Citations

AbstractBackgroundAfrican Americans are at greater risk of Alzheimer’s disease (AD) and AD‐related dementia (ADRD). They are also less likely to access dementia resources or participate in dementia research. The National Alzheimer’s Project Act (NAPA) calls for special attention to dementia‐related health disparities in high risk groups. Identifying effective tools to improve rates of dementia resource utilization and research participation by African Americans is essential to achieving dementia health equity.MethodTwo neighborhoods of Jacksonville, FL, defined by zip codes, were the focus of this study. Both zip codes have a large population of African American residents per 2010 US Census, and a history of hosting outreach activities by our Alzheimer’s Disease Research Center (ADRC). In one neighborhood, we modified the NAPA Dementia Friendly (DF) America toolkit to serve as a model of outreach. The second neighborhood served as a control (CON), in which we maintained our traditional outreach model of community‐based lectures. Primary outcome measures were: (1) enrollment in ADRC center‐related studies and (2) phone call volumes from individuals seeking dementia resource information. The outcomes in the DF and CON neighborhoods were compared via Fisher’s exact test to those in other zip codes in Jacksonville (OT).ResultIn the 18 months following implementation of the DF intervention, 54 African Americans enrolled in ADRC‐related research (19 DF, 3 CON, 32 OT), compared to 21 during the 18 months prior (2 DF, 0 CON, and 19 OT). The increase in DF residents enrolling in research following the intervention was statistically significant (p =0 .02) relative to OT residents. The increase observed in the CON residents was not statistically significant (p=1.0) compared to OT residents. Call volumes from African Americans increased from 13 prior to program implementation (all from OT) to 62 calls after implementation (22 DF, 1 CON, 39 OT). The increase among DF residents seeking information following the intervention was statistically significant (p =0.008) whereas the increase was not significant in the CON residents (p=0.54).ConclusionResults suggest that the NAPA DFA can be leveraged to improve dementia resource utilization and research participation among community‐dwelling African Americans.

AbstractIntroductionTransvenous implantable cardioverter‐defibrillators (TV‐ICD) infection is a serious complication that frequently requires complete device removal for attempted cure, which can be associated with patient morbidity and mortality. The objective of this study is to assess mortality risk associated with TV‐ICD infection in a large Medicare population with de novo TV‐ICD implants.MethodsA survival analysis was conducted using 100% fee‐for‐service Medicare facility‐level claims data to identify patients who underwent de novo TV‐ICD implantation between 7/2016 and 1/2018. TV‐ICD infection within 2 years of implantation was identified using International Classification of Disease, 10th Edition and current procedural terminology codes. Baseline patient risk factors associated with mortality were identified using the Charlson Comorbidity Index categories. Infection was treated as a time‐dependent variable in a multivariate Cox proportional hazards model to account for immortal time bias.ResultsAmong 26,742 Medicare patients with de novo TV‐ICD, 518 (1.9%) had a device‐related infection. The overall number of decedents was 4721 (17.7%) over 2 years, with 4555 (17%) in the noninfection group and 166 (32%) in the infection group. After adjusting for baseline patient demographic characteristics and various comorbidities, the presence of TV‐ICD infection was associated with an increase of 2.4 (95% CI: 2.08–2.85) times in the mortality hazard ratio.ConclusionThe rate of TV‐ICD infection and associated mortality in a large, real‐world Medicare population is noteworthy. The positive association between device‐related infection and risk of mortality further highlights the need to reduce infections

11 Background: Six months of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) remains a standard in high-risk stage III patients. Early treatment discontinuation (ETD) could worsen the prognosis. In addition, there is current lack of data on the prognostic impact of early oxaliplatin only discontinuation (EOD). Methods: We studied the prognostic impact of ETD and EOD in patients with stage III CC who participated in 11 relevant clinical trials of the ACCENT and IDEA databases, where patients were planned to receive 6 months of adjuvant fluoropyrimidine plus oxaliplatin (FOLFOX or CAPOX). ETD was defined as discontinuation of treatment before 75% of cycles of chemotherapy. EOD was defined as discontinuation of oxaliplatin only, while continuing the fluoropyrimidine, before 75% of cycles of oxaliplatin. Association between ETD/EOD and overall survival (OS) and disease-free survival (DFS) was assessed by Cox model adjusted for prognostic factors. Results: ETD analysis included 10,444 patients (FOLFOX n = 7,033; CAPOX n = 3,411), with 20.9% of patients with ETD (17.8% with FOLFOX and 27.2% with CAPOX, p < 0.001). Out of 7,243 patients, 18.8% experienced EOD (17.4% FOLFOX versus 21.4% with CAPOX, p < 0.001). Compared to patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, older, with higher ECOG-PS ≥ 1, and in addition for ETD, a Body Mass Index (BMI) < 18.5 kg/m2. In multivariate analyses, ETD was associated with a decrease in DFS and OS in the overall population (HR: 1.40 95%CI 1.23-1.58, p < 0.001 and HR: 1.51 95%CI 1.31-1.74, p < 0.001, respectively). The same pattern was present with FOLFOX and CAPOX regimen, and also in low-risk and high-risk groups for each regimen with the exception of the CAPOX regimen in the low-risk group for DFS and OS. By contrast, EOD was not associated with reduced DFS or OS in the overall population (HR: 1.10 95%CI 0.77-1.58, p = 0.6 and HR: 0.97 95%CI 0.62-1.52, p = 0.9, respectively), in the low-risk group (HR: 0.97 95%CI 0.56-1.66, p = 0.9 and HR: 0.97 95%CI 0.51-1.82, p = 0.9, respectively) and high-risk group (HR: 1.22 95%CI 0.74-2.02, p = 0.4 and HR: 1.05 95%CI 0.53-2.08, p = 0.9, respectively) and for all subgroups of regimen. Conclusions: In patients treated with 6 months of oxaliplatin-based adjuvant chemotherapy for stage III CC, ETD was associated with a decrease in DFS and OS. By contrast, EOD was not significantly associated with poorer outcomes. In case of relevant neurotoxicity during a 6 months schedule, these data are not in favor of continuing oxaliplatin beyond 75% of planned cycles of adjuvant chemotherapy, and demonstrate that fluoropyrimidines remain the cornerstone of adjuvant chemotherapy in localized CC.

Abstract Background Glycemic traits—such as hyperinsulinemia, hyperglycemia, and type 2 diabetes—have been associated with higher colorectal cancer risk in observational studies; however, causality of these associations is uncertain. We used Mendelian randomization (MR) to estimate the causal effects of fasting insulin, 2-hour glucose, fasting glucose, glycated hemoglobin (HbA1c), and type 2 diabetes with colorectal cancer. Methods Genome-wide association study summary data were used to identify genetic variants associated with circulating levels of fasting insulin (n = 34), 2-hour glucose (n = 13), fasting glucose (n = 70), HbA1c (n = 221), and type 2 diabetes (n = 268). Using 2-sample MR, we examined these variants in relation to colorectal cancer risk (48 214 case patient and 64 159 control patients). Results In inverse-variance models, higher fasting insulin levels increased colorectal cancer risk (odds ratio [OR] per 1-SD = 1.65, 95% confidence interval [CI] = 1.15 to 2.36). We found no evidence of any effect of 2-hour glucose (OR per 1-SD = 1.02, 95% CI = 0.86 to 1.21) or fasting glucose (OR per 1-SD = 1.04, 95% CI = 0.88 to 1.23) concentrations on colorectal cancer risk. Genetic liability to type 2 diabetes (OR per 1-unit increase in log odds = 1.04, 95% CI = 1.01 to 1.07) and higher HbA1c levels (OR per 1-SD = 1.09, 95% CI = 1.00 to 1.19) increased colorectal cancer risk, although these findings may have been biased by pleiotropy. Higher HbA1c concentrations increased rectal cancer risk in men (OR per 1-SD = 1.21, 95% CI = 1.05 to 1.40), but not in women. Conclusions Our results support a causal effect of higher fasting insulin, but not glucose traits or type 2 diabetes, on increased colorectal cancer risk. This suggests that pharmacological or lifestyle interventions that lower circulating insulin levels may be beneficial in preventing colorectal tumorigenesis.

Background. The risk of donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ (heart, lung, liver, kidney, pancreas, and intestine) transplant recipients is poorly understood. Since hematogenous transmission of SARS-CoV-2 has not been documented to date, nonlung solid organs might be suitable for transplantation since they likely portend a low risk of viral transmission. Methods. Abdominal solid organs from SARS-CoV-2–infected donors were transplanted into uninfected recipients. Results. Between April 18, 2021, and October 30, 2021, we performed transplants of 2 livers, 1 simultaneous liver and kidney, 1 kidney, and 1 simultaneous kidney and pancreas from SARS-CoV-2–infected donors into 5 uninfected recipients. None of the recipients developed SARS-CoV-2 infection or coronavirus disease 2019, and when tested, allograft biopsies showed no evidence of SARS-CoV-2 RNA. Conclusions. Transplanting nonlung organs from SARS-CoV-2–infected donors into uninfected recipients demonstrated no evidence of virus transmission.

Abstract Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective The aim is to examine the association between genetically predicted dairy intake and PD using two‐sample Mendelian randomization (MR). Methods We genotyped a well‐established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage‐PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Results Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95% confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003; P ‐difference with women = 0.029). Conclusions Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society

Abstract Background: Lung-protective ventilation is often used in critically ill patients with acute respiratory failure, including those without acute respiratory distress syndrome. While disparities exist in the delivery of critical care based on gender, race, and insurance status, it is unknown whether there are disparities in the use of lung-protective ventilation. The objective of our study was to determine whether gender-, racial / ethnic-, or insurance status-based disparities exist in the use of lung-protective ventilation for critically ill mechanically ventilated patients in the United States (U.S.).Methods: This was a secondary data analysis of the U.S. Critical Illness and Injury Trials Group Critical Illness Outcomes Study, a prospective multi-center cohort study conducted from 2010 - 2012. The dependent variable of interest was the proportion of patients receiving tidal volume > 8 mL/kg predicted body weight (PBW). The independent variables of interest were gender, insurance status, and race / ethnicity. Results: Our primary analysis included 1,595 mechanically ventilated patients from 59 intensive care units (ICUs) in the U.S. Women were more likely to receive tidal volumes > 8 ml/kg PBW than men (odds ratio [OR] = 3.25, 95% confidence interval [CI] = 2.58 – 4.09), though this relationship was substantially weakened after adjusting for gender differences in height (OR = 1.26 95% CI = 0.94 – 1.71). The underinsured were significantly more likely to receive tidal volume > 8 ml/kg PBW than the insured in multivariable analysis (odds ratio = 1.54, 95% confidence interval = 1.16 – 2.04). The prescription of > 8 ml/kg PBW tidal volume did not differ by racial or ethnic categories. Conclusions: In this prospective nationwide cohort of critically ill mechanically ventilated patients, women and the underinsured were less likely than their comparators to receive lung protective ventilation, with no apparent differences based on race / ethnicity alone. Differences in height between men and women do not fully explain this disparity. Future research should evaluate whether implicit bias affects tidal volume choice and other management decisions in critical care.