Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy

BACKGROUND: To mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y12 receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD. METHODS: This prospective (April 2013-December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI. DISCUSSION: The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI. TRIAL REGISTRATION: Trial registration name is "Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy" (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage

Thunderstorm-associated bronchial Asthma: A forgotten but very present epidemic

Acute episodes of bronchial asthma are associated with specific etiological factors such as air pollutants and meteorological conditions including thunderstorms. Evidence suggests that thunderstorm-associated asthma (TAA) may be a distinct subset of asthmatics, and, epidemics have been reported, but none from Saudi Arabia. The trigger for this review was the TAA epidemic in November 2002, Eastern Saudi Arabia. The bulk of patients were seen in the King Fahd Hospital of the University, Al-Khobar. The steady influx of acute cases were managed effectively and involved all neighboring hospitals, without evoking any "Major Incident Plan". Three groups of factors are implicated as causes of TAA: pollutants (aerobiologic or chemical) and meteorological conditions. Aerobiological pollutants include air-borne allergens: pollen and spores of molds. Their asthma-inducing effect is augmented during thunderstorms. Chemical pollutants include greenhouse gases, heavy metals, ozone, nitrogen dioxide, sulfur dioxide, fumes from engines and particulate matter. Their relation to rain-associated asthma is mediated by sulfuric and nitric acid. Outbreaks of non-epidemic asthma are associated with high rainfall, drop in maximum air temperature and pressure, lightning strikes and increased humidity. Thunderstorm can cause all of these and it seems to be related to the onset of asthma epidemic. Patients in epidemics of TAA are usually young atopic adults not on prophylaxis steroid inhalers. The epidemic is usually their first known attack. These features are consistent with the hypothesis that TAA is related to both aero-allergens and weather effects. Subjects allergic to pollen who are in the path of thunderstorm can inhale air loaded with pollen allergen and so have acute asthmatic response. TAA runs a benign course Doctors should be aware of this phenomenon and the potential outbreak of asthma during heavy rains. A & E departments and ICU should be alert for possible rush of asthmatic admissions and reinforce ventilators and requirements of cardio-pulmonary resuscitation. Scientific approach should be adopted to investigate such outbreaks in the future and must include meteorological, bio-aerosole pollutants and chemical pollutant assessment. Regional team work is mandatory

Ranking Web of Universities: Is Webometrics a Reliable Academic Ranking?

Global university rankings continue to gain growing interest and have high visibility from all stakeholders. Of these, Webometrics Ranking (WR) faces many criticisms about its function. Some people believe WR evaluates only the websites of universities but not their global performance and impact as mentioned by WR authors. This stimulates us to examine the idea of using WR as a reliable academic ranking for the world universities. To test this hypothesis, we apply the WR results with two widely accepted indexes, i.e., the global university rankings and the bibliometrics. Therefore, the WR ranking of the Top 100 institutions are correlated with the corresponding values of six world ranking systems’ 2015 edition (ARWU, USNWR, QS, THE, NTU and URAP) that commonly accepted to evaluate the academic performance of the university, as well as with the objectively bibliometric indicators gathered from the Web of Science (WOS) InCitesTM - Thomson Reuters. The findings revealed that the WR results provide a good correlation with both ranking systems’ results and with 12 bibliometric variables namely: WOS Documents, Times Cited, Citation Impact (CI), Citation Impact: Category Normalized (CNCI), Citation Impact: Journal Normalized (JNCI), Impact Relative to World, % of Top 1% Documents, % of Top 10% Documents, Highly Cited Papers, h-index, International Collaborations, and % Industry Collaborations. The consistency between WR and the studied six rankings increases with increasing the weight percent of the research or bibliometric indicators in these six global rankings. Moreover, the consistency between WR and survey-based rankings (USNWR, THE and QS) increases with decreasing the weight of the subjective reputation survey indicators. The North American, especially USA universities are characterized by the extremely high visibility in WR as well as in the studied seven global rankings. Thus, web-based indicators ranking (WR) offers results of comparable and similar quality to those of the six major global university rankings. Accordingly, they have the capability to rank institutional academic performance. Moreover, the reliability could be enhanced if each university has only one web-domain that accurately reflects its actual performance and activity. We recommend all institutions to apply all ranking systems together since their criteria and indicators complement each other and can form a comprehensive index for covering various HEIs activities/functions worldwide

Ranking Web of Universities: Is Webometrics a Reliable Academic Ranking?

Global university rankings continue to gain growing interest and have high visibility from all stakeholders. Of these, Webometrics Ranking (WR) faces many criticisms about its function. Some people believe WR evaluates only the websites of universities but not their global performance and impact as mentioned by WR authors. This stimulates us to examine the idea of using WR as a reliable academic ranking for the world universities. To test this hypothesis, we apply the WR results with two widely accepted indexes, i.e., the global university rankings and the bibliometrics. Therefore, the WR ranking of the Top 100 institutions are correlated with the corresponding values of six world ranking systems&rsquo; 2015 edition (ARWU, USNWR, QS, THE, NTU and URAP) that commonly accepted to evaluate the academic performance of the university, as well as with the objectively bibliometric indicators gathered from the Web of Science (WOS) InCitesTM - Thomson Reuters. The findings revealed that the WR results provide a good correlation with both ranking systems&rsquo; results and with 12 bibliometric variables namely: WOS Documents, Times Cited, Citation Impact (CI), Citation Impact: Category Normalized (CNCI), Citation Impact: Journal Normalized (JNCI), Impact Relative to World, % of Top 1% Documents, % of Top 10% Documents, Highly Cited Papers, h-index, International Collaborations, and % Industry Collaborations. The consistency between WR and the studied six rankings increases with increasing the weight percent of the research or bibliometric indicators in these six global rankings. Moreover, the consistency between WR and survey-based rankings (USNWR, THE and QS) increases with decreasing the weight of the subjective reputation survey indicators. The North American, especially USA universities are characterized by the extremely high visibility in WR as well as in the studied seven global rankings. Thus, web-based indicators ranking (WR) offers results of comparable and similar quality to those of the six major global university rankings. Accordingly, they have the capability to rank institutional academic performance. Moreover, the reliability could be enhanced if each university has only one web-domain that accurately reflects its actual performance and activity. We recommend all institutions to apply all ranking systems together since their criteria and indicators complement each other and can form a comprehensive index for covering various HEIs activities/functions worldwide. </p

Perspective: A novel prognostic for sickle cell disease

Sickle hemoglobin (α2βS2) polymerization drives disease pathophysiology in sickle cell anemia. Fetal hemoglobin (α2γ2) restricts disease severity by inhibiting the polymerization of sickle hemoglobin in a concentration-dependent manner. Clinical decision-making relies on diagnostic technologies evaluating fetal hemoglobin as mean percent or mean quantity in blood. Limitation of this approach is exemplified by patients with significant high fetal hemoglobin levels and severe disease, suggesting that fetal hemoglobin is unevenly distributed across F-cells. Therefore, determination of fetal hemoglobin/F-cell would provide a new paradigm for ascertaining prognosis and response to fetal hemoglobin-inducing agents. Measurement of fetal hemoglobin/F-cell, ultimately adapted to widespread standardized analytical use, is a promising fetal hemoglobin-related prognostic approach to monitor the severity of sickle cell disease and the best “phenotype” to follow when developing new candidate fetal hemoglobin inducers or titrating hydroxyurea in treated sickle cell patients

JOB SATISFACTION AMONG THE ACADEMIC STAFF OF A SAUDI UNIVERSITY: AN EVALUATIVE STUDY

Background: Job satisfaction is a major determinant of job performance, manpower retention and employee well-being. Objectives: To explore the state of job satisfaction among the academic staff of King Faisal University - Dammam (KFU-D), and detect the areas and groups at a higher risk of being dissatisfied. Method: A fully-structured 5-option Likert-type Job Satisfaction Questionnaire (JSQ) composed of an evaluative item and eleven domains making a total of 46 items was used. It was distributed by internal mail to all the 340 academic staff, 248 of whom returned completed questionnaires (response rate = 72.9 %). Findings: The overall mean Job Satisfaction Rate (JSR) was 73.6 %. The highest JSR′s were found in three domains ("Supervision", "Responsibility", and "Interpersonal Relationships"), and the lowest in four others ("Salary", "My Work Itself", "Working Conditions", and "Advancement"). The JSR was significantly lower among Saudi nationals, females, those below age 40, those from clinical medical and Dentistry departments. Multiple Regression identified six independent variables which conjointly explained 25 % of the variance in job satisfaction (p < 0.0001). These were: being an expatriate, above the age of 50, serving the university for less than one or more than ten years, and, not from a clinical department of Medicine or Dentistry. Conclusions : Most staff were satisfied with many aspects of their jobs, but there was significant dissatisfaction with several job-related aspects and demographic features. Appropriate interventions are indicated. Further studies are needed to confirm the present findings and to monitor future trends