Trial Cohort Research Articles

Dynamic heterogeneity in COVID-19: Insights from a mathematical model.

Critical illness, such as severe COVID-19, is heterogenous in presentation and treatment response. However, it remains possible that clinical course may be influenced by dynamic and/or random events such that similar patients subject to similar injuries may yet follow different trajectories. We deployed a mechanistic mathematical model of COVID-19 to determine the range of possible clinical courses after SARS-CoV-2 infection, which may follow from specific changes in viral properties, immune properties, treatment modality and random external factors such as initial viral load. We find that treatment efficacy and baseline patient or viral features are not the sole determinant of outcome. We found patients with enhanced innate or adaptive immune responses can experience poor viral control, resolution of infection or non-infectious inflammatory injury depending on treatment efficacy and initial viral load. Hypoxemia may result from poor viral control or ongoing inflammation despite effective viral control. Adaptive immune responses may be inhibited by very early effective therapy, resulting in viral load rebound after cessation of therapy. Our model suggests individual disease course may be influenced by the interaction between external and patient-intrinsic factors. These data have implications for the reproducibility of clinical trial cohorts and timing of optimal treatment.

Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

Emerging evidence suggests that a number of factors can influence blood-based biomarker levels for Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD). We examined the associations that demographic and clinical characteristics have with AD/ADRD blood-based biomarker levels in an observational continuation of a clinical trial cohort of older individuals with type 2 diabetes and overweight or obesity. Participants aged 45-76 years were randomized to a 10-year Intensive Lifestyle Intervention (ILI) or a diabetes support and education (DSE) condition. Stored baseline and end of intervention (8-13 years later) plasma samples were analyzed with the Quanterix Simoa HD-X Analyzer. Changes in Aβ42, Aβ40, Aβ42/Aβ40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic, and clinical characteristics. In a sample of 779 participants from the Look AHEAD cohort, we found significant associations between blood-based biomarkers for AD/ADRD and 15 of 18 demographic (age, gender, race and ethnicity, education) and clinical characteristics (APOE, depression, alcohol use, smoking, body mass index, HbA1c, diabetes duration, diabetes treatment, estimated glomerular filtration rate, hypertension, and history of cardiovascular disease) . Blood-based biomarkers of AD/ADRD are influenced by common demographic and clinical characteristics. These factors should be considered carefully when interpreting these AD/ADRD blood biomarker values for clinical or research purposes.

Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial

ObjectivesThe gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on...

Dental prosthesis use moderates association between tooth loss and risk of depressive symptoms in older adults with severe tooth loss: The JAGES cohort trial.

Depression is a leading cause of disability. Although tooth loss increases the risk of depressive symptoms, it is unclear whether dental prosthesis use moderates this risk. This study aimed to investigate whether dental prosthesis use moderates the association between tooth loss and new depressive symptoms in older adults. This cohort study used data from the 2016 and 2019 Japan Gerontological Evaluation Study (JAGES). The participants were independent older adults aged ≥65 years without depressive symptoms in 2016. The onset of depressive symptoms in 2019 was the outcome variable. The explanatory variables were dental status (≥20 teeth, 10-19 teeth with or without dental prostheses, and 0-9 teeth with or without dental prostheses) in 2016. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Poisson regression models with potential confounders as covariates. The analysis included 50,169 participants (mean age: 72.8 [standard deviation, 5.4] years). During follow-up, the incidence of depressive symptoms was 11.3%. Compared to those who had ≥20 teeth, the RR of depressive symptom onset was highest among those who had 0-9 teeth without dental prostheses (RR, 1.27; 95% CI, 1.04-1.56), after the adjustment for confounders. However, this risk was lower in those with 0-9 teeth and dental prostheses (RR, 1.08; 95% CI, 1.01-1.15). These data highlight the potential of dental prostheses as an important factor in reducing the risk of depressive symptoms among individuals with severe tooth loss.

A multicentral prospective cohort trial of a pharmacist-led nutritional intervention on serum potassium levels in outpatients with chronic kidney disease: The MieYaku-Chronic Kidney Disease project.

Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156-0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427-2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793-1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272-1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD.

Definition of clinically relevant intraoperative hypotension: A data-driven approach.

Associations between intraoperative hypotension (IOH) and various postoperative outcomes were shown in retrospective trials using a variety of different definitions of IOH. This complicates the comparability of these trials and makes clinical application difficult. Information about the best performing definitions of IOH regarding 30-day mortality, hospital length of stay (hLOS), and postanesthesia care unit length of stay (PACU-LOS) is missing. A retrospective cohort trial was conducted using data from patients undergoing noncardiothoracic surgery. We split the obtained dataset into two subsets. First, we used one subset to choose the best fitting definitions of IOH for the outcomes 30-day mortality, hLOS, and PACU-LOS. The other subset was used to independently assess the performance of the chosen definitions of IOH. The final cohort consisted of 65,454 patients. In the shaping subset, nearly all tested definitions of IOH showed associations with the three outcomes, where the risk of adverse outcomes often increased continuously with decreasing MAP. The best fitting definitions were relative time with a MAP (mean arterial pressure) of <80 mmHg for 30-day mortality, lowest MAP for one minute for hLOS, and lowest MAP for one cumulative minute for PACU-LOS. Testing these three definitions of IOH in the independent second subset confirmed the associations of IOH with 30-day mortality, hLOS, and PACU-LOS. Using a data-driven approach, we identified the best fitting definitions of IOH for 30-day mortality, hLOS, and PACU-LOS. Our results demonstrate the need for careful selection of IOH definitions. Clinical trial number: n/a, EC #2245/2020.

Full-endoscopic versus Conventional Microsurgical Therapy of Lumbar Disc Herniation: A Prospective, Controlled, Single-Center, Comprehensive Cohort Trial (FEMT-LDH Trial)

Full-endoscopic versus Conventional Microsurgical Therapy of Lumbar Disc Herniation: A Prospective, Controlled, Single-Center, Comprehensive Cohort Trial (FEMT-LDH Trial)

Device Related Thrombosis and Bleeding in Pediatric Health Care: A Meta-analysis.

The risk of invasive device-related thrombosis and bleeding contributes to morbidity and mortality, yet their prevalence by device-types is poorly understood. This study aimed to estimate pooled proportions and rates of thrombotic and bleeding complications associated with invasive devices in pediatric health care. Medline, CINAHL, Embase, Web of Science, Scopus, Cochrane CENTRAL, clinical trial registries, and unpublished study databases were searched. Cohort studies and trials published from January 2011 to June 2022, including (1) indwelling invasive devices, (2) pediatric participants admitted to a hospital, (3) reporting thrombotic and bleeding complications, and (4) published in English, were included. Meta-analysis of observational studies in epidemiology guidelines for abstracting and assessing data quality and validity were used. Device-specific pooled thromboses (symptomatic, asymptomatic, unspecified) and bleeding (major, minor). Of the 107 studies, 71 (66%) focused on central venous access devices. Symptomatic venous thromboembolism in central venous access devices was 4% (95% confidence interval [CI], 3-5; incidence rate 0.03 per 1000 device-days, 95% CI, 0.00-0.07), whereas asymptomatic was 10% (95% CI, 7-13; incidence rate 0.25 per 1000 device-days, 95% CI, 0.14-0.36). Both ventricular assist devices (28%; 95% CI, 19-39) and extracorporeal membrane oxygenation (67%; 95% CI, 52-81) were often associated with major bleeding complications. This comprehensive estimate of the incidence and prevalence of device-related thrombosis and bleeding complications in children can inform clinical decision-making, guide risk assessment, and surveillance.

Infection Associated With Invasive Devices in Pediatric Health Care: A Meta-analysis.

Indwelling invasive devices inserted into the body for extended are associated with infections. This study aimed to estimate infection proportion and rates associated with invasive devices in pediatric healthcare. Medline, CINAHL, Embase, Web of Science, Scopus, Cochrane CENTRAL, clinical trial registries, and unpublished study databases were searched. Cohort studies and trials published from January 2011 to June 2022, including (1) indwelling invasive devices, (2) pediatric participants admitted to a hospital, (3) postinsertion infection complications, and (4) published in English, were included. Meta-analysis of observational studies in epidemiology guidelines for abstracting and assessing data quality and validity were used. Device local, organ, and bloodstream infection (BSIs) pooled proportion and incidence rate (IR) per-1000-device-days per device type were reported. A total of 116 studies (61 554 devices and 3 632 364 device-days) were included. The highest number of studies were central venous access devices associated BSI (CVAD-BSI), which had a pooled proportion of 8% (95% confidence interval [CI], 6-11; 50 studies) and IR of 0.96 per-1000-device-days (95% CI, 0.78-1.14). This was followed by ventilator-associated pneumonia in respiratory devices, which was 19% (95% CI, 14-24) and IR of 14.08 per-1000-device-days (95%CI, 10.57-17.58). Although CVAD-BSI and ventilator associated pneumonia are well-documented, there is a scarcity of reporting on tissue and local organ infections. Standard guidelines and compliance initiatives similar to those dedicated to CVADs should be implemented in other devices in the future.

Shared medical appointments (SMA) for metabolic syndrome patients in the Hague, the Netherlands

The pilot with the Shared Medical Appointment (SMA)started in januari 2021 in the Schilderswijk which is a deprived area of the Hague , with low health literacy and high prevelence of metabolic syndrome . This group of patients are are seen in the SMA together with a multidisciplinair Team (MDT) of professionals and scientists.&#x0D; The patient journey of the participants starts at population care towards customized patient orientated care.&#x0D; This proactive, integrative towards personalized care migth benefit applying a quadruple or quintuple aim.&#x0D; The study desing is a quasi experimental population based controlled cohort trial&#x0D; The study employs a dif -in -dif design using a regional control group on non participating GP ‘s&#x0D; Good collaboration is important between the primary care , the social care , welvare , and science.&#x0D; A shared shavings contract could proved financial incentives to realize efficiency gain value based competition.&#x0D; The SMA will be evaluated in 2023-2024 to measure the effects of the Sma intervention.&#x0D; Thank you In behalf of the team members&#x0D; Loïse Jacz, GP, Msc PHM i.o&#x0D; Rimke Vos , ass Prof&#x0D; Martin Bread , sportcoach&#x0D; Emma Witte : student Sportscience&#x0D; Maud Verhoeven : Msc PHM i.o&#x0D; Anil Samlal: experience expert&#x0D; Frank Kanhai : walking coach NDC&#x0D; Younes Bouadi: NDC coordinator

Genicular artery embolization for knee osteoarthritis: Results of the LipioJoint-1 trial

PurposeThe purpose of this study was to evaluate the safety and efficacy of transient genicular artery embolization (GAE) using an ethiodized oil-based emulsion for the treatment of knee osteoarthritis (KOA). Materials and methodsThis prospective, single-arm, open-label, multicenter, first-in-human cohort trial was registered on ClinicalTrials.gov (NCT04733092). The main inclusion criterion was diagnosis of KOA according to a visual analogue scale (VAS) pain score ≥ 40 mm (score range: 0–100 mm), despite conservative treatment for at least three months. Treatment efficacy was assessed using changes in VAS pain score, Mean Western Ontario & McMaster Universities osteoarthritis (WOMAC) function score (normalized to 100; score ranging from 0 to100) and outcome measures in rheumatoid arthritis clinical trials (OMERACT)-Osteoarthritis Research Society (OARSI) set of responder criteria. ResultsTwenty-two consecutive participants (13 women; mean age, 66 ± 9 [standard deviation (SD)]) were included and underwent GAE. Emulsion consisted in a mixture of ioversol and ethiodized oil (ratio 1:3, respectively) prepared extemporaneously. The rate of serious adverse events attributed to GAE within one month was 5% (1/22), corresponding to reversible worsening of renal function. Immediate technical success rate was 100%. Mean VAS pain score dropped from 74.4 ± 16.5 (SD) mm at baseline to 37.2 ± 26.7 (SD) mm at three months (P < 0.001). Mean WOMAC function score (normalized to 100: score ranging from 0 to 100) decreased from 57.3 ± 17.1 (SD) at baseline to 33.5 ± 25.9 (SD) at three months (P < 0.001). At three months, 16 out of 22 participants (73%) were considered responders according to the OMERACT-OARSI set of responder criteria, including high improvement in either pain or WOMAC function, or improvement in both pain and WOMAC function. ConclusionGAE using an ethiodized oil-based emulsion is safe and improves pain and function in participants with KOA for at least three months.

A Human Adenovirus C Infection-Related Gene Panel for Predicting Survival and Treatment Responsiveness in Glioma Patients

Viruses are critical for the regulation of cancer development and for therapy. Human adenovirus C (HadVC) has been detected in central nervous system and glioma tissue. The objective of the present study was the development of a robust prognostic model based on HadVC infection (HadVCi)-relevant genes. The genome, transcriptome, and virome were systemically analyzed using The Cancer Genome Atlas dataset for training and 2 cohorts from the Chinese Glioma Genome Atlas and an immunotherapy trial cohort with 17 patients receiving anti-PD-1 treatment for validation. HadVCi-relevant gene selection from differentially expressed genes between HadVC-infected and non-HadVC-infected glioma patients using least absolute shrinkage and selection operator regression was followed by Cox regression modeling to establish a prognostic HadVCi score. Kaplan-Meier and receiver operating characteristic curve analyses were performed to estimate the predictive capacity of the HadVCi score. The χ2, Spearman, and Mann-Whitney U tests were used to identify the correlation with the clinicopathological parameters, treatment responsiveness, and immune landscape. Temozolomide-resistant glioma cells were established and analyzed at the transcriptional level using RNA sequencing data. The HadVCi score was (-0.2526673∗TRPC6)+(-0.2244276∗RNF207)+ (-0.0894468∗SEC31B)+ (-0.0190214∗ZCRB1)+ (-0.017122∗DNPH1)+ (0.0495818∗CCDC34)+ (0.1196349∗PURG)+ (0.1778997∗LILRA5). The score possesses a strong ability to predict overall survival. Further analysis revealed a higher HadVCi score correlated with a malignant phenotype and poorer treatment responsiveness to temozolomide-based chemotherapy and combined therapies. Additionally, transcriptomic analysis showed malignancy-, stemness-, and radioresistant-related gene activation in the HadVCi group, which characterized the poor outcomes and limited sensitivity to standard therapy. The HadVCi score could be an effective tool for survival prediction and treatment guidance for patients with glioma.

Improving Inclusivity, Equity, and Diversity in Oncology Clinical Trials: A European Perspective

Historically, clinical trials in cancer medicine are, unfortunately, often poorly representative of the diverse populations who ultimately receive the intervention in real-world settings. This discrepancy could relate to age, extent of comorbidity, ethnicity, socioeconomic status (SES), and/or disability. This is particularly important, as medication efficacy and/or toxicity are known to be influenced by such variables. Many cancers also disproportionately affect individuals in underserved communities. If a highly selected cohort of individuals are recruited to a trial, theoretically, the findings should only be translated to equivalent cohorts in the community. Therefore, the more representative a trial cohort is of the target population, the more generalisable and applicable findings will be. If we aim to lessen disparities and improve equity, clinical trials must strive to become more inclusive, improving our knowledge of disease in these underserved groups, and therefore improving the care we provide to them in wider clinical practice. This review summarises the current European perspective on this topical issue, suggesting potential strategies to proactively improve inclusivity and diversity in cancer trials, by encouraging enthusiastic collaboration between the pharmaceutical industry, healthcare authorities, study sponsors, research networks, and clinicians.

The pre-anesthesia induction patient safety (PIPS) checklist: Testing dynamic versus static implementation strategies

BackgroundRetrospective studies and large-scale reviews suggest multiple properties of effective checklist implementation, such as active leadership, ongoing feedback, and local modification. We hypothesized that the use of these effective checklist implementation strategies would yield better results as compared to a more fixed implementation strategy of the Pre-anesthesia Induction Patient Safety (PIPS) checklist. MethodsWe conducted a prospective, pre-post, pragmatic cohort trial of a checklist implementation using a prospective difference-in-difference design observing simultaneous implementation of the same PIPS checklist in two community hospitals. At one hospital, we created a multidisciplinary committee of stakeholders to oversee implementation and provide active leadership, ongoing feedback, and local modification of the checklist (“Dynamic Implementation”). At the second hospital, a single clinical champion implemented the checklist with no local modification (“Static Implementation”). We examined checklist compliance and proximal outcomes three months before and nine months after implementation. We conducted surveys and interviews to examine attitudes and implementation barriers. ResultsWe observed 477 anesthesia inductions. The “Dynamic” cohort demonstrated significantly greater checklist compliance post-implementation compared to the “Static” cohort (B = 0.26, p < .001 for observable action and B = 0.24, p < .001 for verbal compliance). We were underpowered to detect changes in errors, or near-misses, but observers captured anecdotal checklist-related patient safety evidence, suggesting more research should be done in this area. There were no differences between cohorts on changes in team communication, or attitudes toward checklists. Participant interviews showed that two of the major criticisms of the PIPS checklist, ambiguity and redundancy, were more effectively resolved with the “Dynamic” implementation. ConclusionsDynamic implementation yielded significantly better compliance with the checklist than a more static approach. However, barriers such as time pressure and lack of team buy-in remain. Larger scale studies are needed to determine the full impact of the PIPS checklist on safety related outcomes such as near-misses.

Abstract LB_A14: Factors associated with enrollment, participation, and survival of patients on early phase cancer clinical trials

Abstract Background: Enrollment and participation of a diverse patient (pt) population for early phase clinical trials is crucial for determining the safety and efficacy of new cancer therapies. However, strict eligibility criteria, co-occurring conditions, and socioeconomic barriers can limit pt participation. Improving methods of pt recruitment, enrollment, and support while on clinical trials has the potential to accelerate trial accrual and diversity within trial cohorts. Methods: We conducted a retrospective chart review of oncology pts seen by the Early Phase Clinic Trials Unit (EPTU) at the Mount Sinai Hospital between July 2018 and October 2022. Pts had advanced solid tumors and had already received standard of care treatment. Data including demographics, cancer diagnosis, clinical trial enrollment, and overall survival (OS) were obtained from the electronic medical record. Demographic and clinical differences were compared between patients who enrolled on an early phase trial (T) and those who did not (NT). Univariable logistic regression was used to determine predictors of successful trial enrollment. Univariable Cox proportional hazards models were conducted to analyze factors associated with survival time on trial treating death of any cause as the outcome and censoring pts lost to follow-up or alive at trial termination. Results: 261 referrals were evaluated representing 234 unique patients. Of these, 60 pts (25.64%) enrolled in a clinical trial. No significant differences were found between T and NT pts in gender, race, ethnicity, language, or insurance status. In univariable logistic regression, number of previous systemic therapies was inversely associated with likelihood of going on trial (OR 0.87 95% CI [0.75, 1.00] p= 0.045). Pts with skin cancer had a higher likelihood of going on trial compared to those with other tumor types (OR 4.57 95% CI [1.27, 18.4] p=0.021). Of T patients, 27 (45.00%) were White, 8 (13.33%) were Black, 9 (15.00%) were Asian, and 12 (20.00%) were Hispanic; 12 (20.00%) did not speak English. The median time between initial appointment and Day 1 on trial was 0.67 months. Median length of time on trial was 2.07 months, and median OS from enrollment was 4.16 months (IQR [2.21, 8.16]). In univariable Cox regression, an ECOG PS of 1 compared to 0 was associated with increased risk of death (HR 1.91 95% CI [1.01, 3.61] p=0.050). Both Spanish speaking and all non-English speaking T pts had an increased risk of death compared to English speaking T pts (HR 5.09 95% CI [2.00, 12.19]; HR 2.34 95% CI [1.04, 5.25]). Conclusion: There were no significant demographic barriers to trial enrollment. However, times on trial and overall survival were modest, with the latter associated with poorer performance status. Given their increased risk of death, more support is needed for non-English speaking patients who participate on early phase trials. Citation Format: Elena Baldwin, Grace Van Hyfte, Natalie Lucas, Kathy Wu, Gary Shelton, Suzan Aird, Grace Chung, Gabriela Fazilov, Lisa Fitzgerald, Olivia Hapanowicz, Khadijah Holley, Paula King, Ashley Lu, Nathasha Melukkaran, Miriam San Lucas, Issamar Urena, Aleksandra Wawrzyniak, Marshall Posner, Matthew D Galsky, Thomas U Marron, Deborah B Doroshow. Factors associated with enrollment, participation, and survival of patients on early phase cancer clinical trials [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A14.

U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER): Baseline Characteristics of a Trial Cohort Enriched for Risk of Cognitive Decline

AbstractBackgroundU.S. POINTER is a two‐year clinical trial to evaluate whether lifestyle interventions targeting multiple risk factors protect cognitive function in older adults at increased risk for cognitive decline. We describe the baseline characteristics of the U.S. POINTER clinical trial cohort overall, and before and after changes in risk factor enrichment inclusion criteria.MethodU.S. POINTER is a Phase 3, multicenter, randomized 2‐year clinical trial of two lifestyle interventions varying in intensity and format, in older adults at increased risk for cognitive decline and dementia. The study closed enrollment with 2111 individuals at 5 sites (North Carolina, Northern California, Chicagoland, Houston, Rhode Island). Eligible participants were sedentary and consumed a suboptimum diet and met other risk enrichment criteria that included first degree family history of memory impairment, and suboptimum cardiovascular health status (meeting specific cut‐points of systolic blood pressure, LDL cholesterol or hemoglobin A1c). 20 months into enrollment, risk enrichment criteria were revised to account for two other factors: older age (70‐79 years), and African American/Black or Native American race or Hispanic/Latine ethnicity.ResultMean age at baseline is 68.2 years, 31% represent communities of color, 69% are women, and 30% are not college graduates. 58% reported maternal memory loss, mean systolic blood pressure = 131 mmHg, mean total cholesterol = 193 mg/dl, mean HbA1C = 5.9%, and mean body mass index (BMI) = 29.9 kg/m2. Mean adjusted modified Telephone Interview for Cognitive Status (TICSm) score is = 37.6 (max = 50 pts), Geriatric Depression Score (GDS) is = 1.8, and Short Physical Performance Battery Chair Stand Score (SPBC) is = 3.3. Some baseline characteristics (BMI, total cholesterol, SBBP chair stand) vary by clinical site. The change to risk score enrichment criteria (Table 1) increased representation of participants from communities of color and number of males in the study cohort.ConclusionU.S. POINTER successfully enrolled 2111 participants across 5 sites who are at high risk for cognitive decline and dementia, with appropriate representation by groups typically underrepresented in clinical trials, individuals aged 75 or older, and men, with the expansion of risk score enrichment criteria.

The Impact of the COVID-19 Pandemic on Medical Education: a Systematic Review of Distance Learning, Student’s Perceptions, and Mental Health

Introduction: the COVID-19 pandemic has impacted on mortality and several adverse health outcomes. It has also affected education as schools and universities had to adapt to remote learning due to social isolation strategies. Objective: to analyze the pandemic’s impact on medical education including undergraduate and graduate students and lecturers, as follow: i) teaching methods adopted by education institutes during shutdown, ii) students and lecturers’ perceptions and iii) impacts on students’ mental health. Methods: this systematic review includes the following study designs: cross-sectional, surveys, case-control, cohort, and clinical trials. The literature search was performed in four databases: PubMed, Scopus, Embase, and SciELO . The risk of bias and the quality of the evidence were evaluated. Results: a total of 1,576 articles were identified through searching databases, and 40 articles were included. We found the use of several teaching methods such as virtual platforms and social media, pre-recorded videos, discussion forums and others. Student’s challenges related to interference during online study such as family distractions, lack of a study room, challenges with internet connectivity, difficulties in communication between students and lecturers, gaps encountered during clinical skills learning. Lecturers’ challenges were difficulty in grasping students’ progress and learning outcomes and the lack of experience in online teaching. Only five studies explored mental health issues of medical students and found the occurrence of depression, anxiety, and stress. However, their prevalence was not comparable due to the use of different diagnostic instruments. Conclusion: there has been a wide range of teaching methods implemented for distance learning of medical students globally. The perceptions of medical students about these methods and their impact were also varied. Infrastructure, family, and curriculum problems represented the greatest difficulties in adherence and satisfaction with distance learning. However, the flexibility of digital learning was one of the factors that helped reduce these problems. Regarding mental health, the occurrence of anxiety, depression, and stress was reported.

Reduction of apathy and caregiver distress using a combination of tetrahydrocannabinol and melatonin in dementia due to Alzheimer’s disease

AbstractBackgroundApathy is one of the most frequent and long‐lasting neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD). Up to 78% of AD patients exhibit apathy, which is related to caregiver distress, decreased quality of life, and increased morbidity. While many medications and behavioral interventions are used to treat apathy, the effects are often limited and lack in‐depth research to support these approaches. We present preliminary data for improvement in NPI‐apathy (NPI‐ap) scores and NPI Caregiver Distress (NPI‐D) scores using IGC‐AD1, a tetrahydrocannabinol (THC) and melatonin combination.MethodTwelve patients with mild (15.38%) to moderate (84.6%) AD (NIA‐criteria, 10‐active, 2‐placebo, 81.5±5.5yrs, 69.2% women) participated in a three Cohort, Phase‐1, MAD, safety and tolerability trial (IND146069, NCT04749563). In Cohort‐1, IGC‐AD1 was administered QD at 1ml for 14‐days (EOT). In Cohorts‐2 and 3, one ml BID and TID were administered respectively, with a minimum of 4‐days washout between Cohorts. Solicited and non‐solicited adverse events (AEs) were monitored daily.In each Cohort, seven participants (5‐active, 2‐placebo) had apathy at baseline, as rated by the NPI‐ap. They were administered the NPI‐ap at EOT and the Wilcoxon matched pairs signed‐rank test (R‐Studio, dplyr) was used to compare the difference in NPI‐ap scores between baseline and EOT. A similar analysis was carried out for NPI‐D.ResultIn Cohort‐1 mean NPI‐ap at baseline and EOT was 5.4 and 3 respectively (mean difference = ‐2.4, v = 6, p = 0.091). In Cohort‐2 mean NPI‐ap at baseline and EOT was 5.2 and 2.4 respectively (mean difference = ‐2.8, v = 6, p = 0.087). In Cohort‐3 mean NPI‐ap at baseline and EOT was 5.2 and 2.6 respectively (mean difference = ‐2.6, v = 6, p = 0.087). Results for NPI‐D: (Cohort‐1:mean difference = ‐0.6, 37.5%, v = 6, p = 0.075; Cohort‐2:mean difference = ‐1.8, 69.2%, v = 15, p = 0.028; Cohort‐3:mean difference = ‐0.2, 12.5%, v = 2, p = 0.5). No serious AEs, no deaths, and no dropouts due to AEs were reported. No major changes in concomitant medications were observed.ConclusionAs IGC‐AD1 contains THC, the results are intriguing because cannabis use has been associated with apathy but also increased empathy and sociality. In Cohort‐1, Cohort‐2, and Cohort‐3 NPI‐ap was reduced 44.44%, 53.85%, and 50% respectively. These results, while not statistically significant (p&gt;0.05), appear clinically significant (reduction≥30%). A larger placebo‐controlled study is warranted.

Recruitment and Retention of Underrepresented Minorities in Interventional Alzheimer’s Disease Clinical Trials

AbstractBackgroundAlzheimer’s disease is a progressive neurodegenerative disorder that affects thinking, and behavior and is the most common cause of dementia. In Alzheimer’s disease (AD) clinical trials, there is a severe lack of underrepresented and marginalized populations. Despite overwhelming evidence that these groups are more likely to develop AD, various recruitment barriers impair them from being accepted into current AD clinical studies, which threatens these findings' overall generalizability and scientific impact. As a result, there is less understanding of overall needs, no mechanism for identifying and comparing disease variations, and a limited range of available interventions. In this study, we aim to analyze the recruitment, reporting, and retention strategies of Hispanic/Latinx and Black individuals in AD Clinical Trials for the last 35 years to create a novel model system to increase the diversity and inclusion of minoritized groups in Alzheimer’s Clinical Trials.MethodWe extracted the data from the clinicaltrials.gov database and applied the inclusion criteria: Year: 1999‐Present, Population: Older Adults (65&gt;), Alzheimer’s Diagnosed, and Healthy. Intervention: Pharmaceutical/drug. Funding: NIH, Industry. Status: Completed. For our outcome variables, we included the following: Reported and non‐reported recruitment demographic, the inclusion of white, Hispanic/Latin, Black/African American, Asian, and Unknown. For our analyses, we performed a Linear regression on cohort demographic makeup in five‐year intervals, reported vs. non‐reported demographic, and the percentage of ethnicity recruited.ResultOur search yielded n = 117 clinical trials. 28% of NIH‐sponsored drug‐based clinical trials have reported cohort demographic makeup. 61% of Industry‐sponsored drug‐based reported cohort demographic make‐up.ConclusionWe found that despite the increasing research focusing on the importance of the inclusion of underrepresented individuals in clinical trials. The number of underrepresented minorities in AD clinical trials continues to be significantly and alarmingly low, hindering the scientific process of developing therapeutic methods for Alzheimer’s Disease. Moreover, several laws and policies have been released to enforce the reporting of ethnicity/race of clinical trials cohort have not been adequately enforced and followed, raising concerns for policy efficacy.

LBA1 Combined expression of FOXC1, MKI67, and PDL1 predicts efficacy of immune checkpoint inhibitor therapy and hyperprogressive disease risk in advanced/metastatic renal cell cancer: Validation in the Javelin 101 clinical trial cohort

LBA1 Combined expression of FOXC1, MKI67, and PDL1 predicts efficacy of immune checkpoint inhibitor therapy and hyperprogressive disease risk in advanced/metastatic renal cell cancer: Validation in the Javelin 101 clinical trial cohort