Virtual Clinical Encounter Examination (VICEE): A novel approach for assessing medical students' non-psychomotor clinical competency.

INTRODUCTION: The Corona Virus Disease-19 (COVID-19) pandemic disrupted medical education across the world. Online teaching has grown rapidly under lockdown. Yet the online approach for assessment presents a number of challenges, particularly when evaluating clinical competencies. The aim of this study was to investigate the feasibility, acceptability, reliability and validity of an online Virtual Clinical Encounter Examination (VICEE) to assess non-psychomotor competencies (non-procedure or manual skills) of medical students. METHOD: Sixty-one final year medical students took the VICEE as part of the final summative examination. A panel of faculty experts developed the exam cases and competencies. They administered the test online via real-time interaction with artificial intelligence (AI) based virtual patients, along with faculty and IT support. RESULTS: Student and faculty surveys demonstrated satisfaction with the experience. Confirmatory factor analysis supported convergent validity of VICEE with Direct Observation Clinical Encounter Examination (DOCEE), a previously validated clinical examination. The observed sensitivity was 81.8%, specificity 64.1% and likelihood ratio 12.6, supporting the ability of VICEE to diagnose 'clinical incompetence' among students. CONCLUSION: Our results suggest that online AI-based virtual patient high fidelity simulation may be used as an alternative tool to assess some aspects of non-psychometric competencies.

Ghrelin modulates intracellular signalling pathways that are critical for podocyte survival.

Damage to podocytes is a key event in glomerulopathies. While energy dense food can contribute to kidney damage, the role of the orixegenic hormone "ghrelin" in podocyte biology is still unknown. In the present study, we investigated the effect of ghrelin on podocyte survival as well as the signalling pathways mediating ghrelin effect in immortalized cultured rat podocytes. RT-PCR analysis revealed that GHS-R1 is expressed in rat podocytes. Western blot analysis showed that ghrelin upregulated COX-2 protein expression in a time and dose-dependent manner. Additionally, ghrelin activated P38 MAPK, AKT, and ERK1/2 pathways and also induced P38 MAPK phosphorylation in high glucose conditions. Ghrelin induced ROS release and dose dependently reduced podocyte survival. Ghrelin mediated podocyte cell death was partially reversed by pharmacologically inhibiting P38 MAPK or phospholipase C (PLC). Furthermore, PLC inhibitor (U73122) inhibited ghrelin induced P38 MAPK activation. While PI3K inhibitor (LY294002) was without effect on cell survival or P38 MAPK activation, it inhibited ghrelin induced ERK1/2 phosphorylation. Finally, ghrelin induced TAU phosphorylation was reversed by pharmacologic inhibitors of either P38 MAPK or PKA. In conclusion, ghrelin activated harmful molecular pathways in podocytes that can be damaging to the glomerular filtration barrier SIGNIFICANCE OF THE STUDY: Endocrine derangements secondary to obesity are major players in the aetiology of renal injuries. Furthermore, energy dense diet is thought to be the major element in developing obesity. Appetite and increase in energy intake are regulated by complex hormonal pathways which mainly include the orexigenic hormone "ghrelin" in addition to leptin. To date no study have highlighted a significant role for ghrelin in kidney biology, and therefore, it is thought that its endocrine effect is mostly limited to adipose tissue metabolism and appetite regulation. In this study, we first showed that ghrelin receptor is expressed on glomerular podocytes. Also, ghrelin showed negative impact on podocyte survival through modulating signalling pathways such as P38 MAPK and AKT known to play a key role in podocyte health. Moreover, the negative effects of ghrelin on podocytes were further exacerbated in hyperglycemic conditions. Of note, podocytes contribute to the formation and the maintenance of the glomerular filtration barrier and thus are important for normal renal function. Therefore, ghrelin secretion in the context of obesity could be involved in the aetiology of kidney injury, a well-known hallmark found in obese patients.

Renal function decline in recipients and donors of kidney grafts: role of aortic stiffness.

BACKGROUND/AIMS: Renal function decreases over time as a result of reduction in the number of functioning nephrons with age. In recipients and donors of kidney grafts, renal function decline may be linked differently to various parameters, namely arterial stiffness. METHODS: We conducted a prospective cohort study including 101 recipients of kidney grafts and their donors aiming at determining the factors correlated to the renal function decline over time. Aortic stiffness was evaluated by the non-invasive measurement of aortic pulse wave velocity. The glomerular filtration rate was estimated using the Modification of Diet in Renal Disease (MDRD) equation and the annualized change was determined. RESULTS: Decline in renal function was estimated at 1-year post-transplantation and annually thereafter (median follow-up 8 years, range 3.6-18.3), as the mean of the annualized decrease in the glomerular filtration rate. In recipients, filtration rate decreased by 4.8 ± 19.7 ml/min/1.73 m(2) the first post-transplant year and at a yearly rate of 2.2 ± 3.8 ml/min/1.73 m(2) thereafter. The first-year decline was related to smoking and acute rejection. Later decline was significantly associated with donor age and aortic stiffness. In living donors, renal function decline after the first year corresponded to 0.7 ml/min/1.73 m(2), was significantly lower than that of recipients (p < 0.001), and was determined by donor age at nephrectomy. CONCLUSION: Recipients of kidney grafts show a glomerular filtration rate decline over time that is significantly associated with donor age and aortic stiffness after the first post-transplant year, while donors demonstrate a lower decline that is mostly determined by age at nephrectomy.

Outcome analysis of brain-death referral to NOD-Lb: A retrospective chart review of a single hospital experience over 3 years.

BACKGROUND: Organ donation shortage and in particular organ procurement is an international concern as the gap between the number of donors and recipients is steadily growing. Organ procurement is a chain of steps with donor identification and referral (ID&R) as the very first link in this chain. Failure of this step hinders the progress in the organ transplantation program. OBJECTIVES: Our study was conducted to evaluate and highlight the gap between the national system and the practice at the identification and referral (ID&R) step of the organ procurement chain in a single tertiary-care academic health center in Beirut: the Lebanese American University Medical Center-Rizk Hospital (LAUMC-RH), and to appraise the literature for challenges at this step and for possible interventions for improvement based on the international experience. MATERIALS AND METHODS: This retrospective study was a descriptive case series of ICU and ED deceased patients at a single tertiary-care university hospital in Beirut. Patients' characteristics were collected from medical records for all patients who died between 2017 and 2019 while in the ICU or the ED and shared with the National Organization for Organ and Tissue Donation and Transplantation (NOD-Lb), for each subject separately, to decide on the donor status. All data collected from the patient cohort was analyzed using R version 3.6.1. Wilcoxon signed-rank test, chi-squared, and fisher-exact tests were used to compare differences in clinical characteristics in terms of donor status when appropriate. RESULTS: This study served as 3 years audit of a single hospital experience, and it demonstrates failure to make any referrals to NOD-Lb and zero actual organ and tissue donations over the study period. The review of 295 deceased subjects' charts demonstrates 295 missed alerts to NOD-Lb and the overall missing of 5 organ and tissue donors and 24 cornea donors assuming the organ procurement chain of steps will continue uninterrupted after ID&R. CONCLUSION: The data gathered suggests the presence of an inefficient identification and referral system that is translated into a complete failure of reporting to NOD-Lb from LAUMC-RH. A systematic evidence-based approach to evaluate for the most cost-effective intervention to increase identification and referral rates is needed with a serious effort to examine and account for any inefficient implantation.

Sleep Medicine Knowledge Among Graduating Medical Students in Lebanon During an Economic and Political Crisis: A Preliminary Survey.

Objectives Sleep disorders are prevalent and underrecognized during both economic and political crises. They are a major reason for poor overall health and decreased quality of life. Sleep medicine education is limited at most medical schools, resulting in limited awareness of this important aspect of healthcare. The aim of the study is to assess sleep medicine knowledge of graduating medical students in Lebanon and to assess their readiness to tackle sleep health issues in a country during an unprecedented crisis. Methods Final-year medical students at 7 medical schools in Lebanon were invited to fill a survey between January 2020 and March 2021. The Assessment of Sleep Knowledge in Medical Education survey was used to assess their knowledge in sleep medicine. The curriculum organizers at the medical schools were also surveyed. Student's t -test was used for analysis. Results 158 and 58 students completed the survey during 2020 and 2021, with a mean overall score on sleep knowledge of was 17.5 and 15.9 /30, respectively. There was no difference in mean knowledge scores by gender, age, American versus European medical school systems, and between medical schools that included sleep medicine in their curriculum versus those that did not. Conclusions Presence of sleep medicine education in the curriculum was associated with higher scores on ASKME among graduating Lebanese medical students. Given the low response rate, however, this descriptive pilot data could be used as a launching pad for a larger study, with a more representative sample, for generalizable results.

The association between sleep disturbances and blood pressure variability: a review of the literature.

STUDY OBJECTIVES: Sleep disturbances are an underrecognized public health issue that results in various adverse outcomes and disturbed quality of life. Blood pressure variability (BPV) is an emerging entity in assessing cardiovascular disease risk and accumulating evidence suggests that BPV is closely associated with end-organ damage. This review aims to explore the association between sleep disturbances and BPV. METHODS: A comprehensive systematic literature search was conducted electronically using Web of Science, Ovid MEDLINE, , and SCOPUS. The electronic search was restricted to relevant English-language studies published between 1985 and August 2020. Most studies were prospective cohorts in design. After applying eligibility criteria, 29 articles were included for synthesis. RESULTS: This review shows that sleep disturbances are linked to short-term, midterm, and long-term BPV. Restless legs syndrome, shift work, insomnia, short sleep, long sleep, obstructive sleep apnea, and sleep deprivation were all positively associated with systolic blood pressure or diastolic blood pressure fluctuations. CONCLUSIONS: Given the prognostic implications of BPV and sleep disturbances on cardiovascular mortality, recognizing and treating both disorders is essential. More research is needed to examine the impact of sleep disorder treatment on BPV and cardiovascular mortality. CITATION: Al Haddad N, Costanian C, Zibara V, et al. The association between sleep disturbances and blood pressure variability: a review of the literature. J Clin Sleep Med. 2023;19(8):1533-1544.

Cardiovascular and renal outcome in recipients of kidney grafts from living donors: role of aortic stiffness.

BACKGROUND: Cardiovascular (CV) risk remains high in renal transplant patients despite a clear improvement conferred by transplantation. This risk is attributed mostly to recipient-related risk factors. Donor vascular characteristics, such as arterial stiffness, have been poorly investigated in this regard. METHODS: Recipients of living-related (n = 75) and living-unrelated (n = 20) kidney grafts were recruited at a mean time of 107 ± 41 months after transplantation for baseline evaluation and follow-up for the occurrence of the following composite outcome: myocardial infarction, stroke, CV death, doubling of serum creatinine or development of end-stage renal disease (ESRD). At inclusion, recipients and their corresponding donors underwent complete history, physical examination, laboratory tests and non-invasive measurement of aortic pulse wave velocity (PWV). RESULTS: During a mean follow-up of 56 ± 18 months, 20 recipients doubled their serum creatinine, of whom 16 reached ESRD, and 9 suffered of a new CV event (5 of which were fatal). Cox proportional hazards regression analysis showed that, in addition to recipient-related parameters, such as the presence of CV event and the estimated glomerular filtration rate at inclusion, donor aortic PWV was a strong and independent predictor of the composite recipient outcome. CONCLUSIONS: Donor large artery stiffness may predict recipient CV and graft outcome. This finding demonstrates the tight link that exists between the vascular system and the kidneys and suggests that donor contribution to recipient outcome goes beyond simple parameters like age, gender and even familial or non-familial donor type.

Aortic stiffness, kidney disease, and renal transplantation.

In subjects with chronic kidney disease (CKD), treatment of high systolic blood pressure is a key element in preventing disease progression and the occurrence of cardiovascular (CV) events. This relationship between the large arterial system and kidney function was demonstrated in different renal populations. In subjects with mild to severe renal insufficiency, increased aortic stiffness and reduced creatinine clearance are closely related and are independent of traditional CV risk factors. In renal transplant patients, aortic stiffness is significantly increased irrespective of donor type. Donor age and/or acute rejection contribute independently to the increased stiffness. In the presence of renal dysfunction, an increase in systemic pulse pressure frequently may be observed and transmitted to the glomeruli. This alteration potentially initiates renal damage and favors CV events. In subjects with end-stage renal disease and high CV risk, pharmacologic modulation of the renin-angiotensin system might prevent CKD progression and CV events.

Clinical relevance of aortic stiffness in end-stage renal disease and diabetes: implication for hypertension management.

: Evidence suggests that aortic stiffness may antedate and contribute initially to the development of hypertension and cardiovascular risk (CVR). In treated hypertensive patients, both diabetes and end-stage renal disease (ESRD) are comorbid conditions associated with increased aortic stiffness and high CVR. Thus, the pathophysiological relationship between aortic stiffness, blood pressure (BP) and CVR may have clinical implication in the management of hypertension. In patients with diabetes or ESRD, aortic stiffness is a significant predictor of CVR, independently of BP control. The hallmark of accelerated aortic stiffening in these patients associates the presence of vascular calcification, which is considered as a time-dependent process. Aortic stiffness represents a marker of structural but also functional arterial damage associated with increased pressure pulsatility. Carotid-femoral pulse wave velocity (cf-PWV), as a marker of aortic stiffness, may provide a readily available information for the effectiveness of risk reduction strategies. SBP, hyperglycemia and progressive alteration of renal function are considered as determinants of accelerated aortic stiffening. These findings suggest that earlier and intensive treatment of glycemia and BP could be important to limit or even reverse stiffening process. In patients with ESRD, more specific and potentially modifiable kidney disease-related parameters such as phosphocalcic disorders and vitamin K deficiency, appear correlated with aortic calcification and cf-PWV. An important and recent finding is that the magnitude of longitudinal increase in cf-PWV may represent a clinically pertinent surrogate for cardiovascular events. Aortic stiffness may be, thus, considered as an intermediate marker to monitor effectiveness of preventive strategies in these high-risk patients.

Longitudinal Study of Hypertensive Subjects With Type 2 Diabetes Mellitus: Overall and Cardiovascular Risk.

Despite adequate glycemic and blood pressure control, treated type 2 diabetic hypertensive subjects have a significantly elevated overall/cardiovascular risk. We studied 244 816 normotensive and 99 720 hypertensive subjects (including 7480 type 2 diabetics) attending medical checkups between 1992 and 2011. We sought to identify significant differences in overall/cardiovascular risk between hypertension with and without diabetes mellitus. Mean follow-up was 12.7 years; 14 050 all-cause deaths were reported. From normotensive to hypertensive populations, a significant progression in overall/cardiovascular mortality was observed. Mortality was significantly greater among diabetic than nondiabetic hypertensive subjects (all-cause mortality, 14.05% versus 7.43%; and cardiovascular mortality, 1.28% versus 0.7%). No interaction was observed between hemodynamic measurements and overall/cardiovascular risk, suggesting that blood pressure factors, even during drug therapy, could not explain the differences in mortality rates between diabetic and nondiabetic hypertensive patients. Using cross-sectional regression models, a significant association was observed between higher education levels, lower levels of anxiety and depression, and reduced overall mortality in diabetic hypertensive subjects, while impaired renal function, a history of stroke and myocardial infarction, and increased alcohol and tobacco consumption were significantly associated with increased mortality. Blood pressure and glycemic control alone cannot reverse overall/cardiovascular risk in diabetics with hypertension. Together with cardiovascular measures, overall prevention should include recommendations to reduce alcohol and tobacco consumption and improve stress, education levels, and physical activity.

Vitamin K2 supplementation and arterial stiffness among renal transplant recipients-a single-arm, single-center clinical trial.

Subclinical vitamin K deficiency is prevalent among renal transplant recipients and is associated with an increased risk of cardiovascular disease. However, the association between vitamin K supplementation and improvement of arterial stiffness has not been explored in the renal transplant population. The KING trial (vitamin K2 In reNal Graft) is a single-arm study that evaluated the association between the change in vitamin K status and indices of arterial stiffness following 8 weeks of menaquinone-7 (vitamin K2) supplementation (360 µg once daily) among renal transplant recipients (n = 60). Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Subclinical vitamin K deficiency was defined as plasma concentration of dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.At baseline, 53.3% of the study subjects had subclinical vitamin K deficiency. Supplementation was associated with a 14.2% reduction in mean cfPWV at 8 weeks (cfPWV pre-vitamin K2 = 9.8 ± 2.2 m/s vs. cfPWV post-vitamin K2 = 8.4 ± 1.5 m/s; P < .001). Mean dp-ucMGP concentrations were also significantly reduced by 55.1% following menaquinone-7 supplementation with a reduction in the prevalence of subclinical deficiency by 40% (P = .001). When controlled for age, durations of hemodialysis and transplantation, and the change in 24-hour mean arterial pressure, the improvement in arterial stiffness was independently associated with the reduction in dp-ucMGP concentration (P = .014).Among renal transplant recipients with stable graft function, vitamin K2 supplementation was associated with improvement in subclinical vitamin K deficiency and arterial stiffness. (Clinicaltrials.gov: NCT02517580).

Change in Pulse Wave Velocity and Short-Term Development of Cardiovascular Events in the Hemodialysis Population.

The association between single measurements of carotid-femoral pulse wave velocity (cfPWV) and cardiovascular (CV) events is driven by late events beyond 12 months of follow-up. This prospective study compares single measurements of cfPWV vs the 2-year delta cfPWV and the association with short-term development of CV events in hemodialysis patients. cfPWV was performed at t=0 and t=1 two years later, and patients were followed-up for development of CV events through 12 months (n=66). In Cox regression models adjusted for CV risk factors, history of CV events and delta cfPWV remained associated with the development of CV events (hazard ratio for prior CV events=8.9, P=.03; hazard ratio for delta cfPWV=1.14; P=.002). When delta cfPWV was substituted for single cfPWV measurement, none of the single measures were associated with new CV events. The change in cfPWV, but not single measurements of cfPWV, was associated with the development of CV events through 12 months.

Aortic stiffness, living donors, and renal transplantation.

In subjects with renal disease, reduced renal function and increased arterial stiffness are significantly associated in cross-sectional studies. The relationship is independent of age, blood pressure (BP), and atherosclerosis. Because both variables are independent predictors of cardiovascular risk, time-dependent relationships between them are important to determine. Aortic pulse wave velocity was measured noninvasively by comparison with healthy volunteers in 101 living kidney donors and their 101 corresponding recipients. Healthy volunteers were divided into 2 groups: one was recipient related through familial links and the other was nonrecipient related. Independently of age, gender, and BP, pulse wave velocity was significantly elevated in donors and recipients by comparison with the 2 groups of healthy volunteers. Pulse wave velocity was significantly higher in the recipient-related than in the nonrecipient-related group. Whereas in healthy volunteers, pulse wave velocity was exclusively related to age, gender, and BP, in donors and recipients, it was rather associated with a cluster of cardiovascular risk factors, including smoking habits and plasma glucose. Major factors related to pulse wave velocity were renal: time since nephrectomy (donation date) in donors, in whom pulse pressure was specifically associated with proteinuria, and renal rejection in recipients. Plasma creatinine doubling secondary to chronic allograft nephropathy was significantly associated with renal rejection and donor pulse wave velocity, independent of age. Our findings strongly suggest consistent interactions (including familial factors) between kidney function and arterial stiffness. Assessment of cause-effect relationships and implication of biochemical and/or genetic factors warrant additional studies.

Aortic pulse wave velocity in renal transplant patients.

BACKGROUND: In subjects with end-stage renal disease (ESRD) undergoing hemodialysis, aortic pulse wave velocity (PWV) is increased independently of blood pressure level and mostly is a strong predictor of cardiovascular risk. Few studies on this subject have been performed in renal transplant patients. METHODS: Aortic PWV was determined noninvasively in 106 patients with kidney transplantation and treated using a standard immunosuppression protocol. Mean age was 43 +/- 14 years. During the follow-up period (mean duration 54.3 +/- 28.9 months), the following parameters were studied: characteristics of the renal graft, degree of renal insufficiency, number of acute rejections, cardiovascular risk factors, drug medications, and cardiovascular complications. RESULTS: Aortic PWV was increased in subjects with renal transplants independently of age and mean blood pressure. Acute renal rejection and smoking habits were the principal factors modulating together: the increase of aortic PWV and the reduction of the glomerular filtration rate (GFR). The latter renal parameter was also influenced by the donor age. Two main parameters were predictors of cardiovascular events: a past history of cardiovascular disease and the pulse pressure x heart rate product, the major mechanical consequence of increased PWV. CONCLUSION: In renal transplant subjects, tobacco consumption and mostly acute renal rejection modulate both aortic stiffness and chronic renal failure independent of blood pressure level and donor characteristics. Pulsatile stress mediates cardiovascular complications and predicts cardiovascular risk, particularly in the presence of increased heart rate.