVE: We aim to evaluate the effectiveness of electronic reminders (ERs) to improve the response rates and time to response of postal questionnaires in a health research setting. STUDY DESIGN AND SETTING: This pragmatic randomized controlled trial (RCT) was nested within a multicenter RCT of yoga for lower back pain. Participants who provided an electronic mail address and/or mobile phone number were randomized to receive an ER or no reminder (controls) on the day they were due to receive a follow-up questionnaire. RESULTS: One hundred twenty-five participants (32 males and 93 females) mean age 46 (standard deviation: 11, range: 20-65) were randomized to ER (n=62) or controls (n=63). Overall 85.6% of participants returned postal questionnaires (87.1% ER group and 84.1% from controls). No significant differences were found between the two groups for response rate (difference between groups=3.0%, 95% confidence interval [CI]=-10, 16; P=0.64) or time to response after adjusting for age, gender, and treatment allocation (χ(2) ([3df])=7.10; P=0.07). CONCLUSION: In the present RCT, we found little evidence for the effectiveness of ERs to increase response rates or time to respond for the return of questionnaires in this study population group.

A pragmatic multi-centred randomised controlled trial of yoga for chronic low back pain: trial protocol.

UNLABELLED: A systematic review revealed three small randomised controlled trials of yoga for low back pain, all of which showed effects on back pain that favoured the yoga group. To build on these studies a larger trial, with longer term follow-up, and a number of different yoga teachers delivering the intervention is required. This study protocol describes the details of a randomised controlled trial (RCT) to determine the effectiveness and cost-effectiveness of Yoga for chronic Low Back Pain, which is funded by Arthritis Research Campaign (arc) and is being conducted by the University of York. 262 patients will be recruited from GP practices in 5 centres in England. Patients will be randomised to receive usual care or 12 weekly classes of yoga. A yoga programme will be devised that can be delivered by yoga teachers of the two main national yoga organisations in the UK (British Wheel of Yoga and Iyengar Yoga Association (UK)). TRIAL REGISTRATION: Current controlled trials registry ISRCTN81079604 (date registered 30/03/2007).