Qatar Foundation Annual Research Forum Volume 2012 Issue 1

Objectives: Little is known about the ethnic variability in trends of the etiologies of atrial fibrillation (AF) and related mortality. This was examined in this study in patients hospitalized with AF in a real-world population in a Middle Eastern country. Methods: Retrospective analysis of prospective registry of all patients hospitalized with AF in Qatar from 1991 through 2010 was made. Rates and trends of clinical characteristics, cardiac comorbidities and in-hospital mortality were analyzed according to ethnicity. Results: During the 20-year period; 2857 Arabs and 548 Asians were hospitalized for AF. Arabs were 9 years older and more likely to have hypertension, diabetes mellitus, chronic renal impairment and dyslipidemia compared to Asians. Valvular heart disease and acute coronary syndromes were more common among Asians while congestive heart failure was more common in Arabs. Overall in-hospital mortality was lower for Asians compared to Arabs while stroke rates were comparable [Table1]. There was an increase in the prevalence of diabetes mellitus and hypertension in both groups in the latter years of the study period but, more so in Arabs when compared to patients hospitalized in the earlier years. Associated valvular heart disease was trending lower in both groups while ischemic heart disease prevalence was trending higher with no significant differences between the two groups. Rheumatic heart disease was statistically trending lower in prevalence; however it remained more prevalent among Asian patients over the study period. There were no significant differences in mortality trends over the study period between the two groups [Table 2]. Conclusions: The current study is the first ever report of comparative ethnic trends in etiologies and outcome of AF among Middle Eastern Arab and South Asian patients over a 20-year period. The current study underscores the need to study differences in atrial fibrillation among various ethnicities.

Background and Objectives: Most previous explanations of fatigue during repeated sprint exercise have focused on muscular factors associated with cellular mechanisms. At present, the nature of the neural adjustments and the extent to which corticospinal responsiveness is altered after the completion of repeated sprint exercise are yet to be elucidated. This study was undertaken to test the hypothesis that, in addition to the large peripheral fatigue, supraspinal factors would contribute substantially to neuromuscular adjustments of the quadriceps muscle in response to a repeated sprint cycling exercise. Methods: Twelve active individuals performed 10 x 6-s 'all out' sprints on a cycle ergometer (recovery= 30 s), followed 6 min latter by 5 x 6-s sprints (recovery= 30 s). Surface electromyographic activity was continuously recorded during the exercise. In addition, transcranial magnetic and electrical femoral nerve stimulations during brief (5-s) and sustained (30-s) isometric contractions of the knee extensors were performed before and 3 min post-exercise. Results: Peak power output and vastus lateralis root mean square activity decreased across sprint repetitions (P <0.001). These decrements were significantly (r= 0.89; P <0.001) correlated. Maximal strength of the knee extensors decreased during brief and sustained contractions (∼11% and 9%, respectively; P <0.001). Cortical voluntary activation values (∼90%), motor evoked potential amplitude and silent period duration responses measured during briefs contractions were unaltered. While cortical voluntary activation declined (P <0.01) during the sustained maximal contraction in both test sessions, larger reductions occurred (P <0.05) after exercise. Lastly, resting twitch amplitude in response to both femoral nerve and cortical stimulation was largely reduced (>40%, P <0.001) following exercise. Conclusion: The novel findings provided by motor cortex stimulation are that exercise induced reductions in cortical voluntary activation were seen in sustained, but not brief, maximal isometric contractions of the knee extensors. This, along with the lack of corticospinal responsiveness impairment from pre- to post-exercise, indicates that supraspinal processes do not necessarily limit repeated sprint ability. Rather, fatigue exhibited by the quadriceps when cycling sprints are repeated resides within the muscle itself, due to limitations in energy supply and/or the intramuscular accumulation of metabolic by-products.

Background and Objectives: The provision of emergency care is globally recognized as among the most difficult and challenging elements of any healthcare system. Hamad Medical Corporation (HMC) was facing increasing pressure to introduce initiatives to significantly ease problems with congestion at Hamad General Hospital's (HGH) Emergency Department (ED). This ED is one of the busiest in the world, with an average daily census of 1,500 patients. Due to the large number of patients, fragmented design and inappropriate placement and distribution of resources, all previous attempts at decongesting the ED and improving patient flow were unsuccessful. HGH leaders knew from internal data that the large volume of the male low-acuity patients represented approximately 70% of total ED patients, and were the main reason for congestion and crowding. Therefore, targeting this group would bring about the most significant impact. Methods: Data were studied in order to predict the number of patients who would fit the low-acuity criteria. This study confirmed that up to 70% of all ED patients fell within the low-acuity criteria. Lean process mapping was conducted to determine the current state of patient flow, processes, and practices in the male low-acuity areas of the ED. The impact of the existing fragmented facility design was also studied. Detailed analysis of a patient's journey from arrival to disposition was undertaken. Results: The process mapping confirmed many unacceptable variations when managing low-acuity cases in the ED and it was evident new design and processes were required. A 'See and Treat' service was opened on 7 March 2010 resulting in: reduction in door-to-door transit time, reduction in adverse events and complaints, improvements in maintaining patients' privacy and confidentiality, more appropriate resource utilization, routine referring orthopedic team, better pathway for x-ray, pharmacy and cashier, and new documentation to support efficiency. Conclusions: We believe that the remarkable success of the 'See and Treat' service in such a challenging and unique department as ours is a clear evidence that it should be acknowledged as a benchmark for best practice for the provision of efficient and safe patient care in an emergency department, particularly when managing high-volume, low-acuity presentations.

Background and Objectives: There is an escalating interest among patients and consumers in the use of complementary and alternative medicines (CAM), specifically natural health products, for a variety of illnesses. The public interest in CAM makes it important to explore the attitudes and beliefs of pharmacists involved in selling and dispensing these products. Our objectives were to explore the attitudes of community pharmacists towards CAM and to gauge their opinions about the challenges faced when dispensing CAM during their daily practice. Methods: A qualitative exploratory study was conducted in Doha, Qatar. The Study utilized focus group meetings and a purposive sample of community pharmacists whose pharmacies sell CAM. Recruiting for focus group meetings continued until a point of saturation was reached. The discussions and responses to questions were audio-taped and transcribed verbatim. All recordings were analyzed for recurring themes and subsequently coded and categorized. Results: Most pharmacists felt they were not equipped with sufficient information to competently recommend CAM to their clients and all have no access to information resources to update their knowledge. Pharmacists who graduated from the Indian subcontinent shared strong belief in traditional Indian remedies which shaped their practice in respect to CAM. Pharmacists have doubts about the safety of CAM and felt their undergraduate pharmacy courses did not prepare them to adequately assist their patients. Conclusion: Pharmacists were not confident in dispensing or recommending CAM to their patients. In view of the escalating interest in CAM, and in order for pharmacists to support patient autonomy in selecting health care interventions, colleges of pharmacy should make radical changes in those undergraduate courses that teach subjects related to CAM.

Background and Objectives: Neonatal mortality, a component of United Nations Millennium Development Goal 4 (MDG-4) (two thirds reduction in childhood mortality by 2015), has been a focus of all global health improvement strategies and plans of action since 1990. Our study aims to prospectively ascertain Qatar's neonatal mortality rate (NMR) during 2011, analyze trends between 1975 and 2011, and compare with recent data from high income countries. Methods: A 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 epidemiologic study funded by Qatar National Research Fund. The study quantifies 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 and compared with historical neonatal mortality data (1975-2011) ascertained from the database of maternity and neonatal units of the Women's Hospital and annual reports of HMC. Inter-country comparisons were made using World Health statistics 2011 and the European perinatal health report 2008. Results: Total live births during the study period were 20,583 and neonatal deaths 102. NMR was 4.9, early neonatal mortality rate (ENMR) 2.7, late neonatal mortality rate (LNMR) 2.2 and corrected neonatal mortality rate (cNMR) 3.26. Between 1975 and 2011, relative risk of NMR decreased by 87% (RR 0.13, 95% CI 0.10-0.18, p <0.001), ENMR by 91% (RR 0.09, 95% CI 0.06-0.12, p <0.001) and LNMR by 58% (RR 0.42, 95% CI 0.23-0.74, p= 0.002) though the population increased by 10 fold and number of deliveries by 7.2 folds. The comparable NMR from selected high income countries are between 3 and 5. Conclusion: Qatar has achieved its target MDG-4 by 2011. The improvement has been more marked in ENMR than LNMR. The current NMR, ENMR, LNMR and cNMR are comparable with selected high income counties. Further in-depth analysis of correlates and determinants of neonatal survival in Qatar may form the basis of a strategic global neonatal mortality improvement plan.

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.

Background and Objectives: Posaconazole (PSZ), is an antifungal prophylactic therapy that is used in hematologic cancer patients. It is approved for prophylaxis in hematologic cancer patients ≥13 years in USA, Canada, Australia, and ≥18 years in the European Union. In 2010, PSZ was added to the formulary of Al-Amal Hospital, the only adult cancer hospital in Qatar. The objective of this study is to conduct a drug use evaluation (DUE) study of posaconazole at Al-Amal Hospital. Methods: A retrospective, single centered, observational DUE study was conducted to include a convenient sample of hematologic cancer patients who used PSZ prophylactically during the year 2010. All patients, thirty-one, who received PSZ in 2010 were nominated of which 20 patients' profiles were reviewed, data were collected into a pre-prepared collection sheet and descriptive analysis was performed. Results: In Qatar, PSZ was used prophylactically in hematologic cancer patients >15 years with febrile and afebrile neutropenia. It is also planned to be used prophylactically for the upcoming bone marrow transplantation unit patients. All the 20 patients, 17 males and 3 females, received the PSZ for prophylaxis and were compliant. More than 50% of patients received proton pump inhibitors concurrently with posaconazole. Only 1 case had a recorded recommendation regarding the administration of PSZ with food. Five patients received vincristine-based chemotherapy protocol, one of which received it concurrently with PSZ for two cycles and developed seizure. Two patients developed mild breakthrough fungal infection, oral thrush, while on PSZ prophylactically. Conclusion: The PSZ regulations in Qatar are similar to the worldwide recommendations. The PSZ practice in Al-Amal hospital abides by the regulations. However, three points need to be addressed: PSZ has low bioavailability that can be enhanced by taking it with meals and by dividing the total daily dose. PSZ co-administration with proton pump inhibitors should be stopped as it may result in PSZ sub-therapeutic levels. Possible serious PSZ drug-drug interactions, seizures, in adult hematologic cancer patients should be highlighted and carefully monitored.

Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) marked by a risk of thrombotic and hemorrhagic complications, and by a long-term risk of evolution to myelofibrosis (MF), and acute leukemia (AL). Methods: Inclusion criteria: ET diagnosed as per WHO classification 2008, age 18 to 45 year. Exclusion criteria: (hepatic and renal dysfunction, history of psychiatric disorder, in particular depression, autoimmune hepatitis, severe cardiac dysfunction, known hypersensitivity to IFN. Complete hematologic response (CR) as per ELN guidelines and molecular response (MR) was defined as 'complete' when JAK2V617F became undetectable with the technique used (i.e., V617F <1%), 'partial' when >50% decrease of baseline V617F was obtained, and 'minor' when V617F decrease was between 20% and 49%. After inclusion, Pegasys was started subcutaneously at 50 microgram weekly for 4 weeks then 135 microgramg/week from week 5. Results: Baseline characteristics of the patients are age 19-44 years, 16 males and 24 females. Five patients had a history of major thrombotic events. All the patients responded to Pegasys at the 12-month evaluation including 35 hematologic CRs (94.6%), and 5 PRs (5.4%). Cumulative incidences of hematologic CRs and PRs showed that 100% of responses were achieved within 12 months. After the first year, V617F continued to decrease without evidence of plateau, the proportion of mutant JAK2 being always similar or lower in the last sample compared with the previous one. None of the responding patients experienced an increase of V617F during follow-up. Median V617F was 58% at 12 months (P <0.001). Hematologic response was achieved in all patients within 2 months and were sustained beyond the first year. Toxicities included musculoskeletal pain in 6 patients, skin toxicity in 4, and GI symptoms in 2, none of the toxicity exceeds WHO Grade 2. Conclusion: PEGylated interferon alfa-2a is an effective and promising treatment for ET reducing the vascular risk and preventing evolution to MF, MDS, and AL. With low toxicity profiles and good hematological and molecular responses, percentage of V617F appears to be a good tool to monitor minimal residual disease and to evaluate treatment efficacy. However, further studies are needed to confirm these results.

Background and Objectives: Reference assisted assembly requires the use of a reference sequence, as a model, to assist in the assembly of novel genomes. The standard method for identifying the best reference sequence for the assembly of a novel genome aims at counting the number of reads of the novel genome that align to the reference sequences and then choosing the reference sequence which has the highest number of reads aligning to it. This work explores the use of minimum description length (MDL) principle and its two variants, the two-part MDL and sophisticated MDL, in identifying the optimal reference sequence for genome assembly. Methods: The relevance of MDL to genome assembly can be realized by understanding that genome assembly is an inference problem where the task at hand is to infer the novel genome from read data obtained from sequencing. The task of MDL is to identify the model that best describes the data and within comparative assembly framework the same meaning applies to finding the reference sequences that best describe the set of reads. This work explores the potential of three variants of MDL: two-part MDL, sophisticated MDL and minimax regret for the selection of the optimal reference sequence for comparative assembly. Results: The proposed scheme based on sophisticated MDL has been shown to work successfully for the four possible set of mutations: SNPs, insertions, inversions and deletions. The proposed scheme chooses the reference sequence which has the smaller number of SNPs, insertions and deletions. The MDL scheme is able to detect all inversions and rectify them. Conclusions: The work compared the MDL scheme with the standard method of counting the number of reads that align to the reference sequence, and found that though the standard method is a necessary condition for finding the optimal sequence, it is not the sufficient condition. Therefore, the proposed MDL scheme encompassed within itself the standard method of: counting the number of reads, by defining it in an inverted fashion as counting the number of reads that did not align to the reference sequence.

Objectives: To formulate and evaluate oral dosage forms of metformin hydrochloride (MH) having sustained-release properties that would also increase MH bioavailability and address the shortcomings in the currently marketed sustained-release tablets. Methods: MH micronized powder was dispersed in molten polymeric matrices composed of Gelucire® 50/13 and various proportions of high molecular weight hydrophilic polymers, hydrophobic oily semisolid excipients, and mucoadhesive polymeric materials. The MH loaded matrices were filled in hard gelatin capsules (HGC) each containing 500 mg MH and were subsequently characterized using differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The prepared HGC were subjected to content uniformity and in vitro dissolution testing according to the USP-35 compendium requirements. The dissolution data were compared to instant and sustained-release marketed tablets. The effect of incorporating various proportions of the semisolid excipients on MH dissolution release rate, were also investigated. Results: MH content of the prepared HGC ranged between 96 to 103%. All the prepared semisolid filled HGC resulted in extended-release profiles of MH that lasted between 5 to 11 hours and demonstrated a release pattern which typically follows the release from mixes of triglycerides with polyethylene glycol esters of fatty acids. The incorporation of mucoadhesive excipients like carbomer to the Gelucire® 50/13-MH semisolid matrices extended the release of MH from 5 hours initially to 9 hours as a result of the formation of a gel layer around the matrix. However, the incorporation of different hydrophilic excipients like PEG35000 and Gelucire® 44/14 along with the mucoadhesive excipients sustained the release of MH up to 11 hours. XRD analysis of the MH prepared matrices demonstrated minor changes in the crystalline nature of MH. Depending on the loading ratios and the nature of the semisolid matrices used, DSC analysis revealed the changes in MH crystallinity to be from 100 to 23%. Conclusion: HGC formulated using semisolid matrices showed promising results in extending the release of MH. However, bioavailability studies to test the ability of such Gelucire based HGC of MH to improve its bioavailability and in vivo residence times are future plans.

Background and Objectives: A pregnant female requested prenatal diagnosis for a congenital and complex eye disease segregating in her family. The three-generation pedigree of Romanian ethnic origin was suggestive of an X-linked inheritance, due to exclusively affected males and no father-to-son transmission. Affected individuals had bilateral optic nerve atrophy, microphthalmia, nystagmus, leukocoria, cataract, retinal detachment, eye tumors reported as retinoblastomas, moderate mental and motor retardation, and seizures. All efforts to obtain the detailed medical records of affected individuals were fruitless. Methods: The disease locus was mapped utilizing 78 microsatellite markers that span the X-chromosome at ~2 Mb intervals, followed by candidate genes analysis and mutations detection by Sanger sequencing. Results: Affected individuals share an ~10 Mb region between DXS1056 and GATA160B08 at Xp11.23-11.4. Candidate genes in this linkage interval included BCOR and NDP. Mutation screening identified a c.267C>A p.F89L mutation in the NPD gene in all affected individuals, previously described in a single unrelated Dutch family and speculated as causing Norrie disease. Conclusions: In retrospect, clinical symptomatology fits the Norrie disease phenotype. The reported retinoblastomas were most likely pseudogliomas characteristic of Norrie disease. Detection of the c.C267A p.F89L mutation in a second unrelated family confirms the pathogenic nature of the mutation for Norrie disease. Utilization of gene mapping through linkage analyses and candidate gene screening previously utilized exclusively for research applications, were applied at a diagnostic setting and were essential in deciphering the offending molecular defect and diagnosing a disease which due to lack of medical records and poor and misleading clinical history would have no chance of being diagnosed correctly. Clinical diagnosis and mutation identification were essential prerequisites for providing proper genetic counseling and prenatal diagnosis in this family.

Background: Metabolic syndrome is associated with the rising incidence of obesity in developed countries, particularly in urban settings and is reaching epidemic proportions. Qatar, a rapidly modernizing country, has witnessed dramatic changes in urbanization and lifestyle. Recent studies demonstrate a significant prevalence of obesity and metabolic syndrome in Qatari population. According to a New York Times article (April 2010), the International Association for the Study of Obesity has ranked Qatar sixth globally for prevalence of obesity. Epidemiological studies suggest that a poor uterine environment elicited by maternal environmental exposure may program fetus susceptibility to develop cardiovascular and metabolic disease in childhood and later in life. Several studies have demonstrated the associations between pre-pregnancy obesity, chronic hypertension and dyslipidemia, and high risk of preterm birth and intrauterine growth restriction. However, there are no studies to examine the metabolic profile of Arabian pregnant women in early pregnancy with birth outcomes. Objectives: The objective of the present proposal is to examine the association between metabolic syndrome and obesity in early pregnancy of Qatari women and the risk of delivery preterm or growth restricted singletons. Methods: Qatari mother-child cohort: a prospective cohort examining a population sample of pregnant women and their children at the prefecture of Doha, Qatar within 1 year. The pregnant mothers, at maternity clinics and hospitals of Doha, were contacted. The consented participants were invited to provide biological samples in two time points of their pregnancy. Participants were interviewed to obtain information on several environmental and dietary factors, together with anthropometric measurements and blood pressure. Biochemical analyses were performed on serum triglycerides, total cholesterol, high and low density lipoprotein cholesterol, glucose, apolipoproteins, leptin, adiponectin and Interleukins. Expected results: At the national level this will be the first mother-child cohort study in Qatar. The study shall provide evidence-based relationship between maternal occupational/environmental exposure, such as sedentary life style, obesity, and other metabolic syndromes, and the subsequent birth outcomes on the Qatari population. Conclusion: Based on the study results, the public health perspective will be addressed by policy makers at the Supreme Council of Health in Qatar.

Background and Objectives: Trauma is the leading cause of death among the young population in the Middle East, including Qatar. A significant number of trauma and injured patients will require sophisticated critical care services and a disproportionately high level of hospital resources are centered within critical care units. The introduction of an advanced ACGME structured Trauma & Critical Care (TCC) Fellowship Program at the Hamad General Hospital (HGH) in Doha, Qatar will improve patient safety and outcomes, medical care and professional satisfaction. Methods: A review of the clinical impact of the TCC Fellowship Program in the trauma service at HGH, the only tertiary and national trauma center in Qatar, was conducted after the second year of implementation to evaluate the healthcare delivery to the severely injured patients, using tools from the ICU resource, evaluation, and patient outcomes rating tool (ICU Report)®. Results: Since the implementation of the TCC Fellowship Program in 2008, structured educational and training curriculum have been implemented for physicians assigned to the trauma service at the HGH. Nine fellows have successfully completed the program and graduated. A 40% decrease of intra-hospital mortality has been observed in our trauma service. Three fellows have been promoted to consultant level and six to critical care teaching staff, enhancing staff satisfaction and the overall score of our trauma ICU. Conclusions: Advanced postgraduate medical education and training program in trauma and critical care medicine have significantly contributed to patient safety and outcome of critically injured patients in Qatar and have enhanced the overall performance of our trauma service and staff satisfaction. The fellowship program is expanding to other disciplines, and is enrolling national and international candidates in emergency medicine and anesthesia in our institution and is impacting healthcare delivery of the complex cases of injured patients in the country.

Background Consanguinity and endogamy are common in the Middle East, resulting in a higher frequency of autosomal recessive (AR) disorders. This consanguinity facilitates discovery of disease causative genes particularly after introduction of the new techniques such as Whole Exome Sequencing (WES). In order to reduce the overall socio-economic burden of such diseases, the development of diagnostic tools and prevention strategies must be a priority. To achieve these goals, the causal genes underlying human genetic diseases should be first discovered. The goal of this study is to identify novel genes causing AR diseases in Qatari population using WES. Methods Genomic DNAs were captured with the Illumina TruSeq library and sequenced with Illumina HiSeq2000. The reads were aligned to the reference genome using BWA. Variants calling and annotation were performed by SAMtools and ANNOVAR, respectively. Novel variants were defined as those having an allele frequency <0.05 in the 1000 Genomes database and predicted to be nonsynonymous substitutions. Results WES was applied on affected individuals of 3 consanguineous families with Mental Retardation (MR: 2 siblings), Peripheral Neuropathy (PN: 2 siblings) and Eye Anomaly (EA: 1 male). The mode of inheritance was assumed to be AR in MR and PN families. This led to identification of 3 and 4 homozygous candidate variants, shared by two siblings, respectively. The mode of inheritance in EA was considered to be AR and/or X-linked that led to the identification of 26 autosomal homozygous and 6 X-linked genes. The function of one of the genes on X-chromosome was related to the patient phenotype. Conclusions These preliminary interesting results highlight the power of WES, to identify potential candidate genes for AR disorders. The identified genes will be considered for functional follow-up investigation and further characterization. However, our results also highlight that the large number of population-specific variants - which may be common polymorphisms in Qatar but are so far absent from public databases - make diagnosis and discovery more difficult than in well-studied Caucasian populations. We urge genetics researchers in Qatar to actively participate in the creation of a local variant database, which will greatly facilitate such future studies.

Background and Objective: Cells exposed to stress conserve energy for the repair of cellular damage by inhibiting translational initiation. The stress stimuli can trigger several stress response pathways leading to global translational attenuation, chiefly by the phosphorylation of eIF2α and disruption of the 43S assembly, which correlates to the compartmentalization of untranslated polyadenylated mRNA in discrete cytoplasmic ribonucleoprotein complexes known as Stress Granules (SGs). In a diabetic milieu, endothelial cells (ECs) that line the lumen of the blood vessels are constantly exposed to high glucose (HG) concentration (stress), which contributes to increased oxidative stress in these cells that in turn is responsible for high rates of cardiovascular complications among diabetic individuals. However, the effect of high glucose as a stress in relation to SG assembly in ECs remains unclear. The central objective of the present study is to evaluate the role of HG-induced oxidative stress in SG assembly in ECs and whether antioxidant treatment could aid in the reversal of these effects. Methods: Mouse microvascular endothelial cells (MMECs) cultured in DMEM were exposed to normal (NG, 11mM) and high (HG, 40mM) glucose for 0-48h. DHE staining was performed to evaluate oxidative stress in ECs upon HG exposure. Fixed cells were probed for SG marker proteins (G3BP and TIAR) followed by immunofluorescence confocal microscopy. Immunoblotting was performed using protein lysate samples and was probed for p-PERK, PERK, p-eIF2α and eIF2a. N-acetyl cysteine was used as the anti-oxidant in order to study the role of oxidative stress in HG induced SG formation. Results: DHE staining indicated that oxidative stress significantly increased in HG exposed MMECs while this effect was reversed upon in NAC treatment. NAC treatment also markedly decreased HG-induced SG assembly. Conclusion: The data suggest that HG-induced oxidative stress plays a major role in SG assembly in ECs. However, more studies are warranted to evaluate the process of assembly and dis-assembly of SGs in ECs upon HG exposure, which may provide a better understanding of the role of SG formation in balancing EC apoptosis and survival in a diabetic milieu. This project was funded by QNRF-NPRP # 08-165-3-054 & 4-910-3-244.

Background & Objectives: Despite the solid foundation on epidemiological evidence and basic science research, nearly 90% of the randomized controlled trials (RCT) designed to measure the efficacy of interventions on HIV incidence failed to measure a statistically significant efficacy against HIV incidence. Here, we propose the use of computer simulations to control trials as a useful tool to overcome the difficulty of effect size estimation and outcome interpretation derived from HIV intervention RCTs. Methods: We simulated the Partners in Prevention HSV/HIV transmission study recently conducted to test the efficacy of herpes simplex virus type 2 (HSV-2) suppressive therapy by acyclovir in reducing HIV transmission. We also simulated different variations of this trial, and the Rakai male circumcision trial. We developed individual-based Monte-Carlo models parameterized by the data of these RCTs and simulated the RCTs 1000 times. To measure the efficacy of the intervention, we conducted a log-rank survival analysis for each RCT realization and estimated the statistical power as the fraction of realizations that rejected the null hypothesis. Results: Our analyses indicated that the partners in prevention RCT had only 14% likelihood to observe a statistically significant efficacy for the intervention. In contrast, a different and more potent regimen for HSV-2 suppression had 87% chance of observing a statistically significant efficacy. For the Rakai male circumcision trial simulation, 94% of the RCT realizations showed statistically significant efficacy for the intervention. Conclusions: The simulations indicate that several unexpected odds have colluded to undermine the statistical power of the partners in prevention study, and therefore it would be premature to discredit the concept of acyclovir therapy for HIV prevention based on the outcome of the partners in prevention trial. Our study highlights how in silico simulations of RCTs can provide powerful tools for optimizing the design of RCTs and predicting their outcome. Observational and biological evidence summarized in computer simulations could help us on the estimation of effect size ranges and a better understanding of the system, which might provide a powerful tool to enhance the success of any HIV intervention RCT.