Performance measurement for co-occurring mental health and substance use disorders

<p>Abstract</p> <p>Background</p> <p>Co-occurring mental health and substance use disorders (COD) are the norm rather than the exception. It is therefore critical that performance measures are developed to assess the quality of care for individuals with COD irrespective of whether they seek care in mental health systems or substance abuse systems or both.</p> <p>Methods</p> <p>We convened an expert panel and asked them to rate a series of structure, process, and outcomes measures for COD using a structured evaluation tool with domains for importance, usefulness, validity, and practicality.</p> <p>Results</p> <p>We chose twelve measures that demonstrated promise for future pilot testing and refinement. The criteria that we applied to select these measures included: balance across structure, process, and outcome measures, quantitative ratings from the panelists, narrative comments from the panelists, and evidence the measure had been tested in a similar form elsewhere.</p> <p>Conclusion</p> <p>To be successful performance measures need to be developed in such a way that they align with needs of administrators and providers. Policymakers need to work with all stakeholders to establish a concrete agenda for developing, piloting and implementing performance measures that include COD. Future research could begin to consider strategies that increase our ability to use administrative coding in mental health and substance use disorder systems to efficiently capture quality relevant clinical data.</p

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 role of ender rodding in tibial fractures with an intact fibula

Thirty-three patients with tibia fractures and intact fibula were studied to determine the efficacy of Ender rod fixation in preventing a varus deformity of the tibia. Twenty-one patients were treated nonoperatively with five (23.8%) developing a significant varus angulation (greater than five degrees). No varus malunions were noted in those patients treated with Ender rods. Those patients treated with Ender rods and early weight-bearing had a shorter average time to union than those treated nonoperatively. We therefore feel that Ender rod fixation is a viable treatment modality in tibia fractures with an intact fibula. In these fractures the use of Ender rods helps prevent significant varus malunion and allows early weight-bearing, thus permitting early mobilization of the traumatized patient. © 1990 Raven Press, Ltd., New York

A view on the role of epigenetics in the biology of malaria parasites

Cells and unicellular organisms are similar to their progenitors because information is transmitted from one generation to the next. The information is mainly transmitted in the primary sequence of the genome (genetic information), but there are heritable traits that are transmitted by other mechanisms. Epigenetics studies these alternative modes of inheritance. According to classic definitions, epigenetics refers to heritable differences between cells or organisms that occur without changes in DNA sequence, and do not depend on different external conditions