Qatar Foundation Annual Research Forum Volume 2012 Issue 1

Background: Coronary artery disease remains one of the leading causes of morbidity and mortality in developed countries and is projected to be the leading cause of death in the developing world by 2010. Affecting nearly 12 million people in the USA, it accounts for 50% of all cardiovascular deaths and is the leading cause of congestive heart failure as well as premature permanent disability in workers. About 1.1 million myocardial infarctions and >400,000 new cases of congestive heart failure each year, cardiovascular disease severely impacts men and women as well as various ethnic groups. Objectives: The aim of this study is to evaluate the results of transmyocardial laser revascularization (TMLR) in patients with coronary artery disease, in whom percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) cannot be done. Method: Fifty patients were included in the study: 1) Canadian cardiovascular angina class (CCS) III or IV patients (only 5 patients with CCS class II were included and those patients were the early trial in year 1997 where the recommendations for TMLR was not yet established); 2) Ejection fraction of 30%; 3) Those with evidence of reversible ischemia (based on stress thallium perfusion scanning); 4) Candidates of neither CABG or PTCA (according to the results of coronary angiography). The laser system used was a heart laser system (PLC medical systems). Results: There was a significant improvement in the severity of angina as assessed by Canadian Cardiovascular Society grading after the procedure. Improvement was noticed after 1 month and the improvement was most significant after 3 months and then slightly declined after 6 months but still significant in comparison to the pre-procedural values (P <0.05). Also, there was a significant improvement in the grade of dyspnoea as assessed by the New York Heart Association functional dyspnoea class and the most significant improvement was after 3 months and the degree of improvement decreased but still significantly better than the pre-procedural values (P <0.05). Conclusion: TMLR offers consistent amelioration of severe angina in patients having no conventional therapeutic alternative. Surgeons should recognize that the procedure is intended only for the purpose of reducing angina symptoms.

Background and Objectives: Type 2 diabetes mellitus (T2DM) is a major health problem in Qatar. The prevalence of T2DM in the adult population of Qatar is approximately 16% (twice that in the USA) and the country is ranked sixth in the world for diabetes prevalence. The number of cases of childhood diabetes in Qatar has doubled in ten years. The rapid rise of T2DM cases is thought to be due, in part, to genetic factors that interact with lifestyle factors including, but not limited to, poor nutrition, lack of physical activity and obesity. Recent evidence suggests that lack of vitamin D and inflammation may also play a role. Methods: We examined the current knowledge from literature linking T2DM to the chronic low-grade inflammation and the possible role of vitamin D in attenuating the inflammatory factors and, thereby, preventing T2DM. Results: Low-grade inflammation resulting from imbalances in the innate immune system has been associated with an array of chronic disorders that predispose to the later development of T2DM (e.g., obesity, metabolic syndrome, and insulin resistance). As a result, inflammation may contribute to the pathogenesis of T2DM. Therefore, attenuation of this inflammatory response via modulating the innate immune system could lead to improved insulin sensitivity and delayed disease onset. Dietary supplementation with vitamin D, may present a novel strategy toward the prevention and control of T2DM at the population level due to its anti-inflammatory and antioxidant properties. Conclusion: The concept that vitamin D, via attenuating inflammation, could be employed as a novel preventative measure for T2DM, is evaluated in the context of its relevance to healthcare and public health practices. Overall, to reduce the disease risk and burden at the population level, preventative strategies can be developed to include vitamin D supplementation into the traditional intervention protocols (e.g., exercise, life-style modification, etc.).

Background & Objectives: A recent randomized clinical trial, CAPRISA 004, reported levels of HIV incidence rate among general population women in South Africa that are comparable or higher than those observed among high-risk populations such as female sex workers, men who have sex with men, or injecting drug users despite low coital frequency. Understanding the factors leading to such high HIV incidence levels is critical for guiding prevention efforts. To this end, we have assessed the risk of HIV transmission among stable couples across a range of epidemic settings in Sub-Saharan Africa (SSA). Methods: We constructed a mathematical model describing the process of HIV discordancy in a population in the context of an HIV epidemic to estimate the risk of HIV transmission within stable partnerships. The model was parameterized using nationally representative demographic health survey data for 20 countries in SSA. Uncertainty and sensitivity analyses were performed to explore the robustness of our estimates to systematic biases in model parameters. Results: HIV incidence rate among discordant couples hovered around 10 per 100 person-years across SSA. A clustering based on HIV prevalence was observed with a median of 7.8 per 100 person-years in low HIV prevalence countries (<5%) compared to 18.4 per 100 person-years in high prevalence countries (>5%). HIV population prevalence explained 49% of the variation in HIV transmission, with every 1% increase in HIV prevalence implying an increase of 1.2 per 100 person-years in HIV infectiousness. The uncertainty and sensitivity analyses suggested that potential systematic biases are more likely to lead to a slight overestimation in HIV incidence rate particularly in high prevalence countries. Conclusions: Our results suggest that a variability in HIV infectiousness may have contributed to the contrasting HIV epidemic trajectories across Africa. The key drivers of this variability may include male circumcision, different circulating virus subtypes, sexually transmitted co-infections, tropical co-infections, hormonal contraception, and host genetics and immunology. The role of behavioral cofactors such as coital frequency and the uptake of condom use are less evident.

Background: Myeloproliferative neoplasms (MPNs), that is, essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are a group of MPNs that can lead to significant rates of morbidity and mortality among affected patients. Symptomatic burden in MPNs is present in most of MPN patients. We sought to use the broadly applicable instrument MPN symptom assessment form (MPN-SAF) to assess symptoms in MF, ET and PV among populations of Qatar. Methods: Using the MF-SAF as a base instrument, we added several key additional symptoms previously identified as present in all subtypes of MPNs including headaches, concentration, dizziness, insomnia, sexual problems and mood changes on a 0 (absent) to 10 (worst-imaginable) scale. The MPN-SAF was administered jointly with the EORTC-QLQ-C30 as the co-validation instrument using prospective cohorts in Qatar. Results: MPN-SAF patient data: 123 MPN-SAF surveys were administered (English (45%), Arabic (55%) in 45 ET patients (36.5%); 35 PV patients (28.5%); 15 MF patients (12.2%); 28 MPN unclassified (22.7%); an average of 7.8 years (range 0 - 43 years)) from their MPN diagnosis. Participants were of age range (26 - 58 years) and gender (52% female) characteristic of disease. Prior hemorrhage (10%) and thrombosis (25%) were frequent. 78% of the patients currently receive cytoreductive therapy and 87% received cytoreductive therapy in the past. Patients and Symptomatic Burden: 19 items assessed in the MPN-SAF demonstrated consistently that the most common symptoms were decreased quality of life (93%), fatigue (84%) and insomnia (65%). The least common symptoms (<50% prevalence) were fevers (15%) and weight loss (10%), although symptoms are present in all 3 MPN subgroups. The majority found the MPN-SAF easy to understand (92%) and "addressed most of my MPN symptoms" (95%). Comparison to EORTC-QLQ-C30: Strong correlations existed between individual items represented on both the MPN-SAF and the EORTC-QLQC30 including pain, fatigue, appetite and insomnia (all p <0.001). Symptoms characteristic of advanced disease including weight loss, fever, and cough displayed lower Pearson correlations (r= 0.46, -0.08, and 0.38 respectively). Conclusions: The MPN-SAF is a comprehensive and reliable instrument which is available in multiple languages (including Arabic and English) to evaluate MPN-associated symptoms.

Background: Osteoarthritis (OA) is the most common joint disease in middle aged and older people. Despite the multiple modalities of treatment, the outcome is still poor and focuses on temporary measures to alleviate the symptoms. Objectives: We want to determine whether or not an intra-articular injection of a single dose of chondrogenic induced bone marrow mesenchymal stem cells (BMSC) can promote cartilage regeneration in surgically induced osteoarthritis in sheep. Methods: Sheep BMSCs were isolated and divided into two groups. One group was cultured in chondrogenic media containing 5 ng/ml TGFβ3 + 50 ng/ml IGF-1, and the other group was cultured in basal non-chondrogenic media for the duration of 3 weeks. The procedure for surgically inducing osteoarthritis was performed on the donor sheep six weeks prior to intra-articular injection to the knee joint. The injection is a single dose of BMSCs from either group, suspended in 5 ml Dulbecco's Modified Eagle Medium (DMEM) at density of 2 million cells/ml. The control groups were injected with basic cell free media. Results: Six weeks after injection, evidence of articular cartilage regeneration and meniscus repair in osteoarthritic knee joints treated with autologous BMSCs cultured in chondrogenic medium were observed. No evidence of regeneration and meniscus repair was observed for the control group and the group treated with BMSCs cultured in basal medium. Conclusions: Intra-articular injection of a single dose of BMSCs in chondrogenic culture could stimulate regeneration of articular cartilage and meniscal tissue.

Background and Objectives: A major challenge to global health initiatives is food safety. In the USA it is estimated that 76 million foodborne illnesses occur each year causing 300,000 hospitalizations and 5,000 deaths. Escherichia coli O157:H7, Campylobacter and Salmonella enterica are among the leading causes of these illnesses including inflammatory bowel disease (IBD) with severe sequelae. The severity of illness is in part attributable to the virulent factors encoded by genes present in individual pathogens. Data on the risk associated with infection by foodborne bacterial pathogens in Qatar and the complement of virulent factors in these pathogens is lacking. Cost-effective intervention strategies rely on accurate microbial risk assessment (MRA) of the adverse consequences of exposure and infection with specific pathogens (dose-response relationships), but also according to the complement of virulent factors present in each agent. We carried out molecular studies to investigate the profile of virulent genes of three major foodborne bacterial pathogens isolated from humans in Qatar in support of developing accurate MRA. Methods: Multiplex polymerase chain reactions (PCR) test and PCR restriction fragment length polymorphism were used to examine E. coli O157:H7 isolates for virulent factors. PCR amplification was used to screen C. jejuni and C. coli for the presence of cytolethal distending toxin (cdt) subtypes (cdtA, cdtB, and cdtC). Results: E. coli isolates had a number of virulent factors in common. The enterotoxigenic E. coli (ETEC) pathotypes were detected in human samples at a rate of 40%, while Shiga-toxin producing E. coli (STEC) pathotype was detected at a much lesser rate. The attaching and effacing E. coli (AEEC) pathotype which included several serotypes (O26, O45, O103, O111, O121 and O145) causing illnesses in 2010 were detected at a rate of 60%. The cdtB gene was detected in 82% and 30% of the C. jejuni and C. coli isolates, respectively. The majority of Salmonella enterica isolates expressed cdtB gene. Conclusions: The data indicate that infection by foodborne bacterial pathogens are common causes of gastroenteritis in Qatar. Implementation of cost-effective control measures for these important foodborne pathogens require intervention strategies that take into account MRA within the context of Qatar.

Background: Anterior cruciate ligament (ACL) tears are common injuries occurring upwards of 250,000 times annually only in the US. These injuries create an annual billion dollar expense in the US alone. It is important to understand these mechanisms of injury as these injuries continue to be one of the largest problems in orthopedic sports medicine. Improved understanding of the injury mechanisms may improve prevention, rehabilitation and surgical procedures. Objectives: To perform a parametric study of knee joint movement to highlight which movement combinations are most detrimental to the ligaments of the knee joint, and also to study the effect of ramping rate on varus and valgus failure angle. The study provides a spectrum of injury propensity based on internal and external femoral rotation and varus or valgus angle as well as showing the effect of ramping rate on the prescribed boundary conditions. Methods: Bones and ligaments were digitized from magnetic resonance images (MRI). Bone was modeled as rigid, and a transversely isotropic visco-elastic material was applied to the ligament structures. This study incorporates a novel approach for developing bundle specific prestrain within 3D ligament structures. The bundles were stretched from their zero load lengths to their reference lengths, producing a strain field mimicking the in vivo strain conditions of the ACL at full knee extension. A failure locus was created by performing multiple FE simulations of knee joint motion combinations until ACL failure at different ramping rates to investigate the effect of rate dependency on the valgus and varus failure angle of the ACL. Results: Loading rate had negligible effect on the valgus or varus ACL failure angle. External femoral rotation scenarios were more susceptible to ligament failure than internal femoral rotation. The postero-lateral bundle showed more injury susceptibility compared to the anteromedial bundle. Varus simulations showed less angle needed for failure when compared to valgus simulations. Conclusions: These results have various clinical applications. In sports where ACL injuries are prevalent, training programs can be adapted to address the avoidance of harmful knee orientations.

Background and Objectives: The State of Qatar has achieved maternal, neonatal and perinatal survival rates which are comparable to many high income countries, both from the West and East. Our study aims to analyze sociodemographic, economic and cultural determinants of Qatar's neonatal mortality rate (NMR) during 2011. Methodology: PEARL study (Perinatal Neonatal Outcomes Research Study in the Arabian Gulf), a joint collaborative research project between Hamad Medical Corporation (HMC), Qatar, and University of Gloucestershire, United Kingdom, is Qatar's prospective national perinatal epidemiological study funded by Qatar National Research Fund. The study is quantifying maternal, neonatal and perinatal mortality, morbidities and their correlates by establishing a national neonatal perinatal registry for Qatar called Q-Peri-Reg. Data on live births and neonatal mortality was collected from all public and private maternity facilities in Qatar during 2011. Data on sociodemographic, economic and cultural determinants was ascertained by direct interviews from the mothers using predesigned performas. Univariate and multivariate regression analysis was done using Epi Info and SPSS-20. Results: Qatar's NMR during 2011 was 4.9. Babies born to mothers with no or less than secondary level of education were twice at risk of death as compared to mothers with secondary or more level of education (RR 2.08, 95% CI 1.23-3.53, p= 0.009). The rate of maternal literacy was 90%. Nationality, gender, consanguinity, maternal occupation, family income and status, type and ownership of housing did not have any statistically significant correlation with the risk of neonatal mortality (Table1). Conclusion: High level of maternal literacy in Qatar appears to have contributed significantly to its improved neonatal survival rates. The outcome is independent of nationality, gender, social, economic and living status which supports the notion of an equitable health system in Qatar.

Background and Objectives: Vitamin D is thought to modulate cardiometabolic disease risk through effects on an array of disease-associated pathways, such as glucose and lipid metabolism and inflammation. Although vitamin D insufficiency is thought to play a role in the susceptibility to cardiometabolic disease, the association between the two conditions is yet to be investigated in both men and women from the general population. Methods: Subjects (n= 1,928, age range 16-79 yrs) from Canada were examined. Plasma 25-hydroxyvitamin D [25(OH)D] by month of clinic visit were plotted for men and women to examine the monthly fluctuation patterns. Linear regression models adjusted for sex, waist circumference, physical activity, hormone use, and season of clinic visit examined the linear associations between 25(OH)D and cardiometabolic biomarkers [glucose, insulin, HOMA-IR, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total:HDL-C ratio, apolipoprotein(apo)A1, apoB] and biomarkers of inflammation [C reactive protein (CRP), fibrinogen, and homocysteine]. Analyses were repeated separately for men and women. Results: Monthly variation in 25(OH)D was noted for both men and women, with mean levels fluctuating more widely throughout the year in men (50 to 80 nmol/L) than in women (60 to 75 nmol/L). Significant inverse associations with 25(OH)D were noted for insulin (β= -0.16, p=0 .003), HOMA-IR (β= -0.18, p= 0.002), triglycerides (β= -0.21, p= 0.004), total cholesterol (β= -0.31, p= 0.046), LDL-C (β= 0.09, p= 0.02), and total:HDL-C ratio (β= -0.09, p= 0.004). When the population was stratified by sex, significant inverse associations with 25(OH)D were observed for insulin (β= -0.21, p= 0.002), HOMA-IR (β= -0.24, p= 0.002), and triglycerides (β= -0.26, p= 0.01) among men, and insulin (β= 0.13, p= 0.05), HOMA-IR (β= -0.14, p= 0.03), total cholesterol (β= -0.34, p= 0.05), LDL-C (β= -0.10, p= 0.02), and total:HDL-C ratio (β= -0.10, p= 0.001) among women. Conclusions: Plasma 25(OH)D levels vary month-to-month, and fluctuate more widely in men than in women. Vitamin D may modulate multiple processes related to the cardiometabolic biomarkers and disease risk and may, thereby, play a role in disease prevention.

Background and Objectives: Globally around half of new HIV infections occur in the age group 15-24. New reported cases of HIV/AIDS in Lebanon show that a younger age group (20-30) is being affected more than ever before. Lebanon is moving forward in implementing a national sexuality education curriculum in all public schools, as a mechanism for raising awareness and for preventing sexually transmitted infections (STI) including HIV among adolescents. However, little is known about adolescents' actual sexual behavior, the extent to which students are confident of their refusal skills, and the factors that determine these. Young adolescents, who have limited sexual knowledge and experience, may have difficulty in adopting the appropriate protective behavioral responses to prevent negative health outcomes including STI and HIV infection. Methods: This research identified the prevalence and risk factors for perceived sex refusal skills among Lebanese adolescents in grades 7-9 in public and private schools using the nationally representative Lebanon Global School Health Survey. Results: Results indicated that more than 40% (50.4% of boys and 34.8% of girls) of students did not feel confident that they could tell someone they did not want to have sexual intercourse with them. Multivariate logistic regression analysis indicated that being female, older and having close parental supervision predicted having perceived sex refusal skills among Lebanese adolescents. Moreover, having knowledge and/or education about risky behaviors was the strongest predictor for having perceived sex refusal skills among Lebanese adolescents. Conclusion: This study contributes to the limited literature on perceived sex refusal skills in Lebanon, the Middle East and North Africa. A number of recommendations for research and prevention programs can be drawn from this research. Advocacy efforts should target policy makers to ensure that policies are reviewed to support comprehensive sexuality education in Lebanese schools because of identified vulnerabilities of sexual violence, low levels of education or knowledge of risky behaviors including HIV risk, and low levels of perceived sex refusal skills.