Molecular investigation of the tandem Tudor domain and plant homeodomain histone binding domains of the epigenetic regulator UHRF2.

Ubiquitin-like containing PHD and ring finger (UHRF)1 and UHRF2 are multidomain epigenetic proteins that play a critical role in bridging crosstalk between histone modifications and DNA methylation. Both proteins contain two histone reader domains, called tandem Tudor domain (TTD) and plant homeodomain (PHD), which read the modification status on histone H3 to regulate DNA methylation and gene expression. To shed light on the mechanism of histone binding by UHRF2, we have undergone a detailed molecular investigation with the TTD, PHD and TTD-PHD domains and compared the binding activity to its UHRF1 counterpart. We found that unlike UHRF1 where the PHD is the primary binding contributor, the TTD of UHRF2 has modestly higher affinity toward the H3 tail, while the PHD has a weaker binding interaction. We also demonstrated that like UHRF1, the aromatic amino acids within the TTD are important for binding to H3K9me3 and a conserved aspartic acid within the PHD forms an ionic interaction with R2 of H3. However, while the aromatic amino acids in the TTD of UHRF1 contribute to selectivity, the analogous residues in UHRF2 contribute to both selectivity and affinity. We also discovered that the PHD of UHRF2 contains a distinct asparagine in the H3R2 binding pocket that lowers the binding affinity of the PHD by reducing a potential electrostatic interaction with the H3 tail. Furthermore, we demonstrate the PHD and TTD of UHRF2 cooperate to interact with the H3 tail and that dual domain engagement with the H3 tail relies on specific amino acids. Lastly, our data indicate that the unique stretch region in the TTD of UHRF2 can decrease the melting temperature of the TTD-PHD and represents a disordered region. Thus, these subtle but important mechanistic differences are potential avenues for selectively targeting the histone binding interactions of UHRF1 and UHRF2 with small molecules.

Integration of Pharmacy Students Into Family Medicine Residency Clinics.

BACKGROUND AND OBJECTIVES: As interprofessional education opportunities become more prevalent within family medicine residency clinics, the benefit of the integration of pharmacy students is unclear in the current literature. Our study objective was to determine the impact of pharmacy student integration into a family medicine residency clinic on family medicine residents' attitudes toward interprofessional collaboration and satisfaction. METHODS: Twenty-two pharmacy students on clinical rotation were individually paired with family medicine residents for approximately 4-5 half days per week over a 10-month period. Residents and students were given a pre/post-validated survey on attitudes toward interprofessional collaboration. Satisfaction surveys were also administered to the residents at the end of the study period. Written components of satisfaction surveys were evaluated for commonly occurring themes. RESULTS: Matched survey responses were available for over 80% of the residents. Both pre- and post-survey responses showed positive attitudes toward physician-pharmacist collaboration. A statistically significant positive change was seen for one item in the family medicine resident surveys. Favorable written comments revealed positive themes toward pharmacy students providing mediation reviews, therapeutic recommendations, and patient education. CONCLUSIONS: Pharmacy students can be integrated into family medicine residency clinics while maintaining positive levels of interprofessional collaboration and providing a perceived benefit to the family medicine residents.

Discontinuation of Statins: What Are the Risks?

The key benefits of statin therapy have been well established in both primary and secondary prevention cardiovascular patients. Many studies have shown a significant statin discontinuation rate within the first year of initiation whether for primary or secondary prevention. National guidelines for the management of dyslipidemia highlight the lack of benefit seen with statin therapy in patients with chronic kidney disease receiving dialysis, heart failure with reduced ejection fraction, and patients greater than 75 years of age without atherosclerotic cardiovascular disease. Available data outside of these patient populations do not support discontinuation of statin therapy. Recent studies support an association with statin discontinuation and increased risk of myocardial infarction and cardiovascular death. Based on the available data, discontinuation of statin therapy should be carefully considered.

Statin-Associated Diabetes Mellitus: Review and Clinical Guide.

A small but significant link between new-onset diabetes mellitus (NOD) and statin therapy was noted with rosuvastatin users in the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin study. Since then multiple analyses have further confirmed this association, with most studies demonstrating a modest increase in NOD with statin therapy, especially among individuals with risk factors for developing diabetes mellitus. More recent observational analyses suggest a stronger correlation between statin use and NOD, however. A definitive mechanism confirming causation between statins and glucose impairment remains elusive, but many have been proposed. Although considered a class effect by the US Food and Drug Administration, most data indicate NOD is dependent upon the dose and potency of the statin, with certain agents appearing to be less diabetogenic. The consensus is that the benefits of statin therapy far outweigh the risk of NOD, especially among patients with high cardiovascular risk. Nonetheless, more studies are needed to better understand this association and long-term clinical implications. In the meantime, we provide clinicians with a practical guide to assist with clinical decision making when prescribing statin therapy. Overall, this article serves to provide the primary care physician with a timely review of the most clinically relevant data regarding statins and NOD, with hopes to ultimately optimize statin prescribing and limit any potential drug-induced glucose impairment.

Using Communication Technology to Enhance Interprofessional Education Simulations.

OBJECTIVE: To determine the impact of simulations using an alternative method of communication on students' satisfaction, attitudes, confidence, and performance related to interprofessional communication. DESIGN: One hundred sixty-three pharmacy students participated in a required applications-based capstone course. Students were randomly assigned to one of three interprofessional education (IPE) simulations with other health professions students using communication methods such as telephone, e-mail, and video conferencing. ASSESSMENT: Pharmacy students completed a validated survey instrument, Attitude Toward Healthcare Teams Scale (ATHCTS) prior to and after course participation. Significant positive changes occurred for 5 out of 20 items. Written reflection papers and student satisfaction surveys completed after participation showed positive themes and satisfaction. Course instructors evaluated student performance using rubrics for formative feedback. CONCLUSION: Implementation of IPE simulations using various methods of communication technology is an effective way for pharmacy schools to incorporate IPE into their curriculum.

An Interprofessional Simulation Using the SBAR Communication Tool.

Objective. To determine the impact of an interprofessional simulation using the SBAR (situation-background-assessment-recommendation/request) communication tool on pharmacy students' self-perception of interprofessional competence and reactions towards interprofessional collaboration. Design. Ninety-six pharmacy students participated in an interprofessional simulation within a required applications-based capstone course. Pharmacy students collaborated with nursing students on multiple patient cases in various settings using the SBAR communication tool over the telephone. Assessment. Pharmacy students' responses to all 20 items on the Interprofessional Collaborative Competency Attainment Survey (ICCAS) completed after participating in the simulation indicated significant positive changes. The themes identified in students' reflection papers indicated the simulation was beneficial and student responses on satisfaction surveys were positive with a mean score of 4.2 on a 5-point Likert scale. Conclusion. Implementation of an interprofessional simulation using the SBAR communication tool improved pharmacy students' self-perception of interprofessional competence and attitudes toward interprofessional collaboration.

Evaluation of fracture risk and potential drug holidays for postmenopausal women on long-term bisphosphonate therapy.

STUDY OBJECTIVE: To describe characteristics of postmenopausal women on long-term bisphosphonate therapy who fall into one of four fracture risk categories (low, mild, moderate, high), and to determine the prevalence of women eligible for a drug holiday. DESIGN: Retrospective electronic health record review. SETTING: Eight primary care clinics within a university-based health care system. PATIENTS: A total of 201 postmenopausal women of ages 55-89 years, with osteopenia or osteoporosis, prescribed bisphosphonate therapy for >4 years, between October 10, 2002 and September 9, 2012. MAIN RESULTS: The patients' mean age was 71.4 (±8.2) years; their mean body mass index was 25.3 (±5.6) kg/m(2); and 73.1% were white. Seventy-four out of 201 patients (36.8%) were low-risk; 10/201 (5.0%) were mild-risk; 72/201 (35.8%) were moderate-risk; and 45/201 (22.4%) were high-risk. Eighty-one women (40.3%) were eligible for a drug holiday or discontinuation. The estimated drug cost avoided per eligible patient was $574.80. Calcium and/or vitamin D supplementation was documented in 52.7% of women. CONCLUSION: More than one-third of postmenopausal women taking long-term bisphosphonate therapy had low fracture risk, and over 40% of our patients were eligible for a drug holiday or discontinuation. These data emphasize the need to accurately assess risk and benefit in patients treated with bisphosphonate therapy.

Evaluation of factors associated with achieving glycemic control in a pharmacist-managed diabetes clinic.

The aim of this study was to identify factors that are associated with patients achieving goal A1c after 6 months in a pharmacist-managed diabetes clinic. This study is a descriptive, retrospective chart review of patients with type 2 diabetes enrolled in a pharmacist-managed diabetes clinic. The primary endpoint was the odds of each identified factor being associated with achievement of goal A1c after 6 months of enrollment. The factors were also evaluated within 2 subgroups: those with a baseline A1c >7% and those with a baseline A1c >9%. Of 112 patients enrolled, 58 were included in the analysis. There was a positive association with reaching goal for patients who had <1 failure to show (FTS) to office visits in 6 months [odds ratio (OR) 8.10, 95% confidence interval (CI) 1.47-58.65], had canceled or FTS to <50% of office visits (OR 10.0, 95% CI 1.8-72.79), and brought >75% of blood glucose logs to their office visits (OR 7.36, 95% CI 1.87-30.88). There was a negative association with reaching the goal for patients with documented social worker involvement (OR 0.22, 95% CI 0.04-0.99) and noninsulin or insulin dose increases at >50% of office visits (OR 0.10, 95% CI 0.01-0.55). Overall, this analysis found that patients who had <1 FTS, had canceled or FTS to <50% of office visits, or who brought >75% logs to office visits were more likely to achieve goal A1c, whereas patients with social work assistance or dose increases at >50% of office visits were less likely to reach goal A1c.