Europhilosophie Winterkurs Coimbra 2020

Report of the study visit in Coimbra

Remote Assessment Preferences of NIA Alzheimer’s Disease Research Center Participants During COVID-19 Pandemic

Background In a progressively technology-infused world, older adults are becoming accustomed to the digitization of research participation. During the COVID-19 pandemic, it became necessary to conduct remote study visits typically carried out over the telephone or using video calling programs (e.g. Zoom). Methods The National Alzheimer’s Coordinating Center developed a COVID-19 Technology Accessibility Survey to determine preferred types of study visits for study participants and to understand how this older population accesses the internet. Results Seven Alzheimer Disease Research Centers collected 1282 survey responses (mean age: ±71.8 years, mean education: 16.5±2.5 years, race/ethnicity: 86% White/non-Hispanic). In respondents aged 65-80, internet access was endorsed by 73% regarding smartphones, 61% for laptops, and 46% for tablets. Interest in wearable devices was expressed by 21% of respondents and interest in smart homes by 6%. Study visit preference among this age group was 42% in favor of in-person, 25% via phone, and 33% via video. In respondents aged >80 internet access was endorsed by 47% regarding smartphones, 47% for laptops, and 34% for tablets. Interest in wearable devices was expressed by 9% of respondents and interest in smart homes by 3%. Study visit preference among this age group was 38% in favor of in-person, 34% via phone, and 29% via video. Discussion In light of the COVID-19 pandemic, the survey suggests many study participants are interested in remote visits. Significant age group differences are present regarding internet access. Further studies are required to increase the understanding of the efficacy of this research visit format.

Pharmacokinetics of L-Glutamine (Endari) in Pediatric and Adult Sickle Cell Disease Patients: A Phase 4, Open-Label, Single-Center Study

Introduction: L-glutamine (Endari ®, Emmaus Medical, Inc.) is an amino acid approved for the treatment of sickle cell disease (SCD) by the United States Food and Drug Association (FDA) after 2 clinical trials demonstrated a reduction in painful episodes and hospitalizations. L-glutamine has many roles, including de novo synthesis of intracellular glutathione that may protect sickle erythrocytes from oxidant injury. Despite its licensure, the pharmacokinetics (PK) of multi-dose oral L-glutamine for SCD have not been studied. Methods: We conducted a dose-escalation PK trial from January to June 2021 (NCT04684381) on 3 cohorts with 4 participants each: pediatric SCD patients (0 - 18 y, cohort 1), adult SCD patients (>18 y, cohort 2), and adult healthy volunteers (>18 y, cohort 3). There were 4 weekly study visits to assess 3 ascending dose levels (Figure 1). For each visit, participants arrived in the research clinic after an overnight fast. Plasma L-glutamine and other amino acid levels were obtained before and after oral L-glutamine doses at each visit and quantified by ion exchange chromatography. On study visit 1, a dose of 0.1 g/kg of L-glutamine was administered and amino acids were measured at 30±5, 60±10, 120±15, 180±15 and 240±20 minutes after the dose. The procedure was repeated in the afternoon after a standardized meal. On study visit 2, the dose was increased to 0.3 g/kg twice daily (approximate FDA-approved dosing). On study visit 3, a single oral dose of 0.6 g/kg (once daily dosing) was given for fasting PK levels, and on study visit 4 the 0.6 g/kg dose was given with a standardized meal. After the first 3 study visits, participants continued L-glutamine at the corresponding dose level at home and completed a daily phone survey to document adherence and adverse events. Results: Baseline characteristics are summarized in Table 1. Baseline L-glutamine levels similar across the three study cohorts (Table 1). One participant from cohort 1 withdrew during study visit 1 and was replaced. Another participant from cohort 2 was withdrawn due to hospitalization for severe anemia and was replaced. One participant from cohort 3 did not complete visit 4 due to dyspepsia. Non-compartmental PK analysis (NCA) was conducted using Phoenix WinNonlin® Professional Version 8.4 (Certara, NJ, US; Figure 2). After oral administration, L-glutamine plasma levels peaked (T max) at an average (mean ± SD) of 1.2 ± 0.9 hours. Compared to doses 0.1 g/kg and 0.3 g/kg, the T max was later for 0.6 g/kg (p<0.05) indicating slower absorption at higher doses. At the lowest dose (0.1 g/kg), L-glutamine concentrations returned to baseline levels within 4 hours. However, at 0.3 or 0.6 g/kg, the plasma L-glutamine concentration remained higher than baseline at 4 hours, indicating slower elimination at higher doses. There was no significant change in the baseline plasma L-glutamine concentration levels during the study, however, indicating no evidence of drug accumulation. Peak L-glutamine concentration levels (C max) were higher at each successive dose escalation, but when the levels were normalized by dose there was a decrease in the normalized concentration with dose escalation, which implied a potential saturable absorption. Inter-patient variability in plasma L-glutamine levels was higher at 0.6 mg/kg than at lower doses. The elimination half-life (T 1/2), calculated as 0.693/elimination rate constant (λz), had an average value of 1.0 ± 0.7 hours. The most common grade 2 adverse events were dyspepsia and headache (3 instances each). There was no significant elevation in ammonia levels, and plasma concentrations of the metabolite L-glutamate was similar to L-glutamine (Figure 2). Conclusions: This is the first multi-dose PK study of L-glutamine (Endari) for SCD. Daily dosing was overall well-tolerated, with rapid absorption of 0.1 and 0.3 g/kg doses and no drug accumulation. The highest 0.6 g/kg dose was limited by palatability and featured slower and saturable absorption, so further dose escalation is likely not feasible. Ongoing analyses include possible food-drug interactions and PK-pharmacodynamic (PK-PD) studies to identify salutary effects on erythrocytes. Our findings will help inform the proper dosing of L-glutamine for patients with SCD, and potentially permit individualized PK-guided dosing to maximize treatment benefits. This was an investigator-initiated trial funded by Emmaus Medical, Inc. Figure 1 Figure 1. Disclosures Sadaf: Emmaus Medical, Inc: Research Funding. Ware: Bristol Myers Squibb: Research Funding; Addmedica: Research Funding; Hemex Health: Research Funding; Nova Laboratories: Research Funding; Novartis: Other: DSMB Chair; Editas: Other: DSMB Chair. Quinn: Emmaus Medical: Research Funding; Novo Nordisk: Consultancy; Aruvant: Research Funding; Forma Therapeutics: Consultancy. OffLabel Disclosure: Endari (L-glutamine) is FDA approved for the treatment of Sickle Cell Disease at a dose of 0.3 g/kg. However, in our pharmacokinetic study we tested doses 0.1, 0.3 and 0.6 g/kg.

Proportion of Subjects Achieving a Molluscum Lesion Count of 0 or 1 at the Day 84 End of Study Visit in Phase 3 Clinical Trials with VP-102 CAMP-1 and CAMP-2

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Racial Differences in Blood Pressure Control Following Stroke: The REGARDS Study

Background and Purpose: In the general population, Black adults are less likely than White adults to have controlled blood pressure (BP), and when not controlled, they are at greater risk for stroke compared with White adults. High BP is a major modifiable risk factor for recurrent stroke, but few studies have examined racial differences in BP control among stroke survivors. Methods: We used data from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) to examine disparities in BP control between Black and White adults, with and without a history of stroke. We studied participants taking antihypertensive medication who did and did not experience an adjudicated stroke (n=306 and 7693 participants, respectively) between baseline (2003–2007) and a second study visit (2013–2016). BP control at the second study visit was defined as systolic BP <130 mm Hg and diastolic BP <80 mm Hg except for low-risk adults ≥65 years of age (ie, those without diabetes, chronic kidney disease, history of cardiovascular disease, and with a 10-year predicted atherosclerotic cardiovascular disease risk <10%) for whom BP control was defined as systolic BP <130 mm Hg. Results: Among participants with a history of stroke, 50.3% of White compared with 39.3% of Black participants had controlled BP. Among participants without a history of stroke, 56.0% of White compared with 50.2% of Black participants had controlled BP. After multivariable adjustment, there was a tendency for Black participants to be less likely than White participants to have controlled BP (prevalence ratio, 0.77 [95% CI, 0.59–1.02] for those with a history of stroke and 0.92 [95% CI, 0.88–0.97] for those without a history of stroke). Conclusions: There was a lower proportion of controlled BP among Black compared with White adults with or without stroke, with no statistically significant differences after multivariable adjustment.

Abstract 064: Prevalence, Risk Factors And Cardiovascular Outcomes Associated With Persistent Blood Pressure Control: The Jackson Heart Study

Introduction: Cross-sectional studies have reported the proportion of African-American adults with controlled blood pressure (BP) at a single time point, but few data are available on the proportion that maintains controlled BP over time and the extent to which it is associated with cardiovascular disease (CVD) risk. Methods: We analyzed data from 1,414 African-American Jackson Heart Study (JHS) participants taking antihypertensive medication to estimate the proportion with persistent BP control, defined by having controlled BP at the three JHS visits, conducted over a median of 8 years. At each visit, BP control was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg. Follow-up for CVD events began after the third visit. We calculated risk ratios (RR) for factors associated with persistent BP control and hazard ratios (HR) for incident CVD events among participants with versus without persistent BP control. Results: At baseline, 76.5% (n=1,081) of participants had controlled BP, among which 64.4% (n=696) had persistent BP control. Overall, 49.2% (n=696) of participants had persistent BP control. After adjustment for sex, participants ≥65 compared with <65 years of age were less likely (RR; 95% CI) to have persistent BP control (0.73; 0.64 - 0.83). After age and sex adjustment, participants were more likely to have persistent BP control if they had income ≥$25,000 a year at each study visit (1.25; 1.11 - 1.40), a high school education (1.20; 1.01 - 1.41) and health insurance (1.28; 1.05 - 1.57) at Visit 1, and visited a health professional in the past year at each study visit (1.21; 1.07 - 1.37). The multivariable adjusted HR (95% CI) comparing participants with versus without persistent BP control was 0.71 (0.45 - 1.14) for CVD, 0.85 (0.41 - 1.79) for coronary heart disease, 0.68 (0.28 - 1.64) for stroke, and 0.57 (0.33 - 0.98) for heart failure (HF) ( Table ). Conclusions: Less than half of JHS participants taking antihypertensive medication had persistent BP control, putting them at increased risk for CVD, particularly HF.

Levodopa–carbidopa intrajejunal infusion in Parkinson’s disease: untangling the role of age

Objectives Levodopa–Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson’s disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG. Methods Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson’s disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA. Results No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive–compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups. Conclusion Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD.

Engaging with the cultural ‘other’: The ‘colonial signature’ and learning from intercultural engagements

In this article, the idea of the ‘colonial signature’ is advanced as a potentially pivotal response to triggers that deepen or act as barriers to intercultural learning. From a postcolonial positioning, empirical data is then examined to consider the responses to intercultural-learning triggers of 14 UK-based student teachers on a study visit to India specifically through an analysis of their reflective writing and interviews. Participants’ responses to varied triggers became significant colonial signatures to their intercultural learning. The learning deepened where responses were reflexive and articulated with reference to the global powerbase that underpins study visits to the Global South. Where responses to triggers provoked more shallow comparisons with home, the colonial signatures resulted in closed-down discussion, thus acting as a barrier to further learning. This has implications not only for study visits, but also, more widely, for the approach to global learning.

The Seosan Park Cheomji Nori as Example of the Republic of Korea’s Intangible Cultural Heritage Safeguarding at Regional Level

The author presents results of a research conducted during a five-month study visit to the National Folk Museum of Korea in 2017 as a part of the International Partnership Program for Cultural Partnership Initiative (CPI) of the Ministry of Culture, Sports and Tourism of the Republic of Korea. The objective of this visit was to study the Korean system of safeguarding their intangible heritage as well as its effects at the institutional and communal level. The paper deals with the latter and focuses on practices of safeguarding the local specific puppet play Park Cheomji Nori, which has been included into the regional Register of the intangible cultural heritage.

Abstract 17167: Black Women Have Evidence of Cardiometabolic Risk and Damage to the Microvascular Glycocalyx 1 to 10 Years After Uncomplicated Pregnancy

Introduction: Endothelial glycocalyx (GCX) is a proteoglycan/glycoprotein rich surface layer that regulates vascular health and function and can be damaged in diabetes and cardiovascular disease. Given the excess risk of adverse pregnancy outcomes (APO), chronic hypertension and CVD in Black compared to White women, we considered that microvasculature and glycocalyx may also differ between groups and contribute to adverse clinical outcomes. Objective: The first step was examining the microvasculature in women with no complications in the index pregnancy (from the medical record) and cardiometabolic risk markers. Methods: Sidestream dark-field imaging of the sublingual microcirculation and glycocalyx was used to compare density, median diameter, perfusion (RBC filling %), and penetration of red cells into the glycocalyx of vessel segments of 20-25μm diameter (PBR), in women 1-10 years after the index pregnancy (mean 8 years after index pregnancy). The study included 67 Black women and 167 White women with no complications (preeclampsia, gestation hypertension, preterm delivery, intrauterine growth restriction or gestational diabetes) in the index pregnancy. Health and pregnancy history were obtained by questionnaire at the study visit. Results: Black women had a greater penetration of red blood cells into the glycocalyx of microvascular segments20-25μm (PBR:2.54±0.41 vs White women 2.40±0.43μm, p=0.02). Perfusion in Black women was reduced (70.5±4.2% vs 72±4.8% p=0.003) compared to white women. Associations remain after adjusting for age, BMI, and time to follow-up. Black women were significantly younger (25± 6 vs 30±5 yrs p<0.001) at index delivery and study visit (34±6 vs 38±6yrs p=0.001); they also had higher BMI both pre-pregnancy (28±7 vs 25±6, p=0.007) and at the study visit (32±7 vs 27±7, p<0.001) and higher fasting insulin(17±36 vs 7±9 p=0.002) at the visit compared to White women. Self-reported history of hypertension, diabetes and APO (outside the index pregnancy) was significantly more common among Black at follow-up. Conclusion: Compared to White women, Black women of reproductive age had evidence of more pronounced microvascular changes potentially related to cardiometabolic risk 1-10 years after an uncomplicated index pregnancy.