Fenofibrate slows the progression of clinical diabetic retinopathy (DR), but its mechanism of action in the retina remains unclear. Fenofibrate is a known agonist of peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor critical for regulating metabolism, inflammation and oxidative stress. Using a DR mouse model, db/db, we tested the hypothesis that fenofibrate slows early DR progression by activating PPARα in the retina. Relative to healthy littermates, six-month-old db/db mice exhibited elevated serum triglycerides and cholesterol, retinal gliosis, and electroretinography (ERG) changes including reduced b-wave amplitudes and delayed oscillatory potentials. These pathologic changes in the retina were improved by oral fenofibrate. However, fenofibrate did not induce PPARα target gene expression in whole retina or isolated Müller glia. The capacity of the retina to respond to PPARα was further tested by delivering the PPARα agonist GW590735 to the intraperitoneal or intravitreous space in mice carrying the peroxisome proliferator response element (PPRE)-luciferase reporter. We observed strong induction of the reporter in the liver, but no induction in the retina. In summary, fenofibrate treatment of db/db mice prevents the development of early DR but is not associated with induction of PPARα in the retina.
Diabetes Mellitus (DM) complicates the treatment of burn injuries. Foot burns in diabetic patients are challenging problems with unfavorable outcomes. National-scale evaluations are needed, especially with regard to limb salvage. We aim to characterize lower extremity burns in persons with DM and evaluate the likelihood of amputation. The National Trauma Data Bank (NTDB) was queried from 2007-2015 extracting encounters with primary burn injuries of the feet using International Classification of Diseases (ICD) 9 th Edition codes. Logistic regression modeled predictors of lower extremity amputation. Covariables included age, sex, race/ethnicity, comorbidities including DM, % burn total body surface area (TBSA), mechanism, and region of burn center. Poisson regression evaluated temporal incidence rate changes in DM foot burns. Of 116,796 adult burn encounters, 7,963 (7%) had foot burns. Of this group, 1,308 (16%) had DM. 5.6% of encounters with DM foot burns underwent amputation compared to 1.5% of non-DM encounters (p<0.001). Independent predictors of lower extremity amputation included DM (OR 3.70, 95% CI 2.98 – 4.59), alcohol use, smoking, chronic kidney disease, burn size >20%, African American/Black race, male sex, and age>40 years (all p<0.01). The incidence of DM foot burns increased over the study period with an incidence rate ratio (IRR) of 1.07 (95% CI 1.05 – 1.10, p<0.001). In conclusion, DM was associated with nearly a 4-fold increase in amputation after adjusting for covariables. Furthermore, the incidence of DM foot burns is increasing. Strategies for optimizing care in persons with DM foot burns are need to improve limb salvage.
Introduction Pediatric patients with sickle cell disease (SCD) face racial bias and healthcare stigma compounded by limited age-appropriate health education. Due in part to a lack of dedicated SCD education, providers can hold misconceptions about SCD and biases against patients. Gamification improves disease education and mitigates stigma in various clinical settings. In this study, we created the GRAPES tool (Game to Raise Awareness for Patient/Provider/Public Education of SCD, www.tinyurl.com/GRAPESgame), a free, online, trivia-based educational game. We hypothesized that utilization of the GRAPES tool will improve patient and provider SCD knowledge and mitigate SCD stigma among providers. Methods The GRAPES tool is a single-player, interactive game developed using Figma, a collaborative user-interface design software. Multiple-choice questions are structured into five educational modules (science, treatment, epidemiology, myths, and symptoms) with customizable red blood cell characters and hand-drawn screens to promote user-friendliness. Hyperlinked resources and an answer booklet provide further education. To promote health literacy for users of all ages, especially children, content is written at a fifth-grade Lexile level. The GRAPES tool was tested in two cohorts at St. Louis Children's Hospital: 1) pediatric patients 10 years of age or older with any genotype of SCD and 2) registered nurses at any career stage who care for patients with SCD. Both cohorts completed a 20-question, multiple-choice knowledge questionnaire pre- and post-gameplay to assess knowledge gains. Provider healthcare experiences were assessed pre- and post-gameplay through the 17-item short-form General Perceptions About Sickle Cell Patients Scale (GPASPS, Haywood et al., 2010). Post-gameplay, both cohorts completed a satisfaction scale and provided written feedback for game improvement. Non-parametric testing was used to compare paired-sample pre- and post-assessments. Results Of the 29 pediatric hematology-oncology nurses approached, 25 nurses (18 inpatient, 7 outpatient) were recruited. 49 patients with SCD were approached, and 25 patients (20 HbSS, 2 HbSβ 0, 1 HbSC, 1 HbSβ +, 1 HPHF) consented (Table 1). Four of the patients with SCD had prior curative hematopoietic stem cell transplants. The providers worked in the nursing field for a median of 6.0 [IQR 3.0-9.0] years. Recruited participants completed all study activities, including pre- and post-gameplay assessments. Patients with SCD completed the game with a median time of 17.0 [IQR 11.5-20.5] minutes. With data from 12 providers, the median gameplay time was 12.5 [IQR 10.0-16.5] minutes. All participants (p < 0.001), including within the provider (p < 0.001) and patient (p = 0.019) cohorts, showed increase in knowledge after gameplay (Fig. 1). Both providers and patients indicated the game was of high quality and relevance (Table 2). Patients wrote: "It was helpful to know about my sickness. The treatment part was helpful," and, "The terms were helpful because I didn't know them before." One provider wrote, "I liked how there were helpful links that I could click on for more info." Some suggestions for improvement included an introductory slide about SCD and a back button. Provider negative attitudes (Q1-6, Fig. 2) were reduced (p = 0.0072) post-gameplay, but positive attitudes did not significantly change (Q7-10, Fig. 2). Providers also showed a significant decrease (p=0.0014) in the belief that patients changing their behavior around providers indicates inappropriate drug-seeking behavior (Fig. 3). Conclusion Patients and providers demonstrated significant improvement in SCD knowledge after playing GRAPES. Providers also held reduced negative attitudes towards patients with SCD post-gameplay. In the context of positive feedback from both cohorts, this study demonstrates the feasibility and acceptability of the GRAPES tool as a potential digital, behavioral intervention to decrease stigma against SCD patients and provide engaging educational materials for patients and their providers in different clinical settings. Our GRAPES tool won first prize in the 2021 NHLBI Hope for SCD Challenge (www.tinyurl.com/NIHgrapes). We are excited to continue evaluating the benefits of the GRAPES tool in a larger multi-institutional study and collaborate with the NHLBI for future dissemination among patients, families, and providers. Figure 1 Figure 1. Disclosures Badawy: Vertex Pharmaceuticals Inc: Consultancy; Bluebird Bio Inc: Consultancy; Sanofi Genzyme: Consultancy. Fields: Global Blood Therapeutics: Consultancy; Proclara Biosciences: Current equity holder in publicly-traded company.
Introduction Diabetes Mellitus (DM) is an epidemic in the US that complicates the treatment of burn injuries. Lower extremity burns in diabetic patients, particularly the feet, are challenging problems with predictably unfavorable outcomes, as demonstrated by single-institution studies. National evaluations are absent, especially with regard to limb salvage. We aim to characterize lower extremity burns in persons with DM and evaluate the likelihood of amputation. We hypothesize that the incidence of DM associated foot burns is increasing in the US, and these patients are more likely to undergo lower extremity amputation than those without DM. Methods The National Trauma Data Bank (NTDB) was queried from 2007-2015 extracting encounters with primary burn injuries of the feet using International Classification of Diseases (ICD) 9th Edition codes. DM is a predefined comorbidity within the NTDB, allowing for cohort comparisons. Logistic regression modeled predictors of lower extremity amputation. Patient covariables included age, sex, race/ethnicity, and comorbidities. Burn covariables included % burn total body surface area (TBSA), mechanism, and region of burn center. Poisson regression evaluated for significance in temporal changes in DM foot burns. Results There were 116,796 adult burn encounters of which 7,963 (7%) had foot burns. Of this group, 1,308 (16%) had DM. DM foot burn encounters were older, more likely to be male, and had more comorbidities than non-DM foot burn encounters (all p< 0.001). DM foot burn encounters were more likely to sustain a scald injury (compared to flame) and had smaller %TBSA (all p< 0.001). Additionally, 5.6% of encounters with DM foot burns underwent amputation compared to 1.5% of non-DM encounters (p< 0.001). Independent predictors of lower extremity amputation included DM (OR 3.70, 95% CI 2.98 – 4.59), alcohol use, smoking, chronic kidney disease, burn size >20%, African American/Black race, male sex, and age >40 years (all p< 0.01). The incidence of DM foot burns increased over the study period with an incidence rate ratio (IRR) of 1.09 (95% CI 1.07 – 1.12, p< 0.001). Conclusions In the largest cohort study to date, DM was associated with nearly a 4-fold increase in amputation after adjusting for available confounders. Furthermore, the incidence of DM foot burns is increasing. Strategies for optimizing care in persons with DM foot burns are need to improve limb salvage.
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