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Background: The Lebanese American University has a well-functioning inter-professional education (IPE) programme; this is a fundamental pedagogical approach in healthcare education in which students from different professions learn together, ultimately leading to improving the skills of the health care workforce and thus improving patient outcomes. The programme includes nursing, nutrition, medicine, pharmacy and social work students, and has now been running for 6 years. Aims: This paper aims at describing the implementation of an IPE programme in Lebanon by focusing on how to overcome the main challenges. Methods: We describe our experience using the categories of challenges developed by Sunguya et al. (2014), where they analysed published reports of IPE programmes in developed countries. We identified three additional challenges that might be relevant throughout the Middle East/North Africa (MENA) region or in countries with similar socioeconomic characteristics. Results: The challenges encountered in designing and implementing the IPE programme were similar to other programmes: curriculum, leadership, resources, stereotypes and attitudes, variety of students, IPE concept, teaching, enthusiasm, professional jargon and accreditation as well as assessment of learning, security and logistics. Conclusions: This paper provides data and successful strategies that can be used by planned or implemented programmes in similar socioeconomic contexts in the MENA region.

La sclérose latérale amyotrophique (SLA) est une maladie neurodégénérative fatale. Le seul traitement ayant reçu l'AMM est le riluzole (RLZ). La minocycline (MNC) a montré être neuroprotectrice dans un modèle murin de SLA. L'objectif de ce travail a été d'explorer le passage cérébral du RLZ et de la MNC et plus particulièrement les mécanismes d'efflux médiés par les transporteurs ABC: la P-gp et la BCRP. Nous avons aussi exploré l'intéraction médicamenteuse entre RLZ et MNC. Nos essais ont montré que le RLZ et la MNC sont transportés par la P-gp et que le RLZ est aussi transporté par la BCRP. La MNC est inhibitrice de la P-gp et potentialise ainsi le passage intracérébral du RLZ qui lui a montré pouvoir induire la BCRP. Sur un modèle murin de SLA, l'expression cérébrale de la P-gp est induite et les concentrations cérébrales en RLZ sont plus faibles. Ces études devraient, être intégrées en préclinique, quand une association médicamenteuse est envisagée.

The onset of coronary artery disease (CAD) is influenced by cardiovascular risk factors that often occur in clusters and may build on one another. The objective of this study is to examine the relationship between hypertension and CAD age of onset in the Lebanese population. This retrospective analysis was performed on data extracted from Lebanese patients (n = 3,753). Logistic regression examined the association of hypertension with the age at CAD diagnosis after controlling for other traditional risk factors. The effect of antihypertensive drugs and lifestyle changes on the onset of CAD was also investigated. Results showed that hypertension is associated with late onset CAD (OR=0.656, 95% CI=0.504-0.853, p=0.001). Use of antihypertensive drugs showed a similar association with delayed CAD onset. When comparing age of onset in CAD patients with traditional risk factors such as hypertension, diabetes, hyperlipidemia, obesity, smoking and family history of CAD, the age of onset was significantly higher for patients with hypertension compared to those with any of the other risk factors studied (p < 0.001). In conclusion, hypertension and its treatment are associated with late coronary atherosclerotic manifestations in Lebanese population. This observation is currently under investigation to clarify its genetic and/or environmental mechanisms.

ABCB1 (MDR1/P-glycoprotein) is an ATP-dependant transmenbrane protein widely expressed in human organs, protecting them against xenobiotics. ABCB1 is involved in drug pharmacokinetics: at the blood-brain barrier level, due to its luminal localisation, ABCB1 limits drug transport and plays an important role in central detoxification. Many interindividual variabilities have been described on ABCB1 expression and functionality. Variabilities may play a role in the pathogenesis in neurological diseases. Furthermore, ABCB1 expression and/or functionality may modify drug efficacity or increase central adverse events. This paper reviews the implication of ABCB1 in the physiopathogenesis of neurological diseases and its role in the cerebral distribution of drugs.

Amyotrophic lateral sclerosis is a neurodegenerative fataldisease. The only drug recognized to increase the survivaltime is riluzole(RLZ). In animal models, minocycline (MNC)delayed the onset of the disease and increased the survivaltime (in combination with RLZ). The objective of our workwas to study the interactions between RLZ, MNC and theefflux pump p-glycoprotein (p-gp) at the blood–brain barrier.We investigated these two drugs as: (i) p-gp substrates bycomparing their brain uptake in CF1 mdr1a ()/)) and mdr1a(+/+) mice, (ii) p-gp modulators by studying their effect onthe cerebral uptake of digoxin. mdr1a ()/) ) mice showedhigher brain uptake of MNC and RLZ than mdr1a (+/+) (in a1.6- and 1.4-fold, respectively); and in mdr1a (+/+) micepre-treated with repeated doses of MNC, brain uptake ofdigoxin was increased. When both drugs were administratedto mdr1a (+/+) mice, MNC increased the brain uptake ofRLZ in a 2.1-fold. In conclusion, MNC and RLZ are bothp-gp substrates. MNC is also a p-gp inhibitor and increasesthe brain diffusion of RLZ. In vitro experiments with theGPNT cell line confirmed these results. These interactionsshould be taken into account in the design of future clinicaltrials.

The Lebanese American University Interprofessional Education (LAU IPE) Steps Framework consists of a five-step workshop-based series that is offered throughout the curriculum of health and social care students at an American university in Lebanon. The aim of the present study was to report students’ perceptions of their readiness for interprofessional learning before and after completing the IPE steps, their evaluations of interprofessional learning outcomes, as well as their satisfaction with the learning experience as a whole. A longitudinal survey design was used: questionnaires were completed by students before IPE exposure and after each step. The results showed that before IPE exposure, students’ perceptions of their readiness for interprofessional learning were generally favourable, with differences across genders (stronger professional identity in females compared to males) and across professions (higher teamwork and collaboration in pharmacy and nutrition students compared to other professions and lower patient centredness in nursing students compared to others). After participation in the IPE steps, students showed enhanced readiness for interprofessional learning and differences between genders and professions decreased. Participants were satisfied with the learning experience and assessment scores showed that all IPE learning outcomes were met. The LAU IPE Steps Framework may be of value to other interprofessional education course developers.

Background As the world becomes increasingly digital, advances in technology have changed how students access evidence-based information. Research suggests that students overestimate their ability to locate quality online research and lack the skills needed to evaluate the scientific literature. Clinical nurses report relying on personal experience to answer clinical questions rather than searching evidence-based sources. To address the problem, a web-based, evidence-based research (EBR) tool that is usable from a computer, smartphone, or iPad was developed and tested. The purpose of the EBR tool is to guide students through the basic steps needed to locate and critically appraise the online scientific literature while linking users to quality electronic resources to support evidence-based practice (EBP). Methods Testing of the tool took place in a mixed-method, quasi-experimental, and two-population randomized controlled trial (RCT) design in a U.S. and Middle East university. Results A statistically significant improvement in overall research skills was supported in the quasi-experimental nursing student group and RCT nutrition student group using the EBR tool. A statistically significant proportional difference was supported in the RCT nutrition and PharmD intervention groups in participants’ ability to distinguish the credibility of online source materials compared with controls. The majority of participants could correctly apply PICOTS to a case study when using the tool. Conclusions The data from this preliminary study suggests that the EBR tool enhanced student overall research skills and selected EBP skills while generating data for assessment of learning outcomes. Linking Evidence to Action The EBR tool places evidence-based resources at the fingertips of users by addressing some of the most commonly cited barriers to research utilization while exposing users to information and online literacy standards of practice, meeting a growing need within nursing cur

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disease. Drugs used in this disease need to cross the blood–brain barrier (BBB). Only riluzole is approved for ALS treatment. We have investigated riluzole as a breast cancer resistance protein (BCRP) substrate by studying its brain transport in CF1 mdr1a (−/−) mice and its intracellular uptake on BeWo cells (human placental choriocarcinoma cell line). We have also investigated the effect of riluzole on BCRP expression level and on its activity using the prazocin as a test probe for brain transport and intracellular uptake. Assays on mdr1a (−/−) mice and BeWo cells showed a higher uptake of riluzole when pretreated with a BCRP inhibitor. After repeated doses of riluzole, BCRP activity was increased in CF1 mdr1a (−/−) mice, riluzole uptake was decrease and both BCRP expression and activity were increased in BeWo cells. In conclusion, we report in this study that riluzole is transported by BCRP at the BBB level and can enhance its function. These results taken with our previous studies on riluzole and P-glycoprotein show that drug–drug interactions between riluzole and efflux transporters substrates may occur at the BBB level and should be taken into account in future clinical trial design in ALS.

Diagnosis of Parkinson’s disease can be emotionally and psychologically challenging to patients. The aim of this study is to investigate the association between Parkinson’s disease and depression and the impact of the disease stage and patients’ age and gender on this association. Method: This is a cross-sectional retrospective study on 200 patients aged above 35 years old from 10 different nationalities. Results: Depression was diagnosed in 46% of the patients enrolled. Most of these patients were treated with an antidepressant. Young age, female gender, and moderate Parkinson’s disease stage were found to be significantly associated with depression (odds ratio of 1.19, 1.23, and 1.22, respectively, p < .05). Conclusion: This study, the first of its kind in Lebanon and the Middle East and North Africa region, highlights the importance of studying depression in Parkinson’s disease and the need for identifying and treating depression symptoms when treating Parkinson’s disease patients.

Purpose. Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by the loss of motorneurons. The only drug approved is riluzole. Minocycline is an antibiotic with numerous neuroprotective properties. riluzole and minocycline were given to an animal model of ALS and had beneficial effect on the disease. The combination was then tested in humans in phase II and phase III studies with less beneficial effects and a faster decline of the disease in the group treated with minocycline. In a previous study, we showed that riluzole is transported out of the brain by the P-glycoprotein at the bloodbrain barrier level. In this work, we tested the hypothesis of a drug-drug interaction between riluzole and minocycline. Methods. We studied in CF1 mice, the plasma and brain pharmacokinetics of riluzole combined or not with minocycline. Results. Our results showed that riluzole pharmacokinetics are not linear with dose, but that brain AUC0-t increase proportionally with plasma AUC0-t. At the dose of 10 mg/kg, the brain AUC0-t /plasma AUC0-t ratio was 4.6 in mdr1a (-/-) mice and 2.4 in mdr1a (+/+) mice. The combination of minocycline (170 mg/kg) and riluzole (10 mg/kg) induced a 2 fold increase in the brain AUC0-t of riluzole and induced a neuromuscular toxicity in mice. This effect of minocycline was not found at low concentration (10 mg/kg of minocycline). Conclusions. If our results are confirmed in humans, riluzole brain concentrations could be predicted by plasma concentrations. Furthermore, the combination of high doses of minocycline with riluzole could induce neurological toxicity that lead to deceiving results in ALS clinical studies. Hence, a dose-range of minocycline combined with riluzole should be tested in further clinical studies.

The efflux pumps located at the blood–brain barrier (BBB) prevent drugs entering the brain. As such, efflux pumps are a major obstacle to drug brain distribution. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with little therapeutics available: riluzole is the only drug approved in its treatment. The lack of response to treatment in ALS may be, at least in part, due to increased activities of efflux pumps in relation to disease, leading to subtherapeutic brain concentrations of drugs. In the present study, we used a transgenic mouse model of ALS (G86R mSOD1 mice) to test this hypothesis. Expression and functionality of P-glycoprotein (ABCB1, P-gp) and Breast Cancer Resistance Protein (ABCG2, BCRP), two major efflux pumps, were studied. We observed an increased P-gp expression (1.5-fold) in presymptomatic mSOD1 mice compared to wild-type controls. Consistent with this, P-gp function was also increased by 1.5-fold and riluzole brain disposition was decreased by 1.7-fold in mSOD1 mice. Contrasting with this, BCRP expression and function were unaltered by the pathology. These results demonstrate that BBB transport proteins are modified in G86R mSOD1 mice ALS model. Such findings underline potential problems in extrapolating the results of animal studies to humans and developing clinical trials, especially for drugs transported by P-gp.

Background Elevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease. Aims The rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine. Methods A total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach. Results Traditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia. Conclusions Hyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics’ intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction.

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Prognosis of GBM patients is poor with median overall survival around 15 months. Temozolomide is the chemotherapeutic agent used in the standard of care of newly diagnosed GBM patients relying on radiotherapy with concurrent chemotherapy followed by chemotherapy alone. Irinotecan has shown some efficacy in recurrent malignant gliomas. Bevacizumab has been combined with irinotecan in the treatment of recurrent GBM and with temozolomide in newly diagnosed GBM. As the efficacy of GBM treatments relies on their brain distribution through the blood brain barrier, the aim of the present preclinical work was to study, in in vivo models, the impact of bevacizumab on brain and tumor distribution of temozolomide and irinotecan. Our results show that bevacizumab pre-treatment was associated with a reduced temozolomide brain distribution in tumor-free mice. In tumor bearing mice, bevacizumab increased temozolomide tumor distribution, although not statistically significant. In both tumor-free and tumor-bearing mice, bevacizumab does not modify brain distribution of irinotecan and its metabolite SN-38. Bevacizumab impacts brain distribution of some anti-tumor drugs and potentially their efficacy in GBM. Further studies are warranted to investigate other therapeutic combination.

Purpose: MPTP-induced dopaminergic degeneration is an experimental model commonly used to explore Parkinson’s disease. Cerebral drug transport by ABC transporters in MPTP models has never been reported. Methods: We have investigated the transport of bromocriptine through the blood-brain barrier (BBB) in a MPTP model to understand the influence of the dopaminergic degeneration on ABCB1 and ABCG2. Results: We have shown that in MPTP treated mice, bromocriptine is widely distributed to brain (2.3-fold versus control, p<0.001) suggesting either disruption of BBB or alteration of active efflux of the drug. The investigation of BBB did not evidence a modification of permeability. Studies of ABCB1 and ABCG2 activity showed that MPTP intoxication did not alter their functionality. Conversely, ABCG2 expression studied on brain capillaries from MPTP-treated mice was decreased (1.3-fold, p<0.05) and ABCB1 expression increased (1.43-fold, p<0.05) as an off-setting of brain transport. Conclusions: These data demonstrate that MPTP intoxication does not alter BBB permeability. However, bromocriptine brain distribution is increased in MPTP animals. Hence, MPTP may interact with another transport mechanism such as uptake and/or other efflux transporters. Inflammation and Parkinson’s-like lesions induced by MPTP intoxication could lead to modification of drug pharmacokinetics and have clinical consequences, such as neurotoxicity.

Background: More evidence is emerging on the strong association between chronic kidney disease (CKD) and cardiovascular disease. We assessed the relationship between coronary artery disease (CAD) and renal dysfunction level (RDL) in a group of Lebanese patients. Methods: A total of 1268 patients undergoing cardiac catheterization were sequentially enrolled in a multicenter cross sectional study. Angiograms were reviewed and CAD severity scores (CADSS) were determined. Estimated glomerular filtration rate (eGFR) was calculated and clinical and laboratory data were obtained. CKD was defined as eGFR < 60 ml/min. Logistic regression model was performed using multivariate analysis including all traditional risk factors associated with both diseases. ANOVA and the Tukeytestswere used to compare subgroups of patients and to assess the impact of each disease on the severity of the other. Results: Among the 82% patients who exhibited variable degrees of CAD, 20.6% had an eGFR < 60 ml/min. Logistic regression analysis revealed a bidirectional independent association between CAD and CKD with an OR = 2.01 (P < 0.01) and an OR = 1.99 (P < 0.01) for CAD and CKD frequencies, respectively. We observed a steady increase in the CADSS mean as eGFR declined and a progressive reduction in renal function with the worsening of CAD (P < 0.05). This correlation remained highly significant despite considerable inter-patient variability and was at its highest at the most advanced stages of both diseases. Conclusions: Our results show a strong, independent and graded bidirectional relationship between CAD severity and RDL. We propose to add CAD to the list of risk factors for the development and progression of CKD.