Comparison of 2 Population Health Management Approaches to Increase Vitamin B12 Monitoring in Patients Taking Metformin.

BACKGROUND: Population health management uses proactive, targeted interventions to improve health outcomes. OBJECTIVES: To compare the effectiveness of and time required for 2 pharmacist-driven population health management interventions to improve vitamin B12 monitoring in patients taking metformin. METHODS: Physicians were randomized to 1 of 2 population health management interventions. For all patients of physicians assigned to the patient portal intervention, a pharmacist communicated need for vitamin B12 monitoring directly to the patient using an electronic patient portal. For all patients of physicians assigned to the office visit intervention, a pharmacist communicated monitoring recommendations to the physician prior to a scheduled office visit through the electronic health record. The proportion of patients in each group who received vitamin B12 monitoring 30 days after the intervention was quantified. RESULTS: A total of 489 patients of 26 physicians within 5 general internal medicine clinics who had taken metformin for at least 1 year and had not received vitamin B12 monitoring within the past year were identified. The intervention delivered as part of an office visit resulted in increased serum vitamin B12 monitoring compared with the intervention using electronic communication through a patient portal (odds ratio = 4.05; 95% CI = 1.22, 13.46; P = 0.03). The office visit intervention and the patient portal intervention took an average of 8.2 and 0.9 minutes per patient, respectively. CONCLUSIONS: Population health management completed during the course of office visits was more effective at increasing vitamin B12 monitoring and required more time than an intervention delivered through an electronic patient portal.

Diagnostic tools for bivariate accelerated life regression models.

We propose graphical diagnostic tools to assess the fit of a bivariate accelerated lifetime regression model. Using univariate residuals for each response measurement in a pair, we assess their dependence structure via the bivariate probability integral transformation of univariate residuals, which we call V-residuals. To reduce the computational burden associated with plots of V-residuals, as well as some uncertainty associated with parameter estimation, we next develop K-residuals. We also devise adjusted V- and K-residuals to account for right censoring of any response. Via simulation studies, we examine the statistical behaviour of Q-Q plots of the estimated K-residuals, and demonstrate the potential of these plots to identify an appropriate choice of frailty distribution in bivariate modeling. We apply our proposed diagnostic tools to the Diabetic Retinopathy Study and assess the goodness of fit of various models fitted to these study data using different choices of frailty distributions combined with several baseline survivor functions.

Developing supervisory and precepting skills through simulation: Near peer teaching in a skills laboratory.

BACKGROUND AND PURPOSE: Near-peer teaching is an innovative approach to teaching the skills of supervising and precepting while benefiting students with different levels of experience and academic training. This study describes near-peer activities in skills-based laboratory courses that provided opportunities for one-on-one teaching to benefit learners in the introductory lab courses while simultaneously training more advanced students for future supervisory and precepting roles. EDUCATIONAL ACTIVITY & SETTING: Three community pharmacy near-peer teaching simulations were designed and implemented: 1) Patient Counseling and Medication Adherence, 2) Dispensing and Patient Counseling, and 3) Drug Utilization Review and Prescriber Calls. These activities took place over two semesters of a pharmacy skills lab with all first- and third-year Doctor of Pharmacy students. FINDINGS: In Autumn 2019, 80% (111/139) of P1s and 67% (80/119) of P3s responded to the course evaluation survey. In Spring 2020, 73% (100/137) of P1s and 68% (80/118) of P3s responded to the course evaluation survey. The P3s reported increased confidence in their ability to provide meaningful feedback, while P1s reported increased confidence in communicating with patients and healthcare providers. Performance data revealed that most P1s and P3s completed dispensing and communication activities accurately using a near-peer approach. Overall, the P1s and P3s felt the activities were valuable learning experiences. SUMMARY: The near-peer activities described in this study fill a gap in the training of pharmacy graduates for future precepting and supervisory roles. Evaluation of these near-peer activities suggest that both junior and senior learners benefit from simulated preceptor-intern interactions, supporting this innovative approach to address supervisory and precepting responsibilities.

Improving Knowledge of Top 200 Medications Through Retrieval Practice, Content Alignment, and Autonomous Learning.

Objective. To determine the impact of the holistic redesign of top 200 medications learning activities within a Doctor of Pharmacy (PharmD) curriculum by comparing student performances on a comprehensive examination before and after the redesign.Methods. During a curricular revision at The Ohio State University College of Pharmacy that began with the class of 2020, learning activities involving the top 200 medications were implemented that involved repeated retrieval and mastery concepts, alignment with therapeutic coursework, and autonomous learning regarding the top 200 medications. A high-stakes comprehensive top 200 medications examination was administered to students at the end of their third professional year both before and after implementation of these activities. The difference in the percentage of students who achieved a satisfactory score on the comprehensive examination was compared between cohorts prior to and following the curricular redesign.Results. The study analyzed results from 134, 130, and 120 students from three PharmD classes (one before and two after the redesign of top 200 medications activities). Following the redesign, a higher percentage of students achieved a satisfactory score of 85% on the examination (class of 2020: 116/130, 89.2%; class of 2022: 107/120, 89.2%) compared to before the redesign (class of 2019: 88/134, 65.7%).Conclusion. The combination of repeated retrieval and mastery, alignment with therapeutic coursework, and development of autonomous learning can significantly increase student knowledge and retention of top 200 medications.

Empirical likelihood for cumulative hazard ratio estimation with covariate adjustment.

In medical studies, it is often of scientific interest to evaluate the treatment effect via the ratio of cumulative hazards, especially when those hazards may be nonproportional. To deal with nonproportionality in the Cox regression model, investigators usually assume that the treatment effect has some functional form. However, to do so may create a model misspecification problem because it is generally difficult to justify the specific parametric form chosen for the treatment effect. In this article, we employ empirical likelihood (EL) to develop a nonparametric estimator of the cumulative hazard ratio with covariate adjustment under two nonproportional hazard models, one that is stratified, as well as a less restrictive framework involving group-specific treatment adjustment. The asymptotic properties of the EL ratio statistic are derived in each situation and the finite-sample properties of EL-based estimators are assessed via simulation studies. Simultaneous confidence bands for all values of the adjusted cumulative hazard ratio in a fixed interval of interest are also developed. The proposed methods are illustrated using two different datasets concerning the survival experience of patients with non-Hodgkin's lymphoma or ovarian cancer.

Determination of Interrater Reliability of a Universal Evaluator Rubric to Assess Student Pharmacist Communication Skills.

Objective. To evaluate the interrater reliability of a universal evaluator rubric used to assess student pharmacist communication skills during patient education sessions.Methods. Six US schools and colleges of pharmacy each submitted 10 student videos of a simulated community pharmacy patient education session and recruited two raters in each of the five rater groups (faculty, standardized patients, postgraduate year one residents, student pharmacists, and pharmacy preceptors). Raters used a rubric containing 20 items and a global assessment to evaluate student communication of 12 videos. Agreement was computed for individual items and overall rubric score within each rater group, and for each item across all rater groups. Average overall rubric agreement scores were compared between rater groups. Agreement coefficient scores were categorized as no to minimal, weak, moderate, strong, or almost perfect agreement.Results. Fifty-five raters representing five rater groups and six pharmacy schools evaluated student communication. Item agreement analysis for all raters revealed five items with no to minimal or weak agreement, 10 items with moderate agreement, one item with strong agreement, and five items with almost perfect agreement. Overall average agreement across all rater groups was 0.73 (95% CI, 0.66-0.81). The preceptor rater group exhibited the lowest agreement score of 0.68 (95% CI, 0.58-0.78), which significantly deviated from the overall average.Conclusion. While strong or almost perfect agreement scores were not observed for all rubric items, overall average interrater reliability results support the use of this rubric in a variety of raters to assess student pharmacist communication skills during patient education sessions.

Educating Pharmacy Students About Underserved Populations Using Patient Speakers and Simulation Activities.

Objective. To assess the impact of the Patient Voices series on Doctor of Pharmacy (PharmD) students.Methods. A series of patient speakers and integrated simulation activities focused on underserved populations, otherwise known as the Patient Voices series, was embedded into a pharmacy skills laboratory curriculum. First-year PharmD students' self-ratings of confidence were compared on pre- and post-course surveys. Using evaluations from first-year introductory pharmacy practice experiences (IPPEs), student self-evaluation data were compared to preceptor evaluations of student performance. Open-ended responses to course evaluations from first- and second-year PharmD students and student reflections from third-year PharmD students were assessed using conventional content analysis to identify and characterize student perceptions.Results. Significant increases were observed in first-year students' confidence to show empathy (mean, 4.2 to 4.7) and to interact with patients from underserved communities (mean, 2.2 to 4.2). Preceptor ratings of students' empathy were consistent with the students' self-rated abilities, while students' self-ratings on cultural sensitivity were higher than the preceptors' ratings. Qualitative analysis of course evaluation surveys and reflections revealed common themes identified by students, such as understanding different perspectives, increased empathy for patients, and the value of including this content in the curriculum.Conclusion. Student confidence to interact with patients from a variety of underserved populations increased following introduction of the Patient Voices series into the PharmD curriculum. Students perceived the series to be a valuable learning experience.

Improving the Remediation Process for Skills-based Laboratory Courses in the Doctor of Pharmacy Curriculum.

When students fail to meet minimum competence standards on summative pharmacy skills-based assessments, remediation can be used to ensure student readiness for progression. Skills-based remediation is challenging as a high volume of resources is required to develop an action plan that addresses the heterogeneity in student needs and to create and execute another assessment equivalent to the initial assessment. Although many Doctor of Pharmacy (PharmD) programs face these same challenges, there is no consensus on how to best address them. Recently, faculty from six PharmD programs convened to share ideas and approaches to overcoming these challenges. This commentary aims to define remediation as it pertains to summative skills-based assessments, share our consensus views regarding remediation best practices, and highlight areas where there is more work to be done. Our intent is to advance the ongoing conversation and empower institutions to develop their own effective and impactful skills-based remediation policies, procedures, and activities.

Nucleotide diversity maps reveal variation in diversity among wheat genomes and chromosomes.

BACKGROUND: A genome-wide assessment of nucleotide diversity in a polyploid species must minimize the inclusion of homoeologous sequences into diversity estimates and reliably allocate individual haplotypes into their respective genomes. The same requirements complicate the development and deployment of single nucleotide polymorphism (SNP) markers in polyploid species. We report here a strategy that satisfies these requirements and deploy it in the sequencing of genes in cultivated hexaploid wheat (Triticum aestivum, genomes AABBDD) and wild tetraploid wheat (Triticum turgidum ssp. dicoccoides, genomes AABB) from the putative site of wheat domestication in Turkey. Data are used to assess the distribution of diversity among and within wheat genomes and to develop a panel of SNP markers for polyploid wheat. RESULTS: Nucleotide diversity was estimated in 2114 wheat genes and was similar between the A and B genomes and reduced in the D genome. Within a genome, diversity was diminished on some chromosomes. Low diversity was always accompanied by an excess of rare alleles. A total of 5,471 SNPs was discovered in 1791 wheat genes. Totals of 1,271, 1,218, and 2,203 SNPs were discovered in 488, 463, and 641 genes of wheat putative diploid ancestors, T. urartu, Aegilops speltoides, and Ae. tauschii, respectively. A public database containing genome-specific primers, SNPs, and other information was constructed. A total of 987 genes with nucleotide diversity estimated in one or more of the wheat genomes was placed on an Ae. tauschii genetic map, and the map was superimposed on wheat deletion-bin maps. The agreement between the maps was assessed. CONCLUSIONS: In a young polyploid, exemplified by T. aestivum, ancestral species are the primary source of genetic diversity. Low effective recombination due to self-pollination and a genetic mechanism precluding homoeologous chromosome pairing during polyploid meiosis can lead to the loss of diversity from large chromosomal regions. The net effect of these factors in T. aestivum is large variation in diversity among genomes and chromosomes, which impacts the development of SNP markers and their practical utility. Accumulation of new mutations in older polyploid species, such as wild emmer, results in increased diversity and its more uniform distribution across the genome.

Development and implementation of high-throughput SNP genotyping in barley.

BACKGROUND: High density genetic maps of plants have, nearly without exception, made use of marker datasets containing missing or questionable genotype calls derived from a variety of genic and non-genic or anonymous markers, and been presented as a single linear order of genetic loci for each linkage group. The consequences of missing or erroneous data include falsely separated markers, expansion of cM distances and incorrect marker order. These imperfections are amplified in consensus maps and problematic when fine resolution is critical including comparative genome analyses and map-based cloning. Here we provide a new paradigm, a high-density consensus genetic map of barley based only on complete and error-free datasets and genic markers, represented accurately by graphs and approximately by a best-fit linear order, and supported by a readily available SNP genotyping resource. RESULTS: Approximately 22,000 SNPs were identified from barley ESTs and sequenced amplicons; 4,596 of them were tested for performance in three pilot phase Illumina GoldenGate assays. Data from three barley doubled haploid mapping populations supported the production of an initial consensus map. Over 200 germplasm selections, principally European and US breeding material, were used to estimate minor allele frequency (MAF) for each SNP. We selected 3,072 of these tested SNPs based on technical performance, map location, MAF and biological interest to fill two 1536-SNP "production" assays (BOPA1 and BOPA2), which were made available to the barley genetics community. Data were added using BOPA1 from a fourth mapping population to yield a consensus map containing 2,943 SNP loci in 975 marker bins covering a genetic distance of 1099 cM. CONCLUSION: The unprecedented density of genic markers and marker bins enabled a high resolution comparison of the genomes of barley and rice. Low recombination in pericentric regions is evident from bins containing many more than the average number of markers, meaning that a large number of genes are recombinationally locked into the genetic centromeric regions of several barley chromosomes. Examination of US breeding germplasm illustrated the usefulness of BOPA1 and BOPA2 in that they provide excellent marker density and sensitivity for detection of minor alleles in this genetically narrow material.

Plant and crop databases.

Databases have become an integral part of all aspects of biological research, including basic and applied plant biology. The importance of databases continues to increase as the volume of data from direct and indirect genomics approaches expands. What is not always obvious to users of databases is the range of available database resources, their access points, or some basic elements of database querying. This chapter briefly summarizes the history of data access via the Internet and reviews some basic terms and considerations in dealing with plant and crop databases. The reader is directed to some of the major publicly available Internet-accessible relevant databases with summaries of the major focuses of those databases, and several examples are given to illustrate how to access plant genomics data. Finally, an outline is given of some of the issues facing the future of plant and crop databases.

GrainGenes, the genome database for small-grain crops.

GrainGenes, http://www.graingenes.org, is the international database for the wheat, barley, rye and oat genomes. For these species it is the primary repository for information about genetic maps, mapping probes and primers, genes, alleles and QTLs. Documentation includes such data as primer sequences, polymorphism descriptions, genotype and trait scoring data, experimental protocols used, and photographs of marker polymorphisms, disease symptoms and mutant phenotypes. These data, curated with the help of many members of the research community, are integrated with sequence and bibliographic records selected from external databases and results of BLAST searches of the ESTs. Records are linked to corresponding records in other important databases, e.g. Gramene's EST homologies to rice BAC/PACs, TIGR's Gene Indices and GenBank. In addition to this information within the GrainGenes database itself, the GrainGenes homepage at http://wheat.pw.usda.gov provides many other community resources including publications (the annual newsletters for wheat, barley and oat, monographs and articles), individual datasets (mapping and QTL studies, polymorphism surveys, variety performance evaluations), specialized databases (Triticeae repeat sequences, EST unigene sets) and pages to facilitate coordination of cooperative research efforts in specific areas such as SNP development, EST-SSRs and taxonomy. The goal is to serve as a central point for obtaining and contributing information about the genetics and biology of these cereal crops.

The Triticeae Toolbox: Combining Phenotype and Genotype Data to Advance Small-Grains Breeding.

The Triticeae Toolbox (; T3) is the database schema enabling plant breeders and researchers to combine, visualize, and interrogate the wealth of phenotype and genotype data generated by the Triticeae Coordinated Agricultural Project (TCAP). T3 enables users to define specific data sets for download in formats compatible with the external tools TASSEL, Flapjack, and R; or to use by software residing on the T3 server for operations such as Genome Wide Association and Genomic Prediction. New T3 tools to assist plant breeders include a Selection Index Generator, analytical tools to compare phenotype trials using common or user-defined indices, and a histogram generator for nursery reports, with applications using the Android OS, and a Field Plot Layout Designer in development. Researchers using T3 will soon enjoy the ability to design training sets, define core germplasm sets, and perform multivariate analysis. An increased collaboration with GrainGenes and integration with the small grains reference sequence resources will place T3 in a pivotal role for on-the-fly data analysis, with instant access to the knowledge databases for wheat and barley. T3 software is available under the GNU General Public License and is freely downloadable.

Pancreatic duct strictures are a common cause of recurrent pancreatitis after successful management of pancreatic necrosis.

BACKGROUND: Successful surgical management of pancreatic necrosis can result in structural changes that cause recurrent pancreatitis. The purpose of this study is to review our clinical experience managing recurrent pancreatitis in patients after successful pancreatic debridement. METHODS: We retrospectively reviewed 98 patients with pancreatic necrosis treated by debridement who made a complete recovery at our institution over an 8-year period (January 1995 to January 2003). RESULTS: Fourteen patients (14%) developed recurrent pancreatitis 5 to 39 months (median, 15 months) after recovery. Five patients (36%) had pancreatic pseudocysts and 9 (64%) had radiologic evidence of obstructive pancreatitis. All patients had either a high-grade pancreatic duct stricture (N=7) or complete duct cutoff (N=7), localized to the pancreatic neck (N=10) or proximal pancreatic body (N=4) identified by either endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. Two patients failed endoscopic stent therapy. All patients required re-operative treatment: 6 distal pancreatectomy, 6 pancreatico-jejunostomy Roux-en-Y, and 2 cystojejunostomy Roux-en-Y with no recurrence of pancreatitis after a median follow-up of 22 months. CONCLUSIONS: Recurrent pancreatitis occurs in 14% of patients after successful pancreatic debridement. Pancreatic duct obstruction in the neck or proximal body is the primary etiologic factor. Re-operation directed at alleviating this ductal obstruction by resection or drainage is effective.

Colorectal cancer screening at a Veterans Affairs hospital.

BACKGROUND: Because of limited resources and common barriers to widespread screening, the Surgery Service of the Indianapolis Veterans Affairs Medical Center has focused its colorectal screening program on patients undergoing hernia repair. Our objective was to examine the success, safety, pathology results, and educational benefit of this nontraditional screening program. METHODS: The study was a retrospective analysis of a prospectively collected database (1991 to 2002). Initial screening colonoscopy was performed on 263 average-risk Veterans Affairs patients, 217 (83%) in conjunction with hernia repair. Visualized polyps were removed or biopsied during colonoscopy and pathology reports for all specimens were examined. Results were compared with published screening studies. RESULTS: Complete colonoscopy, defined as cecal intubation, was performed in 93% of initial screening colonoscopies. There were no major complications, including perforation, excessive bleeding, or death, from colonoscopy. Initial colonoscopy showed adenomas in 67 patients (25%), hyperplastic polyps in 34 (13%), and invasive cancer in 4 (1.5%). Follow-up endoscopies revealed cancer in 2 additional patients, 3 and 5 years after initial screening. CONCLUSIONS: This program is an important training resource for surgical residents. Screening colonoscopy performed in conjunction with hernia repair has produced results consistent with more conventional methods. The Surgery Service at the Indianapolis Veterans Affairs Medical Center is providing colorectal cancer screening with a high degree of safety and success in the face of limited resources and common barriers to implementation of widespread screening.

GrainGenes 2.0. an improved resource for the small-grains community.

GrainGenes (http://wheat.pw.usda.gov) is an international database for genetic and genomic information about Triticeae species (wheat [Triticum aestivum], barley [Hordeum vulgare], rye [Secale cereale], and their wild relatives) and oat (Avena sativa) and its wild relatives. A major strength of the GrainGenes project is the interaction of the curators with database users in the research community, placing GrainGenes as both a data repository and information hub. The primary intensively curated data classes are genetic and physical maps, probes used for mapping, classical genes, quantitative trait loci, and contact information for Triticeae and oat scientists. Curation of these classes involves important contributions from the GrainGenes community, both as primary data sources and reviewers of published data. Other partially automated data classes include literature references, sequences, and links to other databases. Beyond the GrainGenes database per se, the Web site incorporates other more specific databases, informational topics, and downloadable files. For example, unique BLAST datasets of sequences applicable to Triticeae research include mapped wheat expressed sequence tags, expressed sequence tag-derived simple sequence repeats, and repetitive sequences. In 2004, the GrainGenes project migrated from the AceDB database and separate Web site to an integrated relational database and Internet resource, a major step forward in database delivery. The process of this migration and its impacts on database curation and maintenance are described, and a perspective on how a genomic database can expedite research and crop improvement is provided.

Maximum likelihood estimation of a survival function with a change point for truncated and interval-censored data.

This paper considers estimation of a survival function when there exists a change point and the survival time of interest is defined as elapsed time between two related events. Furthermore, there exists censoring on observations on the occurrences of both events and truncation on observations on the occurrence of the second event and thus the survival time of interest. To obtain the maximum likelihood estimator of a survival function, an EM algorithm is developed when the survival function is completely unknown before the change point and known up to a vector of unknown parameters after the change point. The idea is a generalization of that discussed in Moeschberger and Klein. Simulations and an example are used to evaluate and illustrate the algorithm.

Data mining for simple sequence repeats in expressed sequence tags from barley, maize, rice, sorghum and wheat.

Plant genomics projects involving model species and many agriculturally important crops are resulting in a rapidly increasing database of genomic and expressed DNA sequences. The publicly available collection of expressed sequence tags (ESTs) from several grass species can be used in the analysis of both structural and functional relationships in these genomes. We analyzed over 260000 EST sequences from five different cereals for their potential use in developing simple sequence repeat (SSR) markers. The frequency of SSR-containing ESTs (SSR-ESTs) in this collection varied from 1.5% for maize to 4.7% for rice. In addition, we identified several ESTs that are related to the SSR-ESTs by BLAST analysis. The SSR-ESTs and the related sequences were clustered within each species in order to reduce the redundancy and to produce a longer consensus sequence. The consensus and singleton sequences from each species were pooled and clustered to identify cross-species matches. Overall a reduction in the redundancy by 85% was observed when the resulting consensus and singleton sequences (3569) were compared to the total number of SSR-EST and related sequences analyzed (24 606). This information can be useful for the development of SSR markers that can amplify across the grass genera for comparative mapping and genetics. Functional analysis may reveal their role in plant metabolism and gene evolution.

Comparative DNA sequence analysis of wheat and rice genomes.

The use of DNA sequence-based comparative genomics for evolutionary studies and for transferring information from model species to crop species has revolutionized molecular genetics and crop improvement strategies. This study compared 4485 expressed sequence tags (ESTs) that were physically mapped in wheat chromosome bins, to the public rice genome sequence data from 2251 ordered BAC/PAC clones using BLAST. A rice genome view of homologous wheat genome locations based on comparative sequence analysis revealed numerous chromosomal rearrangements that will significantly complicate the use of rice as a model for cross-species transfer of information in nonconserved regions.