Atlantic University College

Although levodopa remains the gold standard treatment for Parkinson's disease (PD), its chronic use is associated with levodopa-induced dyskinesia (LID), a motor complication that impacts prognosis, quality of life, and treatment costs. Most known LID-associated factors have been identified in European-descendant populations. To describe the epidemiology of LID in Latin American and Caribbean (LATAM) countries and assess the relevance of known and novel LID-associated factors in this population. We conducted a cross-sectional study using data from the Latin American Research consortium on the Genetics of Parkinson's Disease (LARGE-PD). We included PD patients with information on LID status and levodopa use from eight LATAM countries. LID prevalence was calculated overall and by country. Countries were compared on demographic and clinical variables. Logistic regression was used to identify associations with LID. A total of 3,695 PD patients (58.8% male) were included. Overall LID prevalence was 25.4% [95% CI: 24.06-26.87], ranging from 9.3% in Colombia to 45.1% in Puerto Rico. Prevalence increased progressively with longer disease duration. Country comparisons showed that not all known LID-associated factors explained prevalence differences. In logistic regression, fast disease progression was significantly associated with LID (OR: 1.55, 95%CI: 1.16-2.07), while sex was not (OR: 1.02, 95%CI: 0.87-1.18). This is the largest study on LID epidemiology in LATAM. While some known risk factors remain relevant, others, like sex, do not, underscoring the need for population-specific studies. Future work should integrate environmental, clinical, and genetic data to better understand LID mechanisms.

Robustness of evidence from randomized controlled trials (RCTs) is crucial for guiding clinical decisions in rectal cancer. We evaluated the reliability of RCTs cited by the National Comprehensive Cancer Network (NCCN) guidelines for rectal cancer using the Fragility Index (FI) that quantifies the stability of trial outcomes. RCTs referenced in the latest NCCN guidelines for rectal cancer were reviewed. Data from eligible trials were extracted. FI was calculated to assess the robustness of evidence across different treatment modalities. Sixty‐seven RCTs (published: 1987–2022) involving 16,990 patients were analyzed. Most studies (58.2%) were conducted in Europe. Common treatment areas included metastatic liver disease (28.9%) and neoadjuvant chemotherapy (14.9%). Primary outcomes were disease‐free survival and overall survival (OS) in 15 studies each (22.4%), local recurrence rates in 6 (9%), and tumor response in 5 (7.5%). The median FI was 9 (interquartile range [IQR] 2–20). Studies on surgical interventions had the highest median FI (21 [IQR 7–27]) followed by studies on neoadjuvant radiotherapy (19 [IQR 14–25]). Neoadjuvant immunotherapy studies had the lowest median FI of 0, indicating less robust evidence. Notably, surgical intervention studies showed the largest gap between FI and patients lost to follow‐up (21 vs. 13.5), while neoadjuvant immunotherapy studies showed more patients lost to follow‐up than the median FI (0 vs. 5), highlighting the need for stronger evidence. In conclusion, evidence supporting most treatments for rectal cancer in the NCCN guidelines is robust, although neoadjuvant immunotherapy requires further scrutiny due to its low FI. FI offers a nuanced perspective on the reliability of trial outcomes.

Background: Pharmacogenomic assisted prescribing of medications utilizes individual genetic information to identify drug-gene interactions. We aimed to assess potential pharmacogenomic drug-gene interactions in geriatric emergency department (ED) patients that have sustained a fall. Methods: This was a prospective study involving 25 older adult ED patients with fall related injury. Data collected included current medications, demographics and mechanism of injury. All patients provided a DNA sample for pharmacogenomic testing, MatchMyMeds (DNA Labs, Boca Raton, FL) which assessed genetic data for 23 enzyme systems and reports on potential drug-gene interactions for 134 medications. Each patients medications were reviewed against their pharmacogenomic report and categorized as Green (go), Yellow (caution) or Red (stop) based on their genetic information and published interactions by the Clinical Pharmacogenetics Implementation Consortium (CPIC), Dutch Pharmacogenetics Working Group (DPWG) and Food and Drug Administration-approved drug label information. The main study outcome was pharmacogenomic drug-gene interactions. Results: Of the 25 patients enrolled (median age, 81 years, IQR: 76-85), 68% were female. Patients were taking a median of 8 medications (IQR: 5-11). The most common types were antihypertensives, statins, anticoagulants, and anti-platelet medications. Significant drug-gene interactions (Yellow or Red) were identified in 14/25 (56%) patients. Further, 6/25 (24%) had one or more potentially serious (Red) interactions identified. Conclusions: In geriatric ED patients with a fall-related injury, a majority have a significant pharmacogenomic drug-gene interactions. DNA testing identifies these interactions and can assist with pharmacogenomic-guided medication prescribing which may decrease ADEs and improve clinical outcomes.

Greater health care engagement with social determinants of health (SDOH) is critical to improving health equity. However, no national studies have compared programs to address patient social needs among critical access hospitals (CAHs), which are lifelines for rural communities. CAHs generally have fewer resources and receive governmental support to maintain operations. This study considers the extent to which CAHs engage in community health improvement, particularly upstream SDOH, and whether organizational or community factors predict involvement. Using descriptive statistics and Poisson regression, we compared 3 types of programs (screening, in-house strategies, and external partnerships) to address the patient social needs between CAHs and non-CAHs, independent of key organizational, county, and state factors. CAHs were less likely than non-CAHs to have programs to screen patients for social needs, address unmet social needs of patients, and enact community partnerships to address SDOH. When we stratified hospitals according to whether they endorsed an equity-focused approach as an organization, CAHs matched their non-CAH counterparts on all 3 types of programs. CAHs lag relative to their urban and non-CAH counterparts in their ability to address nonmedical needs of their patients and broader communities. While the Flex Program has shown success in offering technical assistance to rural hospitals, this program has mainly focused on traditional hospital services to address patients' acute health care needs. Our findings suggest that organizational and policy efforts surrounding health equity could bring CAHs in line with other hospitals in terms of their ability to support rural population health.