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INTRODUCTION: Computerized Decision Support Systems (CDSSs) connect health care professionals with high-quality, evidence-based information at the point-of-care to guide clinical decision-making. Current research shows the potential of CDSSs to improve the efficiency and quality of patient care. The mere provision of the technology, however, does not guarantee its uptake. This qualitative study aims to explore the barriers and facilitators to the use of CDSSs as identified by health providers. METHODS: The study was performed in three Italian hospitals, each characterized by a different level of familiarity with the CDSS technology. We interviewed frontline physicians, nurses, information technology staff, and members of the hospital board of directors (n=24). A grounded theory approach informed our sampling criteria as well as the data collection and analysis. RESULTS: The adoption of CDSSs by health care professionals can be represented as a process that consists of six "positionings," each corresponding to an individual's use and perceived mastery of the technology. In conditions of low mastery, the CDSS is perceived as an object of threat, an unfamiliar tool that is difficult to control. On the other hand, individuals in conditions of high mastery view the CDSS as a helpful tool that can be locally adapted and integrated with clinicians' competences to fulfil their needs. In the first positionings, the uptake of CDSSs is hindered by representational obstacles. The last positionings, alternatively, featured technical obstacles to CDSS uptake. DISCUSSION: Our model of CDSS adoption can guide hospital administrators interested in the future integration of CDSSs to evaluate their organizational contexts, identify potential challenges to the implementation of the technology, and develop an effective strategy to address them. Our findings also allow reflections concerning the misalignment between most Italian hospitals and the current innovation trends toward the uptake of computerized decision support technologies.

Background Selection of appropriate outcome measures is crucial in clinical trials in order to minimize bias and allow for precise comparisons of effects between interventions [1-3]. Objective We aimed to assess the frequency and completeness of outcome measures in randomized controlled trials (RCTs) included in Cochrane systematic reviews (SRs), focusing on evaluations of the efficacy and safety of rehabilitation interventions for mechanical LBP. Materials and methods We performed a cross-sectional study of all RCTs included in all Cochrane SRs (full-text) published on The Cochrane Database of Systematic Reviews in February 2013. Two authors independently evaluated the type and frequency of each outcome measure reported in the fulltext of RCTs, the methods used to measure outcomes, and the proportion of outcomes fully replicable based on the reported information (Figure 1). Results Our literature search identified 11 Cochrane SRs, including 185 RCTs. Across all RCTs, thirty-six different outcomes were investigated. The outcomes most commonly reported were pain (165/185; 89,2%, 95% Confidence Interval (CI) 84.7% – 93.7 %), disability (118/185; 63,8%, 95% CI 56.9% – 70.7 %), range of motion (72/185; 38.9% 95% CI 31.9% – 45.9%), and quality of life (45/185; 24,3%, 95% CI 18.1% – 30.5%) measured respectively by 70, 43, 41, 19 different measurement instruments (Figure 2). The procedure of blinding assessment was reported in 49.7% of the RCTs for pain (n= 82 RCTs) and 45% of RCTs for disability (n=53 RCTs). Pain, disability, range of motion, and quality of life outcomes were reported as fully replicable in 10.3% (n= 17 RCTs), 10.1% (n= 12 RCTs), 5.5% (n= 4 RCTs), and 6.6% (n= 3 RCTs) of the RCTs, respectively (Figure 3). Conclusions A large number of outcome measures and a myriad of measurement instruments were used across all RCTs. The reporting was largely incomplete, suggesting better opportunities for the standardization of approaches and reporting.

Background: Advanced Computerized Decision Support Systems (CDSSs) assist clinicians in their decision-making process, generating recommendations based on up-to-date scientific evidence. Although this technology has the potential to improve the quality of patient care, its mere provision does not guarantee uptake: even where CDSSs are available, clinicians often fail to adopt their recommendations. This study examines the barriers and facilitators to the uptake of an evidence-based CDSS as perceived by diverse health professionals in hospitals at different stages of CDSS adoption. Methods: Qualitative study conducted as part of a series of randomized controlled trials of CDSSs. The sample includes two hospitals using a CDSS and two hospitals that aim to adopt a CDSS in the future. We interviewed physicians, nurses, information technology staff and members of the boards of directors (n=30). We used a constant comparative approach to develop a framework for guiding implementation. Findings: We identified six clusters of experiences of, and attitudes towards CDSSs, which we label as ‘positions’. The six positions represent a gradient of acquisition of control over CDSSs (from low to high) and are characterized by different types of barriers to CDSS uptake. The most severe barriers (prevalent in the first positions) include clinicians’ perception that the CDSSs may reduce their professional autonomy or may be used against them in the event of medical-legal controversies. Moving towards the last positions, these barriers are substituted by technical and usability problems related with the technology interface. When all barriers are overcome, CDSSs are perceived as a working tool at the service of its users, integrating clinicians’ reasoning and fostering organizational learning. Discussion: Barriers and facilitators to the use of CDSSs are dynamic and may exist prior to their introduction in clinical contexts; providing a static list of obstacles and facilitators, irrespective of the specific implementation phase and context, may not be sufficient or useful to facilitate uptake. Factors such as clinicians’ attitudes towards scientific evidences and guidelines, the quality of inter-disciplinary relationships and an organizational ethos of transparency and accountability need to considered when exploring the readiness of a hospital to adopt CDSSs., This work is supported by the Italian Ministry of Health (GR-2009-1606736), Regione Lombardia (D.R.G. IX/4340 26/10/2012), and the Wellcome Trust (WT097899).

Background: Advanced Computerized Decision Support Systems (CDSSs) assist clinicians in their decision-making process, generating recommendations based on up-to-date scientific evidence. Although this technology has the potential to improve the quality of patient care, its mere provision does not guarantee uptake: even where CDSSs are available, clinicians often fail to adopt their recommendations. This study examines the barriers and facilitators to the uptake of an evidence-based CDSS as perceived by diverse health professionals in hospitals at different stages of CDSS adoption. Methods: Qualitative study conducted as part of a series of randomized controlled trials of CDSSs. The sample includes two hospitals using a CDSS and two hospitals that aim to adopt a CDSS in the future. We interviewed physicians, nurses, information technology staff and members of the boards of directors (n=30). We used a constant comparative approach to develop a framework for guiding implementation. Findings: We identified six clusters of experiences of, and attitudes towards CDSSs, which we label as ‘positions’. The six positions represent a gradient of acquisition of control over CDSSs (from low to high) and are characterized by different types of barriers to CDSS uptake. The most severe barriers (prevalent in the first positions) include clinicians’ perception that the CDSSs may reduce their professional autonomy or may be used against them in the event of medical-legal controversies. Moving towards the last positions, these barriers are substituted by technical and usability problems related with the technology interface. When all barriers are overcome, CDSSs are perceived as a working tool at the service of its users, integrating clinicians’ reasoning and fostering organizational learning. Discussion: Barriers and facilitators to the use of CDSSs are dynamic and may exist prior to their introduction in clinical contexts; providing a static list of obstacles and facilitators, irrespective of the specific implementation phase and context, may not be sufficient or useful to facilitate uptake. Factors such as clinicians’ attitudes towards scientific evidences and guidelines, the quality of inter-disciplinary relationships and an organizational ethos of transparency and accountability need to considered when exploring the readiness of a hospital to adopt CDSSs.

Background Non-specific low back pain (LBP) is the leading cause of disability worldwide. Acute LBP usually has a good prognosis, with rapid improvement within the first 6 weeks. However, the majority of patients develop chronic LBP and suffer from recurrences. For clinical management, a plethora of treatments is currently available but evidence of the most effective options is lacking. The objective of this study will be to identify the most effective interventions to relieve pain and reduce disability in acute and sub-acute non-specific LBP. Methods/design We will search electronic databases (MEDLINE, Embase, CENTRAL) from inception onwards. The eligible population will be individuals with non-specific LBP older than 18 years, both males and females, who experience pain less than 6 weeks (acute) or between 6 and 12 weeks (subacute). Eligible interventions and comparators will include all conservative rehabilitation or pharmacological treatments provided by any health professional; the only eligible study design will be a randomized controlled trial. The primary outcomes will be pain intensity and back-specific functional status. Secondary outcomes will be any adverse events. Studies published in languages other than English will also potentially be included. Two reviewers will independently screen the titles and abstracts retrieved from a literature search, as well as potentially relevant full-text articles. General characteristics, potential effect modifiers, and outcome data will be extracted from the included studies, and the risk of bias will be appraised. Conflicts at all levels of screening and abstraction will be resolved through team discussions. After describing the results of the review, if appropriate, a random effects meta-analysis and network meta-analysis will be conducted in a frequentist setting, assuming equal heterogeneity across all treatment comparisons and accounting for correlations induced by multi-arm studies using a multivariate normal model. Discussion Our systematic review will address the uncertainties in the use of pharmacological or non-pharmacological treatments, and their relative efficacy, for acute and subacute LBP. These findings will be useful for patients, healthcare providers, and policymakers. Systematic review registration PROSPERO CRD42018102527 Electronic supplementary material The online version of this article (10.1186/s13643-019-1116-3) contains supplementary material, which is available to authorized users.

The aim of this study was to describe the clinical use of bevacizumab in Lombardy (9.5 million inhabitants), Italy, during 2006–2007 in patients with metastatic colorectal cancer (mCRC) to evaluate compliance with the Italian Medicine Agency (AIFA) indications, the incidence of adverse events, and the survival rate. We performed computerized record linkage among three different Lombardy health care databases: File F registry, Regional discharge database, and Registry Office records. Patients were classified into approved and off-label uses according to the AIFA indications. Treatment with bevacizumab was administered to 780 patients, of whom 81.7% (n = 637) had mCRC. Among these, 37.8% (n = 241) of patients received the drug in observance of AIFA indications. Overall, ∼10% of patients had serious treatment-related toxicities (fistula, 3.5%; venous thromboembolism, 2.8%; hemorrhage, 1.9%; intestinal perforation and arterial thromboembolism, There was a gap between the bevacizumab approved indication and clinical practice pattern: overall, less than one half of the patients received bevacizumab in observance with the regulatory indication. The main reason for nonadherence to the indication was use as a second-line or advanced line of therapy. The incidence of serious adverse events and the survival rates of mCRC patients were similar to those reported in clinical trials.

ObjectiveTo assess the effectiveness of interventions for acute and subacute non-specific low back pain (NS-LBP) based on pain and disability outcomes.DesignA systematic review of the literature with network meta-analysis.Data sourcesMedline, Embase and CENTRAL databases were searched from inception until 17 October 2020.Eligibility criteria for selecting studiesRandomised clinical trials (RCTs) involving adults with NS-LBP who experienced pain for less than 6 weeks (acute) or between 6 and 12 weeks (subacute).ResultsForty-six RCTs (n=8765) were included; risk of bias was low in 9 trials (19.6%), unclear in 20 (43.5%), and high in 17 (36.9%). At immediate-term follow-up, for pain decrease, the most efficacious treatments against an inert therapy were: exercise (standardised mean difference (SMD) −1.40; 95% confidence interval (CI) −2.41 to –0.40), heat wrap (SMD −1.38; 95% CI −2.60 to –0.17), opioids (SMD −0.86; 95% CI −1.62 to –0.10), manual therapy (SMD −0.72; 95% CI −1.40 to –0.04) and non-steroidal anti-inflammatory drugs (NSAIDs) (SMD −0.53; 95% CI −0.97 to –0.09). Similar findings were confirmed for disability reduction in non-pharmacological and pharmacological networks, including muscle relaxants (SMD -0.24; 95% CI -0.43 to -0.04). Mild or moderate adverse events were reported in the opioids (65.7%), NSAIDs (54.3%) and steroids (46.9%) trial arms.ConclusionWith uncertainty of evidence, NS-LBP should be managed with non-pharmacological treatments which seem to mitigate pain and disability at immediate-term. Among pharmacological interventions, NSAIDs and muscle relaxants appear to offer the best harm–benefit balance.

Objective To systematically assess the reporting of sample size calculation in randomized controlled trials (RCTs) on rehabilitation interventions for mechanical low back pain. Data Sources The Cochrane Database of Systematic Reviews was searched through February 2015. Study Selection We conducted an electronic database search for RCTs published from January 1, 1968 to February 28, 2015 and included in the Cochrane Systematic Reviews. Data Extraction Two investigators independently used an ad hoc 6-item checklist derived from the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement recommendations to extract data on sample size calculation. The primary outcome was the proportion of RCTs that reported sample size calculation; the secondary outcome was the completeness of sample size analysis reporting. We also evaluated improvement in reporting of sample size calculation over time. Data Synthesis Sample size calculation was reported in 80 (36.0%) of the 222 eligible RCTs included in 14 Cochrane Systematic Reviews. Only 13 (16.3%) of these RCT reports gave a complete description, and about half reported ≥4 of the 6 elements of sample size calculation (median, 4; interquartile range, 3–5). Completeness of reporting of sample size calculation improved from 1968 to 2013; since 2005, the number of RCTs reporting sample size calculation has increased compared with the number of RCTs not reporting it. Conclusions Despite improvement, reporting of sample size calculation and power analysis remains inadequate, limiting the reader's ability to assess the quality and accuracy of rehabilitation studies.

The evidence on efficacy and safety of trastuzumab in metastatic breast cancers (MBC) mainly derives from randomized clinical trials. We assessed short- and long-term overall survival (OS) and cardiotoxicity in a large cohort of women with MBC treated with trastuzumab in clinical settings. Using healthcare administrative data of Lombardy (10 millions inhabitants), we identified a cohort of women receiving trastuzumab for MBC between 2006 and 2009. The cumulative risk of severe cardiac events and the OS from the first trastuzumab administration were estimated using the Kaplan-Meier method. Their predictors were assessed using Cox regression models. We found 681 trastuzumab MBC users. Thirty two (4.7%) women experienced severe cardiac adverse events. The cumulative risk increased sharply, reaching a value of 2.4% and 4.3% during the first and second year; thereafter it increased of about 1% per year. Age was a strong predictor of cardiotoxicity. The OS was 81.8%, 64.0%, 50.2%, 41.1% and 37.2% at 1, 2, 3, 4 and 5 years, respectively. Independent predictors of worse OS were: age, brain liver or lung metastasis compared to other metastasis, use of taxanes and other chemotherapies, a cardiac adverse event after trastuzumab use, and a higher time between metastasis and BC diagnoses. The incidence of cardiotoxicity among women treated with trastuzumab for HER2-positive MBC appeared higher than that reported in RCTs, particularly in elder patients. In spite of this, median survival, was, if anything, better.

Background The results of meta-analyses are all too often elusive, making it difficult to interpret their relevance for clinical practice. Reporting them in minimal important difference (MID) units could improve the interpretation of evidence in meta-analyses. The aim of this study was to compare, via calculation of MID units, outcomes after multidisciplinary biopsychosocial rehabilitation (MBR) versus usual care for pain relief in chronic low back pain (LBP). Methods We re-analyzed the data of a published Cochrane review on MBR. To attribute a MID to each pain instrument, we first searched the literature for MIDs. The MID was imputed for instruments without an established MID. We compared outcomes after MBR versus usual care for chronic LBP in the short ( 3 and

SummaryBackground 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.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the benefits and harms of kinesio taping in adults with shoulder pain due to rotator cuff disease.

We aimed to determine the accuracy and failure of OAK device, an automated screening, for the assessment of fall risk in a prospective cohort of healthy adults aged over 65 years. The algorithm for fall risk assessment of the centers for disease control and prevention (CDC) was used as reference standard. Of the 183 individuals recruited, the CDC algorithm classified 80 as being at moderate/high risk and 103 at low risk of falling. OAK device failure incidence was 4.9% (confidence interval [CI] upper limit 7.7%), below the preset threshold for futility-early termination of the study (i.e., not above 15%). The OAK device showed a sensitivity of 84% and a specificity of 67% (receiver operating characteristic [ROC] area 82%; 95% confidence interval [CI] 76-88%), not reaching the preplanned target sensitivity (not lower than 85%). Diagnostic accuracy was not far from the sensitivity levels similar to those obtained with other fall risk assessment. However, some limitations can be considered.ClinicalTrials.gov identifier: NCT02655796.

Background. Concerns have been raised about the cardiac safety profile of trastuzumab for the adjuvant treatment of early stage breast cancer in clinical practice. We assessed tras- tuzumab-related cardiotoxicity and its predictors in a large co-hort of Italian women. Methods. Through a record linkage between four regional health care databases, we identified the rate of severe car-diac adverse events among women treated with trastu-zumab for early breast cancer in Lombardy. The cumulative risk of cardiotoxicity was estimated using the Kaplan-Meier method, and independent predictors were assessed using the Cox model. Results. Of 2,046 trastuzumab users, 53 (2.6%) experienced at least one hospitalization for a cardiac event, and there were two cardiac deaths. The cumulative risk of cardiotoxicity in- creased up to 2 years after starting treatment, reaching a pla-teau at 2.8%. The risk was low (0.2%) among young women, whereas the incidence was approximately 10% in women aged >70 years, irrespective of cardiovascular risk factors. Age and history of cardiac disease were strong predictors of cardiotoxicity, with a hazard ratio of 11.3 (95% confidence in-terval [CI]: 3.5-36.6) for women aged >70 years as compared with those

Study design Methodological review of randomized controlled trials (RCTs). Objective To assess the quality of reporting of rehabilitation interventions for mechanical low back pain (LBP) in published RCTs. Summary of background data Reporting of interventions in RCTs often focused on the outcome value and failed to describe interventions adequately. Methods We systematically searched for all RCTs in Cochrane systematic reviews on LBP published in the Cochrane Database of Systematic Reviews until December 2013. The description of rehabilitation interventions of each RCT was evaluated independently by 2 of the investigators, using an ad hoc checklist of 7 items. The primary outcome was the number of items reported in sufficient details to be replicable in a new RCT or in everyday practice. Results We found 11 systematic reviews, including 220 eligible RCTs, on LBP. Of those, 185 RCTs were included. The median publication year was 1998 (I-III quartiles, 1990 to 2004). The most reported items were the characteristics of participants (91.3%; 95% confidence interval [CI], 87.3-95.4), the intervention providers (81.1%; 95% CI, 75.4-86.7), and the intervention schedule (69.7%; 95% CI, 63-76). Based on the description of the intervention, less than one fifth would be replicable clinically. The proportion of trials providing all essential information about the participants and interventions increased from 14% (n = 7) in 1971 to 1980 to 20% (n = 75) in 2001 to 2010. Conclusion Despite the remarkable amount of energy spent producing RCTs in LBP rehabilitation, the majority of RCTs failed to report sufficient information that would allow the intervention to be replicated in clinical practice. Improving the quality of intervention description is urgently needed to better transfer research into rehabilitation practices. Level of evidence 1.

Purpose: To evaluate the number of published randomized controlled trials (RCTs) focusing on mechanical low back pain (MLBP) rehabilitation, the secular (i.e., long-term) trend, and the distribution of interventions studied. Methods: All included RCTs were extracted from all Cochrane systematic reviews focusing on rehabilitation therapies for MLBP, and two independent reviewers screened and analyzed the information on interventions. Results: After removal of duplicates, the data set consisted of 196 RCTs published between 1961 and 2010. The number of RCTs published increased consistently over time: 2 trials (1% of the total) were published in 1961–1970, 10 (5%) in 1971–1980, 41 (21%) in 1981–1990, 68 (35%) in 1991–2000, and 75 (38%) in 2001–2010. The intervention of interest in the majority of RCTs was exercise therapy (115/399; 29%), followed by spinal manipulation therapies (60/399; 15%). Conclusion: The number of RCTs focusing on MLBP has risen over time; of all interventions studied, exercise therapy has attracted the most research interest.

Purpose: To assess reporting completeness of the most frequent outcome measures used in randomized controlled trials (RCTs) of rehabilitation interventions for mechanical low back pain. Methods: We performed a cross-sectional study of RCTs included in all Cochrane systematic reviews (SRs) published up to May 2013. Two authors independently evaluated the type and frequency of each outcome measure reported, the methods used to measure outcomes, the completeness of outcome reporting using a eight-item checklist, and the proportion of outcomes fully replicable by an independent assessor. Results: Our literature search identified 11 SRs, including 185 RCTs. Thirty-six different outcomes were investigated across all RCTs. The 2 most commonly reported outcomes were pain (n=165 RCTs; 89.2%) and disability (n=118 RCTs; 63.8%), which were assessed by 66 and 44 measurement tools, respectively. Pain and disability outcomes were found replicable in only 10.3% (n=17) and 10.2% (n=12) of the RCTs, respectively. Only 40 RCTs (21.6%) distinguished between primary and secondary outcomes. Conclusions: A large number of outcome measures and a myriad of measurement instruments were used across all RCTs. The reporting was largely incomplete, suggesting an opportunity for a standardized approach to reporting in rehabilitation science.

International audience; BACKGROUND AND AIMS:Diagnostic delay is frequent in patients with Crohn's disease (CD). We developed a tool to predict early diagnosis.METHODS:A systematic literature review and 12 CD specialists identified 'Red Flags', i.e. symptoms or signs suggestive of CD. A 21-item questionnaire was administered to 36 healthy subjects, 80 patients with irritable bowel syndrome (non-CD group) and 85 patients with recently diagnosed (

Background Although research on non-surgical treatments for neck pain (NP) is progressing, there remains uncertainty about the efficacy of cognitive-behavioural therapy (CBT) for this population. Addressing cognitive and behavioural factors might reduce the clinical burden and the costs of NP in society. Objectives To assess the effects of CBT among individuals with subacute and chronic NP. Specifically, the following comparisons were investigated: (1) cognitive-behavioural therapy versus placebo, no treatment, or waiting list controls; (2) cognitive-behavioural therapy versus other types of interventions; (3) cognitive-behavioural therapy in addition to another intervention (e.g. physiotherapy) versus the other intervention alone. Search methods We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, SCOPUS, Web of Science, and PubMed, as well as ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform up to November 2014. Reference lists and citations of identified trials and relevant systematic reviews were screened. Selection criteria We included randomised controlled trials that assessed the use of CBT in adults with subacute and chronic NP. Data collection and analysis Two review authors independently assessed the risk of bias in each study and extracted the data. If sufficient homogeneity existed among studies in the pre-defined comparisons, a meta-analysis was performed. We determined the quality of the evidence for each comparison with the GRADE approach. Main results We included 10 randomised trials (836 participants) in this review. Four trials (40%) had low risk of bias, the remaining 60% of trials had a high risk of bias. The quality of the evidence for the effects of CBT on patients with chronic NP was from very low to moderate. There was low quality evidence that CBT was better than no treatment for improving pain (standard mean difference (SMD) -0.58, 95% confidence interval (CI) -1.01 to -0.16), disability (SMD -0.61, 95% CI -1.21 to -0.01), and quality of life (SMD -0.93, 95% CI -1.54 to -0.31) at short-term follow-up, while there was from very low to low quality evidence of no effect on various psychological indicators at short-term follow-up. Both at short- and intermediate-term follow-up, CBT did not affect pain (SMD -0.06, 95% CI -0.33 to 0.21, low quality, at short-term follow-up; MD -0.89, 95% CI -2.73 to 0.94, low quality, at intermediate-term follow-up) or disability (SMD -0.10, 95% CI -0.40 to 0.20, moderate quality, at short-term follow-up; SMD -0.24, 95% CI-0.54 to 0.07, moderate quality, at intermediate-term follow-up) compared to other types of interventions. There was moderate quality evidence that CBT was better than other interventions for improving kinesiophobia at intermediate-term follow-up (SMD -0.39, 95% CI -0.69 to -0.08, I2 = 0%). Finally, there was very low quality evidence that CBT in addition to another intervention did not differ from the other intervention alone in terms of effect on pain (SMD -0.36, 95% CI -0.73 to 0.02) and disability (SMD -0.10, 95% CI -0.56 to 0.36) at short-term follow-up. For patients with subacute NP, there was low quality evidence that CBT was better than other interventions at reducing pain at short-term follow-up (SMD -0.24, 95% CI -0.48 to 0.00), while no difference was found in terms of effect on disability (SMD -0.12, 95% CI -0.36 to 0.12) and kinesiophobia. None of the included studies reported on adverse effects. Authors' conclusions With regard to chronic neck pain, CBT was found to be statistically significantly more effective for short-term pain reduction only when compared to no treatment, but these effects could not be considered clinically meaningful. When comparing both CBT to other types of interventions and CBT in addition to another intervention to the other intervention alone, no differences were found. For patients with subacute NP, CBT was significantly better than other types of interventions at reducing pain at short-term follow-up, while no difference was found for disability and kinesiophobia. Further research is recommended to investigate the long-term benefits and risks of CBT including for the different subgroups of subjects with NP.

This review was undertaken to determine the effects of cognitive-behavioral therapy among individuals with subacute and chronic neck pain. We included 10 randomized-controlled studies and found with a low-quality evidence that cognitive-behavioral therapy can lead to some improvements on pain relief, but the effects were not clinically relevant. Study Design. Systematic review of randomized-controlled trials (RCTs). Objective. To assess the effects of cognitive-behavioral therapy (CBT) on neck pain (NP). Summary of Background Data. Although research on nonpharmacological and nonsurgical treatments for NP is progressing, there remains uncertainty about the efficacy of CBT. Methods. We searched electronic databases for RCTs. We included RCTs assessing the use of CBT on adults with subacute and chronic NP. 2 independent reviewers extracted data on pain (primary outcome), disability, psychological indicator, and quality of life. We calculated standardized mean differences and 95% confidence intervals. We used the Cochrane Collaboration's tool to assess risk of bias and the GRADE approach to evaluate the quality of evidence and summarize conclusions. Results. We included 10 studies (836 participants), 4 at low risk of bias. With regard to chronic NP, there was low quality evidence that CBT was better than no treatment for improving pain, disability, and quality of life, whereas no effect was found on kinesiophobia. The clinical importance of these benefits is uncertain. When comparing both CBT to other interventions and CBT in addition to another intervention to the other intervention alone, no difference was found for pain and disability, whereas a positive effect was achieved for kinesiophobia only when comparing CBT with other interventions. On subacute NP, CBT was found to be better than other interventions for pain, whereas no difference was found for secondary outcomes. Conclusion. CBT was shown to induce changes on pain and disability for chronic NP only when compared with no treatment. On subacute NP, benefit was found on pain relief but not on disability when comparing CBT with other interventions. However, none of these effects were clinically meaningful. Due to the low quality of the evidence, our conclusions might change over time whereas new data are available.

Background. The evidence supporting the use of trastuzumab (T) in a metastatic setting comes from studies that included (almost) only patients who never received prior T. We investigated the effectiveness of T as first-line therapy for metastatic breast cancer (mBC) in women previously treated with T in the adjuvant setting. Materials and Methods. By using record linkage of five administrative health care databases of Lombardy, Italy, we identified 2,046 women treated with T for early breast cancer (eBC) in 2006–2009, 96 of whom developed a metastasis and were retreated with T in first-line treatment for mBC (treatment group). We compared the overall survival (OS) of these women with that of 197 women treated with T in first-line treatment for mBC, who were treated with therapies other than T for early disease (control group). We computed Kaplan-Meier 2-year OS and used a proportional hazard model to estimate the multivariate hazard ratio (HR) of death in the intervention group compared with the control group, adjusted by age, use of endocrine therapy, and site of metastasis. Results. Two-year OS was 60.0% in the treatment group and 59.5% in the control group. The adjusted HR of death in the treatment group compared with the control group was 0.79 (95% confidence interval, 0.50–1.26). Conclusion. Our data provide convincing evidence that the outcome of women receiving first-line T treatment for mBC after T failure in the adjuvant setting is comparable to that of women not receiving T for eBC. These data are of specific interest, given the unavailability of data from randomized clinical trials.

Correction: Volume: 349 Article Number: g4921 DOI: 10.1136/bmj.g4921 OBJECTIVE: To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. DESIGN: Cohort of protocols of randomised controlled trial and subsequent full journal publications. SETTING: Six research ethics committees in Switzerland, Germany, and Canada. DATA SOURCES: 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. RESULTS: Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P

Biological agents are emerging treatment options for the management of ulcerative colitis (UC).To assess the comparative efficacy and harm of biological agents in adult patients with moderately to severely active UC who are naive to biological agents.MEDLINE, EMBASE, and Cochrane Library from inception through December 2013, without language restrictions, and ClinicalTrials.gov, European Medicines Agency, and U.S. Food and Drug Administration Web sites.Randomized, placebo-controlled or head-to-head trials assessing biological agents as induction or maintenance therapy for moderately to severely active UC.Two reviewers independently abstracted study data and outcomes and rated each trial's risk of bias.There were no head-to-head trials. There were 7 double-blind, placebo-controlled trials that were rated as low risk of bias and showed that all biological agents (adalimumab, golimumab, infliximab, and vedolizumab) resulted in more clinical responses, clinical remissions, and mucosal healings than placebo for induction therapy. The results of network meta-analysis suggested that infliximab is more effective to induce clinical response (odds ratio, 2.36 [95% credible interval, 1.22 to 4.63]) and mucosal healing (odds ratio, 2.02 [95% credible interval, 1.13 to 3.59]) than adalimumab. No other indirect comparison reached statistical significance. For maintenance, 6 double-blind, placebo-controlled trials that were rated high risk of bias showed that all biological agents have greater clinical efficacy than placebo. The occurrence of adverse events was not different between biological agents and placebo.Few trials, no head-to-head comparisons, and inadequate follow-up in maintenance trials.Biological agents are effective treatments for UC, but head-to-head trials are warranted to establish the best therapeutic option.

Background: Trial sequential analysis (TSA) may establish when firm evidence about the efficacy of interventions is reached in a cumulative meta-analysis, combining a required information size with adjusted thresholds for conservative statistical significance. Our aim was to demonstrate TSA results on randomized controlled trials (RCTs) included in a Cochrane systematic review on the effectiveness of constraint-induced movement therapy (CIMT) for stroke patients. Methods: We extracted data on the functional independence measure (FIM) and the action research arm test (ARAT) from RCTs that compared CIMT versus other rehabilitative techniques. Mean differences (MD) were analyzed using a random-effects model. We calculated the information size and the cumulative Z-statistic, applying the O'Brien-Fleming monitoring boundaries. Results: We included data from 14 RCTs. In the conventional meta-analysis (seven trials, 233 patients), the effect of CIMT on FIM was reported as significant (MD 2.88, 95% CI 0.08 to 5.68; P = 0.04). The diversity-adjusted required information size was 142 patients, and the cumulative Z-score did not cross the trial sequential monitoring boundary for benefit (adjusted 95% CI -0.02 to 5.78). The effect of CIMT on ARAT (nine trials, 199 patients) was reported as significant (MD 7.78, 95% CI 1.19 to 14.37; P = 0.02). However, the diversity-adjusted required information size was 252 patients, and the Z-score did not cross the trial sequential monitoring boundary for benefit (adjusted 95% CI -0.06 to 15.62). Conclusions: Although conventional meta-analyses of CIMT reached statistical significance, their overall results remain inconclusive and might be spurious. Researchers should not be overconfident on CIMT efficacy based on the results of meta-analyses and derived recommendations.

Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age

Background: Computerized clinical decision support systems (CDSSs) have been shown to improve the efficiency and quality of patient care by connecting healthcare professionals with high quality, evidence-based information at the point-of-care. The mere provision of CDSSs, however, does not guarantee their uptake. Rather, individual and institutional perceptions can foster or inhibit the integration of CDSSs into routine clinical workflow. Current studies exploring health professionals’ perceptions of CDSSs focus primarily on technical and usability issues, overlooking the social or cultural variables as well as broader administrative or organizational roles that may influence CDSS adoption. Moreover, there is a lack of data on the evolution of perceived barriers or facilitators to CDSS uptake across different stages of implementation. Methods: We will conduct a qualitative, cross-sectional study in three Italian specialty hospitals involving frontline physicians, nurses, information technology staff, and members of the hospital board of directors. We will use semi-structured interviews following the Grounded Theory framework, progressively recruiting participants until no new information is gained from the interviews. Discussion: CDSSs are likely to become an integral and diffuse part of clinical practice. Various factors must be considered when planning their introduction in healthcare settings. The findings of this study will guide the development of strategies to facilitate the successful integration of CDSSs into the regular clinical workflow. The evaluation of diverse health professionals across multiple hospital settings in different stages of CDSS uptake will better capture the complexity of roles and contextual factors affecting CDSS uptake.

Background: Heart failure (HF) patients show high morbidity and mortality rate with increased risk of malignant arrhythmia and thromboembolism. Anticoagulation reduces embolic event and death rates in HF patients with atrial fibrillation, but if antithrombotic therapy is beneficial in patients with HF in sinus rhythm is still debated. Methodology and Principal Findings: We conducted a systematic review of prospective, randomized controlled trials (RCTs) to assess the efficacy and safety of oral anticoagulant therapies (OATs) compared to antiplatelet treatment in HF patients in sinus rhythm. MEDLINE, Web of Science, CENTRAL and Scopus databases were searched up to May 2012. Four RCTs were identified and a total of 3663 patients were included in the meta-analysis. Patients with both ischemic and non-ischemic HF were included. There was no significant difference in mortality (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.86 to 1.19) between OATs group and antiplatelet drug group. OATs have reduced ischemic stroke risk (OR 0.49, 95% CI 0.32 to 0.74), but have increased major bleeding risk (OR 2.01, 95% CI 1.40 to 2.88) compared to antiplatelet treatment. Conclusion: In HF patients in sinus rhythm OATs do not show a better risk-benefit profile compared to antiplatelet treatment in cardioembolism prevention. Warfarin and aspirin seem to be similar in reducing mortality. Warfarin reduces the incidence of ischemic stroke, but increases major bleedings. Thus, it is possible to speculate that aspirin prescription be indicated in patients with high risk of bleeding, whereas warfarin could be preferred in patients with high thromboembolic risk. © 2013 Rengo et al.

Background Although muscular dystrophy causes muscle weakness and muscle loss, the role of exercise in the management of this disease remains controversial. Objective The purpose of this systematic review is to evaluate the role of exercise interventions on muscle strength in patients with muscular dystrophy. Methods We performed systematic electronic searches in Medline, Embase, Web of Science, Scopus and Pedro as well as a list of reference literature. We included trials assessing muscle exercise in patients with muscular dystrophy. Two reviewers independently abstracted data and appraised risk of bias. Results We identified five small (two controlled and three randomized clinical) trials comprising 242 patients and two ongoing randomized controlled trials. We were able to perform two meta-analyses. We found an absence of evidence for a difference in muscle strength (MD 4.18, 95% CIs - 2.03 to 10.39; p = 0.91) and in endurance (MD −0.53, 95% CIs –1.11 to 0.05; p = 0.26). In both, the direction of effects favored muscle exercise. Conclusions The first included trial about the efficacy of muscular exercise was published in 1978. Even though some benefits of muscle exercise were consistently reported across studies, the benefits might be due to the small size of studies and other biases. Detrimental effects are still possible. After several decades of research, doctors cannot give advice and patients are, thus, denied basic information. A multi-center randomized trial investigating the strength of muscles, fatigue, and functional limitations is needed.

Background Systematic reviews (SRs) have become increasingly important for informing clinical practice; however, little is known about the reporting characteristics and the quality of the SRs relevant to the practice of rehabilitation health professionals. Objective The purpose of this study was to examine the reporting quality of a representative sample of published SRs on rehabilitation, focusing on the descriptive, reporting, and bias-related characteristics. Methods A cross-sectional study was conducted by searching MEDLINE for aggregative and configurative SRs indexed in 2011 that focused on rehabilitation as restorative of functional limitations. Two reviewers independently screened and selected the SRs and extracted data using a 38-item data collection form derived from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The data were analyzed descriptively. Results Eighty-eight SRs published in 59 journals were sampled. The median compliance with the PRISMA items was 17 (63%) out of 27 items (interquartile ratio=13–22 [48%–82%]). Two thirds of the SRs (n=66) focused on interventions for which efficacy is best addressed through a randomized controlled trial (RCT) design, and almost all of these SRs included RCTs (63/66 [95%]). More than two thirds of the SRs assessed the quality of primary studies (74/88 [84%]). Twenty-eight reviews (28/88 [32%]) meta-analyzed the results for at least one outcome. One half of the SRs reported positive statistically significant findings (46%), whereas a detrimental result was present only in one review. Conclusions This sample of SRs in the rehabilitation field showed heterogeneous characteristics and a moderate quality of reporting. Poor control of potential source of bias might be improved if more widely agreed-upon evidence-based reporting guidelines will be actively endorsed and adhered to by authors and journals.