Objective To investigate the effect of an additional review based on reporting guidelines such as STROBE and CONSORT on quality of manuscripts.Design Masked randomised trial.Population Original research manuscripts submitted to the Medicina Clínica journal from May 2008 to April 2009 and considered suitable for publication.Intervention Control group: conventional peer reviews alone. Intervention group: conventional review plus an additional review looking for missing items from reporting guidelines.Outcomes Manuscript quality, assessed with a 5 point Likert scale (primary: overall quality; secondary: average quality of specific items in paper). Main analysis compared groups as allocated, after adjustment for baseline factors (analysis of covariance); sensitivity analysis compared groups as reviewed. Adherence to reviewer suggestions assessed with Likert scale.Results Of 126 consecutive papers receiving conventional review, 34 were not suitable for publication. The remaining 92 papers were allocated to receive conventional reviews alone (n=41) or additional reviews (n=51). Four papers assigned to the conventional review group deviated from protocol; they received an additional review based on reporting guidelines. We saw an improvement in manuscript quality in favour of the additional review group (comparison as allocated, 0.25, 95% confidence interval –0.05 to 0.54; as reviewed, 0.33, 0.03 to 0.63). More papers with additional reviews than with conventional reviews alone improved from baseline (22 (43%) v eight (20%), difference 23.6% (3.2% to 44.0%), number needed to treat 4.2 (from 2.3 to 31.2), relative risk 2.21 (1.10 to 4.44)). Authors in the additional review group adhered more to suggestions from conventional reviews than to those from additional reviews (average increase 0.43 Likert points (0.19 to 0.67)).Conclusions Additional reviews based on reporting guidelines improve manuscript quality, although the observed effect was smaller than hypothesised and not definitively demonstrated. Authors adhere more to suggestions from conventional reviews than to those from additional reviews, showing difficulties in adhering to high methodological standards at the latest research phases. To boost paper quality and impact, authors should be aware of future requirements of reporting guidelines at the very beginning of their study. Trial registration and protocol Although registries do not include trials of peer review, the protocol design was submitted to sponsored research projects (Instituto de Salud Carlos III, PI081903).

BACKGROUND: Electrical impedance tomography measures changes in lung impedance, which are mainly related to changes in lung volume. We used electrical impedance tomography to investigate the effects of high-flow nasal cannula (HFNC) and body position on global and regional end-expiratory lung impedance variation (⌬EELI). METHODS: Prospective study with 20 healthy adults. Two periods were defined: the first in supine position and the second in prone position. Each period was divided into 3 phases. In the first and the third phases the subjects were breathing ambient air, and in the second HFNC was implemented. Four regions of interest were defined: 2 ventral and 2 dorsal. All men by nature desire to know.-Aristotle, Metaphysics

Although there are probably more molecular mechanisms by which PhA exerts its beneficial effects in stroke outcomes, our observation regarding the potential role of VEGF is plausible and in line with previous experimental studies. Further research in this field is needed.

Rationale Optimal pre-hospital delivery pathways for acute stroke patients suspected to harbor a large vessel occlusion have not been assessed in randomized trials. Aim To establish whether stroke subjects with rapid arterial occlusion evaluation scale based suspicion of large vessel occlusion evaluated by emergency medical services in the field have higher rates of favorable outcome when transferred directly to an endovascular center (endovascular treatment stroke center), as compared to the standard transfer to the closest local stroke center (local-SC). Design Multicenter, superiority, cluster randomized within a cohort trial with blinded endpoint assessment. Procedure Eligible patients must be 18 or older, have acute stroke symptoms and not have an immediate life threatening condition requiring emergent medical intervention. They must be suspected to have intracranial large vessel occlusion based on a pre-hospital rapid arterial occlusion evaluation scale of ≥5, be located in geographical areas where the default health authority assigned referral stroke center is a non-thrombectomy capable hospital, and estimated arrival at a thrombectomy capable stroke hospital in less than 7 h from time last seen well. Cluster randomization is performed according to a pre-established temporal sequence (temporal cluster design) with three strata: day/night, distance to the endovascular treatment stroke center, and week/week-end day. Study outcome The primary endpoint is the modified Rankin Scale score at 90 days. The primary safety outcome is mortality at 90 days. Analysis The primary endpoint based on the modified intention-to-treat population is the distribution of modified Rankin Scale scores at 90 days analyzed under a sequential triangular design. The maximum sample size is 1754 patients, with two planned interim analyses when 701 (40%) and 1227 patients have completed follow-up. Hypothesized common odds ratio is 1.35.

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Background: Precision medicine is the Holy Grail of interventions that are tailored to a patient’s individual characteristics. However, conventional clinical trials are designed to find differences in averages, and interpreting these differences depends on untestable assumptions. Although only an ideal, a constant effect of treatment would facilitate individual management. A direct consequence of a constant effect is that the variance of the outcome measure would be the same in the treated and control arms. We reviewed the literature to explore the similarity of these variances as a foundation for examining whether and how often precision medicine is definitively required. Methods: We reviewed parallel clinical trials with numerical primary endpoints published in 2004, 2007, 2010 and 2013. We collected the baseline and final standard deviations of the main outcome measure. We assessed homoscedasticity by comparing the variance of the primary endpoint between arms through the outcome variance ratio (treated to control group). Results: The review provided 208 articles with enough information to conduct the analysis. One out of five studies (n = 40, 19.2%) had statistically different variances between groups, implying a non-constant-effect. The adjusted point estimate of the mean outcome variance ratio (treated to control group) is 0.89 (95% CI 0.81 to 0.97). Conclusions: The mean variance ratio is significantly lower than 1 and the lower variance was found more often in the intervention group than in the control group, suggesting it is more usual for treated patients to be stable. This observed reduction in variance might also imply that there could be a subgroup of less ill patients who derive no benefit from treatment. This would require further study as to whether the treatment effect outweighs the side effects as well as the economic costs. We have shown that there are ways to analyze the apparently unobservable constant effect.

Background: Precision medicine is the Holy Grail of interventions that are tailored to a patient’s individual characteristics. However, conventional clinical trials are designed to find differences in averages, and interpreting these differences depends on untestable assumptions. Although ideal, a constant effect would facilitate individual management. Another consequence of a constant effect is that the outcome variance would be the same in treated and control arms. We reviewed the literature to explore the similarity of these variances as a foundation for examining whether and how often precision medicine is definitively needed. Methods: We reviewed parallel trials with quantitative outcomes published in 2004, 2007, 2010 and 2013. We collected baseline and final standard deviations of the main outcome. We assessed homoscedasticity by comparing the variance of the primary endpoint between arms through the outcome variance ratio (treated to control group). Results: The review provided 208 articles with enough information to conduct the analysis. One out of seven studies (n = 30, 14.4%) had statistically different variances between groups, leading a non-constant-effect. The adjusted point estimate of the mean outcome variance ratio (treated to control group) is 0.89 (95% CI 0.81 to 0.97). Conclusions: We found that the outcome variance was more often smaller in the intervention group, suggesting that treated patients may end up pertaining more often to reference values. This observed reduction in variance might also imply that there could be a subgroup of less ill patients who derive no benefit, which would require studying whether the effect merits enduring the side effects as well as the economic costs. We have shown that the comparison of variances is a useful but not definitive tool for assessing whether or not the assumption of a constant effect holds.