A practice-based randomized controlled trial to improve medication adherence among Latinos with hypertension: study protocol for a randomized controlled trial

BACKGROUND: Latinos experience disproportionately higher rates of uncontrolled hypertension as compared to Blacks and Whites. While poor adherence is a major contributor to disparities in blood pressure control, data in Latino patients are scant. More importantly, translation of interventions to improve medication adherence in community-based primary care practices, where the majority of Latino patients receive their care is non-existent. METHODS: Using a randomized controlled design, this study evaluates the effectiveness of a culturally tailored, practice-based intervention compared to usual care on medication adherence, among 148 Latino patients with uncontrolled hypertension who are non-adherent to their antihypertensive medications. Bilingual medical assistants trained as Health Coaches deliver the intervention using an electronic medical record system-embedded adherence script. Patients randomized to the intervention group receive patient-centered counseling with a Health Coach to develop individualized self-monitoring strategies to overcome barriers and improve adherence behaviors. Health Coach sessions are held biweekly for the first 3 months (6 sessions total) and then monthly for the remaining 3 months (3 sessions total). Patients randomized to the usual care group receive standard hypertension treatment recommendations as determined by their primary care providers. The primary outcome is the rate of medication adherence at 6 months. The secondary outcome is reduction in systolic and diastolic blood pressure at 6 months. DISCUSSION: If successful, findings from this study will provide salient information on the translation of culturally tailored, evidence-based interventions targeted at medication adherence and blood pressure control into practice-based settings for this high-risk population. TRIAL REGISTRATION: NCT01643473 on 16 July 2012

Positive and Negative Regulation of Gli Activity by Kif7 in the Zebrafish Embryo

Loss of function mutations of Kif7, the vertebrate orthologue of the Drosophila Hh pathway component Costal2, cause defects in the limbs and neural tubes of mice, attributable to ectopic expression of Hh target genes. While this implies a functional conservation of Cos2 and Kif7 between flies and vertebrates, the association of Kif7 with the primary cilium, an organelle absent from most Drosophila cells, suggests their mechanisms of action may have diverged. Here, using mutant alleles induced by Zinc Finger Nuclease-mediated targeted mutagenesis, we show that in zebrafish, Kif7 acts principally to suppress the activity of the Gli1 transcription factor. Notably, we find that endogenous Kif7 protein accumulates not only in the primary cilium, as previously observed in mammalian cells, but also in cytoplasmic puncta that disperse in response to Hh pathway activation. Moreover, we show that Drosophila Costal2 can substitute for Kif7, suggesting a conserved mode of action of the two proteins. We show that Kif7 interacts with both Gli1 and Gli2a and suggest that it functions to sequester Gli proteins in the cytoplasm, in a manner analogous to the regulation of Ci by Cos2 in Drosophila. We also show that zebrafish Kif7 potentiates Gli2a activity by promoting its dissociation from the Suppressor of Fused (Sufu) protein and present evidence that it mediates a Smo dependent modification of the full length form of Gli2a. Surprisingly, the function of Kif7 in the zebrafish embryo appears restricted principally to mesodermal derivatives, its inactivation having little effect on neural tube patterning, even when Sufu protein levels are depleted. Remarkably, zebrafish lacking all Kif7 function are viable, in contrast to the peri-natal lethality of mouse kif7 mutants but similar to some Acrocallosal or Joubert syndrome patients who are homozygous for loss of function KIF7 alleles

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

SIMEX: a swot analysis a case study on SIMEX

The objective of this final year report on SIMEX -- a Strength, Weakness, Opportunities and Threats Analysis is to give an overview of the exchange's present operating environment and future avenues of development. The purpose of doing a study on SIMEX is due to the commonly-held opinion that futures and options would be very prominent as a risk management as well as a speculative tool in the next century. The sophistication of investors are at much higher levels than before and it would be highly likely to see great interest in the trade of derivative investment products in the not-too-distant future. As such, we would like to be at the forefront of this trend and be ready for it when it comes.ACCOUNTANC

A Systems-Level Approach to Improving Medication Adherence in Hypertensive Latinos: a Randomized Control Trial

BACKGROUND: Despite numerous interventions targeting medication adherence in patients with uncontrolled hypertension, practice-based trials in Latino patients are scant. OBJECTIVE: To evaluate the effect of a systems-level adherence intervention, delivered by medical assistants (MAs), versus a comparison condition on medication adherence and blood pressure (BP) in 119 hypertensive Latino patients who were initially non-adherent to their antihypertensive medications. STUDY DESIGN: Randomized control trial. PARTICIPANTS: Patients (50% women; mean age, 61 years) were recruited from April 2013 to August 2015 in a community-based practice in New York. INTERVENTION: Systems-level approach that included an office system component built into the electronic health record and a provider support component consisting of nine MA-delivered health coaching sessions for improving medication adherence. The comparison group received the standard health coaching procedures followed at the clinic. MAIN OUTCOME MEASURES: The primary outcome was rate of medication adherence measured by an electronic monitoring device (EMD) across 6 months. The secondary outcomes were self-reported medication adherence measured by the eight-item Morisky Medication Adherence Scale (MMAS-8) and BP reduction from baseline to 6 months. KEY RESULTS: Adherence as measure by EMD worsened for both groups (p = 0.04) with no between-group difference (- 9.6% intervention and - 6.6% control, p = 0.66). While systolic BP improved in both groups, the difference between groups was not significant (- 6 mmHg in intervention vs. - 2.7 mmHg in control, p = 0.34). In contrast, the intervention group had a greater improvement in self-reported adherence (mean change 1.98 vs. 1.26, p = 0.03) when measured using the MMAS-8. CONCLUSIONS: Among Latinos with poorly controlled BP who were non-adherent to their antihypertensive medications, a systems-level intervention did not improve adherence as measured by EMD nor blood pressure. However, many patients reported challenges to using the EMD. Improvements in self-reported adherence suggest that this measure captures different aspects of adherence behavior than EMD. CLINICAL TRIAL REGISTRATION: NCT03560596

Human rights eBrief: INIA: intersex new interdisciplinary approaches

This eBrief summarises the current state of human rights law as it applies to people with variations in their sex characteristics, known in human rights law as intersex people. It examines the situation at international, regional (European and Inter-American) and at some selected national levels