Updating clinical recommendations for breast, colorectal and lung cancer treatments: an opportunity to improve methodology and clinical relevance.

BACKGROUND: clinical guidelines can improve quality of care summarising available knowledge and proposing recommendations for health care decisions. Being up to date is one of their quality requisites. Little experience is available on when and how guidelines should be updated. We report on the update process of evidence-based clinical recommendations on anticancer drugs. METHODS: three multidisciplinary panels, supported by methodology experts, updated the recommendations. The methodologists were in charge of the qualitative and quantitative synthesis of the evidence. The panels were responsible for the final decision about risk/benefit profile of the drugs and strength of the recommendations. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used. RESULTS: six recommendations out of 15 were completely updated in 8 months time. In four cases, the strength of the recommendation changed; in two of them, we moved from a weak to a strong positive one. Despite the increased certainty about the positive risk/benefit profile, this was translated in a change in the strength of the recommendation only in one case out of three. Three recommendations were refined making them more clinically specific. CONCLUSIONS: accumulation of evidence is an opportunity for guideline panels to refine methodological rigour, clinical relevance and to foster consensus on recommendations. This requires time and resource investments.

Prevalence of undertreatment in cancer pain. A review of published literature.

BACKGROUND: Pain is a major health care problem for patients with cancer: despite the existence of guidelines for cancer pain management, undertreatment is a widespread problem. Pain Management Indexes (PMIs) evaluate the congruence between the patient's reported level of pain and the intensity/strength of the analgesic therapy. Negative scores indicate inadequate prescriptions. MATERIALS AND METHODS: We conducted a Medline search using terms for 'pain management', 'index' or 'measure' to select studies which measured undertreatment in cancer settings. Univariate and multivariate logistic regression identified associations between independent predictors and high prevalence of undertreatment. RESULTS: Among the 44 studies identified, 26 studies used the PMI as proposed by Cleeland. The range of negative PMI varied from 8% to 82% with a weighted mean value of 43%. In multivariate analyses, factors associated with negative PMI were date of publication before 2001, provenance from Europe or Asia and countries with a gross national income per capita < $40,000 per year and a care setting not specific for cancer. Age was not a significant predictor for undertreatment. CONCLUSION: Nearly one of two patients with cancer pain is undertreated. The percentage is high, but consists of a large variability of undertreatment across studies and settings.

Systematic review with network meta-analysis: comparative efficacy and safety of budesonide and mesalazine (mesalamine) for Crohn's disease.

BACKGROUND: Budesonide and mesalazine (mesalamine) are commonly used in the medical management of patients with mild to moderate Crohn's disease. AIM: To assess their comparative efficacy and harm using the methodology of network meta-analysis. METHODS: A comprehensive search of Medline, Embase, the Cochrane Library and ClinicalTrials.gov, through October 2014, was performed to identify randomised controlled trials (RCTs) that recruited adult patients with active or quiescent Crohn's disease, and compared budesonide or mesalazine with placebo, or against each other, or different dosing strategies of one drug. RESULTS: Twenty-five RCTs were combined using Bayesian network meta-analysis. Budesonide 9 mg/day, or at higher doses (15 or 18 mg/day), was shown superior to placebo for induction of remission [odds ratio (OR), 2.93; 95% credible interval (CrI), 1.52-5.39, and OR, 3.28; CrI, 1.46-7.55 respectively] and ranks at the top of the hierarchy of the competing treatments. For maintenance of remission, budesonide 6 mg/day demonstrated superiority over placebo (OR, 1.69; CrI, 1.05-2.75), being also at the best ranking position among all compared treatment strategies. No other comparisons (i.e. different doses of mesalazine vs. placebo or budesonide, for induction or maintenance of remission) reached significance. The occurrence of withdrawals due to adverse events was not shown different between budesonide, mesalazine and placebo, in both the induction and maintenance phases. CONCLUSIONS: Budesonide, at the doses of 9 mg/day, or higher, for induction of remission in active mild or moderate Crohn's disease, and at 6 mg/day for maintenance of remission, appears to be the best treatment choice.

Constraint-induced movement therapy in stroke patients: systematic review and meta-analysis.

AIM: Upper extremity paresis is a leading cause of disability after stroke. A Cochrane review found an impact on disability of Constraint-Induced Movement Therapy (CIMT), its modified forms (mCIMT) and Forced Use (FU), with a moderate significant effect and a large significant effect on arm motor function. This article aims to present an update of the Cochrane review and assess the effects of CIMT, mCIMT and FU on disability and arm motor function. METHODS: Electronic databases were searched for Randomised Controlled Trials (RCT) and quasi-RCTs comparing CIMT, mCIMT or FU with other rehabilitative techniques, or none, in adult stroke patients. The primary and secondary outcomes were disability and arm motor function. Two reviewers independently screened search results, documented the methodological quality and extracted data. RESULTS: Four new studies were added to the previous review, for a total of 18 studies. The updated meta-analyses no longer indicate a benefit of CIMT mCIMT and FU on disability (eight studies, 276 participants, Standardised Mean Difference (SMD) 0.21, 95% CI -0.08 to 0.50), and a moderate benefit on arm motor function (14 studies, 479 participants, SMD 0.44, 95% CI 0.03 to 0.93). CONCLUSION: New evidence pushes the overall estimate of benefit toward the null effect. The majority of studies were underpowered and imprecise, exposing these analyses to small-study bias. This may explain why accumulation of evidence makes overall estimates inconsistent. Larger randomised trials to resolve these uncertainties are needed.