Potential Role of aldo-keto Reductase Family 1, member B10 (AKR1B10) as a Molecular Target in Alcoholic Hepatitis

Background: Alcoholic Hepatitis (AH) is the most severe form of Alcoholic Liver Disease (ALD) and current therapies are not fully effective. Targeted therapies are urgently needed. AKR1B10 was recently shown to be overexpressed in patients with AH. Objectives: To analyze the expression of AKR1B10, an aldose reductase, through a translational approach in order to better understand the potential for aldose reductase as a novel target of therapy in AH. Methods: RNA was extracted from human tissue samples from patients with various liver diseases, animal models of fibrosis and alcoholic liver disease, and cultured Hepatic Stellate Cell (HSC) lines stimulated with proinflammatory, profibrogenic, and AKR1B10 treatments, and the samples were quantified using qPCR analysis. Results: Human samples showed nearly a 100-fold increase of AKR1B10 expression in patients with AH. An animal model of liver fibrosis showed a small increase in Akr1b8 (AKR1B10 mouse analogue) expression. HSCs did not show any noticeable increase in expression of AKR1B10 regardless of treatment, and did not show any noticeable increase in expression of proinflammatory or profibrogenic genes when treated with AKR1B10. Conclusion: The increased expression of AKR1B10 and its mouse analogue, while present in patients with AH and fibrotic mice, respectively, may not be mediated by HSCs. Further studies are needed to better understand location and nature of overexpression.Bachelor of Science in Public Healt

Disparities between research attention and burden in liver diseases: implications on uneven advances in pharmacological therapies in Europe and the USA

Effective oral therapies for hepatitis B and C have recently been developed, while there are no approved pharmacological therapies for alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD). We hypothesise that fewer advances in fatty liver diseases could be related to disparities in research attention

A novel patient engagement platform using accessible text messages and calls (Epharmix): Feasibility study

BACKGROUND: Patient noncompliance with therapy, treatments, and appointments represents a significant barrier to improving health care delivery and reducing the cost of care. One method to improve therapeutic adherence is to improve feedback loops in getting clinically acute events and issues to the relevant clinical providers as necessary (ranging from detecting hypoglycemic events for patients with diabetes to notifying the provider when patients are out of medications). Patients often don\u27t know which information should prompt a call to their physician and proactive checks by the clinics themselves can be very resource intensive. We hypothesized that a two-way SMS system combined with a platform web service for providers would enable both high patient engagement but also the ability to detect relevant clinical alerts. OBJECTIVE: The objectives of this study are to develop a feasible two-way automated SMS/phone call + web service platform for patient-provider communication, and then study the feasibility and acceptability of the Epharmix platform. First, we report utilization rates over the course of the first 18 months of operation including total identified clinically significant events, and second, review results of patient user-satisfaction surveys for interventions for patients with diabetes, COPD, congestive heart failure, hypertension, surgical site infections, and breastfeeding difficulties. METHODS: To test this question, we developed a web service + SMS/phone infrastructure ( Epharmix ). Utilization results were measured based on the total number of text messages or calls sent and received, with percentage engagement defined as a patient responding to a text message at least once in a given week, including the number of clinically significant alerts generated. User satisfaction surveys were sent once per month over the 18 months to measure satisfaction with the system, frequency and degree of communication. Descriptive statistics were used to describe the above information. RESULTS: In total, 28,386 text messages and 24,017 calls were sent to 929 patients over 9 months. Patients responded to 80% to 90% of messages allowing the system to detect 1164 clinically significant events. Patients reported increased satisfaction and communication with their provider. Epharmix increased the number of patient-provider interactions to over 10 on average in any given month for patients with diabetes, COPD, congestive heart failure, hypertension, surgical site infections, and breastfeeding difficulties. CONCLUSIONS: Engaging high-risk patients remains a difficult process that may be improved through novel, digital health interventions. The Epharmix platform enables increased patient engagement with very low risk to improve clinical outcomes. We demonstrated that engagement among high-risk populations is possible when health care comes conveniently to where they are

Improving HbA1c with glucose self-monitoring in diabetic patients with EpxDiabetes, a phone call and text message-based telemedicine platform: A randomized controlled trial

Background: We conducted a randomized controlled trial of EpxDiabetes, a novel digital health intervention as an adjunct therapy to reduce HbA(1c) and fasting blood glucose (FBG) among patients with type 2 diabetes mellitus (T2DM). In addition, we examined the effect of social determinants of health on our system. Methods: Sixty-five (n = 65) patients were randomized at a primary care clinic. Self-reported FBG data were collected by EpxDiabetes automated phone calls or text messages. Only intervention group responses were shared with providers, facilitating follow-up and bidirectional communication. ΔHbA(1c) and ΔFBG were analyzed after 6 months. Results: There was an absolute HbA(1c) reduction of 0.69% in the intervention group (95% confidence interval [CI], −1.41 to 0.02) and an absolute reduction of 0.03% in the control group (95% CI, −0.88 to 0.82). For those with baseline HbA(1c) >8%, HbA(1c) decreased significantly by 1.17% in the intervention group (95% CI, −1.90 to −0.44), and decreased by 0.02% in the control group (95% CI, −0.99 to 0.94). FBG decreased in the intervention group by 21.6 mg/dL (95% CI, −37.56 to −5.639), and increased 13.0 mg/dL in the control group (95% CI, −47.67 to 73.69). Engagement (proportion responding to ≥25% of texts or calls over 4 weeks) was 58% for the intervention group (95% CI, 0.373–0.627) and 48% for the control group (95% CI, 0.296–0.621). Smoking, number of comorbidities, and response rate were significant predictors of ΔHbA(1c). Conclusions: EpxDiabetes helps to reduce HbA(1c) in patients with uncontrolled T2DM and fosters patient–provider communication; it has definite merit as an adjunct therapy in diabetes management. Future work will focus on improving the acceptability of the system and implementation on a larger scale trial

Disparities between research attention and burden in liver diseases: implications on uneven advances in pharmacological therapies in Europe and the USA

OBJECTIVES: Effective oral therapies for hepatitis B and C have recently been developed, while there are no approved pharmacological therapies for alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD). We hypothesise that fewer advances in fatty liver diseases could be related to disparities in research attention. METHODS: We developed the Attention-to-Burden Index (ABI) that compares the research activities during 2010–2014, and an estimate of disease burden of these 4 major liver diseases. The resulting ratio reflects either overattention (positive value) or inadequate attention (negative value) compared with disease burden. The mean research attention and disease burden were calculated from 5 and 6 different parameters, respectively. The efficacy rate of current pharmacological therapies was assessed from published clinical trials. FINDINGS: The mean research attention for hepatitis B and C was 31% and 47%, respectively, while NAFLD and ALD received 17% and 5%. The overall burden was 5% and 28% for hepatitis B and C, and 17% and 50% for NAFLD and ALD. The calculated ABI for hepatitis B and C revealed a +6.7-fold and +1.7-fold overattention, respectively. NAFLD received an appropriate attention compared with its burden, while ALD received marked inadequate attention of −9.7-fold. The efficacy rate of current pharmacological agents was 72% for hepatitis B, 89% for hepatitis C, 25% for non-alcoholic steatohepatitis and 13% for alcoholic hepatitis. Importantly, we found a positive correlation between the mean attention and the efficacy rate of current therapies in these 4 major liver diseases. INTERPRETATION: There are important disparities between research attention and disease burden among the major liver diseases. While viral hepatitis has received considerable attention, there is a marked inadequate attention to ALD. There is a critical need to increase awareness of ALD in the liver research community