OVERCOMING THE HURDLE OF IMPLEMENTATION: PUTTING HUMAN RESOURCES FOR HEALTH TOOLS INTO ACTION

ABSTRACT The global human resources for health (HRH) challenge remains persistent. In 2006, the World Health Report identified 57 crisis countries, and, despite increased attention and investment in strengthening the workforce, those countries are still in crisis. While chronic HRH problems still exist, progress has been made in some countries where innovative programs have been implemented that show promise, or specific initiatives have been scaled up. Yet, these have not been substantive enough to move countries out of the "crisis" category. While many countries have HRH plans, this paper asserts that a major reason countries remain in crisis is the lack of sustained implementation to achieve concrete workforce strengthening results. This is true despite the fact that there have been major investments in a broad range of tools and resources aimed to support implementation of plans and initiatives. Given this picture, the paper states that it is critical for HRH leaders to take action to ensure that already available tools are disseminated, adapted and used to foster effective implementation at the country level. The paper highlights four such tools as examples that can be used to build implementation capacity, and acknowledges more like them. Having highlighted these tools, the paper concludes by offering recommendations as to how to support more results-oriented implementation. These recommendations are organized around three linked components: 1) providing sufficient advocacy to leadership at the national level to mobilize and commit them to implementation action, 2) assembling and managing the requisite assets (including the institutional arrangements, people and money) into a coherent and powerful whole, and 3) using accountability as a foundational tool to assess progress in implementation, track key indicators, celebrate achieving key milestones and identify problems when indicators are not achieved

A Systematic Review and Meta-Analysis of Patient Decision Aids for Socially Disadvantaged Populations:Update from the International Patient Decision Aid Standards (IDPAS)

International audienceBackground. The effectiveness of patient decision aids (PtDAs) and other shared decision-making (SDM) interventions for socially disadvantaged populations has not been well studied. Purpose. To assess whether PtDAs and other SDM interventions improve outcomes or decrease health inequalities among socially disadvantaged populations and determine the critical features of successful interventions. Data Sources. MEDLINE, CINAHL, Cochrane, Psy-cINFO, and Web of Science from inception to October 2019. Cochrane systematic reviews on PtDAs. Study Selection. Randomized controlled trials of PtDAs and SDM interventions that included socially disadvantaged populations. Data Extraction. Independent double data extraction using a standardized form and the Template for Intervention Description and Replication checklist. Data Synthesis. Twenty-five PtDA and 13 other SDM intervention trials met our inclusion criteria. Compared with usual care, PtDAs improved knowledge (mean difference = 13.91, 95% confidence interval [CI] 9.01, 18.82 [I 2 = 96%]) and patient-clinician communication (relative risk = 1.62, 95% CI 1.42, 1.84 [I 2 = 0%]). PtDAs reduced decisional conflict (mean difference = 29.59; 95% CI 218.94, 20.24 [I 2 = 84%]) and the proportion undecided (relative risk = 0.39; 95% CI 0.28, 0.53 [I 2 = 75%]). PtDAs did not affect anxiety (standardized mean difference = 0.02, 95% CI 20.22, 0.26 [I 2 = 70%]). Only 1 trial looked at clinical outcomes (hemoglobin A1C). Five of the 12 PtDA studies that compared outcomes by disadvantaged standing found that outcomes improved more for socially disadvantaged participants. No evidence indicated which intervention characteristics were most effective. Results were similar for SDM intervention trials. Limitations. Sixteen PtDA studies had an overall unclear risk of bias. Heterogeneity was high for most outcomes. Most studies only had short-term follow-up. Conclusions. PtDAs led to better outcomes among socially disadvantaged populations but did not reduce health inequalities. We could not determine which intervention features were most effective

Factors associated with intentions to adhere to colorectal cancer screening follow-up exams

BACKGROUND: To increase adherence rate to recommendations for follow-up after abnormal colorectal cancer (CRC) screening results, factors that inhibit and facilitate follow-up must be identified. The purpose of this study was to identify the factors associated with intention to adhere to CRC screening follow-up exams. METHODS: During a 4-week period in October 2003, this survey was conducted with 426 subjects participating in a community-based CRC screening program in Nagano, Japan. Study measures included intention to adhere to recommendation for clinical follow-up in the event of an abnormal fecal occult blood test (FOBT) result, perceived susceptibility and severity of CRC, perceived benefits and barriers related to undergoing follow-up examination, social support, knowledge of CRC risk factors, health status, previous CRC screening, personality and social demographic characteristics. Univariate and multivariate logistic regression analyses on intention to adhere to recommendations for follow-up were performed. RESULTS: Among the 288 individuals analyzed, approximately 74.7% indicated that they would definitely adhere to recommendations for follow-up. After controlling for age, gender, marital status, education, economic status, trait anxiety, bowel symptoms, family history of CRC, and previous screening FOBT, analyses revealed that lower levels of perceived barriers, higher levers of perceived benefits and knowledge of CRC risk factors were significantly associated with high intention respectively. CONCLUSION: The results of this study suggest that future interventions should focus on reducing modifiable barriers by clarifying misperceptions about follow-up, promoting the acceptance of complete diagnostic evaluations, addressing psychological distress, and making follow-up testing more convenient and accessible. Moreover, educating the public regarding the risk factors of CRC and increasing understanding of the benefits of follow-up is also important

BIN1 Localizes the L-Type Calcium Channel to Cardiac T-Tubules

Cardiac tubular-like membrane invaginations contain the membrane scaffolding protein BIN1, which tethers dynamic microtubules that deliver calcium channels directly to T-tubule membrane

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p <2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups

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

Growth And The Growth Hormone-Insulin Like Growth Factor 1 Axis In Children With Chronic Inflammation:Current Evidence, Gaps In Knowledge And Future Directions

Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt is often seen during adolescence. The underlying inflammatory state mediated by pro-inflammatory cytokines, prolonged use of glucocorticoid and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the growth hormone-insulin like growth factor axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate studies further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biologic therapy may lead to improvement of growth in some of these children but approximately one third continue to grow slowly. There is increasing evidence that the use of relatively high dose recombinant human growth hormone may lead to partial catch up growth in chronic inflammatory conditions, although long term follow-up data is currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis, systemic abnormalities of the growth hormone-insulin like growth factor axis and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human growth hormone in these conditions and discuss the role of recombinant human insulin like growth factor-1

Superando el obstáculo de la implementación: poniendo en acción las herramientas para la promoción de recursos humanos en salud

The global human resources for health (HRH) challenge remains persistent. In 2006, the World Health Report identified 57 crisis countries, and, despite increased attention and investment in strengthening the workforce, those countries are still in crisis. While chronic HRH problems still exist, progress has been made in some countries where innovative programs have been implemented that show promise, or specific initiatives have been scaled up. yet, these have not been substantive enough to move countries out of the “crisis” category. While many countries have HRH plans, this paper asserts that a major reason countries remain in crisis is the lack of sustained implementation to achieve concrete workforce strengthening results. This is true despite the fact that there have been major investments in a broad range of tools and resources aimed to support implementation of plans and initiatives.Given this picture, the paper states that it is critical for HRH leaders to take action to ensure that already available tools are disseminated, adapted and used to foster effective implementation at the country level. The paper highlights four such tools as examples that can be used to build implementation capacity, and acknowledges more like them. Having highlighted these tools, the paper concludes by offering recommendations as to how to support more results-oriented implementation. These recommendations are organized around three linked components: 1) providing sufficient advocacy to leadership at the national level to mobilize and commit them to implementation action, 2) assembling and managing the requisite assets (including the institutional arrangements, people and money) into a coherent and powerful whole, and 3) using accountability as a foundational tool to assess progress in implementation, track key indicators, celebrate achieving key milestones and identify problems when indicators are not achieved.Los desafíos de los recursos humanos en salud (RHS) aún persisten a nivel mundial. El Informe Sobre la Salud en el Mundo identificó a 57 países en situación crítica los que, a pesar de la atención e inversión crecientes en el fortalecimiento de la fuerza laboral, siguen en crisis. Pese a la existencia de problemas crónicos en RHS, se ha logrado progresos en algunos países en los que se ha aplicado programas innovadores basados en iniciativas concretas. Sin embargo, este esfuerzo no ha sido suficiente para poder solucionar la crisis de los países involucrados. Una de las razones principales para ello es que pese a que muchos paises tienen planes para los RHS, la falta de implementación sostenida impide alcanzar resultados concretos que fortalezcan la fuerza laboral. Esto es así a pesar de que ha habido grandes inversiones en una amplia gama de herramientas y recursos para apoyar la aplicación de planes e iniciativas. Ante este panorama, es crítico que quienes tienen a su cargo los RHS tomen medidas para garantizar que las herramientas ya disponibles se difundan, se adapten, se utilicen y se apliquen efectivamente a nivel nacional. Este documento destaca cuatro herramientas como ejemplos que pueden utilizarse para construir capacidad de ejecución, se ofrece recomendaciones sobre cómo apoyar la aplicación orientada a resultados. Estas recomendaciones están organizadas alrededor de tres componentes ligados entre sí: 1) proporcionar suficiente abogacía al liderazgo a nivel nacional para movilizar y comprometerles a la acción de implementación, 2) recopilar y gestionar los activos necesarios (incluyendo los acuerdos institucionales, personal y financiamiento) en un todo coherente y 3) utilizar la “rendición de cuentas” de actividades como una herramienta fundamental para evaluar los progresos en la aplicación, realizar un seguimiento de los indicadores claves, celebrar el alcance de hitos clave e identificar problemas subyacentes cuando no se logra el cumplimiento de los indicadores