CHRONIC OPIOID USE IN FIBROMYALGIA SYNDROME: CHARACTERISTICS AND OUTCOMES

Fibromyalgia syndrome (FMS) is a chronic pain condition with significant societal and personal burdens of illness. Chronic opioid therapy in the treatment of chronic nonmalignant pain has increased drastically over the past decade. This is a worrisome trend in general, but specifically, given the pathophysiologic characteristics seen in fibromyalgia syndrome patients, the use of this class of medication deserves special scrutiny. Although the theoretical case against this therapy choice is strong, little empirical evidence exists. In order to supplement this literature, retrospective analysis methods are utilized to examine the association of state-, provider-, and patient level characteristics with the prevalence of chronic opioid use in this disease state. Data gathered through this analysis is then used to develop a propensity index for the identification of an appropriate control group for fibromyalgia patients, a task that has proven difficult in the literature to date. Using propensity stratification and matching techniques analysis of the impact of fibromyalgia, chronic opioid use, and the interaction of these two variables are undertaken. Several key findings and updates to the understanding of chronic opioid use and fibromyalgia syndrome are reported. Wide geographic variation in chronic opioid utilization between states is seen. The role of diagnosing provider type in the rate of chronic opioid prescribing is significant and can be aggregated at various levels. Demographic characteristics, comorbid conditions, and concurrent medication use are all important associates of chronic opioid use in fibromyalgia syndrome. Additionally, chronic opioid use in fibromyalgia patients, independent of propensity to receive that therapy choice is a significant correlate with healthcare costs. A diagnosis of fibromyalgia is a statistically significant source of healthcare costs, though the clinical significance of its impact when compared to a closely matched control group is minimized. Despite the minimization of the role of this diagnosis the impact of the interaction of chronic opioid use with fibromyalgia, despite control for myriad regressors, is significant both statistically and clinically

Educational Innovations: Categories of Bulletin Board Postings Designed to Increase Awareness of Contemporary Pharmaceutical Policy Issues

OBJECTIVE: The goal of this project was to categorize and classify bulletin board postings pertaining to pharmaceutical policy from both the professional and lay press. METHODS: Bulletin board postings were used to supplement in-class discussion to keep students, faculty and staff up-to-date on emerging trends. A bulletin board located in the main classroom area of the College of Pharmacy Building where students would pass by on the way to class and congregate during break periods was used to display articles from various sources concerning topics related to pharmaceutical policy. Information is presented about the primary subject matters addressed in the articles, the types of publications from which they were drawn, and the top ten sources of articles displayed. RESULTS: This project showed that coverage of issues related to pharmacists is predominantly seen in newspapers and most pertinent issues are business related. CONCLUSIONS: It can be seen from this analysis that the issues facing pharmacists are varied. The pharmaceutical policy field is transforming and many of these changes are very relevant to the general population. This is seen from the coverage of all of these issues in the lay press

Testing implementation facilitation of a primary care-based collaborative care clinical program using a hybrid type III interrupted time series design: a study protocol

Abstract Background Dissemination of evidence-based practices that can reduce morbidity and mortality is important to combat the growing opioid overdose crisis in the USA. Research and expert consensus support reducing high-dose opioid therapy, avoiding risky opioid-benzodiazepine combination therapy, and promoting multi-modal, collaborative models of pain care. Collaborative care interventions that support primary care providers have been effective in medication tapering. We developed a patient-centered Primary Care-Integrated Pain Support (PIPS) collaborative care clinical program based on effective components of previous collaborative care interventions. Implementation facilitation, a multi-faceted and dynamic strategy involving the provision of interactive problem-solving and support during implementation of a new program, is used to support key organizational staff throughout PIPS implementation. The primary aim of this study is to evaluate the effectiveness of the implementation facilitation strategy for implementing and sustaining PIPS in the Veterans Health Administration (VHA). The secondary aim is to examine the effect of the program on key patient-level clinical outcomes—transitioning to safer regimens and enhancing access to complementary and integrative health treatments. The tertiary aim is to determine the categorical costs and ultimate budget impact of PIPS implementation. Methods This multi-site study employs an interrupted time series, hybrid type III design to evaluate the effectiveness of implementation facilitation for a collaborative care clinical program—PIPS—in primary care clinics in three geographically diverse VHA health care systems (sites). Participants include pharmacists and allied staff involved in the delivery of clinical pain management services as well as patients. Eligible patients are prescribed either an outpatient opioid prescription greater than or equal to 90 mg morphine equivalent daily dose or a combination opioid-benzodiazepine regimen. They must also have an upcoming appointment in primary care. The Consolidated Framework for Implementation Research will guide the mixed methods work across the formative evaluation phases and informs the selection of activities included in implementation facilitation. The RE-AIM framework will be used to assess Reach, Effectiveness, Adoption, Implementation, and Maintenance of PIPS. Discussion This implementation study will provide important insight into the effectiveness of implementation facilitation to enhance uptake of a collaborative care program in primary care, which targets unsafe opioid prescribing practices.https://deepblue.lib.umich.edu/bitstream/2027.42/146542/1/13012_2018_Article_838.pd

Adopting the RE-AIM analytic framework for rural program evaluation: experiences from the Advance Care Planning via Group Visits (ACP-GV) national evaluation

IntroductionTo support rigorous evaluation across a national portfolio of grants, the United States Department of Veterans Affairs (VA) Office of Rural Health (ORH) adopted an analytic framework to guide their grantees' evaluation of initiatives that reach rural veterans and to standardize the reporting of outcomes and impacts. Advance Care Planning via Group Visits (ACP-GV), one of ORH's Enterprise-Wide Initiatives, also followed the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. ACP-GV is a national patient-centered intervention delivered in a large, veterans integrated healthcare system. This manuscript describes how RE-AIM was used to evaluate this national program and lessons learned from ORH's annual reporting feedback to ACP-GV on their use of the framework to describe evaluation impacts.MethodsWe used patient, provider, and site-level administrative health care data from the VA Corporate Data Warehouse and national program management databases for federal fiscal years (FY) spanning October 1, 2018–September 30, 2023. Measures included cumulative and past FY metrics developed to assess program impacts.ResultsRE-AIM constructs included the following cumulative and annual program evaluation results. ACP-GV reached 54,167 unique veterans, including 19,032 unique rural veterans between FY 2018 to FY 2023. During FY 2023, implementation adherence to the ACP-GV model was noted in 91.7% of program completers, with 55% of these completers reporting a knowledge increase and 14% reporting a substantial knowledge increase (effectiveness). As of FY 2023, 66 ACP-GV sites were active, and 1,556 VA staff were trained in the intervention (adoption). Of the 66 active sites in FY 2023, 27 were sites previously funded by ORH and continued to offer ACP-GV after the conclusion of three years of seed funding (maintenance).DiscussionLessons learned developing RE-AIM metrics collaboratively with program developers, implementers, and evaluators allowed for a balance of clinical and scientific input in decision-making, while the ORH annual reporting feedback provided specificity and emphasis for including both cumulative, annual, and rural specific metrics. ACP-GV's use of RE-AIM metrics is a key step towards improving rural veteran health outcomes and describing real world program impacts

FlexOracle: predicting flexible hinges by identification of stable domains

<p>Abstract</p> <p>Background</p> <p>Protein motions play an essential role in catalysis and protein-ligand interactions, but are difficult to observe directly. A substantial fraction of protein motions involve hinge bending. For these proteins, the accurate identification of flexible hinges connecting rigid domains would provide significant insight into motion. Programs such as GNM and FIRST have made global flexibility predictions available at low computational cost, but are not designed specifically for finding hinge points.</p> <p>Results</p> <p>Here we present the novel FlexOracle hinge prediction approach based on the ideas that energetic interactions are stronger <it>within </it>structural domains than <it>between </it>them, and that fragments generated by cleaving the protein at the hinge site are independently stable. We implement this as a tool within the Database of Macromolecular Motions, MolMovDB.org. For a given structure, we generate pairs of fragments based on scanning all possible cleavage points on the protein chain, compute the energy of the fragments compared with the undivided protein, and predict hinges where this quantity is minimal. We present three specific implementations of this approach. In the first, we consider only pairs of fragments generated by cutting at a <it>single </it>location on the protein chain and then use a standard molecular mechanics force field to calculate the enthalpies of the two fragments. In the second, we generate fragments in the same way but instead compute their free energies using a knowledge based force field. In the third, we generate fragment pairs by cutting at <it>two </it>points on the protein chain and then calculate their free energies.</p> <p>Conclusion</p> <p>Quantitative results demonstrate our method's ability to predict known hinges from the Database of Macromolecular Motions.</p

First Steps in Eukaryogenesis: Physical phenomena in the origin and evolution of chromosome structure

Our present understanding of the origin and evolution of chromosomes differs considerably from current understanding of the origin and evolution of the cell itself. Chromosome origins have been less prominent in research, as the emphasis has not shifted so far appreciably from the phenomenon of primeval nucleic acid encapsulation to that of the origin of gene organization, expression, and regulation. In this work we discuss some reasons why preliminary steps in this direction are being taken. We have been led to examine properties that have contributed to raise the ancestral prokaryotic programmes to a level where we can appreciate in eukaryotes a clear departure from earlier themes in the evolution of the cell from the last common ancestor. We shift our point of view from the evolution of cell morphology to the point of view of the genes. In particular, we focus attention on possible physical bases for the way transmission of information has evolved in eukaryotes, namely, the inactivation of whole chromosomes. The special case of the inactivation of the X chromosome in mammals is discussed, paying particular attention to the physical process of the spread of X inactivation in monotremes (platypus and echidna). When experimental data is unavailable some theoretical analysis is possible based on the idea that in certain cases collective phenomena in genetics, rather than chemical detail, are better correlates of complex chemical processes

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

<div><p>Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in <i>Trypanosoma brucei</i>. We describe an oxidative enzymatic pathway composed of host semicarbazide-sensitive amine oxidase and a trypanosomal aldehyde dehydrogenase TbALDH3. Two sequential reactions through this pathway serve as the key underlying mechanism for activating a series of 4-aminomethylphenoxy-benzoxaboroles as potent trypanocides; the methylamine parental compounds as pro-drugs are transformed first into intermediate aldehyde metabolites, and further into the carboxylate metabolites as effective forms. Moreover, comparative biochemical and crystallographic analyses elucidated the catalytic specificity of TbALDH3 towards the benzaldehyde benzoxaborole metabolites as xenogeneic substrates. Overall, this work proposes a novel drug activation mechanism dependent on both host and parasite metabolism of primary amine containing molecules, which contributes a new perspective to our understanding of the benzoxaborole MoA, and could be further exploited to improve the therapeutic index of antimicrobial compounds.</p></div