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Objectives: To assess whether the use of the revised Cochrane risk of bias tool for randomized trials (RoB2) in systematic reviews (SRs) adheres to RoB2 guidance. Methods: We searched MEDLINE, Embase, Cochrane Library from 2019 to May 2021 to identify SRs using RoB2. We analyzed methods and results sections to see whether risk of bias was assessed at outcome measure level and applied to primary outcomes of the SR as per RoB2 guidance. The relation between SR characteristics and adequacy of RoB2 use was examined by logistic regression analysis. Results: Two hundred-eight SRs were included. We could assess adherence in 137 SRs as 12 declared using RoB2 but actually used RoB1 and 59 did not report the number of primary outcomes. The tool usage was adherent in 69.3% SRs. Considering SRs with multiple primary outcomes, adherence dropped to 28.8%. We found a positive association between RoB2 guidance adherence and the methodological quality of the reviews assessed by AMSTAR2 (p-for-trend 0.007). Multivariable regression analysis suggested journal impact factor [first quartile vs. other quartiles] was associated with RoB2 adherence (OR 0.34; 95% CI: 0.16-0.72). Conclusions: Many SRs did not adhere to RoB2 guidance as they applied the tool at the study level rather than at the outcome measure level. Lack of adherence was more likely among low and very low quality reviews.

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 m

BACKGROUND: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable gas exchange. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs. OBJECTIVES: To assess the benefits and harms of an initial sustained lung inflation (SLI) (> 1 second duration) versus standard inflations (≤ 1 second) in newborn infants receiving resuscitation with intermittent PPV. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3), MEDLINE via PubMed (1966 to 1 April 2019), Embase (1980 to 1 April 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 1 April 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean standard deviation (SD), and weighted mean difference (WMD) for continuous data. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Ten trials enrolling 1467 infants met our inclusion criteria. Investigators in nine trials (1458 infants) administered sus

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.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is associated with increased morbidity and mortality, but the identification of LVAD candidates at risk for RVF remains challenging. We undertook a systematic review and meta-analysis of observational studies of risk factors associated with RVF after LVAD implant. Thirty-six studies published between 1 January 1995 and 30 April 2015, comprising 995 RVF patients out of a pooled final population of 4428 patients, were identified. Meta-analysed prevalence of post-LVAD RVF was 35%. A need for mechanical ventilation [odds ratio (OR) 2.99], or continuous renal replacement therapy (CRRT; OR 4.61, area under the curve 0.78, specificity 0.91) were the clinical variables with the highest effect size (ES) in predicting RVF. International normalized ratio [INR; standardized mean difference (SMD) 0.49] and N-terminal pro-brain natriuretic peptide (NT-proBNP) (SMD 0.52) were the biochemical markers that best discriminated between RVF and No-RVF populations, though NT-proBNP was highly heterogeneous. Right ventricular stroke work index (RVSWI) and central venous pressure (CVP) (SMD −0.58 and 0.47, respectively) were the haemodynamic measures with the highest ES in identifying patients at risk of post-LVAD RVF; CVP was particularly useful in risk stratifying patients undergoing continuous-flow LVAD implant (SMD 0.59, P < 0.001, I2 = 20.9%). Finally, pre-implant moderate to severe right ventricular (RV) dysfunction, as assessed qualitatively (OR 2.82), or a greater RV/LV diameter ratio (SMD 0.51) were the standard echocardiographic measurements with the highest ES in comparing RVF with No-RVF patients. Longitudinal systolic strain of the RV free wall had the highest ES (SMD 0.73) but also the greatest heterogeneity (I2 = 74%) and was thus only marginally significant (P = 0.05). Patients on ventilatory support or CRRT are at high risk for post-LVAD RVF, similarly to patients with slightly incr

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 months), mid (>3 and<12 months), and long (≥12 months) term. The results of the meta-analyses are reported in MID units and interpreted as follows: if the overall effect size was greater than 1, many patients gained clinically important benefits, if it lay between 0.5 and 1.0, an appreciable number benefited, and if it fell below 0.5 few did. Results: Improvement in back pain was observed in an appreciable number of patients in the short- and medium-term after MBR: the MID was lower but still close to 1 (0.75 and 0.86 MID units, respectively). MBR probably had little or no benefit for the majority of patients in the long-term, where the MID approached 0 (0.27 MID units, confidence interval 0.07-0.48). Conclusions: Meta-analyses expressed in MID units may offer better insight into the clinical relevance of MBR: the intervention is highly recommended for reducing pain in the short- and medium-term but cannot be recommended for long-term pain reduction since the benefit decays rapidly.

Background: The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. Methods: We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. Findings: We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium's total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus. Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori, and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae, and Salmonella typhi were included in the high-priority tier. Interpretation: Fu

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.

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.

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.

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 comp

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), disa

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.

Infantile colic can be defined as periods of inconsolable, unexplained, and incessant crying in a seemingly healthy infant that, quite understandably, leads to exhausted, frustrated, and concerned parents seeking to comfort their child (Landgren 2010). The prevalence of excessive crying varies according to the definition used although, most often, it peaks during the second month of life,with a prevalence of 1.5%to 11.9%(Reijneveld 2001).Traditionally, the definition of the condition was based on the rule of three (Wessel 1954): that is, unexplained episodes of paroxysmal crying for more than three hours per day, for three days per week, for at least three weeks. More recently a new definition has been proposed. It refers to a clinical condition of fussing and crying for at least one week in an otherwise healthy infant (Hyman 2006). Colic can be graded as mild, moderate, or severe, though there is no consensus for this classification. Colic can affect up to 10% to 30% of infants worldwide (Clifford 2002; Rosen 2007).

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 2,046women treated with T for early breast cancer (eBC) in 2006-l2009, 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 firstline 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.

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 <40 or ≥70 years compared to age 40-69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.