Jordi Cortés

Effect of using reporting guidelines during peer review on quality of final manuscripts submitted to a biomedical journal: masked randomised trial

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).

Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography.

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 (ΔEELI). 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. For each respiratory cycle, global and regional ΔEELI were measured by electrical impedance tomography and were expressed as a function of the tidal variation of the first stable respiratory cycle (units). RESULTS: HFNC increased global EELI by 1.26 units (95% CI 1.20–1.31, P < .001) in supine position, and by 0.87 units (95% CI 0.82–0.91, P < .001) in prone position. The distribution of ΔEELI was homogeneous in prone position, with no difference between ventral and dorsal lung regions (−0.01 units, 95% CI −0.01 to 0, P = .18), while in supine position a significant difference was found (0.22 units, 95% CI 0.21–0.23, P < .001) with increased EELI in ventral areas. CONCLUSIONS: HFNC increased global EELI in our population, regardless of body position, suggesting an increase in functional residual capacity. Prone positioning was related to a more homogeneous distribution of ΔEELI, while in supine position ΔEELI was higher in the ventral lung regions.

Predictive Value of Modifications of the Prehospital Rapid Arterial Occlusion Evaluation Scale for Large Vessel Occlusion in Patients with Acute Stroke

BACKGROUND Prehospital clinical scales to identify patients with acute stroke with a large vessel occlusion (LVO) and direct them to an endovascular-capable stroke center are needed. We evaluated whether simplification of the Rapid Arterial oCclusion Evaluation (RACE) scale, a 5-item scale previously validated in the field, could maintain its high performance to identify patients with LVO. METHODS Using the original prospective validation cohort of the RACE scale, 7 simpler versions of the RACE scale were designed and retrospectively recalculated for each patient. National Institutes of Health Stroke Scale score and proximal LVO were evaluated in hospital. Receiver operating characteristic analysis was performed to test performance of the simplified versions to identify LVO. For each version, the threshold with sensitivity closest to the original scale (85%) was used, and the variation in specificity and correct classification were assessed. RESULTS The study included 341 patients with suspected stroke; 20% had LVO. The 7 simpler versions of the RACE scale had slightly lower area under the curve for detecting LVO because of lower specificity at the chosen sensitivity level. Correct classification rate decreased 9% if facial palsy was simplified or if eye or gaze deviation was removed, and decreased 4.5% if the aphasia or agnosia cortical sign was removed. CONCLUSIONS We recommend the original RACE scale for prehospital assessment of patients with suspected stroke for its ease of use and its high performance to predict the presence of a LVO. The use of simplified versions would reduce its predictive value.

Circadian Rhythms in the Efficacy of Intravenous Alteplase in Patients With Acute Ischemic Stroke and Middle Cerebral Artery Occlusion

Circadian rhythm interactions of hemostatic factors can modify tissue plasminogen activator (tPA) effects. We assess the relationship of the time frame of intravenous tPA administration with the outcome of patients with acute ischemic stroke (AIS). We studied 135 consecutive patients with AIS and transcranial duplex documented middle cerebral artery (MCA) occlusion treated with intravenous tPA. Complete recanalization was defined as total improvement on thrombolysis in brain ischemia (TIBI) grades 2 h after tPA infusion. Clinical response was evaluated by the modified Rankin scale at 90 days. We determined plasminogen activator inhibitor-1 (PAI-1) levels in 33 patients with available plasma samples before treatment. Our results are follows: 92 (68.1%) patients were treated in the diurnal (9:00–21:00) and 43 (31.8%) in the nocturnal period (21:00–9:00). Complete recanalization was recorded in 52/135 (38.5%) patients. Both the rate of complete recanalization (45.6% vs. 23.2%; p = .01) and good clinical outcome (64.1% vs. 44.2%; p = .02) were significantly higher in the group of diurnal tPA administration compared with those treated in the nocturnal period. The adjusted odds ratio (OR) of diurnal tPA treatment for complete MCA recanalization was 2.37 (95% confidence interval [CI], 1.02–5.52; p = .045). Diurnal tPA infusion significantly improved the overall distribution of scores on the modified Rankin scale, as compared with nocturnal treatment (OR, 2.07; 95% CI, 1.16–4.64 by ordinal regression analysis). Low PAI-1 levels were associated with complete recanalization but did not significantly differ between the two time frames. In conclusion, diurnal administration of tPA is associated with complete MCA recanalization and better functional outcome at 90 days in patients with AIS. (Author correspondence: mgomis.germanstrias@gencat.cat, meritxellgomis@gmail.com)

A hazard ratio was estimated by a ratio of median survival times, but with considerable uncertainty

OBJECTIVES To evaluate the empirical concordance between the hazard ratio (HR) and the median ratio (MR) in survival cancer studies. STUDY DESIGN AND SETTING We selected all cancer survival articles from the New England Journal of Medicine published between 2000 and 2010. The qualitative concordance was estimated by the proportion of measured pairs in which the treatment effects for the MR and HR are in the same direction. The quantitative concordance was assessed through (1) the mean difference between the logarithms of the measures, (2) the Lin coefficient, and (3) the Bland-Altman plot. RESULTS We retrieved 106 measured pairs (HR-MR) corresponding to 54 articles. Concordance was high, at both the qualitative (99 of 106, 93.4%) and quantitative levels (mean MR-to-HR ratio, 1.01; 95% confidence interval: 0.95, 1.06). However, the 95% Bland-Altman discordance limits indicate that the MR can be up to 50% higher or 50% lower than the HR. CONCLUSION The average concordance allows trialists to approximate HR from MR to determine sample size. However, the discordance limits are too great to consider that both measures are interchangeable. The actual policy to report HR only is not enough. Our results emphasize the need to attach descriptive survival measures to the HR.

Reported Prestroke Physical Activity Is Associated with Vascular Endothelial Growth Factor Expression and Good Outcomes after Stroke

INTRODUCTION Physical activity (PhA) prior to stroke has been associated with good outcomes after the ischemic insult, but there is scarce data on the involved molecular mechanisms. METHODS We studied consecutive acute ischemic stroke patients admitted to a single tertiary stroke center. Prestroke PhA was evaluated with the International Physical Activity Questionnaire (metabolic equivalent of minutes/week). We studied several circulating angiogenic and neurogenic factors at different time points: vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and brain-derived neurotrophic factor (BDNF) at admission, day 7, and at 3 months. We considered good functional outcome at 3 months (modified Rankin scale  ≤ 2) as primary end point, and final infarct volume as secondary outcome. RESULTS We studied 83 patients with at least 2 time point serum determinations (mean age 69.6 years, median National Institutes of Health Stroke Scale 17 at admission). Patients more physically active before stroke had a significantly higher increment of serum VEGF on the seventh day when compared to less active patients. This increment was an independent predictor of good functional outcome at 3 months and was associated with smaller infarct volume in multivariate analyses adjusted for relevant covariates. We did not find independent associations of G-CSF or BDNF levels neither with level of prestroke PhA nor with stroke outcomes. CONCLUSIONS 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.

Efficacy of high doses of penicillin versus amoxicillin in the treatment of uncomplicated community acquired pneumonia in adults. A non-inferiority controlled clinical trial

Introduction Community-acquired pneumonia (CAP) is treated with penicillin in some northern European countries. Objectives To evaluate whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-severe CAP. Design Multicentre, parallel, double-blind, controlled, randomized clinical trial. Setting 31 primary care centers in Spain. Participants Patients from 18 to 75 years of age with no significant associated comorbidity and with symptoms of lower respiratory tract infection and radiological confirmation of CAP were randomized to receive either penicillin V 1.6 million units, or amoxicillin 1000 mg three times per day for 10 days. Main measurements The main outcome was clinical cure at 14 days, and the primary hypothesis was that penicillin V would be non-inferior to amoxicillin with regard to this outcome, with a margin of 15% for the difference in proportions. EudraCT register 2012-003511-63. Results A total of 43 subjects (amoxicillin: 28; penicillin: 15) were randomized. Clinical cure was observed in 10 (90.9%) patients assigned to penicillin and in 25 (100%) patients assigned to amoxicillin with a difference of −9.1% (95% CI, −41.3% to 6.4%; p = .951) for non-inferiority. In the intention-to-treat analysis, amoxicillin was found to be 28.6% superior to penicillin (95% CI, 7.3–58.1%; p = .009 for superiority). The number of adverse events was similar in both groups. Conclusions There was a trend favoring high-dose amoxicillin versus high-dose penicillin in adults with uncomplicated CAP. The main limitation of this trial was the low statistical power due to the low number of patients included.

Barcelona baby boom: does sporting success affect birth rate?

Nine months after a celebrated goal by FC Barcelona in 2009, the media reported a spike in the Catalan birth rate. Jesus Montesinos and colleagues test whether the “Iniesta effect” really existed

Characteristics of Apixaban-Treated Patients, Evaluation of the Dose Prescribed, and the Persistence of Treatment: A Cohort Study in Catalonia

Background: Apixaban is a direct oral anticoagulant, which inhibits factor Xa. It has demonstrated clinical efficacy in prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation and a better safety profile compared to warfarin. Objectives: (1) To describe the characteristics of patients with nonvalvular atrial fibrillation beginning treatment with apixaban, (2) to analyze concomitant prescriptions of medications that could potentially interact with apixaban, (3) to evaluate the level of appropriate usage according to the recommended dosage, and (4) to estimate the level of apixaban persistence among naive and non-naive patients. Methods: Cohort study using data from primary care (System for Research in Primary Care database, users of the Institut Català de la Salut; Catalonia, Spain) from August 2013 to December 2015. Results: Mean age for apixaban-treated patients was 71.8 years (standard deviation = 11.1) and 55.6% were male. In all, 3.2% of patients receiving apixaban were taking drugs described as potentially related to either pharmacokinetic or pharmacodynamic interactions. According to the summary of product characteristics, 81.1% of patients with a recommended dose of 2.5 mg twice daily and 51.8% with a recommended dose of 5 mg twice daily actually took this dose. After 1 year of follow-up, 62.6% of the apixaban users showed good adherence. Conclusion: The prescribed dose of apixaban did not fully follow the recommended dose, particularly in patients who were treatment naive. Patients with a prior history of anticoagulant treatment were more likely to remain persistent to treatment with apixaban.