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    Translational Pathways for Ultra Long-Acting Medicines for Chronic Disease: From HIV to Substance Use Disorders

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    Human immunodeficiency virus (HIV) and opioid use disorder (OUD) are among the top global public health challenges, with a significant overlap in the number of cases and higher mortality risks compared to the general population. Treatment and recreational opioid use lead to addictive disorders. Both conditions require repeated dosing of therapy where adherence to a strict lifelong regimen remains a major challenge. Notably, people living with HIV/AIDS (PLWHA) and struggling with opioid use disorders (OUD) show suboptimal adherence to antiretroviral drugs (ARVs). Also, the risk of transmitting HIV and other blood-borne infections through the sharing of needles and other injection equipment is high in patients with OUD. Recent studies have demonstrated that initiation of long-acting treatments among HIV and OUD patients is not only associated with decreased risk for opioid-related adverse events but also improved viral suppression. We hypothesized that the creation of ultra-long-acting (ULA) prodrug formulations could further improve treatment outcomes. We, therefore, sought to develop ultra-long-acting formulations of a broadly used integrase strand transfer inhibitor called dolutegravir (DTG) and mu-opioid receptor (MOR) partial agonist called buprenorphine (BUP), which has demonstrated a significant advantage in reducing opioid overdose deaths. For DTG, a library of monomeric and dimeric prodrug nanoformulations was synthesized and subjected to in vitro and preclinical pharmacokinetic (PK) screening studies that led to the identification of the lead 18-carbon chain-modified ester prodrug nanocrystal candidate (coined NM2DTG) with the potential to sustain therapeutic drug concentrations for over six months after a single intramuscular (IM) dose. Ideal physiochemical and PK properties facilitated slow DTG release from tissue macrophage depot stores at the muscle injection site and adjacent lymphoid tissues following single parenteral injections. Significant plasma drug levels were recorded for up to a year in rodents following a single injection of NM2DTG. Tissue sites for prodrug hydrolysis were dependent on nanocrystal dissolution and prodrug release, drug-depot volume, perfusion, and cell-tissue pH. Each affected an extended NM2DTG apparent half-life recorded by PK parameters. Similarly, a single IM injection of the lead BUP nanoformulations in Sprague Dawley rats sustains plasma BUP levels at or above the target mu-opioid receptor occupancy concentrations for over three months in ongoing PK studies. We hypothesize that BUP prodrugs will prolong the drug’s apparent half-life and allow for creation of organic solvent free ULA formulations. In summary, the development of ultra-long-acting DTG and BUP injectable formulations can improve treatment of HIV and OUD by enhancing adherence and delivery of the two broadly used drugs into sites of action

    Evaluation of a Student Experiential Learning Clinic for Hand Therapy Using a Logic Model

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    Student clinics (SC) provide experiential learning opportunities in occupational therapy (OT) education that develop clinical reasoning, while providing much needed rehabilitation to under and un-insured patients in the community. The Student Experiential Learning Clinic for Hand Therapy (SELC-HT) is a SC that used a logic model for planning, implementing, and evaluating the SELC-HT. The purpose of this study is to report on outcome data on students and patients, as outlined in the evaluation phase of the logic model. The 13 OT master/doctorate students, who delivered care in the SELC-HT, demonstrated growth in self-reported hand therapy knowledge (p=0.002) measured with the Hand Therapy Certification Commission Self-Assessment Tool. Nine of the 12 students responding to alumni survey were employed in hand therapy positions shortly after graduation. Five students authored six manuscripts published in peer-reviewed journals or practice journals about their work in the SELC-HT. Of the 57 patients with baseline data, fractures were the most common diagnosis, and most patients were Black and males. One-third of injuries were due to violence, primarily gunshot wounds. At discharge (n=25) mean disability, measured with the Disability Arm Shoulder Hand, decreased 14.8 points (p=.001), which exceeds minimal clinical difference of 10.83. Statistically significant improvements in work disability (n=18) and work ability (n=21) also occurred. Most importantly, five patients who were not able to work at baseline had returned to work at discharge. These positive student and patient outcomes are due in part to the systematic planning and implementation of procedures defined in the SELC-HT logic model

    Exploring the Usefulness of Pre-Visit Materials for Children with Autism at a Public Museum

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    Abstract Children with autism spectrum disorder (ASD) participate in community-based settings at lower rates than typically developing children. Museums provide a structured, predictable, and supportive place for children with ASD to learn. Visiting a museum may create unique challenges for children with ASD and their families. Sensory processing disorder (SPD) is a common barrier to participation that makes it difficult to process information coming in through the senses. For children who are easily overstimulated, crowds, noise, and long lines can be a source of anxiety and stress. Providing pre-visit materials such as social stories, accessibility maps, and communication books can support engagement in the museum setting. This study explored the usefulness of pre-visit materials for children with ASD who attended a low sensory event at a public museum. Data were collected during interviews with 22 parents and care partners. All participants found the pre-visit materials useful before and during the museum visit. Participants provided recommendations for improvement including developing multiple formats (e.g., audio, video), different languages, and limiting the pictures per page. This study highlights the unique value of occupational therapy in a community setting. Occupational therapists consider how features of the environment may support or limit participation. The pre-visit materials developed in this study may help museums offer more inclusive experiences to children with ASD and their families. Partnerships with disciplines such as occupational therapy may help museums and other community organizations welcome visitors of all abilities. Plain Language Summary Museums are key educational resources in the community. Families of children with autism spectrum disorder (ASD) face unique challenges to participating in museum settings. This study explored the usefulness of pre-visit materials including a social story, accessibility map, and communication book. These materials were developed through a partnership between a public museum, occupational therapy graduate program, and 22 parents and care partners of children with ASD. All participants found the pre-visit materials useful for improving participation in a museum visit. This study highlights the unique value of occupational therapy at a museum. The materials developed for this study could be replicated to promote a more inclusive experience in other community settings. Partnering with disciplines experienced in working with people with disabilities can assist in creating welcoming environments for people of all abilities. Additional research is needed to explore the benefits of collaborative partnerships between community organizations and occupational therapy programs

    Implementing a Standardized Protocol for Early Detection of Undiagnosed Hypertension Patients

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    Introduction: Hypertension is a preventable disease that frequently goes unrecognized and undertreated. Early diagnosis can prevent further comorbidities such as heart disease, stroke, and chronic kidney disease. Implementation of this protocol aims to decrease the number of patients with undiagnosed hypertension and increase the identification of patients with elevated blood pressure who did not have a pre-existing diagnosis of hypertension. The goal of implementing a standardized protocol would help eliminate the number of patients who go undiagnosed. Methods: This quality improvement design had clinical staff flag patients with elevated blood pressure. Identified patients without a diagnosis of hypertension were educated by providers, given an education packet, encouraged to monitor their blood pressure at home, and asked to return for a follow-up appointment in two to four weeks. Results: Prior to the protocol being initiated from June to August 2021, 0 (0%) patients were identified with elevated blood pressure, and 93 (100%) were found to have elevated blood pressure with no pre-existing diagnosis of hypertension. After the protocol was initiated from June to August 2022, however, 49 (13.6%) patients were identified with elevated blood pressure, and 312 (86.4%) were not identified for a total of 361 patients with elevated blood pressure and no current diagnosis of hypertension. Discussion: Overall, the protocol implementation improved identification of patients with high blood pressure without a previous diagnosis of hypertension. The protocol raised awareness within the clinic regarding hypertension and associated comorbidities. There was a large increase in the number of patients found to have elevated blood pressure from 2021 to 2022. This increase is likely influenced by the change from manual to standardized automatic blood pressure cuffs. Despite protocol implementation, there was still a large volume of patients that had elevated blood pressures that remained unidentified. While staff training was done prior to protocol implementation, there was no process in place to monitor the fidelity of proper blood pressure technique and protocol adherence. Continued focus on protocol adherence may improve the number of individuals identified with elevated blood pressure

    Intersections of Occupational Therapy and Translational Science

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    Editorial Welcome

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    Quality of Life among Cancer Survivors: Comparison of Multiple Cancers Using iCaRe2

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    Background: The number of cancer survivors continues to increase due to dramatic improvements in cancer treatment, accounting for approximately 5% of the entire population. As cancer survivors continue to live longer, it is important to understand their quality of life (QoL) in order to maximize supportive care efforts. Objectives: In this study, the quality of life (QoL) among patients with different types of cancer was examined. The objectives were to: 1) compare patient-reported outcome measures of QoL using the Short-Form (SF-36) Health Survey scores among patients of different cancer types and 2) identify demographic, oncologic, and clinical factors that are associated with SF-36 QOL scores. Methods: We performed a retrospective review of prospectively collected data from a multi-center cancer registry data collected between January 2007 and February 2020. Multiple linear regression analysis was conducted to identify demographic and clinical factors that are associated with SF-36 Physical Component Score (PCS) and Mental Component Score (MCS). Findings: Both mental and physical aspects of QoL were affected in all cancer patients, regardless of the type, prognosis, and time since diagnosis and treatment. Individual, socioeconomic, disease, and treatment-related variables were associated with QoL among different cancer populations and should be addressed as part of shared treatment decision-making

    The Physiological Significance of Nitric Oxide Synthase in Staphylococci

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    Staphylococci, particularly Staphylococcus epidermidis, are common causes of implant-associated infections that may result in notable morbidity and mortality. One of the ways the innate immune system attempts to combat these invading pathogens is via the respiratory burst, in which free radical species such as nitric oxide (NO•), toxic to bacterial respiration, are released in large quantities. Despite the toxicity of NO•, some bacteria, including staphylococci, encode an endogenous bacterial nitric oxide synthase (bNOS), whose physiological role has been unclear until now. In this dissertation, we demonstrate that S. epidermidis is able to overcome the toxicity of NO• by converting this NO• to nitrite. Furthermore, this nitrite enhances S. epidermidis growth by actively reducing the production of harmful superoxide, generated by flavohemoglobin Hmp, via promotion of the regulatory CymR-CysK complex. In addition, NOS-dependent CymR-CysK regulation also serves to enhance growth by repressing the expression of polysaccharide intercellular adhesin (PIA) and preventing carbon redirection away from peptidoglycan biosynthesis. Together, these data demonstrate that the activity of bacterial NOS is critical in maintaining optimal growth and homeostasis of staphylococci

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