19 research outputs found

    Variable viral clearance despite adequate ganciclovir plasma levels during valganciclovir treatment for cytomegalovirus disease in D+/R- transplant recipients

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    ABSTRACT: BACKGROUND: Valganciclovir, the oral prodrug of ganciclovir, has been demonstrated equivalent to iv ganciclovir for CMV disease treatment in solid organ transplant recipients. Variability in ganciclovir exposure achieved with valganciclovir could be implicated as a contributing factor for explaining variations in the therapeutic response. This prospective observational study aimed to correlate clinical and cytomegalovirus (CMV) viral load response (DNAemia) with ganciclovir plasma concentrations in patients treated with valganciclovir for CMV infection/disease. METHODS: Seven CMV D+/R- transplant recipients (4 kidney, 2 liver and 1 heart) were treated with valganciclovir (initial dose was 900-1800 mg/day for 3-6.5 weeks, followed by 450-900 mg/day for 2-9 weeks). DNAemia was monitored by real time quantitative PCR and ganciclovir plasma concentration was measured at trough (Ctrough) and 3 h after drug administration (C3h) by HPLC. RESULTS: Four patients presented with CMV syndrome, two had CMV tissue-invasive disease after prophylaxis discontinuation, and one liver recipient was treated pre-emptively for asymptomatic rising CMV viral load 5 weeks post-transplantation in the absence of prophylaxis. CMV DNAemia decreased during the first week of treatment in all recipients except in one patient (median decrease: -1.2 log copies/mL, range: -1.8 to 0) despite satisfactory ganciclovir exposure (AUC0-12 = 48 mg.h/L, range for the 7 patients: 40-118 mg.h/L). Viral clearance was obtained in five patients after a median of time of 34 days (range: 28-82 days). Two patients had recurrent CMV disease despite adequate ganciclovir exposure (65 mg.h/L, range: 44-118 mg.h/L). CONCLUSIONS: Valganciclovir treatment for CMV infection/disease in D+/R- transplant recipients can thus result in variable viral clearance despite adequate ganciclovir plasma concentrations, probably correlating inversely with anti-CMV immune responses after primary infection

    Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

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    Correction: vol 7, 13205, 2016, doi:10.1038/ncomms13205Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in Bone-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h(2) = 0.18, P value = 0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.Peer reviewe

    Mobile health clinic model in the COVID-19 pandemic: Lessons learned and opportunities for policy changes and innovation

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    © 2020 The Author(s). Background: Mobile Clinics represent an untapped resource for our healthcare system. The COVID-19 pandemic has exacerbated its limitations. Mobile health clinic programs in the US already play important, albeit under-appreciated roles in the healthcare system. They provide access to healthcare especially for displaced or isolated individuals; they offer versatility in the setting of a damaged or inadequate healthcare infrastructure; and, as a longstanding community-based service delivery model, they fill gaps in the healthcare safety-net, reaching social-economically underserved populations in both urban and rural areas. Despite an increasing body of evidence of the unique value of this highly adaptable model of care, mobile clinics are not widely supported. This has resulted in a missed opportunity to deploy mobile clinics during national emergencies such as the COVID-19 pandemic, as well as using these already existing, and trusted programs to overcome barriers to access that are experienced by under-resourced communities. Main text: In March, the Mobile Healthcare Association and Mobile Health Map, a program of Harvard Medical School\u27s Family Van, hosted a webinar of over 300 mobile health providers, sharing their experiences, challenges and best practices of responding to COVID 19. They demonstrated the untapped potential of this sector of the healthcare system in responding to healthcare crises. A Call to Action: The flexibility and adaptability of mobile clinics make them ideal partners in responding to pandemics, such as COVID-19. In this commentary we propose three approaches to support further expansion and integration of mobile health clinics into the healthcare system: First, demonstrate the economic contribution of mobile clinics to the healthcare system. Second, expand the number of mobile clinic programs and integrate them into the healthcare infrastructure and emergency preparedness. Third, expand their use of technology to facilitate this integration. Conclusions: Understanding the economic and social impact that mobile clinics are having in our communities should provide the evidence to justify policies that will enable expansion and optimal integration of mobile clinics into our healthcare delivery system, and help us address current and future health crises

    Using Public Data to Predict Demand for Mobile Health Clinics

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    Improving health equity is an urgent task for our society. The advent of mobile clinics plays an important role in enhancing health equity, as they can provide easier access to preventive healthcare for patients from disadvantaged populations. For effective functioning of mobile clinics, accurate prediction of demand (expected number of individuals visiting mobile clinic) is the key to their daily operations and staff/resource allocation. Despite its importance, there have been very limited studies on predicting demand of mobile clinics. To the best of our knowledge, we are among the first to explore this area, using AI-based techniques. A crucial challenge in this task is that there are no known existing data sources from which we can extract useful information to account for the exogenous factors that may affect the demand, while considering protection of client privacy. We propose a novel methodology that completely uses public data sources to extract the features, with several new components that are designed to improve the prediction. Empirical evaluation on a real-world dataset from the mobile clinic The Family Van shows that, by leveraging publicly available data (which introduces no extra monetary cost to the mobile clinics), our AI-based method achieves 26.4% - 51.8% lower Root Mean Squared Error (RMSE) than the historical average-based estimation (which is presently employed by mobile clinics like The Family Van). Our algorithm makes it possible for mobile clinics to plan proactively, rather than reactively, as what has been doing
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