Publications by authors named "Kristin Zimmerman"

37 Publications

Anticholinergic Medication Burden in Parkinson's Disease Outpatients.

J Parkinsons Dis 2022 ;12(2):599-606

Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA.

Background: Individuals with Parkinson's disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications.

Objective: To characterize anticholinergic medication burden, determine the co-occurrence of anticholinergic and cholinesterase inhibitors, and to assess the correlations among anticholinergic burden scales in PD outpatients.

Methods: We studied 670 PD outpatients enrolled in a clinic registry between 2012 and 2020. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Drug Burden Index-Anticholinergic component (DBI-Ach). Correlations between scales were assessed with weighted kappa coefficients.

Results: Between 31.5 to 46.3% of PD patients were taking medications with anticholinergic properties. Among the scales applied, the ACB produced the highest prevalence of medications with anticholinergic properties (46.3%). Considering only medications with definite anticholinergic activity (scores of 2 or 3 on ACB, ADS, or ARS), the most common anticholinergic drug classes were antiparkinsonian (8.2%), antipsychotic (6.4%), and urological (3.3%) medications. Cholinesterase inhibitors and medications with anticholinergic properties were co-prescribed to 5.4% of the total cohort. The most highly correlated scales were ACB and ADS (κ= 0.71), ACB and ARS (κ= 0.67), and ADS and ARS (κ= 0.55).

Conclusion: A high proportion of PD patients (20%) were either taking antiparkinsonian, urological, or antipsychotic anticholinergic medications or were co-prescribed anticholinergic medications and cholinesterase inhibitors. By virtue of its detection of a high prevalence of anticholinergic medication usage and its high correlation with other scales, our data support use of the ACB scale to assess anticholinergic burden in PD patients.
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http://dx.doi.org/10.3233/JPD-212769DOI Listing
April 2022

A narrative review of updates in deprescribing research.

J Am Geriatr Soc 2021 09 15;69(9):2619-2624. Epub 2021 May 15.

General Internal Medicine and Center for Healthcare Organization and Implementation Research, VA Boston Healthcare System, Boston, Massachusetts, USA.

Background/objectives: Deprescribing is a strategy intended to reduce harms associated with potentially inappropriate medications. Reflective of the growing interest in deprescribing, there has been an increase in related research to better understand the landscape, opportunities for improvement, how best to develop and implement interventions, and remaining knowledge gaps that can be addressed with additional study.

Design: We conducted a narrative review of recent deprescribing literature.

Setting: As part of the US Deprescribing Network's inaugural conference in October 2020, we presented a narrative review of recent deprescribing literature to an audience with a range of clinical and research expertise.

Participants: We searched four databases for English-language articles published between January 1, 2019 and August 31, 2020.

Measurements: We evaluated titles, abstracts, and full-length manuscripts for relevance, novelty, rigor and variety of methods; we also aimed for broad representation of authors, institutions, and nations.

Results: The initial search returned 199 citations, from which we reviewed 18 full-length manuscripts, selecting 10 articles to present. Salient themes included missed opportunities to deprescribe in potentially eligible patients, with variable impact of medication- and patient-level factors, along with differing perspectives and behaviors between geriatricians, internists, and cardiologists. Clinical, financial, and economic drivers were also evaluated. Finally, attention was given to issues applicable to deprescribing research, including difficulty recruiting trial participants, perspectives of investigators, and integration of findings into clinical practice.

Conclusion: This narrative review summarizes key advances in the field while also identifying priority areas for additional research.
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http://dx.doi.org/10.1111/jgs.17273DOI Listing
September 2021

Infusing geriatrics expertise in health professions education through interprofessional faculty development.

Gerontol Geriatr Educ 2021 Feb 5:1-13. Epub 2021 Feb 5.

Virginia Center on Aging, College of Health Professions, Virginia Commonwealth University, Richmond, Virginia, USA.

As the population of older adults continues to grow, the need for health care professionals trained in the delivery of interprofessional care for older adult patients is critical. The purpose of this paper is to detail the outcomes of an interprofessional, geriatrics training program for healthcare professionals with a faculty appointment. Specifically, we gathered outcomes at four levels: reactions/satisfaction, learning, behavioral, and organizational. Our findings suggest that programs structured like the Faculty Development Program (FDP) have the potential to increase the amount of geriatrics content introduced in already existing health professions curricula, as well as to offer faculty needed training in how to provide their students with interprofessional learning experiences.
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http://dx.doi.org/10.1080/02701960.2021.1883599DOI Listing
February 2021

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice.

J Bone Miner Res 2021 05 18;36(5):942-955. Epub 2021 Feb 18.

Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1 mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1 mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1 mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1 mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739051PMC
May 2021

Evaluation of an interprofessional, evidence-based falls training.

Gerontol Geriatr Educ 2021 Apr-Jun;42(2):207-223. Epub 2020 Dec 21.

Virginia College of Health Professions, Virginia Center on Aging, Richmond, US.

Fall-related injuries and mortality are increasing in older adults. Evidence suggests a need for a multifactorial, interprofessional approach to reducing falls. The Program for All-Inclusive Care for the Elderly (PACE) utilizes an interprofessional approach to care and serves a high-risk population. The purpose of this study was to investigate the effectiveness of an EBP falls prevention training program conducted at a PACE. The program was a revision of an established program and was led by an interprofessional team. The evaluation used a mixed-methods approach to assess program quality, learning and self-efficacy gains, and intended behavioral changes. Quantitative evaluation demonstrated program satisfaction and qualitative responses identified the depth and interprofessional delivery as favorable. Qualitative data identified opportunities to enhance content and learning design. Overall knowledge gains were statistically significant (mean difference 5%), with the greatest gains related to the evidence base (mean difference 2.67%). Self-efficacy ratings increased significantly after each session. Participants noted changes to team function and a willingness to consider practice changes as a result of the training. The findings support the effectiveness of this interprofessional, EBP training program on falls prevention practices in a PACE and highlight the value of a multifaceted assessment and iterative development.
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http://dx.doi.org/10.1080/02701960.2020.1860956DOI Listing
November 2021

Improving the Pharmacodynamics and In Vivo Activity of ENPP1-Fc Through Protein and Glycosylation Engineering.

Clin Transl Sci 2021 01 20;14(1):362-372. Epub 2020 Oct 20.

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.

Enzyme replacement with ectonucleotide pyrophosphatase phospodiesterase-1 (ENPP1) eliminates mortality in a murine model of the lethal calcification disorder generalized arterial calcification of infancy. We used protein engineering, glycan optimization, and a novel biomanufacturing platform to enhance potency by using a three-prong strategy. First, we added new N-glycans to ENPP1; second, we optimized pH-dependent cellular recycling by protein engineering of the Fc neonatal receptor; finally, we used a two-step process to improve sialylation by first producing ENPP1-Fc in cells stably transfected with human α-2,6-sialyltransferase (ST6) and further enhanced terminal sialylation by supplementing production with 1,3,4-O-Bu ManNAc. These steps sequentially increased the half-life of the parent compound in rodents from 37 hours to ~ 67 hours with an added N-glycan, to ~ 96 hours with optimized pH-dependent Fc recycling, to ~ 204 hours when the therapeutic was produced in ST6-overexpressing cells with 1,3,4-O-Bu ManNAc supplementation. The alterations were demonstrated to increase drug potency by maintaining efficacious levels of plasma phosphoanhydride pyrophosphate in ENPP1-deficient mice when the optimized biologic was administered at a 10-fold lower mass dose less frequently than the parent compound-once every 10 days vs. 3 times a week. We believe these improvements represent a general strategy to rationally optimize protein therapeutics.
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http://dx.doi.org/10.1111/cts.12887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877847PMC
January 2021

The Translational Approaches to Personalized Health Collaborative: Pharmacogenomics for African American Older Adults.

Clin Transl Sci 2021 03 7;14(2):437-444. Epub 2020 Oct 7.

Geriatric Pharmacotherapy Program, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA.

Older adults (i.e., 60 years and older), are the leading consumers of medications, and consequently are suffering the most from medication-related adverse events. Not only are older adults the largest consumers of medications, they are more likely to experience an adverse drug event contributing to increased hospitalization, utilization of emergency medical services, and mortality. Translational Approaches to Personalized Health (TAPH) is a transdisciplinary team of researchers conducting community-engaged participatory research focused on the discovery and translation of pharmacogenomic (PGx) data to improve health outcomes. Underserved and ethnically diverse older adults living in urban settings are significantly under-represented in PGx studies. To address the issue of under-representation, our study enrolls older African American adults into a community-based PGx study. Therefore, we will characterize the frequency of actionable PGx genotypes and identify novel PGx response genes in our cohort of older community dwelling African Americans. The translational component of our work is to use the PGx findings to improve therapeutic outcomes for medication management in older adults. Such findings will serve as a foundation for translational PGx studies aimed at improving medication efficacy and safety for older adults. In this article, we describe the process for launching the TAPH collaborative group, which includes the transdisciplinary team, community-engaged participatory research model, study measures, and the evaluation of PGx genes.
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http://dx.doi.org/10.1111/cts.12885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993264PMC
March 2021

Genetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization.

Bone 2021 01 24;142:115656. Epub 2020 Sep 24.

Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address:

Ectonucleotide phosphatase/phosphodiesterase 1 (ENPP1) deficiency results in either lethal arterial calcifications ('Generalized Arterial Calcification of Infancy' - GACI), phosphate wasting rickets ('Autosomal Recessive Hypophosphatemic Rickets type 2' - ARHR2), early onset osteoporosis, or progressive spinal rigidity ('Ossification of the Posterior Longitudinal Ligament' - OPLL). As ENPP1 generates a strong endogenous mineralization inhibitor - extracellular pyrophosphate (PPi) - ENPP1 deficiency should not result in reduced bone volume, and therefore the mechanism ENPP1 associated osteoporosis is not apparent given current understanding of the enzyme's function. To investigate genetic pathways driving the skeletal phenotype of ENPP1 deficiency we compared gene expression in Enpp1 mice and WT sibling pairs by RNAseq and qPCR in whole bones, and in the liver and kidney by qPCR, directly correlating gene expression with measures of bone microarchitectural and biomechanical phenotypes. Unbiased analysis of the differentially expressed genes compared to relevant human disease phenotypes revealed that Enpp1 mice exhibit strong signatures of osteoporosis, ARHR2 and OPLL. We found that ENPP1 deficient mice exhibited reduced gene transcription of Wnt ligands in whole bone and increased transcription of soluble Wnt inhibitors in the liver and kidney, suggestive of multiorgan inhibition of Wnt activity. Consistent with Wnt suppression in bone, Collagen gene pathways in bone were significantly decreased and Fgf23 was significantly increased, all of which directly correlated with bone microarchitectural defects and fracture risk in Enpp1 mice. Moreover, the bone findings in 10-week old mice correlated with Enpp1 transcript counts but not plasma [PPi], suggesting that the skeletal phenotype at 10 weeks is driven by catalytically independent ENPP1 function. In contrast, the bone findings in 23-week Enpp1 mice strongly correlated with plasma PPi, suggesting that chronically low PPi drives the skeletal phenotype in older mice. Finally, correlation between Enpp1 and Fgf23 transcription suggested ENPP1 regulation of Fgf23, which we confirmed by dosing Enpp1 mice with soluble ENPP1-Fc and observing suppression of intact plasma FGF23 and ALP. In summary, our findings suggest that osteoporosis associated with ENPP1 deficiency involves the suppression of Wnt via catalytically independent Enpp1 pathways, and validates Enpp1 mice as tools to better understand OPLL and Paradoxical Mineralization Disorders.
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http://dx.doi.org/10.1016/j.bone.2020.115656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744330PMC
January 2021

Data Clothing and BigBarChart: Designing Physical Data Reports on Indoor Pollutants for Individuals and Communities.

IEEE Comput Graph Appl 2021 Jan-Feb;41(1):87-98. Epub 2021 Jan 15.

In response to participant preferences and new ethics guidelines, researchers are increasingly sharing data with health study participants, including data on their own household chemical exposures. Data physicalization may be a useful tool for these communications, because it is thought to be accessible to a general audience and emotionally engaged. However, there are limited studies of data physicalization in the wild with diverse communities. Our application of this method in the Green Housing Study is an early example of using data physicalization in environmental health report-back. We gathered feedback through community meetings, prototype testing, and semistructured interviews, leading to the development of data t-shirts and other garments and person-sized bar charts. We found that participants were enthusiastic about data physicalizations, it connected them to their previous experience, and they had varying desires to share their data. Our findings suggest that researchers can enhance environmental communications by further developing the human experience of physicalizations and engaging diverse communities.
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http://dx.doi.org/10.1109/MCG.2020.3025322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959249PMC
July 2021

Challenges in pharmacotherapy for older adults: a framework for pharmacogenomics implementation.

Pharmacogenomics 2020 06 19;21(9):627-635. Epub 2020 May 19.

Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.

Older adults are at high risk for inappropriate prescribing, developing polypharmacy, adverse drug events and poor treatment outcomes due to multimorbidity and geriatric syndromes. Pharmacogenomics could allow healthcare professionals to provide optimal patient care while minimizing the risk of adverse drug events and simplifying complex medication regimens. The implementation of pharmacogenomics in geriatrics medicine requires a broad multilayered bottom-up approach. These include curriculum redesign, rethinking experiential education and patient and provider education. There are barriers associated with adopting pharmacogenomics into clinical practice. These barriers may include economic factors, workflow and informatics support. However, addressing these barriers primarily requires creating a culture of innovative practices in patient care, ongoing interprofessional continuing education and an interdisciplinary approach for patient care.
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http://dx.doi.org/10.2217/pgs-2019-0198DOI Listing
June 2020

An Interprofessional Workshop to Enhance De-prescribing Practices Among Health Care Providers.

J Contin Educ Health Prof 2020 ;40(1):49-57

Mrs. Zimmerman: Associate Professor, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA. Dr. Linsky: Assistant Professor, VA Boston Healthcare System, Department of Medicine, Center for Healthcare Organization and Implementation Research, and Assistant Professor, Boston University School of Medicine, Boston, MA. Dr. Donohoe: Associate Professor, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA. Dr. Hobgood: Associate Professor, Department of Internal Medicine, Division of Geriatric Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA. Dr. Sargent: Assistant Professor, Department of Adult Health and Nursing Systems, Virginia Commonwealth University School of Nursing, Richmond, VA. Dr. Salgado: Assistant Professor, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA.

Introduction: De-prescribing is a complex behavior that benefits from a multifaceted approach to learning. We sought to create and deliver a 1-day interprofessional workshop to enhance de-prescribing knowledge and skills among health care professionals.

Methods: Workshop development was based on the Adult Learning Theory and the Theoretical Domains Framework. The workshop addressed provider-related barriers, was created and delivered by an interprofessional team, and combined didactic and active learning techniques. Targeted participants included physicians, advanced practice providers (nurse practitioners and physician's assistants), pharmacists, and clinic staff. Interprofessional workgroups were created a priori. Participants were asked to complete a postprogram evaluation, including whether they would implement changes to practice, teaching, research, or administrative duties after participation.

Results: We created an in-person, 5.5 credit hour, interprofessional de-prescribing workshop that comprised six sessions: (1) polypharmacy and de-prescribing overview; (2) identification of potentially inappropriate medications; (3) prioritization of medications for de-prescribing; (4) design and implementation of a de-prescribing plan; (5) principles for a patient-centered approach; and (6) suggestions for successful collaboration. Forty-one participants attended the workshop, and 38 (92.7%) completed the postprogram assessment. Participants felt they were likely to implement changes in practice, teaching, research, or administrative duties, rating themselves with a mean of 9.2 (SD = 1.06) on a 1 to 10 scale. Ultimately, 96.6% would recommend the workshop to others.

Discussion: Based on participant feedback, the workshop catalyzed intention to change practice, teaching, research, or administrative duties. Other institutions seeking to change the complex behavior of de-prescribing may wish to model this development and delivery strategy.
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http://dx.doi.org/10.1097/CEH.0000000000000280DOI Listing
April 2021

Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations.

J Bone Miner Res 2020 04 16;35(4):662-670. Epub 2020 Jan 16.

Department of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.

Inactivating mutations of the ENPP1 gene are associated with generalized arterial calcification of infancy (GACI) and less often autosomal-recessive hypophosphatemic rickets type 2 (ARHR2). We aimed to investigate the spectrum of phenotypes in a family with monoallelic and biallelic mutations of ENPP1 after identification through whole exome sequencing of a 54-year-old female with biallelic mutation of ENPP1, c.323G > T; p.Cys108Phe and c.1441C > T; p.Arg481Trp. Including the proband, 2 subjects had biallelic mutations, 5 had monoallelic mutations, and 2 had no mutation of ENPP1. The maternal mutation, a known pathogenic variant associated with GACI, was found in 3 subjects with monoallelic mutations, while the paternal mutation, which was not previously reported, was present in 2 subjects with monoallelic mutations. Both subjects with biallelic mutations had bowing of bilateral femurs, periarticular mineral deposition, normocalcemic primary hyperparathyroidism with multigland parathyroidectomy, increased carotid intima-media thickness, and enthesopathy was also noted in one subject. Intact FGF23 was elevated in both subjects with biallelic mutations, while C-terminal FGF23 was only elevated in one and PPi was reduced in one. Subjects with monoallelic mutations did not have periarticular calcifications or bone deformities. To conclude, patients with biallelic GACI causing mutations can survive well into adulthood, and despite the same biallelic ENPP1 pathogenic variants, clinical and biochemical manifestations can significantly differ, and include enthesopathy and primary hyperparathyroidism, which have not been previously described. Although carriers of monoallelic ENPP1 variants appear unaffected by classic disease manifestations, there may be subtle biochemical and clinical findings that warrant further investigation. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771569PMC
April 2020

Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency.

J Bone Miner Res 2020 03 5;35(3):528-539. Epub 2019 Dec 5.

Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.

Biallelic ENPP1 deficiency in humans induces generalized arterial calcification of infancy (GACI) and/or autosomal recessive hypophosphatemic rickets type 2 (ARHR2). The latter is characterized by markedly increased circulating FGF23 levels and renal phosphate wasting, but aberrant skeletal manifestations associated with heterozygous ENPP1 deficiency are unknown. Here, we report three adult men with early onset osteoporosis who presented with fractures in the thoracic spine and/or left radius, mildly elevated circulating FGF23, and hypophosphatemia. Total hip bone mineral density scans demonstrated osteoporosis (Z-score < -2.5) and HRpQCT demonstrated microarchitectural defects in trabecular and cortical bone. Next-generation sequencing revealed heterozygous loss-of-function mutations in ENPP1 previously observed as biallelic mutations in infants with GACI. In addition, we present bone mass and structure data as well as plasma pyrophosphate (PPi) data of two siblings suffering from ARHR2 in comparison to their heterozygous and wild-type family members indicative of an ENPP1 gene dose effect. The skeletal phenotype in murine Enpp1 deficiency yielded nearly identical findings. Ten-week-old male Enpp1 mice exhibited mild elevations in plasma FGF23 and hypophosphatemia, and micro-CT analysis revealed microarchitectural defects in trabecular and cortical bone of similar magnitude to HRpQCT defects observed in humans. Histomorphometry revealed mild osteomalacia and osteopenia at both 10 and 23 weeks. The biomechanical relevance of these findings was demonstrated by increased bone fragility and ductility in Enpp1 mice. In summary, ENPP1 exerts a gene dose effect such that humans with heterozygous ENPP1 deficiency exhibit intermediate levels of plasma analytes associated with bone mineralization disturbance resulting in early onset osteoporosis. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184798PMC
March 2020

Pharmacists and Medicare's Annual Wellness Visit: implications for pharmacy education and interprofessional primary care.

Pharm Pract (Granada) 2019 Jul-Sep;17(3):1672. Epub 2019 Sep 12.

Department of Family & Community Medicine, Eastern Virginia Medical School. Norfolk, VA (United States).

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http://dx.doi.org/10.18549/PharmPract.2019.3.1672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763310PMC
September 2019

Medicine, pharmacy and nursing trainees' perceptions of curriculum preparation to deprescribe and interprofessional roles in the deprescribing process.

Gerontol Geriatr Educ 2020 Jan-Mar;41(1):63-84. Epub 2019 Sep 5.

Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.

With increasing rates of polypharmacy among older adults, preparedness of current and future health care professionals to identify and deprescribe potentially inappropriate medications (PIMs) is critical. Medicine (n = 28), pharmacy (n = 35) and nursing (n = 11) trainees enrolled in an interprofessional course completed a survey assessing preparedness, confidence and attitudes toward deprescribing, and perception of interprofessional roles in the process. Pharmacy ( = .001) and nursing ( = .007) felt that their curriculum prepared them better to identify and deprescribe PIMs compared to medicine trainees. Pharmacy trainees perceived significantly more barriers to deprescribing compared to medicine ( = .003), but not nursing trainees. Physicians and pharmacists were perceived as the main drivers of the deprescribing process. Current curricular content should be modified to address lack of preparedness to deprescribe in clinical practice. Addressing such gaps as part of an interprofessional team may increase interprofessional role recognition and translate into changes in clinical practice as trainees move into the workforce.
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http://dx.doi.org/10.1080/02701960.2019.1661840DOI Listing
July 2020

Characterization of pharmacy practice research centers across the United States.

Res Social Adm Pharm 2020 02 22;16(2):230-237. Epub 2019 May 22.

Center for Pharmacy Practice Innovation, Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12th Street, Box 980533, Richmond, VA, 23298, United States. Electronic address:

Background: Schools of Pharmacy are important contributors to pharmacy practice research and several have created research centers focusing on this area.

Objectives: To identify and characterize pharmacy practice research centers in the United States.

Methods: A comprehensive list of research centers was gathered using three sources: 1) websites of Schools of Pharmacy obtained from the American Association of Colleges of Pharmacy website; 2) Google; and 3) department chairs. Two independent reviewers applied the following exclusion criteria to the list: 1) no affiliation with a School of Pharmacy; 2) no focus on research; 3) not an independent unit recognized at the school or university levels; and 4) research not focused on advancing pharmacy practice. Inter-rater reliability was calculated using a prevalence-adjusted bias-adjusted kappa (PABAK). A questionnaire was developed comprising 24 questions grouped into three sections - overall structure of the center, research and educational activities - and disseminated through center directors. Descriptive statistics of survey data were obtained.

Results: Twenty centers across 20 different states were identified. Survey response rate was 100%. Three-quarters of centers were at public institutions and half had an advisory board. Full-time equivalents ranged from 0.2 to 21. Areas of research primarily focused on medication and disease-state management and interprofessional collaboration in the ambulatory/outpatient setting. Few centers (35%) conducted experimental studies. Despite 85% centers conducting multi-site studies, the median number of sites engaged was low (range 1-3). Seven centers received over USD 1 million in total funding since inception. A majority of centers (90%) offered educational activities for both students and professionals.

Conclusions: Pharmacy practice research centers are relatively small, received low funding and few conduct multi-site experimental studies. Collaboration among centers could be a means to overcome these issues.
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http://dx.doi.org/10.1016/j.sapharm.2019.05.009DOI Listing
February 2020

Identifying Components of Success Within Health Sciences-Focused Mentoring Programs Through a Review of the Literature.

Am J Pharm Educ 2019 02;83(1):6976

School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia.

To identify programmatic components and structural features associated with success of mentoring programs within the health sciences. Thirty-eight manuscripts representing 34 individual programs were reviewed. Of the institutions represented, 68% were public. Sixty-eight percent of programs included single disciplines only, with four focused in pharmacy, 13 in medicine, and six in nursing. Of the 34 individual programs, all programs reporting participant confidence and self-efficacy reported success in that domain. Eighteen programs reported outcomes related to scholarly activity that included publications or funding/grantsmanship; 16 reported success. Eleven of 16 programs reporting promotion/tenure and/or faculty retention rates reported success. Program components associated with successful programs included frequent meetings (at least monthly) and delivering content within formal curricula. Content categories common within programs reporting success were content related to research, funding/grantsmanship and networking/collaboration. In addition, specific for the promotion/retention domain, content related to curriculum/teaching was commonly found within successful programs. Although somewhat dependent on the program's specific goals, curriculum most commonly associated with success contained content on research, grantsmanship/funding, curriculum/teaching, and networking/collaboration. Among many programs, the reporting lacked objective, standardized metrics and often included only generalized descriptions/categorization of course content. The incomplete and inconsistent reporting limited our ability to draw conclusions regarding individual topics important for each program component. Proper planning, execution, and assessment of faculty mentoring programs is critical to the identification of additional program characteristics for optimal faculty success.
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http://dx.doi.org/10.5688/ajpe6976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418850PMC
February 2019

2018 American Society of Consultant Pharmacists Annual Meeting & Exhibition.

Consult Pharm 2017 Oct;33(10):572-608

Poster abstracts are evaluated based on the following criteria: significance of the problem to healthy aging or medication management; innovativeness of ideas, methods, and/or approach; methodological rigor of methods and approach; presentation of finding; implications identified for future research, practice, and/or policy; and clarity of writing. Submissions are not evaluated through the peer-reviewed process used by . Industry support is indicated, where applicable. Presenting author is in italics. The poster abstract presentation is supported by the ASCP Foundation.
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October 2017

A Prescription for Prescribing: Ensuring Continued Pharmacist Preparedness.

Ann Pharmacother 2018 07 7;52(7):697-699. Epub 2018 Mar 7.

1 Center for Pharmacy Practice Innovation, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.

The scope of practice for pharmacists in the United States increasingly includes elements of prescribing under collaborative practice agreements and statewide protocols. However, as a result of continued health care access concerns, we believe that pharmacists will be called on to serve as independent prescribers in the future. For this anticipated practice expansion to become a successful reality, the assurance of pharmacist preparedness and continuous professional development through profession-wide standards will be imperative.
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http://dx.doi.org/10.1177/1060028018763519DOI Listing
July 2018

Brain Over Bladder: A Systematic Review of Dual Cholinesterase Inhibitor and Urinary Anticholinergic Use.

Drugs Aging 2018 01;35(1):27-41

Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, 410 N. 12th Street, PO Box 980533, Richmond, VA, 23298-0533, USA.

Background: Case reports have demonstrated that dual use of cholinesterase inhibitors (ChIs) and urinary anticholinergics (UAChs) in older adults may be associated with delusions, aggression, changes in cognition, and anxiety, which typically resolve on drug discontinuation. Despite opposing mechanisms of action, these drugs continue to be co-prescribed.

Objective: This systematic review evaluates cognitive and functional outcomes of dual use of ChIs and UAChs and describes its prevalence.

Patients And Methods: A literature search using terms related to ChIs and UAChs was conducted. Observational or interventional studies evaluating cognitive or functional outcomes in subjects receiving dual therapy were included for the primary aim. Articles describing prevalence of dual use were included for the secondary aim.

Results: Of 1340 unique results, five studies met the inclusion criteria for the primary aim. Four of the studies assessed cognitive outcomes-three failed to identify a significant difference in cognitive function with dual use and the fourth study observed a statistically significant improvement in cognition with dual use of high-dose donepezil and solifenacin when compared with baseline. Three studies assessed functional outcomes-one revealed a 50% greater quarterly decline in activities of daily living (p = 0.01) among dual users functioning in the top quartile, another revealed significant functional improvement in dual users, and the final study did not demonstrate a significant difference. Seventeen articles were included for the secondary aim. Prevalence of dual use ranged from 1.2 to 40.5%.

Conclusion: This systematic review revealed a high prevalence of dual use of ChIs and UAChs; however, there are mixed results for cognitive and functional outcomes. Results were limited by methodological flaws. Observational or interventional studies assessing dual users are lacking and further study of cognitive and functional risks of dual ChI and UACh use is needed.
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http://dx.doi.org/10.1007/s40266-017-0510-6DOI Listing
January 2018

Antipsychotic prescription to identify delirium: results from two cohorts.

Clin Pharmacol 2017 3;9:113-117. Epub 2017 Oct 3.

Research and Development Service, Center of Innovation in Long-Term Services and Supports, Providence VA Medical Center.

Objectives: Detection of delirium in hospitalized patients remains challenging. The objective was to determine if the prescription of antipsychotic medications was associated with delirium.

Patients And Methods: Two patient cohorts were utilized from a tertiary Veterans Affairs hospital: a palliative care retrospective cohort and a prospective medical cohort. Patients prescribed outpatient antipsychotics were excluded. Retrospectively, delirium was identified using a validated medical record-review instrument. Prospectively, a clinical expert assessed patients for delirium daily using a standardized interview. Acute antipsychotic medication administration was recorded from the electronic medical record.

Results: In the retrospective cohort (n=217), delirium was found in 31% (n=67) and antipsychotic use in 18% (n=40) of patients. Acute antipsychotic use indicated delirium with 54% sensitivity and 97% specificity. In the prospective cohort (n=100), delirium developed in 23% (n=23) and antipsychotics were used in 5% (n=5) of patients. The sensitivity and specificity of acute antipsychotic use was 22% and 100%, respectively.

Conclusion: Hospitalized patients who are acutely prescribed antipsychotics are likely to have delirium, but not all patients with delirium will be identified with this method. In health systems, utilization of the prescription of acute antipsychotics can be an efficient and specific method to identify delirious patients for targeted intervention.
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http://dx.doi.org/10.2147/CPAA.S138441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633281PMC
October 2017

Medication Reconciliation vs Medication Review.

JAMA 2017 09;318(10):965-966

Center for Pharmacy Practice Innovation, Virginia Commonwealth University School of Pharmacy, Richmond.

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http://dx.doi.org/10.1001/jama.2017.10552DOI Listing
September 2017

Evaluation of the Use of a Virtual Patient on Student Competence and Confidence in Performing Simulated Clinic Visits.

Am J Pharm Educ 2017 Jun;81(5):87

Massachusetts College of Pharmacy and Health Sciences (MCPHS University), Boston, Massachusetts.

To assess the effect of incorporating virtual patient activities in a pharmacy skills lab on student competence and confidence when conducting real-time comprehensive clinic visits with mock patients. Students were randomly assigned to a control or intervention group. The control group completed the clinic visit prior to completing virtual patient activities. The intervention group completed the virtual patient activities prior to the clinic visit. Student proficiency was evaluated in the mock lab. All students completed additional exercises with the virtual patient and were subsequently assessed. Student impressions were assessed via a pre- and post-experience survey. Student performance conducting clinic visits was higher in the intervention group compared to the control group. Overall student performance continued to improve in the subsequent module. There was no change in student confidence from pre- to post-experience. Student rating of the ease of use and realistic simulation of the virtual patient increased; however, student rating of the helpfulness of the virtual patient decreased. Despite student rating of the helpfulness of the virtual patient program, student performance improved. Virtual patient activities enhanced student performance during mock clinic visits. Students felt the virtual patient realistically simulated a real patient. Virtual patients may provide additional learning opportunities for students.
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http://dx.doi.org/10.5688/ajpe81587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508086PMC
June 2017

Palliative Care Interventions for Patients with Heart Failure: A Systematic Review and Meta-Analysis.

J Palliat Med 2017 01 2;20(1):84-92. Epub 2016 Dec 2.

7 Division of Geriatrics and Palliative Care, VA Boston Healthcare System , Boston, Massachusetts.

Objective: To systematically characterize interventions and effectiveness of palliative care for advanced heart failure (HF) patients.

Background: Patients with advanced heart failure experience a high burden of distressing symptoms and diminished quality of life. Palliative care expertise with symptom management and healthcare decision-making benefits HF patients.

Methods: A systematic PubMed search was conducted from inception to June 2016 for studies of palliative care interventions for HF patients. Studies of humans with a HF diagnosis who underwent a palliative care intervention were included. Data were extracted on study design, participant characteristics, intervention components, and in three groups of outcomes: patient-centered outcomes, quality-of-death outcomes, and resource utilization. Study characteristics were examined to determine if meta-analysis was possible.

Results: The fifteen identified studies varied in design (prospective, n = 10; retrospective, n = 5). Studies enrolled older patients, but greater variability was found for race, sex, and marital status. A majority of studies measuring patient-centered outcomes demonstrated improvements including quality of life and satisfaction. Quality-of-death outcomes were mixed with a majority of studies reporting clarification of care preferences, but less improvement in death at home and hospice enrollment. A meta-analysis in three studies found that home-based palliative care consults in HF patients lower the risk of rehospitalization by 42% (RR = 0.58; 95% Confidence Interval 0.44, 0.77).

Discussion: Available evidence suggests that home and team-based palliative interventions for HF patients improve patient-centered outcomes, documentation of preferences, and utilization. Increased high quality studies will aid the determination of the most effective palliative care approaches for the HF population.
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http://dx.doi.org/10.1089/jpm.2016.0330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5177994PMC
January 2017

Medication Complexity, Medication Number, and Their Relationships to Medication Discrepancies.

Ann Pharmacother 2016 07 4;50(7):534-40. Epub 2016 May 4.

VA Boston Healthcare System, Boston, MA, USA Boston University School of Medicine, Boston, MA, USA.

Background: Medication reconciliation to identify discrepancies is a National Patient Safety Goal. Increasing medication number and complex medication regimens are associated with discrepancies, nonadherence, and adverse events. The Medication Regimen Complexity Index (MRCI) integrates information about dosage form, dosing frequency, and additional directions.

Objective: This study evaluates the association of MRCI scores and medication number with medication discrepancies and commissions, a discrepancy subtype.

Methods: This was a retrospective cohort study of a convenience sample of 104 ambulatory care patients seen from April 2010 to July 2011 within the Department of Veterans Affairs. Primary outcomes included any medication discrepancy and commissions. Primary exposures included MRCI scores and medication number. Multivariable logistic regression models associated MRCI scores and medication number with discrepancies. Receiver operating characteristic (ROC) curves provided discrepancy thresholds.

Results: For the 104 patients analyzed, the median MRCI score was 25 (interquartile range [IQR] = 14-43), and the median medication number was 8 (IQR = 5-13); 60% of patients had any discrepancy, whereas 36% had a commission. In adjusted analyses, patients with MRCI scores ≥25 or medication number ≥8 were more likely to have commissions (odds ratio [OR] = 3.64, 95% CI = 1.41-9.41; OR = 4.51, 95% CI = 1.73-11.73, respectively). The unadjusted ROC threshold for commissions was 36 for MRCI (sensitivity, 59%; specificity, 82%) and 9 for medication number (sensitivity 68%; specificity 67%).

Conclusion: Patients with either MRCI scores ≥25 or ≥8 medications were more likely to have commissions. Given equal performance in predicting discrepancies, the efficiency and simplicity of medication number supports its use in identifying patients for intensive medication review beyond medication reconciliation.
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http://dx.doi.org/10.1177/1060028016647067DOI Listing
July 2016

Improving medication management competency of clinical trainees in geriatrics.

J Am Geriatr Soc 2014 Aug 15;62(8):1568-74. Epub 2014 Jul 15.

Brigham and Women's Hospital, Boston, Massachusetts; Veterans Affairs Boston Healthcare System, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.

The authors hypothesized that an interprofessional workshop would improve geriatrics trainees' medication management. The workshop was based on a needs assessment and comprised an interactive session with pharmacists on managing medications in elderly adults. Participants were trainees in their geriatrics rotation at a tertiary care medical center. Trainees completed a medication appropriateness survey for three patients, one of which was their own. After the workshop, trainees reviewed medications of the three patients. Trainees completed online surveys after their rotation and 3 months later. Of 95 trainees rotating through geriatrics, 76 (80%) attended the workshop and completed the worksheet. Trainees' scores on reviewing medication lists improved significantly, from 6.7±2.3 to 7.7±2.0 out of 11 for standardized patient 1 (P<.001) and from 5.7±1.8 to 6.4±1.5 out of 11 for standardized patient 2 (P=.009). Trainees' scores on their own patients' lists also improved significantly, from 5.6±1.5 to 6.6±1.5 out of 10 (P<.001). After the workshop, 95% (71/75) planned to change the medication regimen of the patient they presented, and 93% (68/73) planned to change other patients' medications based on information learned during the workshop. Three months later, 35% (12/34) had made changes to the regimen of the patient they discussed during the workshop, and 71% (15/21) had made changes to other patients' regimens. Seventy-eight percent (18/23) rated the workshop as the top nonclinical experience of their geriatrics rotation. In conclusion, this interprofessional medication management workshop improved trainees' ability to perform medication reviews accurately and led to change in self-reported prescribing behavior.
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http://dx.doi.org/10.1111/jgs.12933DOI Listing
August 2014

Risk versus risk: a review of benzodiazepine reduction in older adults.

Expert Opin Drug Saf 2014 Jul 6;13(7):919-34. Epub 2014 Jun 6.

VA Boston Healthcare System (VABHS) , Boston, MA , USA +1 617 794 6401 ;

Introduction: Benzodiazepines (BZD) are potentially inappropriate for older adults, yet their use persists. Patients and providers may hesitate to discontinue BZDs due to concerns for withdrawal or relapse. We reviewed the literature for BZD reduction protocols to examine common elements, safety and efficacy. A framework is proposed for clinicians to address BZD reduction challenges.

Areas Covered: Following a systematic literature review, this analysis included 28 studies of older out-patients tapering chronic BZDs. Populations included insomnia, depression and anxiety. Protocols included taper alone (32%), taper plus cognitive behavioral therapy (32%) and taper plus medication substitution (36%). Success rates were favorable for all modalities (mean 60%, median 67%, range 25 - 85%) and independent of dose or duration of use. Common schedules included a 25% dose reduction over 1 - 2 weeks until drug-free. Withdrawal symptoms included mainly mild psychological and somatic concerns. No serious safety events were reported.

Expert Opinion: BZD reduction protocols among older adults are feasible and successful. Given unique cognitive and functional abilities and comorbidities of older adults, a patient-centered approach to reduction is needed. Our framework guides clinicians in planning and persisting with BZD reduction, while our checklist addresses tailored tapers. Monitoring and support is emphasized, and taper modifications are proposed for struggling patients.
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http://dx.doi.org/10.1517/14740338.2014.925444DOI Listing
July 2014

Increasing anticholinergic burden and delirium in palliative care inpatients.

Palliat Med 2014 Apr 17;28(4):335-41. Epub 2014 Feb 17.

1Department of Pharmacy Practice, Massachusetts College of Pharmacy & Health Sciences University, Boston, MA, USA.

Background: Delirium may complicate the hospital course and adversely impact remaining quality of life for palliative care inpatients. Medications with anticholinergic properties have been linked to delirium within elderly populations via serum anticholinergic assays.

Aim: The aim of this study is to determine whether increasing anticholinergic burden, as measured using a clinical assessment tool, is associated with an increase in delirium among palliative care inpatients.

Design: This study was completed as a retrospective, case-control study.

Setting/participants: Veterans admitted to the Veterans Affairs Boston Healthcare System and consulted to the palliative care service were considered for inclusion. Increase in anticholinergic burden from admission through hospital day 14 was assessed using the Anticholinergic Risk Scale. Presence of delirium was determined by use of a validated chart review instrument.

Results: A total of 217 patients were analyzed, with a mean age of 72.9 (±12.8) years. The overall delirium rate was 31% (n = 67). Patients with an increase in Anticholinergic Risk Scale (n = 72 (33%)) were 40% more likely to experience delirium (odds ratio = 1.44, 95% confidence interval = 1.07-1.94) compared to those without increase (n = 145 (67%)). After adjustment for age, brain metastasis, intensive care unit admission, illness severity, opiate use, and admission Anticholinergic Risk Scale using multivariable modeling, delirium risk remained significantly higher in patients with an Anticholinergic Risk Scale increase compared to those without increase (adjusted odds ratio = 1.43, 95% confidence interval = 1.04-1.94).

Conclusion: An increase in Anticholinergic Risk Scale from admission was associated with delirium in palliative care inpatients. While additional study is needed, anticholinergic burden should be increased cautiously in palliative inpatients, and those with increases should be closely followed for delirium.
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http://dx.doi.org/10.1177/0269216314522105DOI Listing
April 2014

Improving delirium care: prevention, monitoring, and assessment.

Neurohospitalist 2013 Oct;3(4):194-202

VA Boston Healthcare System, Geriatric Research, Education, and Clinical Center and Division of Geriatrics and Palliative Care, Boston, MA, USA ; Brigham and Women's Hospital, Division of Aging, Boston, MA, USA ; Harvard Medical School, Boston, MA, USA.

Delirium is an acute change in awareness and attention and is common, morbid, and costly for patients and health care systems. While hyperactive delirium is easily identifiable, the hypoactive form is more common and carries a higher mortality. Hospital systems to address delirium should consist of 3 critical steps. First, hospitals must identify patients who develop or are at intermediate or high risk for delirium. Delirium risk may be assessed using known patient-based and illness-based risk factors, including preexisting cognitive impairment. Delirium diagnosis remains a clinical diagnosis that requires a clinical assessment that can be structured using diagnostic criteria. Hospital systems may be useful to efficiently allocate delirium resources to prevent and manage delirium. Second, it is crucial to develop a systematic approach to prevent delirium using multimodal nonpharmacologic delirium prevention methods and to monitor all high-risk patients for its occurrence. Tools such as the modified Richmond Agitation and Sedation Scale can aid in monitoring for changes in mental status that could indicate the development of delirium. Third, hospital systems can utilize established methods to assess and manage delirium in a standardized fashion. The key lies in addressing the underlying cause/causes of delirium, which often involve medical conditions or medications. With a sustained commitment, standardized efforts to identify and prevent delirium can mitigate the long-term morbidity associated with this acute change. In the face of changes in health care funding, delirium serves as an example of a syndrome where care coordination can improve short-term and long-term costs.
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http://dx.doi.org/10.1177/1941874413493185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810833PMC
October 2013

Complexity perplexity: a systematic review to describe the measurement of medication regimen complexity.

Expert Opin Drug Saf 2013 Nov 28;12(6):829-40. Epub 2013 Aug 28.

VA Boston Healthcare System , 150 South Huntington Avenue, Boston, MA 02130 , USA

Introduction: Complex medication regimens are error prone and challenging for patients, which may impact medication adherence and safety. No universal method to assess the complexity of medication regimens (CMRx) exists. The authors aim to review literature for CMRx measurements to establish consistencies and, secondarily, describe CMRx impact on healthcare outcomes.

Areas Covered: A search of EMBASE and PubMed for studies analyzing at least two medications and complexity components, among those self-managing medications, was conducted. Out of 1204 abstracts, 38 studies were included in the final sample. The majority (74%) of studies used one of five validated CMRx scales; their components and scoring were compared.

Expert Opinion: Universal CMRx assessment is needed to identify and reduce complex regimens, and, thus, improve safety. The authors highlight commonalities among five scales to help build consensus. Common components (i.e., regimen factors) included dosing frequency, units per dose, and non-oral routes. Elements (e.g., twice daily) of these components (e.g., dosing frequency) and scoring varied. Patient-specific factors (e.g., dexterity, cognition) were not addressed, which is a shortcoming of current scales and a challenge for future scales. As CMRx has important outcomes, notably adherence and healthcare utilization, a standardized tool has potential for far-reaching clinical, research, and patient-safety impact.
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http://dx.doi.org/10.1517/14740338.2013.823944DOI Listing
November 2013
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