Search

none

Molecular classifications of colorectal cancer are benefitting cancer research by providing insights into subtype-specific disease prognosis and improved therapeutic interventions. Different conventional DNA markers, such as microsatellite instability, CpG island methylator phenotype, chromosomal instability, and BRAF and KRAS mutations, have been used to classify colorectal cancer patients but have not yet shown promising prognostic values. Here, for the first time, to the best of our knowledge, we show a classification of colorectal cancer tumors from Saudi Arabian patients based on the gene expression profile. An existing method of colorectal cancer subtyping has been applied to the gene expression profile of tumors from Saudi colorectal cancer patients. A survival analysis was done on the predicted colorectal cancer subtypes. In silico functional analyses were conducted on the gene signature used for the subtype prediction. The predicted subtypes showed a distinct but statistically insignificant overall survival distribution (log-rank test, P = 0.069). A comparison of the predicted subtypes in Saudi colorectal cancer patients with that of French patients showed significant dissimilarity in the two populations (Chi-square test, P = 0.0091). Functional analyses of the gene signatures used for subtyping suggest their association with “cancer” and “gastrointestinal diseases.” Most of the signature genes were found differentially expressed in colorectal cancer tumors compared to adjacent normal tissues. This classification framework might facilitate the treatment of colorectal cancer patients. Impact statement Colorectal cancer is a heterogeneous disease and subtyping could be useful in implementing precision medicine approach. In this report, we identified molecular subtypes in relatively less studied CRC patients from Saudi Arabia using the prediction model developed on the French population. The predicted subtypes showed distinct overall survival among the six subtypes. Chi-square results exhibited the dissimilarity between French and Saudi colorectal cancer patient population in terms of subtype distribution ( P value = 0.0091). Gene signature (57 genes) used for subtyping was found to be functionally relevant as evident from the pathway analyses. These genes were found to be associated with gastrointestinal disease and cancer. Genes used for subtyping were found to be differentially expressed in Saudi colorectal cancer patient samples when compared with their own normal tissue. Taken together, this study supports a classification method for CRC patients by using patient samples from a different geographical region.

Summary 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. ICU-related 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

Abstract 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 registration ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.

Objectives: The method of colorectal cancer (CRC) tissue sampling would affect its molecular profile and the downstream processing. In this study, we described the impact of CRC tissue sampling procedures on the quality control (QC) metrics of cytoscan HD array. Methods: We employed a high-resolution cytoscan HD microarray platform to investigate the chromosomal aberrations that could be associated with CRC. We compared the tissue extraction procedures and their impact on the QC parameters from the cytoscan HD array determined by chromosome analysis software (Suite3.1). Median of absolute values of all pairwise differences (MAPD), waviness-standard deviation (Waviness-SD), and single nucleotide polymorphism QC (SNPQC) were the QC parameters that were analyzed. Results: From 67 patients, we collected 843 colorectal tissues. Of these, 65.7% were obtained through endoscopic procedures, and the rest was after surgical resections. The mean transit time between tissue excision and preservation was 26 ± 15.5 and 74.6 ± 24.8 min, respectively. The tissues extracted from the surgical procedure showed mean MAPD of 0.28 ± 0.06 compared to 0.24 ± 0.06, for endoscopy, P = 0.005, degree of waviness-SD of 0.20 ± 0.1 compared to 0.2 ± 0.1, P = 0.64, and SNPQC of 9.6 ± 4.2 compared to 11.1 ± 4.6, P = 0.23. Conclusions: This report provides objective results that can help in tissue sampling intended to be used for DNA based molecular studies. Tissue collection protocol should be optimized to support microarray-analysis methods. Tissue extraction from endoscopic procedures had faster transit time and relatively better quality metrics outcome than surgical procedures. However, surgical procedures have less refusal rate, higher tissue quantity, and less negative results for malignancy.

Molecular classifications of colorectal cancer (CRC) are benefitting cancer research by providing insights into subtype-specific disease prognosis and better therapeutic intervention. So far different conventional DNA markers such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), chromosomal instability (CIN), and BRAF and KRAS mutations have been used to classify CRC patients but have not shown promising prognostic values. Here, for the first time, we show classification of CRC tumors from Saudi Arabian patients based on gene expression profile (GEP). An existing method of CRC subtyping has been applied to the GEP of tumors from Saudi CRC patients. Survival analysis was carried out on predicted CRC subtypes. In-silico functional analyses were conducted on the gene signature used for subtype prediction. The predicted subtypes showed distinct but statistically insignificant overall survival distribution (log-rank test, p = 0.069). Comparison of predicted subtypes in Saudi CRC patients with that of the French one showed significant dissimilarity in the two populations (Chi-square test, p = 0.0091). Functional analyses of the gene signature used for subtyping suggest their association with “cancer” and “gastrointestinal diseases”. Most of the signature genes were found differentially expressed in CRC tumors compared to adjacent normal tissues. Such a classification framework might help improve the treatment of colorectal cancer patients.

Background It 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. Methods The 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. Discussion This 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 registration ClinicalTrials.gov, ID: NCT02845843. Registered on 27 July 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2427-0) contains supplementary material, which is available to authorized users.

Introduction The Kingdom of Saudi Arabia (KSA) is one of countries with the world's highest number of deaths per 100,000 populations from road traffic accidents (RTAs). Numerous trauma victims sustain abdomino-pelvic injuries, which are associated with considerable morbidity and mortality. The purpose of this study was to describe profile, outcomes and predictors of mortality of patients with abdomino-pelvic trauma admitted to the intensive care unit (ICU) in a tertiary care trauma centre in Riyadh, KSA. Methods This was a retrospective analysis of prospectively collected ICU database. All consecutive patients older than 14 years with abdomino-pelvic trauma from March 1999 to June 2013 were included. The followings were extracted: demographics, injury severity, mechanism and type of injury, associated injuries, use of vasopressors and mechanical ventilation, and worst laboratory results in the first 24 h. The primary outcome was hospital mortality. We compared profile and outcomes between survivors and non-survivors and reported predictors of mortality. Results Of the 11,374 trauma patients who were admitted to the hospital during the study period, 2120 (18.6%) patients had abdomino-pelvic injuries, out of which 702 (33.1%) patients were admitted to the ICU. The mean age was 30.7 (SD 14.4) years and the majority was male (89.5%). RTA was the most common cause of abdomino-pelvic trauma (70.4%). Pelvis (46.2%), liver (25.8%), and spleen (23.1%) were the most frequently injured organs; and chest (55.6%), head (41.9%), and lower extremities (27.5%) were the most commonly associated injuries. Mechanical ventilation was required in 89.6% with a mean duration of 9.1 (SD 9.2) days and emergency surgery was performed in 45.0% of the patients with prolonged ICU and hospital length of stay (10.8 [SD 10.8], 56.9 [SD 96.7] days; respectively). Of the 702 patients with abdomino-pelvic trauma, 115 (16.4%) patients did not survive. Associated head trauma and retroperitoneal haematoma, higher level of lactic acid on admission and ISS, and advanced age were potential risk factors for hospital mortality. Conclusions Abdomino-pelvic injuries are common in trauma patients, affecting mainly young male victims, and are associated with significant morbidity and mortality, and resource utilisation.

Rationale Corticosteroid therapy is commonly used among critically ill patients with the Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational studies often do not account for patients’ clinical condition at the time of corticosteroid therapy initiation. Objectives To investigate the association of corticosteroid therapy on mortality and on MERS coronavirus RNA clearance in critically ill patients with MERS. Methods MERS ICU patients were included from 14 Saudi Arabian centers between September 2012 and October 2015. We carried out marginal structural modeling to account for baseline and time-varying confounders. Measurements and Main Results Of 309 patients, 151 received corticosteroids. Corticosteroids were initiated at a median of 3.0 days (Quartile Q1, 3: 1.0, 7.0) from ICU admission. Patients who received corticosteroids were more likely to receive invasive ventilation (141/151 [93.4%] vs. 121/158 [76.6%], p≤0.0001) and had higher 90-day crude mortality (112/151 [74.2%] vs. 91/158 [57.6%], p=0.002). Using marginal structural modeling, corticosteroid therapy was not significantly associated with 90-day mortality (adjusted odds ratio 0.75, 95% CI 0.52, 1.07, p=0.12), but was associated with delay in MERS coronavirus RNA clearance (adjusted hazard ratio 0.35, 95% CI: 0.17, 0.72, p=0.005). Conclusions 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.

Nursing research is a scientific method that provides evidence to support nursing practices. Investigation of the critical care nursing research in Saudi Arabia has not been well established. This review aims to examine the numbers, and the characteristics of PubMed-cited critical care nursing articles contributed from Saudi Arabia over the past decade. We conducted a PubMed search to analyze nursing publications in the field of critical care published or contributed in Saudi Arabia for over 10 years (2010–2019). We investigated the number of publications per year, specialty, study design, journal impact factor, and international collaboration. A total of 94 critical care nursing publications were included in this review. International collaborations were noted in 49 (52.1%) articles. The majority 53 (56.4%) of the critical care nursing publications were related to the nursing field and 66 (70.2%) of these articles were classified as clinical practice topics. Observation cohort study was the most used study design 64 (68.1%). The median impact factor for the journals of these publications was 1.76 (1.48, 2.52). Despite the lower rate of published researches, critical care nursing research in Saudi Arabia is increasing over the years. International collaborations had contributed dramatically in the published articles. Developing local strategy for critical care nursing research and promoting local and international collaboration to conduct and use research according to the critical care nursing priority are also warranted. More interventional nursing researches are needed in critical care settings in Saudi Arabia.

ObjectivesClinical trials (CTs) are considered an important method for developing new treatments and providing access to potentially effective drugs that are still under investigation. Measuring the public’s knowledge of and attitudes toward CTs is important for assessing their readiness for and acceptance of human drug testing, which has previously not been assessed in the Kingdom of Saudi Arabia (KSA). The objective of this study is to explore the Saudi public’s knowledge of and attitudes toward CTs as well as participation in trials to test new or approved drugs.DesignCross-sectional.SettingThe 2016 Al Jenadriyah cultural/heritage festival in Riyadh, KSA.ParticipantsParticipating booths and exhibition halls, as well as festival visitors, were approached to participate in the study.Primary and secondary outcome measuresKnowledge of and attitudes toward CTs.ResultsThe final number of participants was 938. The responses were converted to a percentage mean score (out of 100) for each knowledge-related response and attitude. The total mean knowledge score was 56.8±24.8 and the attitude-related score was 61.5±28.0. Although most of the participants supported testing approved or off-label and new drugs on adult and paediatric patients, only a third (30.5%) agreed that new drugs could be tested on healthy volunteers. The results indicated that gender, educational level, income, medical background, age and health insurance were independently associated with the level of knowledge of CTs. In terms of attitudes toward CTs, the factors that were independently associated were gender, educational level and medical background.ConclusionsThe Saudi public has a low level of knowledge and a moderately positive attitude toward CTs. There is a moderate positive correlation between the two factors such that as knowledge of CTs increases, the Saudi public will hold more positive attitudes toward CTs.

Background Computerized Physician Order Entry (CPOE) analgesia-sedation protocols may improve sedation practice and patients’ outcomes. We aimed to evaluate the impact of the introduction of CPOE protocol. Methods This was a prospective, observational cohort study of adult patients receiving mechanical ventilation, requiring intravenous infusion of analgesics and/or sedatives, and expected to stay in the intensive care unit (ICU) ≥24 h. As a quality improvement project, the study had three phases: phase 1, no protocol, July 1st to September 30th, 2010; phase 2, post implementation of CPOE protocol, October 1st to December 31st, 2010; and phase 3, revised (age, kidney and liver function adjusted) CPOE protocol, August 1st to October 31st, 2011. Multivariate analyses were performed to determine the independent predictors of mortality. Results Two hundred seventy nine patients were included (no protocol = 91, CPOE protocol = 97, revised CPOE protocol = 91). Implementation of CPOE protocol was associated with increase of the average daily dose of fentanyl (3720 ± 3286 vs. 2647 ± 2212 mcg/day; p = 0.009) and decrease of hospital length of stay (40 ± 37 vs. 63 ± 85 days, p = 0.02). The revised CPOE protocol was associated with, compared to the CPOE protocol, a decrease of the average daily dose of fentanyl (2208 ± 2115 vs. 3720 ± 3286 mcg/day, p = 0.0002) and lorazepam (0 ± 0 vs. 0.06 ± 0.26 mg/day, p = 0.04), sedation-related complications during ICU stay (3.3 % vs. 29.9 %, p 70 years or with severe kidney or liver impairment. Both the original CPOE protocol and the revised CPOE protocol were not independent predictors of ICU (adjusted odds ratio [aOR] = 1.85, confidence interval [CI] = 0.90–3.78; p = 0.09; aOR = 0.70, CI = 0.32–1.53, p = 0.37; respectively) or hospital mortality (aOR = 1.12, CI = 0.57–2.21, p = 0.74; aOR = 0.80, CI = 0.40–1.59, p = 0.52; respectively). Conclusions The implementation of a CPOE analgesia-sedation protocol was not associated with improved sedation practices or patients’ outcome but with unpredicted increases of an analgesic dose. However, the revised CPOE protocol (age, kidney and liver function adjusted) was associated with improved sedation practices. This study highlights the importance of carefully evaluating the impact of changes in practice to detect unanticipated outcomes.

Critical care research is growing around the world including Saudi Arabia. The objective of this review is to discuss the building capacity in critical care research coordination in Saudi Arabia as a part of the research strategy of the Saudi Critical Care Trials Group (SCCTG). The SCCTG was developed to promote high impact critical care research in Saudi Arabia and to facilitate collaboration in national and international clinical research. Well-organized coordination between all parties is necessary by the presence of qualified clinical research coordinator (CRC). Critical care has unique features that make clinical research conduct more complex and demanding. It is a high-risk area with increased potentiality of error or adverse events occurrence. Critical care providers such as critical care nurses, critical care pharmacists, respiratory therapists, critical care physiotherapists, or intensive care unit physicians with added skills may be appropriate candidates to handle CRC roles in critical care setting. These skills include but not limited to data collection, obtaining consent, patient assessment, patient screening for the study eligibility, data entry, ethics submissions, providing teaching regarding the study protocol and research topics to clinical staff, attending to regulatory requirements, and designing data collection tools. The SCCTG shall focus on training the clinical research coordination skills through providing specialized courses and workshops that enable different hospitals to conduct and participate in clinical research. It will also help developing network group to connect critical care CRCs in Saudi Arabia and worldwide.

Daily sedation interruption and protocol implementation have been recommended to reduce excessive sedation; however, their use has been inconsistent. We hypothesized that the use of an age, kidney and liver function adjusted sedation protocol would be associated with reduced doses and improved outcomes compared with a standard protocol.

Background and objective: Lack of knowledge or poor perception towards the roles and responsibilities of clinical nurse coordinators among cancer patients might lead to a decrease in seeking their services. The objective of the study was to assess the knowledge, perception and attitude towards clinical nurse coordinators among cancer patients at a specialized cancer center in Jordan. Methods: This is a cross sectional study that was conducted by distributing a self-reported and anonymous survey to 240 cancer patients visiting the center. The survey questioned some patient characteristics such as sex, age, educational level, marital status, disease type and duration, type of therapy. The patients’ knowledge (12-statement), the perception (9-statement) regarding the actual roles/responsibilities of coordinators and the attitude (5-statement) towards seeking their services were measured. Responses on Likert scales were converted to percentage mean scores. Results: The overall percentage mean scores ± standard deviation of knowledge was 59 ± 17, perception towards clinical nurse coordinators (79 ± 14) and attitude towards seeking their services (69 ± 16). Linear regression showed that participants on chemotherapy had significantly better perception (higher scores) compared to participants on concurrent therapies (β = -3.91, p = .049). Participants with higher knowledge scores had better perception indicating a better comprehension about the clinical nurse coordinators’ roles, compared to those with lower knowledge percentage mean scores (β = 0.13, p = .019). Female patients had higher percentage mean score of attitude compared to male particpants (β = -3.77, p = .034). Better perception of Clinical nurse coordinators (CNCs) among cancer patients was significantly more associated with a more positive attitude towards seeking CNC services (β = 0.72, p < .001). Conclusions: Patients’ knowledge about the roles and responsibilities of nurse coordinators is associated with a better patients’ perception towards coordinators, which in return is associated with a more positive attitude towards seeking their services. Special consideration should be paid for patients on concurrent therapies who were more likely to have poorer perception towards clinical care coordinators compared to patients on chemotherapy. In addition, coordinators are expected to observe a more negative attitude towards seeking their services among male cancer patients.

Saudi Arabia (KSA) has the world's highest number of deaths from motor vehicle accidents (MVAs). Numerous trauma victims sustain abdomino-pelvic injuries which are associated with considerable morbidity and mortality. The purpose of this study is to describe the profile, outcomes and predictors of mortality of patients with abdomino-pelvic trauma admitted to the ICU in a tertiary care trauma center in Riyadh, KSA.

Colorectal cancer (CRC), which has high prevalence in Saudi Arabia and worldwide, needs better understanding by exploiting the latest available cytogenetic microarrays. We used biopsy tissue from consenting colorectal cancer patients to extract DNA and carry out microarray analysis using a CytoScan HD platform from Affymetrix. Patient specific comparisons of tumor–normal pairs were carried out. To find out the high probability key players, we performed Genomic Identification of Significant Targets in Cancer analysis and found 144 genes to form the list of driver genes. Of these, 24 genes attained high GISTIC scores and suggest being significantly associated with CRC. Loss of heterozygosity and uniparental disomy were found to affect 9 genes and suggest different mechanisms associated with CRC in every patient. Here we present the details of the methods used in carrying out the above analyses. Also, we provide some additional data on biomarker analysis that would complement the findings.