MCCS: a novel recognition pattern-based method for fast track discovery of anti-SARS-CoV-2 drugs.

Given the scale and rapid spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, or 2019-nCoV), there is an urgent need to identify therapeutics that are effective against COVID-19 before vaccines are available. Since the current rate of SARS-CoV-2 knowledge acquisition via traditional research methods is not sufficient to match the rapid spread of the virus, novel strategies of drug discovery for SARS-CoV-2 infection are required. Structure-based virtual screening for example relies primarily on docking scores and does not take the importance of key residues into consideration, which may lead to a significantly higher incidence rate of false-positive results. Our novel in silico approach, which overcomes these limitations, can be utilized to quickly evaluate FDA-approved drugs for repurposing and combination, as well as designing new chemical agents with therapeutic potential for COVID-19. As a result, anti-HIV or antiviral drugs (lopinavir, tenofovir disoproxil, fosamprenavir and ganciclovir), antiflu drugs (peramivir and zanamivir) and an anti-HCV drug (sofosbuvir) are predicted to bind to 3CLPro in SARS-CoV-2 with therapeutic potential for COVID-19 infection by our new protocol. In addition, we also propose three antidiabetic drugs (acarbose, glyburide and tolazamide) for the potential treatment of COVID-19. Finally, we apply our new virus chemogenomics knowledgebase platform with the integrated machine-learning computing algorithms to identify the potential drug combinations (e.g. remdesivir+chloroquine), which are congruent with ongoing clinical trials. In addition, another 10 compounds from CAS COVID-19 antiviral candidate compounds dataset are also suggested by Molecular Complex Characterizing System with potential treatment for COVID-19. Our work provides a novel strategy for the repurposing and combinations of drugs in the market and for prediction of chemical candidates with anti-COVID-19 potential.

Systematic review and meta-analysis of post-transplant lymphoproliferative disorder in lung transplant recipients.

A systematic review of papers in English on post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTR) using MEDLINE, EMBASE, SCOPUS, and Cochrane databases was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were strictly adhered to. Pooled odds ratios (pOR) were calculated from a random-effects model, and heterogeneity among studies was quantitated using I2 values. Fourteen studies published from 2005 to 2015 were included in the meta-analysis. One hundred and sixty-four lung transplant recipients were included. LTRs who received single vs bilateral were associated with a 7.67-fold risk of death after PTLD (6 studies with 64 LTRs; pOR 7.67 95% CI 1.98-29.70; P = .003). pOR of death for early onset PTLD (<1 year post-LT) vs late onset (>1 year post-LT) was not different (3 studies with 72 LTRS; pOR 0.62, 95% CI 0.20-1.86, P = .39). Standardized mean difference (SMD) in time from transplant to PTLD onset between LTRs who died vs alive was not different (9 studies with 109 LTRs; SMD 0.03, 95% CI -0.48-0.53, P = .92). Survival in polymorphic vs monomorphic PTLD and extranodal vs nodal disease was similar (4 studies with 31 LTRs; pOR 0.44, 95% CI 0.08-2.51; P = .36. 6 studies with 81 LTRs; pOR 1.05 95% CI 0.31-3.52, P = .94). This meta-analysis demonstrates that single LTRs are at a higher risk of death vs bilateral LTRs after the development of PTLD.

Janus kinase inhibition for immunosuppression in solid organ transplantation: Is there a role in complex immunologic challenges?

Inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway for immunosuppression in solid organ transplantation is appealing due to its specificity for immune cell function, particularly for JAK3. This is due to its unique association with only the common gamma chain (γc). The γc is an appealing immunosuppression target in transplantation because of the critically important lymphokines that act at it, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Tofacitinib was initially purported to selectively inhibit solely JAK3, but subsequent analyses have also demonstrated its activity at the other members of the JAK family. Clinical outcomes have validated tofacitinib's pan-JAK activity in kidney transplantation after demonstrating an increased risk of infection and malignancy as compared to CNI-based regimens. After these trials, tofacitinib investigation for use in transplantation has effectively ceased. However, a post-hoc analysis has shed new light on the monitoring of tofacitinib exposure in order to predict infection and oncologic events. With new methods to monitor tofacitinib exposure, clinicians may be able to effectively reduce toxicities while providing a high level of immunosuppression. The purpose of this review to identify when, and for whom, JAK inhibitors may provide benefit in solid organ transplantation.

Fellowships in community pharmacy research: Experiences of five schools and colleges of pharmacy.

OBJECTIVE: To describe common facilitators, challenges, and lessons learned in 5 schools and colleges of pharmacy in establishing community pharmacy research fellowships. SETTING: Five schools and colleges of pharmacy in the United States. PRACTICE DESCRIPTION: Schools and colleges of pharmacy with existing community partnerships identified a need and ability to develop opportunities for pharmacists to engage in advanced research training. PRACTICE INNOVATION: Community pharmacy fellowships, each structured as 2 years long and in combination with graduate coursework, have been established at the University of Pittsburgh, Purdue University, East Tennessee State University, University of North Carolina at Chapel Hill, and The Ohio State University. EVALUATION: Program directors from each of the 5 community pharmacy research fellowships identified common themes pertaining to program structure, outcomes, and lessons learned to assist others planning similar programs. RESULTS: Common characteristics across the programs include length of training, prerequisites, graduate coursework, mentoring structure, and immersion into a pharmacist patient care practice. Common facilitators have been the existence of strong community pharmacy partnerships, creating a fellowship advisory team, and networking. A common challenge has been recruitment, with many programs experiencing at least one year without filling the fellowship position. All program graduates (n = 4) have been successful in securing pharmacy faculty positions. CONCLUSION: Five schools and colleges of pharmacy share similar experiences in implementing community pharmacy research fellowships. Early outcomes show promise for this training pathway in growing future pharmacist-scientists focused on community pharmacy practice.

Advancing Pharmacogenomics Education in the Core PharmD Curriculum through Student Personal Genomic Testing.

OBJECTIVE: To develop, implement, and evaluate "Test2Learn" a program to enhance pharmacogenomics education through the use of personal genomic testing (PGT) and real genetic data. DESIGN: One hundred twenty-two second-year doctor of pharmacy (PharmD) students in a required course were offered PGT as part of a larger program approach to teach pharmacogenomics within a robust ethical framework. The program added novel learning objectives, lecture materials, analysis tools, and exercises using individual-level and population-level genetic data. Outcomes were assessed with objective measures and pre/post survey instruments. ASSESSMENT: One hundred students (82%) underwent PGT. Knowledge significantly improved on multiple assessments. Genotyped students reported a greater increase in confidence in understanding test results by the end of the course. Similarly, undergoing PGT improved student's self-perceived ability to empathize with patients compared to those not genotyped. Most students (71%) reported feeling PGT was an important part of the course, and 60% reported they had a better understanding of pharmacogenomics specifically because of the opportunity. CONCLUSION: Implementation of PGT in the core pharmacy curriculum was feasible, well-received, and enhanced student learning of pharmacogenomics.

Utility of a brief screening tool for medication-related problems.

BACKGROUND: Medication therapy management (MTM) services position pharmacists to prevent, detect, and resolve medication-related problems (MRPs.) However, selecting patients for MTM who are most at risk for MRPs is a challenge. Using self-administered scales that are practical for use in clinical practice are one approach. OBJECTIVE: The objective of this study was to estimate the psychometric properties of a brief self-administered scale as a screening tool for MRPs. METHODS: This was a non-randomized study utilizing questionnaires administered cross-sectionally. In Phase 1, patients (n = 394) at community pharmacies and outpatient clinics completed 78 items, provided to the study team by item authors, assessing perceived MRPs. These data were used to select items for further investigation as a brief, self-administered scale, and estimate the reliability and construct validity of the resulting instrument. In Phase 2, a convenience sample of patients (n = 200) at community pharmacies completed a nine-item, self-administered scale. After completion, they were engaged in a comprehensive medication review by their pharmacist who was blinded to questionnaire responses. The main outcome measure for estimating the criterion-related validity of the scale was the number of pharmacist-identified medication-related problems (MRPs.) Item statistics were computed as well as bivariate associations between scale scores and other variables with MRPs. A multivariate model was constructed to examine the influence of scale scores on MRPs after controlling for other significant variables. RESULTS: Higher scores on the questionnaire were positively correlated with more pharmacist-identified MRPs (r = 0.24; P = 0.001) and scores remained as a significant predictor (P = 0.031) when controlling for other relevant variables in a multivariate regression model (R(2) = 0.21; P < 0.001). CONCLUSIONS: Patient responses on the scale may have a modest role in predicting MRPs. The use of self-administered questionnaires such as this may supplement other available patient data in developing patient eligibility criteria for MTM, however, additional research is warranted.

Patient predictors of dexmedetomidine effectiveness for sedation in intensive care units.

BACKGROUND: Dexmedetomidine, a selective α2-adrenergic receptor agonist, is increasingly used as a sedative in intensive care despite variations in patients' responses. OBJECTIVES: To determine the effectiveness of dexmedetomidine as a sedative and specific patient characteristics that play a role in adequate sedation with dexmedetomidine. METHODS: A 6-month, pilot, prospective observational study was performed in a medical intensive care unit at an academic medical center. Patients receiving dexmedetomidine were followed up until use of the drug was stopped and they were classified as nonresponders or responders. Effective sedation was defined as a score of 3 to 4 on the Sedation Agitation Scale after the administration of dexmedetomidine. Patient characteristics, laboratory values, home and inpatient medications, and dexmedetomidine dosing information were collected to identify predictors of clinical response. RESULTS: During the 6-month study period, 38 patients received dexmedetomidine. The drug was ineffective as a sedative in 19 patients (50%) and effective in 11 (29%). Effectiveness could not be assessed in 8 patients because of clinical confounders. According to standard multiple logistic regression analysis, successful sedation was more likely in patients with a lower score on the Acute Physiology and Chronic Health Evaluation II (Odds Ratio [OR] 0.81; 95% CI, -0.39 to -0.03) and patients who took antidepressants at home (OR 10.27; 95% CI, 0.23 to 4.43) than in patients who had a higher score or did not take antidepressants at home. CONCLUSIONS: Effective sedation with dexmedetomidine is variable.

Exploring successful community pharmacist-physician collaborative working relationships using mixed methods.

BACKGROUND: Collaborative working relationships (CWRs) between community pharmacists and physicians may foster the provision of medication therapy management services, disease state management, and other patient care activities; however, pharmacists have expressed difficulty in developing such relationships. Additional work is needed to understand the specific pharmacist-physician exchanges that effectively contribute to the development of CWR. Data from successful pairs of community pharmacists and physicians may provide further insights into these exchange variables and expand research on models of professional collaboration. OBJECTIVE: To describe the professional exchanges that occurred between community pharmacists and physicians engaged in successful CWRs, using a published conceptual model and tool for quantifying the extent of collaboration. METHODS: A national pool of experts in community pharmacy practice identified community pharmacists engaged in CWRs with physicians. Five pairs of community pharmacists and physician colleagues participated in individual semistructured interviews, and 4 of these pairs completed the Pharmacist-Physician Collaborative Index (PPCI). Main outcome measures include quantitative (ie, scores on the PPCI) and qualitative information about professional exchanges within 3 domains found previously to influence relationship development: relationship initiation, trustworthiness, and role specification. RESULTS: On the PPCI, participants scored similarly on trustworthiness; however, physicians scored higher on relationship initiation and role specification. The qualitative interviews revealed that when initiating relationships, it was important for many pharmacists to establish open communication through face-to-face visits with physicians. Furthermore, physicians were able to recognize in these pharmacists a commitment for improved patient care. Trustworthiness was established by pharmacists making consistent contributions to care that improved patient outcomes over time. Open discussions regarding professional roles and an acknowledgment of professional norms (ie, physicians as decision makers) were essential. CONCLUSIONS: The findings support and extend the literature on pharmacist-physician CWRs by examining the exchange domains of relationship initiation, trustworthiness, and role specification qualitatively and quantitatively among pairs of practitioners. Relationships appeared to develop in a manner consistent with a published model for CWRs, including the pharmacist as relationship initiator, the importance of communication during early stages of the relationship, and an emphasis on high-quality pharmacist contributions.

Physician perceptions of pharmacist-provided medication therapy management: qualitative analysis.

OBJECTIVE: To identify physician perceptions of community pharmacist-provided medication therapy management (MTM). METHODS: Three focus groups consisting of family and internal medicine physicians were conducted in Pittsburgh, York, and Philadelphia, PA, using a semistructured topic guide to facilitate discussions. Each participant completed an exit survey at session conclusion. RESULTS: 23 physicians participated in one of three focus groups conducted in Pittsburgh (n = 9), York (n = 6), and Philadelphia (n = 8). Participants identified common medication issues in their practices: nonadherence, adverse effects, drug interactions, medication costs, and incomplete patient understanding of the medication regimen. Receipt of a complete patient medication list was reported as the greatest potential benefit of MTM. Participants believed that physicians would be better suited as MTM providers than pharmacists. Concerns identified were the mechanism of pharmacist payment, reimbursement of time spent by physicians to coordinate care, and the training/preparation of the pharmacist. The need for a trusting relationship between a patient's primary care physician and the pharmacists providing MTM was identified. CONCLUSION: This study provides information to assist pharmacists when approaching physicians to propose collaboration through MTM. Pharmacists should tell physicians that they will receive an updated patient medication list after each visit and emphasize that direct communication is essential to coordinate care.

Generating demand for pharmacist-provided medication therapy management: identifying patient-preferred marketing strategies.

OBJECTIVE: To identify effective strategies for marketing pharmacist-provided medication therapy management (MTM) services to patients in a self-insured employer setting. DESIGN: Qualitative study. SETTING: University of Pittsburgh during March through May 2008. PARTICIPANTS: 26 university employees taking at least one chronic medication. INTERVENTION: Three focus group sessions were conducted using a semistructured topic guide to facilitate the discussion. MAIN OUTCOME MEASURES: Employees' perceived medication-related needs, perceived benefits of pharmacist-provided MTM, potential barriers for employee participation in MTM, and effective strategies for marketing MTM. RESULTS: Participants reported concerns with timing of doses, medication costs, access, and ensuring adherence. Participants generally felt positively toward pharmacists; however, the level of reported patient contact with pharmacists varied among participants. Some participants questioned pharmacists' education and qualifications for this enhanced role in patient care. Perceived benefits of MTM noted by participants included the opportunity to obtain personalized information about their medications and the potential for improved communication among their health providers. Barriers to patient participation were out-of-pocket costs and lack of time for MTM visits. Participants suggested use of alternative words to describe MTM and marketing approaches that involve personal contact. CONCLUSION: Pharmacists should emphasize parts of MTM that patients feel are most beneficial (i.e., provision of a personal medication record) and use patient-friendly language to describe MTM when marketing their practice. Patients will need greater exposure to the concept of MTM and the pharmacists' role in order to correctly describe and assign value to this type of pharmacist patient care practice.

Instructor satisfaction with a technology-based resource for diabetes education.

OBJECTIVES: To evaluate instructor use patterns and satisfaction with DM Educate, a comprehensive, Web-based diabetes course. METHODS: Instructors completed a post-course survey instrument to assess their use of course materials and components, as well as satisfaction with the course content, design, and technology utilized, and to solicit their suggestions for additional content areas. RESULTS: Thirty-eight percent of respondents utilized DM Educate as a standalone elective and 62% had integrated materials into existing courses. The pharmacotherapy module was the most utilized at 91% and slide sets were the most utilized course components at 63%. All instructors stated that they would use the course again the following year. Suggestions for improvement included incorporation of more active-learning activities and patient cases. CONCLUSION: Instructors' were highly satisfied with the course materials and technology used by DM Educate, a Web-based diabetes education course, and indicated they were able to customize the course materials both to establish new courses and supplement existing courses. All instructors planned to use the course again.

A Web-based interprofessional diabetes education course.

OBJECTIVE: To develop a comprehensive diabetes management course for pharmacy students that is available to all colleges and schools of pharmacy via the Internet. DESIGN: DM Educate, a Web-based course consisting of 12 topic modules with video lectures, active-learning exercises, and test questions prepared by nationally recognized experts was developed. The modular design allows use as a standalone, 3-credit course or use of individual module content as a supplement to an existing course. ASSESSMENT: Two pilot studies found the comprehensive, interprofessional nature of the material beneficial for learners. Students showed a significant increase in knowledge of the subject material by correctly answering 26 of 34 questions on the posttest compared to answering only 14 of 34 questions correctly on the pretest (p < 0.001). Student feedback was positive for the flexibility of the Web-based format. CONCLUSION: Pilot studies demonstrated the effectiveness of the course, which became available in the 2006-2007 academic year.

Medication therapy management: its relationship to patient counseling, disease management, and pharmaceutical care.

OBJECTIVE: To delineate the relationship, including similarities and differences, between medication therapy management (MTM) and contemporary pharmacist-provided services, including patient counseling, disease management, and pharmaceutical care, to facilitate the continued evolution of commonly used language and a standard of practice across geographic areas and practice environments. SUMMARY: Incorporation of MTM services into the array of Medicare-funded services affords an opportunity for pharmacists to develop direct patient care services in the community. Defining the role of MTM within the scope of pharmacist-provided patient care activities, including patient counseling, disease management, and all currently provided pharmacy services is essential to the delineation of a viable and sustainable practice model for pharmacists. The definitions of each of these services are offered, as well as comparisons and contrasts of the individual services. In addition to Medicare-eligible patients, MTM services are appropriate for anyone with medication-related needs. MTM is offered as an all-encompassing model that incorporates the philosophy of pharmaceutical care, techniques of patient counseling, and disease management in an environment that facilitates the direct collaboration of patients, pharmacists, and other health professionals. CONCLUSION: Defining the role of MTM within the current patient care models, including patient counseling, disease management, and all who provide pharmacy services, is essential in delineating a viable and sustainable practice model for pharmacists.

A model for supporting and training clinical pharmaceutical scientist PhD students.

OBJECTIVES: To enhance the clinical training and financial support of graduate students in a Clinical Pharmaceutical Scientist PhD Program at the University of Pittsburgh School of Pharmacy. DESIGN: The School of Pharmacy and University of Pittsburgh Medical Center entered into a collaborative agreement to develop the Clinical Scientist Associate (CSA) program, as well as financially support students enrolled in a Pharmaceutical Sciences PhD program. These clinical training experiences are in addition to the didactic and laboratory experiences in the pharmaceutical sciences graduate program. ASSESSMENT: Since 2002, three students have participated as CSAs, simultaneously working on their graduate research and meeting the requirements of the CSA program. CONCLUSIONS: The CSA program is a novel model for clinical training and support of post-PharmD graduate students enrolled in a PhD clinical pharmaceutical scientist program.

Quality of arthritis information on the Internet.

PURPOSE: The quality and reliability of Internet-based arthritis information were studied. METHODS: The search terms "arthritis," "osteoarthritis," and 'rheumatoid arthritis" were entered into the AOL, MSN, Yahoo, Google, and Lycos search engines. The Web sites for the first 40 matches generated by each search engine were grouped by URL suffix and evaluated on the basis of four categories of criteria: disease and medication information content, Web-site navigability, required literacy level, and currentness of information. Ratings were assigned by using an assessment tool derived from published literature (maximum score of 15 points). RESULTS: Of the 600 arthritis Web sites identified, only 69 were unique and included in the analysis. Fifty-seven percent were .com sites, 20% .org sites, 7% .gov sites, 6% .edu sites, and 10% other sites. Total scores for individual sites reviewed ranged from 3 to 14. Eighty percent of .gov sites, 75% of .edu sites, 29% of other sites, 36% of .com sites, and 21% of .org sites were within the top tertile of scores. No Web site met the criterion for being understandable to people with no more than a sixth-grade reading ability. .Gov sites scored significantly higher overall than .com sites, .org sites, and other sites. .Edu sites also scored relatively well. CONCLUSION: The quality of arthritis information on the Internet varied widely. Sites with URLs having suffixes of .gov and .edu were ranked higher than other types of sites.

Retrospective evaluation of unanticipated admissions and readmissions after same day surgery and associated costs.

STUDY OBJECTIVE: To determine the rate of unanticipated admissions and readmissions, and to characterize the associated reasons and costs. DESIGN: Retrospective medical records database analysis. SETTING: University teaching hospital. PATIENTS: Any patient undergoing same day surgery (SDS) during a 12-month period. MEASUREMENTS: All nonelective return visits to the hospital within 30 days and the reasons for return were identified. MAIN RESULTS: There were a total of 20,817 patients who underwent SDS in 1999; 1,195 (5.7%) of these returned to the hospital within 30 days or were admitted directly after surgery. Of those unanticipated admissions and readmissions, 313 (1.5%) were directly related to the original SDS procedure. The mean age of these patients was 51 years, 164 (52%) were female, and 266 (85%) were Caucasian. Pain was the most commonly reported reason for return, occurring in 120 (38%) patients who had an unanticipated admission or readmission. After controlling for SDS volume, the general surgery service had the highest rate of unanticipated admissions or readmissions (3.2%), followed by otolaryngology (3.1%) and urology (2.9%). Of the 120 patients returning with unanticipated admissions and readmissions due to pain, 46 (38%) had orthopedic procedures during their index SDS. Mean charges for patients with unanticipated admissions and readmission due to pain were $1,869 +/- $4,553 per visit, whereas charges for nonpain related readmissions were $12,000 +/- $36,886. CONCLUSION: At our teaching institution, approximately 1.5% of patients undergoing outpatient ambulatory surgery return within 30 days due to problems directly related to the original surgical procedure. Pain accounted for more than one third of return visits, incurring significant costs. Efforts to manage pain should focus not only on pain in the hospital but also anticipation of pain-related issues on discharge.