Motasim Badri

Novel point mutations and mutational complexes in the enhancer II, core promoter and precore regions of hepatitis B virus genotype D1 associated with hepatocellular carcinoma in Saudi Arabia

In this study, a cohort of 182 patients [55 hepatocellular carcinoma (HCC) and 127 non‐HCC] infected with hepatitis B virus (HBV) in Saudi Arabia was investigated to study the relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP) and precore regions of HBV genotype D (HBV/D) and the risk of HCC. HBV genotypes were determined by sequencing analysis and/or enzyme‐linked immunosorbent assay. Variations in the EnhII, BCP and precore regions were compared between 107 non‐HCC and 45 HCC patients infected with HBV/D, followed by age‐matched analysis of 40 cases versus equal number of controls. Age and male gender were significantly associated with HCC (p = 0.0001 and p = 0.03, respectively). Serological markers such as aspartate aminotransferase, albumin and anti‐HBe were significantly associated with HCC (p = 0.0001 for all), whereas HBeAg positivity was associated with non‐HCC (p = 0.0001). The most prevalent HBV genotype was HBV/D (94%), followed by HBV/E (4%), HBV/A (1.6%) and HBV/C (0.5%). For HBV/D1, genomic mutations associated with HCC were T1673/G1679, G1727, C1741, C1761, A1757/T1764/G1766, T1773, T1773/G1775 and C1909. Age‐ and gender‐adjusted stepwise logistic regression analysis indicated that mutations G1727 [odds ratio (OR) = 18.3; 95% confidence interval (CI) = 2.8–118.4; p = 0.002], A1757/T1764/G1766 (OR = 4.7; 95% CI = 1.3–17.2; p = 0.01) and T1773 (OR = 14.06; 95% CI = 2.3–84.8; p = 0.004) are independent predictors of HCC development. These results implicate novel individual and combination patterns of mutations in the X/precore region of HBV/D1 as predictors of HCC. Risk stratification based on these mutation complexes would be useful in determining high‐risk patients and improving diagnostic and treatment strategies for HBV/D1.

Physician well-being: prevalence of burnout and associated risk factors in a tertiary hospital, Riyadh, Saudi Arabia.

BACKGROUND AND OBJECTIVES This study is to determine level and factors associated with burnout among physicians in a tertiary hospital in Saudi Arabia. DESIGN AND SETTINGS This is a cross-sectional study, conducted at the King Fahad National Guard Hospital at in King Abdulaziz Medical City between October 2010 and November 2010. METHODS The Maslach Burnout Inventory questionnaire was used to measure burnout. Socio-demographic-, specialty-, and work-related characteristics were added to explore factors associated with burnout. RESULTS The study included 348 participants; 252 (72%) were males, 189 (54%) were consultants, and 159 (46%) were residents. The mean (SD) age was 35 (9.8) years. The burnout prevalence was 243/348 (70%); 136 (56%) of the 243 were residents and 107 (44%) were consultants. Age, female gender, marital status, number of years in practice, sleep deprivation, presence of back pain, and a negative effect of practice on family life were associated with burnout in the univariate logistic regression analysis. The factors independently associated with burnout in the final multivariate model were as follows: suffering from back pain (odds ratio [OR]=2.1, 95%CI 1.2–3.8, P=.01), sleep deprivation (OR=2.2, 95%CI 1.2–3.8, P=.009), being a resident physician/surgeon (OR=4.9, 95%CI 1.7–14.2, P=.004), and negative effect of practice on family life (OR=2.1, 95%CI 1.1–3.9, P=.02). CONCLUSION In this study, the prevalence of burnout was found to be higher than estimates documented in most other studies. Reported risk factors should be addressed to decrease the prevalence and consequences of burnout.

The relationship of bullying and physical violence to mental health and academic performance: A cross-sectional study among adolescents in Kingdom of Saudi Arabia

Background and objectives Bullying and physical violence are serious public health concerns witnessed during adolescence and are associated with several health and behavioral problems that can persist into adulthood. The relationship between bullying/physical violence and mental health/academic performance in Saudi Arabia is unknown. This study aims at filling this gap through identifying the association of these health risk behaviors and mental health and academic performance. Materials and methods A cross-sectional national survey was conducted in Saudi Arabia between 2011 and 2012. Adolescents attending intermediate and secondary schools were invited to participate through a multi-stage, stratified, cluster random sampling technique. A self-administered questionnaire was used to collect data. Data were analyzed using chi-square tests to identify associations, and odds ratios were calculated. Results A total of 9073 students participated. Twenty-six percent of adolescents reported exposure to bullying in the preceding 30 days, and one out of every three adolescents reported exposure to physical violence at school during the past year. More males than females, and more older adolescents were exposed to bullying. Exposure to physical violence and bullying were both associated with higher odds of having more frequent symptoms of depression and anxiety. Those exposed to physical violence were at higher odds of having poorer academic performance. Conclusion Bullying and physical violence among adolescent students in Saudi Arabia is prevalent and deserves special attention due to its harmful impact on the other aspects of students’ wellbeing.

Clinicopathologic features and prognosis of triple-negative breast cancer in patients 40 years of age and younger in Saudi Arabia

BACKGROUND AND OBJECTIVES Triple-negative breast cancer (TNBC) has a poor prognosis and overall survival (OS) compared to other types of breast cancer tumors. However, there is to date no evidence that this is also the case in Saudi Arabia. DESIGN AND SETTING Retrospective review of breast cancer patients who were treated from January 2001 to December 2008 (517 patients) at the King AbdulAziz Medical City, Riyadh, Saudi Arabia. PATIENTS AND METHODS Patients were selected as TNBC if all three markers of estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor (HER2) tested by immunohistochemistry as negative. They were then age- and stage-matched, and compared with non-TNBC patients to examine differences, if any, in their clinicopathologic features, prognosis and OS. RESULTS Twenty-six patients with a follow up time of at least three years were identified as TNBC. Thirty-three patients who were age- and stage-matched were selected as the non-TNBC controls. Clinicopathologic results illustrated significantly more grade 3 tumors (P=.02) and CK 5/6 expression (P<.001) in the TNBC group compared to the non-TNBC group. TNBC patients aged ≤40 years showed a significantly worse prognosis and OS compared to TNBC patients aged >40 years (P=.01), and when compared to the non-TNBC group (P=.04). CONCLUSION The incidence of TNBC in our cohort is similar to what has been illustrated in previous studies in Western population. There was no significant difference in 3-year survival between TNBC and non-TNBC groups. However, the aggressiveness of this type of tumor and OS is significantly higher in younger patients aged ≤40 years, compared to those over 40 years of age.

Burnout Among Otolaryngology Residents in Saudi Arabia: A Multicenter Study.

OBJECTIVE Determine the prevalence of, and associated risk factors for, burnout among otolaryngologist residents in Saudi Arabia. DESIGN AND SETTING A cross-section study of multicenter hospitals in Saudi Arabia conducted in March 2013. PARTICIPANTS Registered residents in Saudi Otolaryngology Board Program. MAIN OUTCOMES MEASURES The Maslach Burnout Inventory was used to measure burnout status. Questions supplementary to the Maslach Burnout Inventory were also included to identify associated potential risk factors such as demographic data, resident satisfaction, and work conditions. RESULTS Of the initial 123 questionnaires that were distributed, 85 yielded responses, a rate of 69%. The mean age (standard deviation [SD]) of respondents was 29 (2.3) years. Of those, 67% (57/85) were men and 66% (55/85) were married. Resident levels were delineated: level 2, 19%; level 3, 33%; level 4, 29%; and level 5, 19%. The mean number of on-call days/month (SD) was 7 (2), clinics/week (SD) was 3 (1), sleep hours/day (SD) was 6 (1), and operations/week (SD) was 2 (1). The mean emotional exhaustion (EE) and depersonalization scores were high at 29.5 (SD = 9.6) and 10.7 (SD = 6), respectively. The mean personal accomplishment was low at 32.33 (SD = 6). The mean of all subscales did not differ by sex (EE p = 0.5; depersonalization p = 0.09; personal accomplishment p = 0.4). Mean EE differed by marital status, which was 31.2, 31.3, and 25.6 for married, divorced, and single, respectively, analysis of variance test p = 0.045. CONCLUSION Burnout prevalence was found to be high among otolaryngologist residents in Saudi Arabia. The associated variables examined in this study should be addressed to decrease this level of burnout and provide residents with a less stressful work environment.

Co-trimoxazole prophylaxis: the debates continue

Use of prophylactic co-trimoxazole (alone or alongside other drugs) is one of the most debated therapeutic interventions for patients with HIV in sub-Saharan Africa. This debate extends to the complexities of establishing the best timing of initiation and dosing and whether coadministration of the drug should be discontinued after immunological recovery induced by combination antiretroviral therapy (ART), especially after recognition of issues pertaining to coadministration with ART drugs and other interventions, such as antimalarial drug prophylaxis. In The Lancet HIV, Amitabh Suthar and colleagues present a meta-analysis of studies of co-trimoxazole prophylaxis in people with HIV. The researchers conclude that co-trimoxazole should be initiated and continued irrespective of CD4 count in settings with a high burden of infectious diseases and used instead of intermittent preventive treatment for malaria in pregnant women (IPTp) for prevention of malaria complications during pregnancy. Suthar and colleagues used restrictive inclusion criteria that might have excluded much scientifi c literature, basing pooled estimates on few published articles not specifi cally powered to show an eff ect diff erence in some of the outcomes reported. Furthermore, risk diff erences and hazard ratios were interchangeably used as a measure of eff ect—two estimates that can have vastly diff erent scales for the same outcome. These shortcomings might limit the credibility of pooled estimates and, consequently, the recommendations based on these estimates. Before widespread use of ART, the main focus of study was whether co-trimoxazole was eff ective in highly prevalent bacterial infections. Subsequently, the emphasis shifted towards assessing the best timing of drug initiation. In one study in patients not taking ART, benefi ts were recorded only in those with advanced immunosuppression (CD4 count <200 cells per μL). Data presented by Suthar and colleagues suggest that extending this threshold to 350 cells per μL is equally effective in reducing rates of death. However, many participants in the studies included in this sub-analysis had advanced disease (WHO clinical stage 3 or 4 and CD4 count <200 cell per μL) and heterogeneity in the pooled eff ect was very high. In six of the nine studies, administration of co-trimoxazole and ART was not strictly contemporaneous; in some of these studies 69–89% of the patients started co-trimoxazole before ART. Prolonged co-trimoxazole prophylaxis irrespective of CD4 count in sub-Saharan Africa is an issue of dispute. In higher-income countries, the standard of care is to discontinue the drug after sustained ART-induced immune restoration beyond CD4 count 200 cells per μL (or lower in some cases), a defi nite CD4 cell count threshold for Africa is yet to be identifi ed. Evidence for effi cacy varied and is contradictory. In a study by Walker and colleagues, mortality reduction was similar in patients with CD4 counts of 200 cells per μL or lower and in those with more than 200 cells per μL; and after 72 weeks, no reduction was recorded irrespective of count. This fi nding suggests that virulence of bacterial infections falls substantially after ART immune restoration. In children receiving long-term ART, death rates were similar. Anglaret and colleagues noted a similar result in adult patients. However, follow-up of participants in these studies is often short. More studies are needed with longer follow-up in which prolonged use of co-trimoxazole is weighed against pill burden, diagnostically challenging toxic eff ects, adverse drug reaction, and cost-eff ectiveness implications. Patients with HIV are more susceptible to infection with malaria and increased severity of clinical presentation than are healthy people. Malaria infections lead to T-cell activation and increased HIV viral load, which have detrimental eff ects on pregnancy outcome if the infection happens in the third trimester resulting in increased risk of HIV transmission to fetuses. Although co-trimoxazole provides adequate protection against malaria in pregnant women with HIV, defi nitive proof of superior effi cacy is missing. In one of the only two studies included in the analysis, non-inferiority analysis was not assessed because of insuffi cient recruitment of patients. In the other study in pregnant women with CD4 counts of 200 cells per μL or higher, single use of co-trimoxazole was not noninferior to sulfadoxine–pyrimethamine intermittent preventive treatment (SP-IPTp). Parasitemia, placental malaria, and birth outcomes were not diff erent in the two groups of the trial. In pregnant women with CD4 counts of 350 cells per μL or higher, coadministration of Ch ris S at tlb er ge r/ Sc ie nc e Ph ot o Li br ar y

Problem-based learning in undergraduate medical education in Saudi Arabia: Time has come to reflect on the experience

Abstract Background: Problem-based learning (PBL) is being increasingly used in many undergraduate medical schools worldwide due to its recognized advantages. Objectives: To explore views of medical students in the Kingdom of Saudi Arabia (KSA) about the appropriateness of the PBL concepts and process. Differences in students’ views were examined as well. Methods: This is a cross-sectional, questionnaire-based study conducted in two medical colleges in Riyadh, Saudi Arabia, during the period from April to June 2012. Results: One hundred seventy four undergraduate medical students participated in the study. Majority of the participants supported the concept of PBL and thought it is a beneficial learning strategy. However, only about half of them consider the problems used in tutorials are relevant for the local setting. Significant differences have been identified between the gender, schools, and study level of participants and their views on the process of PBL tutorials. About 35% of participants either undecided or will not recommend medical schools that adopt PBL curriculums for their friends. Conclusions: The majority of participants were satisfied with PBL approach and valued its importance in their learning process. Specific concerns have been expressed about relevance of some aspects of PBL. Underlying factors should be further explored in order to improve the outcomes of PBL curriculum in the local Saudi setting.

MERS-CoV infection: Mind the public knowledge gap

Abstract In August 2015, the Corona outbreak caused by Middle East respiratory syndrome coronavirus (MERS-CoV) was the 9th episode since June 2012 in Saudi Arabia. Little is known about the public awareness toward the nature or prevention of the disease. The aim of this work was to assess the knowledge of the adult population in Riyadh toward the MERS-CoV. In this cross-sectional survey, a self-administrated questionnaire was distributed to randomly selected participants visiting malls in Riyadh. The questionnaire contained measurable epidemiological and clinical MERS-CoV knowledge level variables and relevant source of information. The study included 676 participants. Mean age was 32.5 (±SD 8.6) years and 353 (47.8%) were males. Almost all participants heard about the corona disease and causative agent. The study showed a fair overall knowledge (66.0%), less knowledge on epidemiological features of the disease (58.3%), and good knowledge (90.7%) on the clinical manifestation of the MERS-CoV. Internet was the major (89.0%) source of disease information, and other sources including health care providers, SMS, television, magazines and books were low rated (all <25%). In a multivariate logistic regression analysis age ≤30 years (Odds Ratio (OR)=1.647, 95%CI 1.048–2.584, P =0.030), male gender (OR=1.536, 95%CI 1.105–2.134, P =0.01), and no tertiary education (OR=1.957, 95%CI 1.264–3.030, P =0.003) were independent significant predictors of poor epidemiological knowledge. This study concludes that there was inadequate epidemiological knowledge received by the public and the reliance mostly on the clinical manifestations to recognizing the MERS-CoV disease. Comprehensive public health education programs is important to increase awareness of simple epidemiological determinants of the disease is warranted.

A 23 years audit of packed red blood cell consumption in a university hospital in a developing country

BACKGROUND There is paucity of information on the blood transfusion practice in developing countries. The current audit aims to find out the long term trend in the consumption of packed red blood cells (PRBCs) in a large Saudi teaching hospital in Riyadh MATERIALS AND METHODS We analyzed the annual consumption of PRBCs from 1985 to 2007 in seven major hospital divisions (Medicine, General Surgery, Pediatrics, Obstetrics and Gynecology, Cardiac Surgery, Accident and Emergency and Renal Dialysis Unit) at the 850-bed King Khalid University Hospital (KKUH), Riyadh. RESULTS Grand total consumption of PRBCs was 345,642 units. The consumption increased gradually and peaked in the year 1994, dropped to 30.4% 6 years later and then increased gradually thereafter, due to the expansion in the number of patients cared for in the Departments of Medicine, Cardiac Surgery and Accident and Emergency, while in the Department of Pediatrics the drop in consumption continued unabated. In the Renal Dialysis Unit consumption was minimal with the use of erythropoietin therapy. The crossmatch:transfusion ratio uncovered gross over-ordering of PRBCs and wastage of blood bank resources in most hospital divisions most notably in the Department of Obstetrics and Gynecology. CONCLUSION The results obtained indicate clearly that there has been overuse of blood products that dropped markedly in years coinciding with the worldwide apprehension about the safety of transfusion therapy particularly HIV transmission. This factor in addition to the current implementation of strict guidelines is gradually improving transfusion practices in our institute.

Shared clinical decision making. A Saudi Arabian perspective

Objectives: To determine preferences of patients regarding their involvement in the clinical decision making process and the related factors in Saudi Arabia. Methods: This cross-sectional study was conducted in a major family practice center in King Abdulaziz Medical City, Riyadh, Saudi Arabia, between March and May 2012. Multivariate multinomial regression models were fitted to identify factors associated with patients preferences. Results: The study included 236 participants. The most preferred decision-making style was shared decision-making (57%), followed by paternalistic (28%), and informed consumerism (14%). The preference for shared clinical decision making was significantly higher among male patients and those with higher level of education, whereas paternalism was significantly higher among older patients and those with chronic health conditions, and consumerism was significantly higher in younger age groups. In multivariate multinomial regression analysis, compared with the shared group, the consumerism group were more likely to be female [adjusted odds ratio (AOR) =2.87, 95% confidence interval [CI] 1.31-6.27, p=0.008] and non-dyslipidemic (AOR=2.90, 95% CI: 1.03-8.09, p=0.04), and the paternalism group were more likely to be older (AOR=1.03, 95% CI: 1.01-1.05, p=0.04), and female (AOR=2.47, 95% CI: 1.32-4.06, p=0.008). Conclusion: Preferences of patients for involvement in the clinical decision-making varied considerably. In our setting, underlying factors that influence these preferences identified in this study should be considered and tailored individually to achieve optimal treatment outcomes.