Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time-varying confounders but was associated with delayed MERS coronavirus RNA clearance. These findings highlight the challenges and importance of adjusting for baseline and time-varying confounders when estimating clinical effects of treatments using observational studies.

BackgroundIt had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission.MethodsThe protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality.DiscussionThis will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018.Trial registrationClinicalTrials.gov, ID: NCT02845843. Registered on 27 July 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2427-0) contains supplementary material, which is available to authorized users.

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment.Trial registrationClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.

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Genomic abnormalities leading to colorectal cancer (CRC) include somatic events causing copy number aberrations (CNAs) as well as copy neutral manifestations such as loss of heterozygosity (LOH) and uniparental disomy (UPD). We studied the causal effect of these events by analyzing high resolution cytogenetic microarray data of 15 tumor-normal paired samples. We detected 144 genes affected by CNAs. A subset of 91 genes are known to be CRC related yet high GISTIC scores indicate 24 genes on chromosomes 7, 8, 18 and 20 to be strongly relevant. Combining GISTIC ranking with functional analyses and degree of loss/gain we identify three genes in regions of significant loss (ATP8B1, NARS, and ATP5A1) and eight in regions of gain (CTCFL, SPO11, ZNF217, PLEKHA8, HOXA3, GPNMB, IGF2BP3 and PCAT1) as novel in their association with CRC. Pathway and target prediction analysis of CNA affected genes and microRNAs, respectively indicates TGF-β signaling pathway to be involved in causing CRC. Finally, LOH and UPD collectively affected nine cancer related genes. Transcription factor binding sites on regions of >35% copy number loss/gain influenced 16 CRC genes. Our analysis shows patient specific CRC manifestations at the genomic level and that these different events affect individual CRC patients differently.

Incident reporting systems are often used without a structured review process, limiting their utility to learn from defects and compromising their impact on improving the healthcare system. The objective of this study is to describe the experience of implementing a Comprehensive Management System (CMS) for incident reports in the ICU. A physician-led multidisciplinary Incident Report Committee was created to review, analyse and manage the department incident reports. New protocols, policies and procedures, and other patient safety interventions were developed as a result. Information was disseminated to staff through multiple avenues. We compared the pre-and post-intervention periods for the impact on the number of incident reports, level of harm, time needed to close reports and reporting individuals. A total of 1719 incidents were studied. ICUrelated incident reports increased from 20 to 36 incidents per 1000 patient days (P=0.01). After implementing the CMS, there was an increase in reporting 'no harm' from 14.2 to 28.1 incidents per 1000 patient days (P <0.001). There was a significant decrease in the time needed to close incident report after implementing the CMS (median of 70 days [Q1-Q3: 26-212] versus 13 days [Q1-Q3: 6-25, P<0.001]). A physician-led multidisciplinary CMS resulted in significant improvement in the output of the incident reporting system. This may be important to enhance the effectiveness of incident reporting systems in highlighting system defects, increasing learning opportunities and improving patient safety.

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