Development and Testing of an Occupational Therapy Intervention to Promote Medication Adherence

Many persons with chronic health conditions fail to take their medications as prescribed, resulting in declines in health and function. Unfortunately, current interventions for medication nonadherence are not very effective. Medication adherence is a daily activity, which many occupational therapists believe would be responsive to occupational therapy intervention. Unfortunately, few resources support occupational therapists in this role. The purpose of this dissertation is to create the foundational work for occupational therapy medication adherence interventions. In this dissertation, I accomplish five objectives. First, I identify the role of occupational therapy practitioners in the medication adherence field. Second, I create a manualized occupational therapy intervention for medication adherence named the Integrative Medication Self-Management Intervention (or IMedS). Third, I develop a training program to teach the IMedS intervention to entry-level practitioners. Fourth, I investigate the preliminary effectiveness of this intervention in a small two-group experimental blind pre-post randomized controlled trial. Finally, I explore the feasibility of continued research for the IMedS intervention. Findings from this study support occupational therapy’s role in medication adherence intervention and future research in this area

Guidelines for Medication Education for Occupational Therapists

Taking medications is a vital health management activity for people with chronic health conditions. These individuals must take their medications as prescribed to receive the intended benefits and minimize negative effects. Many people with chronic health conditions do not know essential information about their medications, which limits their ability to take their medications as prescribed. Occupational therapists regularly engage in client education to enhance performance of health management. When addressing medications, however, additional considerations are needed because of the highly regulated, interdisciplinary, and complex nature of this occupation. The purpose of this practice guideline is to describe the integration of best practices in patient education, medication education, and the occupational therapist’s scope of practice. Procedures for screening, evaluation, and intervention are discussed

Feasibility of a Self-Paced Educational Intervention Protocol on Standardized Assessment of Public Building Accessibility

Limited research informs the implementation of web-based and mobile learning (mLearning) protocols for the assessment of public building accessibility in occupational therapy graduate students. This study tested the feasibility of a self-paced protocol designed to teach students how to evaluate community environment accessibility. Students across five sites completed an online learning module and community building evaluations. Students were randomized into lecture or lab educational groups and then crossed over to receive the second experience. Outcomes were student satisfaction, self-perceived learning, and knowledge on a researcher-developed measure. Data were analyzed using descriptive statistics. Two hundred and twelve students completed the study. The students were satisfied with their education and their community accessibility knowledge significantly increased from approximately 60% to 85%. Site and order of the learning components did not impact student ability to achieve competence. This multi-site approach is feasible and effective in instructing students in this highly protocolized and specialized area of practice

Estimating cumulative pathway effects on risk for age-related macular degeneration using mixed linear models

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly in developed countries and typically affects more than 10 % of individuals over age 80. AMD has a large genetic component, with heritability estimated to be between 45 % and 70 %. Numerous variants have been identified and implicate various molecular mechanisms and pathways for AMD pathogenesis but those variants only explain a portion of AMD’s heritability. The goal of our study was to estimate the cumulative genetic contribution of common variants on AMD risk for multiple pathways related to the etiology of AMD, including angiogenesis, antioxidant activity, apoptotic signaling, complement activation, inflammatory response, response to nicotine, oxidative phosphorylation, and the tricarboxylic acid cycle. While these mechanisms have been associated with AMD in literature, the overall extent of the contribution to AMD risk for each is unknown. METHODS: In a case–control dataset with 1,813 individuals genotyped for over 600,000 SNPs we used Genome-wide Complex Trait Analysis (GCTA) to estimate the proportion of AMD risk explained by SNPs in genes associated with each pathway. SNPs within a 50 kb region flanking each gene were also assessed, as well as more distant, putatively regulatory SNPs, based on DNaseI hypersensitivity data from ocular tissue in the ENCODE project. RESULTS: We found that 19 previously associated AMD risk SNPs contributed to 13.3 % of the risk for AMD in our dataset, while the remaining genotyped SNPs contributed to 36.7 % of AMD risk. Adjusting for the 19 risk SNPs, the complement activation and inflammatory response pathways still explained a statistically significant proportion of additional risk for AMD (9.8 % and 17.9 %, respectively), with other pathways showing no significant effects (0.3 % – 4.4 %). DISCUSSION: Our results show that SNPs associated with complement activation and inflammation significantly contribute to AMD risk, separately from the risk explained by the 19 known risk SNPs. We found that SNPs within 50 kb regions flanking genes explained additional risk beyond genic SNPs, suggesting a potential regulatory role, but that more distant SNPs explained less than 0.5 % additional risk for each pathway. CONCLUSIONS: From these analyses we find that the impact of complement SNPs on risk for AMD extends beyond the established genome-wide significant SNPs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0760-4) contains supplementary material, which is available to authorized users

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

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

Inclusion of People with Disabilities in Research to Improve Medication Adherence: A Systematic Review

People with disabilities have high rates of chronic health conditions and often require complex medication regimens to manage their health. Approximately 20–50% of people with disabilities fail to take their medication as prescribed. It is unclear, however, to what extent the literature describes the effectiveness of medication adherence interventions for people with disabilities. In this review, the inclusion and exclusion criteria of the 182 studies included in the Cochrane Review on Interventions for Enhancing Medication Adherence were evaluated for their inclusion of people with disabilities. Of the studies, 1% excluded persons for hearing impairment, 3% for motor impairment, 7% for visual impairment, and 32% for cognitive impairment. Most studies (65%) did not exclude persons based on specific impairment. Medication event monitoring systems were used in 21% of studies, and investigators excluded people unable to use this device in 5% of studies. Caregiver assistance was an exclusion criteria in 4% of studies. Additional barriers like the ability of investigators to exclude persons based on their judgement were found. These barriers exist in addition to the known barriers affecting persons with disabilities, such as accessibility of research facilities and access to transportation. These data suggest that people with disabilities are systemically excluded from the medication adherence intervention literature. Subsequently, it cannot be assumed that current adherence interventions are effective for people with disabilities. More research is needed to understand how to address medication adherence for people with disabilities

Best Practices for The Interdisciplinary Rehabilitation Team: A Review of Mental Health Issues in Mild Stroke Survivors

Individuals with mild strokes are generally considered fully functional and do not traditionally receive rehabilitation services. Because patients with mild stroke are assumed to have a good recovery, they may have deficits in other areas, including mental health, that are not addressed. As a result, patients with mild stroke are unable to meet quality of life standards. In addition, healthcare professionals are likely unaware of the potential mental health issues that may arise in mild stroke. To address this gap in knowledge, we review the evidence supporting mental health evaluation and intervention in mild stroke. Specifically, we review comorbid diagnoses including depression, anxiety, fatigue, and sleep disturbances and their potential effects on health and function. Finally, we conclude with general recommendations describing best practice derived from current evidence

Interdisciplinary Approaches to Facilitate Return to Driving and Return to Work in Mild Stroke: A Position Paper

Adults with mild stroke face substantial challenges resuming valued roles in the community. The term “mild” provides false representation of the lived experience for many adults with mild stroke who may continue to experience persistent challenges and unmet needs. Rehabilitation practitioners can identify and consequently intervene to facilitate improved independence, participation, and quality of life by facilitating function and reducing the burden of lost abilities among adults with mild stroke. The Health and Wellness Task Force identified 2 important, and often interdependent, goals that frequently arise among adults living with mild stroke that must be addressed to facilitate improved community reintegration: (1) return to driving and (2) return to work. Adults with mild stroke may not be receiving adequate rehabilitative services to facilitate community reintegration for several reasons but primarily because current practice models are not designed to meet such needs of this specific population. Thus, the Health and Wellness Task Force convened to review current literature and practice trends to (1) identify opportunities based on the evidence of assessment and interventions, for return to driving and return to work; and (2) identify gaps in the literature that must be addressed to take advantage of the opportunities. Based on findings, the task force proposes a new interdisciplinary practice model for adults with mild stroke who are too often discharged from the hospital to the community without needed services to enable successful return to driving and work