Evaluating the Effects of an Interdisciplinary Practice Model with Pharmacist Collaboration on HIV Patient Co-Morbidities

Treatment of HIV now occurs largely within the primary care setting, and the principal focus of most visits has become the management of chronic disease states. The clinical pharmacist’s potential role in improving chronic disease outcomes for HIV patients is unknown. A retrospective cohort study was performed for HIV-positive patients also diagnosed with diabetes, hypertension, or hyperlipidemia. Characteristics and outcomes in 96 patients treated by an interdisciplinary team which included a clinical pharmacist (i.e., the intervention group) were compared to those in 50 patients treated by an individual healthcare provider (i.e., the control group). Primary outcomes were changes from baseline over 18 month period of HbA1c, low density lipoprotein (LDL), and blood pressure, respectively. Secondary outcomes included number of drug-drug interactions, HIV viral load, CD4 count, percent change in smoking status, and percent of patients treated to cardiovascular guideline recommendations. The interdisciplinary team had a significant improvement in lipid management over the control group (LDL: -8.8 vs. +8.4 mg/dL; p=0.014), and the smoking cessation rate over the study period was doubled in the interdisciplinary group (20.4% vs. 11.8%). Among those with an indication for aspirin, a significantly higher percentage of patients were prescribed the medication in the interdisciplinary group compared to the control group (85.5% v. 64.9%; p=0.014). An informal cost analysis estimated savings of more than $3000 per patient treated by the interdisciplinary team. Based on these results, pharmacist involvement in an HIV primary care clinic appears to lead to more appropriate management of chronic co-morbidities in a cost-effective manner

Incidence and Severity of Drug Interactions Before and After Switching Antiretroviral Therapy to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Treatment-Experienced Patients.

Background: Switching antiretroviral therapy (ART) in people with HIV (PWH) can influence their risk for drug-drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Methods: This was a multicenter retrospective cohort study of PWH on ART and at least 1 concomitant medication (CM) who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool\u27s HIV Drug Interaction Database, 2 DDI analyses were performed for each patient. The first assessed patients\u27 preswitch ART regimens with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a score of 0 (no or potential weak interaction), 1 (potential interaction), or 2 (contraindicated interaction). A paired Results: Among 411 patients, 236 (57%) had at least 1 DDI present at baseline. On average, baseline DDI scores (SD) were 1.4 (1.8) and decreased by 1 point (95% CI, -1.1 to -0.8) after patients switched to BIC/FTC/TAF ( Conclusions: Treatment-experienced PWH eligible to switch their ART may experience significant declines in number and severity of DDIs if switched to BIC/FTC/TAF

The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The Pharmacist\u27s Expanding Role in HIV Pre-Exposure Prophylaxis

he efficacy of pre-exposure prophylaxis (PrEP) to prevent HIV has been firmly established; however, the success of PrEP largely depends on access to care as well as high levels of medication adherence. One of the key areas of focus for the National HIV/AIDS Strategy for 2020 in the United States calls for full access to comprehensive PrEP services where appropriate and desired, with support for medication adherence. Despite advances and advocacy for PrEP since approval for adults in 2012, large rates of prescribing disparity exist among gender and race/ethnicity. In 2016, only 3.7% of all PrEP users were women and only 11.2% were black. As one of the most widely accessible health care resources, pharmacists are well positioned to improve patient understanding, promote medication adherence, provide key risk reduction counseling, and enhance PrEP efficacy. Pharmacists\u27 knowledge and accessibility in nearly every urban and rural community can be leveraged as part of a comprehensive HIV prevention strategy to expand access to care and improve population health. As trusted health care professionals, pharmacists develop a strong rapport with patients and may be the key to address current disparities in PrEP prescribing patterns as well as serve as an essential liaison between patients and other members of the multi-disciplinary care team. The purpose of this review is to summarize available data on pharmacist involvement in various models of care providing PrEP services and to identify opportunities to maximize and expand the role of the pharmacist to improve access to PrEP

Concomitant Treatment of Hepatitis C Virus and Diffuse Large B-Cell Lymphoma with Direct-Acting Antivirals in HIV Coinfection: A Case Report

This report describes a case of concomitant treatment of advanced diffuse large B-cell lymphoma with chemoimmunotherapy along with direct-acting antivirals for hepatitis C virus in a patient coinfected with HIV. The patient tolerated gemcitabine, dexamethasone, cisplatin, and rituximab and achieved sustained virologic response after treatment with ledipasvir/sofosbuvir

Optimal Use of Space-Borne Advanced Infrared and Microwave Soundings for Regional Numerical Weather Prediction

Satellite observations can either be assimilated as radiances or as retrieved physical parameters to reduce error in the initial conditions used by the Numerical Weather Prediction (NWP) model. Assimilation of radiances requires a radiative transfer model to convert atmospheric state in model space to that in radiance space, thus requiring a lot of computational resources especially for hyperspectral instruments with thousands of channels. On the other hand, assimilating the retrieved physical parameters is computationally more efficient as they are already in thermodynamic states, which can be compared with NWP model outputs through the objective analysis scheme. A microwave (MW) sounder and an infrared (IR) sounder have their respective observational limitation due to the characteristics of adopted spectra. The MW sounder observes at much larger field-of-view (FOV) compared to an IR sounder. On the other hand, MW has the capability to reveal the atmospheric sounding when the clouds are presented, but IR observations are highly sensitive to clouds, The advanced IR sounder is able to reduce uncertainties in the retrieved atmospheric temperature and moisture profiles due to its higher spectral-resolution than the MW sounder which has much broader spectra bands. This study tries to quantify the optimal use of soundings retrieved from the microwave sounder AMSU and infrared sounder AIRS onboard the AQUA satellite in the regional Weather and Research Forecasting (WRF) model through three-dimensional variational (3D-var) data assimilation scheme. Four experiments are conducted by assimilating soundings from: (1) clear AIRS single field-of-view (SFOV); (2) retrieved from using clear AMSU and AIRS observations at AMSU field-of-view (SUP); (3) all SFOV soundings within AMSU FOVs must be clear; and (4) SUP soundings which must have all clear SFOV soundings within the AMSU FOV. A baseline experiment assimilating only conventional data is generated for comparison. Various atmospheric state variables at different pressure levels are used to assess the impact from assimilating these different data by comparing them with European Centre for Medium Range Weather Forecast (ECMWF) reanalysis data. Results indicate assimilation of SUP soundings improve the mid and upper troposphere, whereas assimilation of SFOV soundings has positive impact on the lower troposphere. Two additional assimilation experiments are carried out to determine the combination of SUP and SFOV soundings that will provide the best performance throughout the troposphere. The results indicate that optimal combination is to assimilate clear-sky matched IR retrievals with non-matched MW soundings