Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts.

Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk due to a high rate of consanguinity. Genome-wide genotyping (GWG), imputation and GWAS followed by meta-analysis were performed based on two independent Saudi Arabian studies comprising 3950 MI patients and 2324 non-MI controls. Meta-analyses were then performed with these two Saudi MI studies and the CardioGRAMplusC4D and UK BioBank GWAS as controls. Meta-analyses of the two Saudi MI studies resulted in 17 SNPs with genome-wide significance. Meta-analyses of all 4 studies revealed 66 loci with genome-wide significance levels of p < 5 × 10-8. All of these variants, except rs2764203, have previously been reported as MI-associated loci or to have high linkage disequilibrium with known loci. One SNP association in Shisa family member 5 (SHISA5) (rs11707229) was evident at a much higher frequency in the Saudi MI populations (> 12% MAF). In conclusion, our results replicated many MI associations, whereas in Saudi-only GWAS (meta-analyses), several new loci were implicated that require future validation and functional analyses.

Interplay of Mendelian and polygenic risk factors in Arab breast cancer patients.

BACKGROUND: Breast cancer patients from the indigenous Arab population present much earlier than patients from Western countries and have traditionally been underrepresented in cancer genomics studies. The contribution of polygenic and Mendelian risk toward the earlier onset of breast cancer in the population remains elusive. METHODS: We performed low-pass whole genome sequencing (lpWGS) and whole-exome sequencing (WES) from 220 female breast cancer patients unselected for positive family history from the indigenous Arab population. Using publicly available resources, we imputed population-specific variants and calculated breast cancer burden-sensitive polygenic risk scores (PRS). Variant pathogenicity was also evaluated on exome variants with high coverage. RESULTS: Variants imputed from lpWGS showed high concordance with paired exome (median dosage correlation: 0.9459, Interquartile range: 0.9410-0.9490). After adjusting the PRS to the Arab population, we found significant associations between PRS performance in risk prediction and first-degree relative breast cancer history prediction (Spearman rho=0.43, p = 0.03), where breast cancer patients in the top PRS decile are 5.53 (95% CI 1.76-17.97, p = 0.003) times more likely also to have a first-degree relative diagnosed with breast cancer compared to those in the middle deciles. In addition, we found evidence for the genetic liability threshold model of breast cancer where among patients with a family history of breast cancer, pathogenic rare variant carriers had significantly lower PRS than non-carriers (p = 0.0205, Mann-Whitney U test) while for non-carriers every standard deviation increase in PRS corresponded to 4.52 years (95% CI 8.88-0.17, p = 0.042) earlier age of presentation. CONCLUSIONS: Overall, our study provides a framework to assess polygenic risk in an understudied population using lpWGS and identifies common variant risk as a factor independent of pathogenic variant carrier status for earlier age of onset of breast cancer among indigenous Arab breast cancer patients.

Profiling of pharmacogenomic variants in CYP2D6 and DPYD in indigenous Arab breast cancer patients.

Aim: The indigenous Arab population is underrepresented in genomic studies and the landscape of actionable pharmacogenomic variants among Arab breast cancer patients remains unclear. Materials & methods: Exome sequencing was performed on 220 unselected Arab female breast cancer patients and germline variants in CYP2D6 and DPYD were profiled using a deep learning method. Results: In total, 13 (5.9%) patients had clinically actionable results and 56 (25.5%) carried an allele in DYPD or CYP2D6 with unknown impact on drug metabolism. In addition, four unique novel missense variants were discovered, including one in CYP2D6 (p.Arg64Leu) with high predicted pathogenicity. Conclusion: A nontrivial subset of Arab breast cancer patients can potentially benefit from pretreatment molecular profiling, and further study is needed to improve characterization of the pharmacogenomic landscape.

Emergency Physicians' Awareness of Medico-Legal Case Management: A Cross-Sectional Study from Saudi Arabia.

Background: Emergency department physicians often encounter medico-legal cases when patients initially present to the hospital, and thus there is a strong need for them to have robust medico-legal management and reporting knowledge. Objective: To assess the awareness of emergency department physicians of two major hospitals in the Eastern Province of Saudi Arabia in managing medico-legal cases. Methods: This descriptive cross-sectional survey-based study included all adult and pediatric emergency physicians working at King Fahd Hospital of the University and King Fahd Specialist Hospital, two major government hospitals in the Eastern Province of Saudi Arabia. The questionnaire included questions about demographic information, the workload in the emergency department, previous medico-legal training, and information about physicians' perspectives regarding medico-legal situations. Results: A total of 85 physicians completed the questionnaire, with most being Saudis (78.8%) and consultants (44.7%). Most participants (84.7%) immediately notified the police authority through the official procedure on suspicion of a case being criminal. However, only 28.2% of the participants were aware of how to complete the medico-legal report, and the majority (82.4%) had not received any specific training or attended specific courses in writing medico-legal reports. Most participants (91.8%) expressed the need for additional medico-legal case training programs, with continuous education (29.4%) being the preferred mode. In addition, 60% of the consultants were dissatisfied with the current medico-legal reporting and management workflow in their hospital. About half of the participants did not obtain photographs in medico-legal cases and did not know if their workplace provided a protocol for collecting evidentiary material such as clothes, swabs, bullets, remnants of foreign bodies, etc. Conclusions: The results of the present study indicate the necessity to consider periodical continuing medical education programs and workshops for emergency department physicians in the Eastern Province of Saudi Arabia to help them in appropriately handling medico-legal cases.

The Role of Activated Charcoal in Prehospital Care.

Background: Administration of a single-dose activated charcoal (SDAC) is an effective method used for gastric decontamination and for other types of poisoning and overdose. This is only true when given within the first hour of poison ingestion as the effectivity of SDAC reduces over time. In addition, generally, not all patients are able to avail treatment within the specified period. Hence, multi-dose activated charcoal is regarded as a solution to a delayed process, although, no proof outweighs the use of SDAC. Objective: This study aimed to review and assess the adequacy of the past and current use of AC. The author also aimed to offer recommendations believed to be the best method to consider for prehospital care. Methods: The author conducted 6,337 online literature searches for this review, wherein seven papers met eligibility criteria for inclusion and analysis. Results: In this review, routine administration of AC in poisoning was found not related to the duration of hospital stay nor any other subsequent outcomes following poison ingestion. Further, this review did not establish that administration of AC could improve patient's clinical outcome. Further research and clinical trials is required to determine the efficacy of this therapy to appropriate patients in the prehospital setting. Conclusion: Activated charcoal can be used to treat highly acute to life-threatening poisoning if it is administered within the first hour of ingestion. Further studies would be necessary to investigate if this would affect clinical outcome..

Post-COVID-19 non-traumatic iliopsoas hematoma: A case report.

Background: Critically ill COVID-19 patients have an elevated risk of experiencing hypercoagulable conditions. Currently, many COVID-19 patients have been administered anticoagulation or antiplatelet therapies to lower the risk of systematic thrombosis. Iliopsoas hematoma is a potentially fatal and rare complication of bleeding disorders or anticoagulation therapy which sometimes grows to become clinically significant. The main purpose of this case review is to emphasize the importance of diagnosing iliopsoas hematomas and the possibility of antiplatelet contribution to its development. Case Presentation: We are reporting a rare presentation of non-traumatic iliopsoas hematoma in a non-anticoagulated patient. The patient is a 59-year-old male, with known type-2 diabetes, on oral hypoglycemic medications, 3-weeks post-COVID-19. He had started aspirin 81 mg orally, once daily, to prevent thrombotic events associated with COVID 19 infection, with no anticoagulant use and no other medications. He came in through the ED, presenting with two weeks history of progressive right lower limb weakness in which an iliopsoas hematoma diagnosis was confirmed based on radiological investigation. Conclusion: The possibility of iliopsoas hematoma should be considered in non-anticoagulated patients with no inherited or acquired coagulation disorders presenting with limb weakness. The link between antiplatelet use in a COVID-19 patient and the development of soft tissue bleeding (e.g., iliopsoas hematoma) must be studied further.

Saudi Healthcare Students' Perceptions and Beliefs About Immunizations: a Descriptive, Cross-Sectional Study.

Background: Immunization has been one of the most successful public health measures ever undertaken. However, a degree of hesitancy about vaccine use still exists. Healthcare professionals are in a unique position to provide advice and education to the public and may influence the decision to undergo immunization. Objective: The aim of this study was to explore perceptions and beliefs regarding immunizations and immunization-preventable diseases. Methods: A descriptive cross-sectional study was undertaken at the Imam Abdulrahman bin Faisal University, located in Dammam, Saudi Arabia. In the Kingdom of Saudi Arabia, a survey of 564 Saudi undergraduate healthcare students was conducted. 77.8% of participants replied (439). Information was collected regarding perceptions of; severity of immunization-preventable diseases, contracting these diseases, immunization safety, and immunization beliefs. The statistical analysis was performed using the Statistical Package for the Social Sciences (IBM SPSS v25). Non-parametric analyses were utilized. Descriptive data were generated as appropriate, including frequencies, median, and inter-quartile range. Statistical relationships of demographic variables were explored using Kruskal Wallis H-Test and Spearman's Rank-Order Correlation. A p-value < 0.05 was considered statistically significant. Results: Meningitis was perceived as the most severe disease and COVID-19 as having the highest likelihood of infection. Concern regarding vaccine side effects was most evident for the COVID-19 vaccine. Student year level and profession resulted in statistically significant differences for all three assessed perceptions. Substantial differences were also identified regarding views on immunization belief statements. Conclusion: This study identified considerable heterogeneity in Saudi healthcare students' perceptions and beliefs regarding immunization-preventable diseases and vaccination. Further education is required to produce well-informed and confident healthcare professionals around these issues.

Characteristics of Medico-Legal Cases and Errors in Medico-Legal Reports at a Teaching Hospital in Saudi Arabia.

INTRODUCTION: A medico-legal case (MLC) involves any injury or medical condition in which law enforcement agencies investigate and fix the responsibility regarding of an injury or medical condition. Incorrect or incomplete medico-legal reports (MLRs) may trigger a pause or delay in legal proceedings and patients' rights could be violated. The aim of this study is to describe the characteristics of MLCs and to identify errors in the MLRs. MATERIALS AND METHODS: This retrospective, descriptive study was conducted in a teaching hospital in the Eastern Province of Saudi Arabia. In total, 418 MLRs furnished during a 6-month period and reviewed for characteristics of MLCs and identification of errors. RESULTS: A total of 418 MLRs were included in the present study. Fights or physical assault and battery formed the major proportion of MLCs amounting to 83% of MLCs. Blunt injury was the dominant type of injury in most of the cases (81.8%). In relation to errors in MLRs, no MLR in the present study were without errors. CONCLUSION: Fights or physical assault and battery formed the major proportion of MLCs. Multiple errors were identified in the MLRs furnished by the physicians. Writing MLRs must follow standardized guidelines as it has a bearing on legal proceedings and patients' rights. We recommend training for physicians in writing MLRs in the interest of proper administration of justice.

High-Flow Nasal Cannula Treatment in Patients with COVID-19 Acute Hypoxemic Respiratory Failure: A Prospective Cohort Study.

BACKGROUND: Early use of high-flow nasal cannula (HFNC) decreases the need for endotracheal intubation (EI) in different respiratory failure causes. While HFNC is used in coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF) under weak recommendations, its efficacy remains to be investigated. OBJECTIVES: The primary objective was to examine HFNC efficacy in preventing EI among COVID-19 patients with AHRF. Secondary objectives were to determine predictors of HFNC success/failure, mortality rate, and length of hospital and intensive care unit (ICU) stay. PATIENTS AND METHODS: This is a prospective cohort study conducted at a single tertiary care centre in Saudi Arabia from April to August 2020. Adult patients admitted to the ICU with AHRF secondary to COVID-19 pneumonia and managed with HFNC were included. We excluded patients who were intubated or managed with non-invasive ventilation before HFNC. RESULTS: Forty-four patients received HFNC for a median duration of 3 days (interquartile range, 1-5 days). The mean age was 57 ± 14 years, and 86% were men. HFNC failure and EI occurred in 29 (66%) patients. Patients in whom HNFC treatment failed had a higher risk of death (52% versus 0%; P = 0.001). After adjusting for confounding factors, a high SOFA score and a low ROX index were significantly associated with HFNC failure (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.04-1.93; P = 0.025; and HR, 0.61; 95% CI, 0.42-0.88; P = 0.008, respectively). CONCLUSIONS: One-third of hypoxemic COVID-19 patients who received HFNC did not require intubation. High SOFA score and low ROX index were associated with HFNC failure.

Assessment on CPR Knowledge and AED Availability in Saudi Malls by Security Personnel: Public Safety Perspective.

Security personnel are the first ones who attend the scene in the case of out-of-hospital cardiac arrest (OHCA) at malls. Cardiopulmonary resuscitation (CPR) is not enough for those patients; they need an automated external defibrillator (AED) to bring the heart to function normally. This study aimed to assess the current status of CPR and AED knowledge and availability in Saudi malls by security personnel. Using a descriptive design, a study was conducted at seven malls located in the Eastern Province of Saudi Arabia. Two hundred and fifty participants were surveyed using the American Heart Association (AHA) 2015 guidelines to assess CPR and AED knowledge and availability in Saudi malls. The sample mean age was 32.60 years (SD = 10.02), and 87% of participants were working as security personnel. The majority of the participants had not received training about CPR and AED (75.8% and 95.2%, respectively). Common misconceptions are fallen into all categories of CPR and AED knowledge. Correctly answered statements ranged from 7.2% in the compression rate to 24.2% in hand placement. The study results indicated a poor training knowledge of CPR and AED in public settings. Integrating high-quality CPR and AED knowledge within the school and college curricula is a vital need. However, in order to maximize the survival rate, it is important to set laws and legislation adopted by stakeholders and decision makers to advocate the people who try to help, mandate AED installation in crowded places, and mandate teaching hands-only CPR and AED together as a package.

Study protocol for a randomized, blinded, controlled trial of ketamine for acute painful crisis of sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is an inherited hematological disorder where the shape of red blood cells is altered, resulting in the destruction of red blood cells, anemia, and other complications. SCD is prevalent in the southern and eastern provinces of the Arabian peninsula. The most common complications for individuals with SCD are acute painful episodes that require several doses of intravenous opioids, making pain control for these individuals challenging. Instead of opioids, some studies have suggested that ketamine might be used for pain control in acute pain episodes of individuals with SCD. This study aims to evaluate whether the addition of ketamine to morphine can achieve better pain control, decreasing the number of repeated doses of opiates. We hypothesize that early administration of ketamine would lead to a more rapid improvement in pain score and lower opioid requirements. METHODS AND ANALYSIS: This study will be a prospective, randomized, concealed, blinded, pragmatic parallel group, controlled trial enrolling adult patients with SCD and acute vaso-occlusive crisis pain. All patients will receive standard analgesic therapy during evaluation. Patients randomized to the treatment arm will receive low-dose ketamine (0.3 mg/kg in 0.9% sodium chloride, 100 ml bag) in addition to standard intravenous hydration, while those in the control group will receive a standard dose of morphine (0.1 mg/kg in 0.9% sodium chloride, 100 ml bag) in addition to the standard intravenous hydration. All healthcare providers will be blinded to the treatment arm. Data will be analyzed according to the intention-to-treat principle. The primary outcome is improvement in pain severity using the Numerical Pain Rating Score. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03431285 . Registered on 13 February 2018.

A characterization of synthetic cannabinoid exposures reported to the National Poison Data System in 2010.

STUDY OBJECTIVE: Δ-9-Tetrahydrocannabinol homologs have been increasingly abused since their introduction in 2004. Such products were used as a "legal high" for those wishing to experience cannabinoid effects while evading basic drugs-of-abuse testing. We describe a series of exposures to products marketed as synthetic cannabinoids to better characterize the clinical effects in these patients. METHODS: All Δ-9-tetrahydrocannabinol homolog exposures reported to the National Poison Data System between January 1, 2010, and October 1, 2010, were extracted with National Poison Data System generic codes and product codes for Δ-9-tetrahydrocannabinol homologs. Only cases involving a single-agent exposure to Δ-9-tetrahydrocannabinol homologs as the major category were analyzed. Descriptive statistics were generated for demographic data, management site, products involved, symptoms, duration of effects, treatments, and severity of clinical effects. RESULTS: During the 9-month study period, there were 1,898 exposures to Δ-9-tetrahydrocannabinol homologs; 1,353 of these cases were single-agent exposures. The mean age was 22.5 years (SD 8.86 years). Most cases were reported in men (n=1,005; 74.3%). The majority of exposures were acute (88.2%; n=1,193). The most common clinical effect was tachycardia (37.7%; n=510). Seizures were reported in 52 patients (3.8%). The majority of clinical effects lasted for fewer than 8 hours (n=711; 78.4%) and resulted in 1,011 non-life-threatening clinical effects (92.9%). The most common therapeutic intervention was intravenous fluids (n=343; 25.3%). There was 1 death (0.1%). CONCLUSION: The majority of cases were in young men intentionally abusing spice. Most exposures resulted in non-life-threatening effects not requiring treatment, although a minority of exposures resulted in more severe effects, including seizures.