Uncoupling histone modification crosstalk by engineering lysine demethylase LSD1.

Biochemical crosstalk between two or more histone modifications is often observed in epigenetic enzyme regulation, but its functional significance in cells has been difficult to discern. Previous enzymatic studies revealed that Lys14 acetylation of histone H3 can inhibit Lys4 demethylation by lysine-specific demethylase 1 (LSD1). In the present study, we engineered a mutant form of LSD1, Y391K, which renders the nucleosome demethylase activity of LSD1 insensitive to Lys14 acetylation. K562 cells with the Y391K LSD1 CRISPR knockin show decreased expression of a set of genes associated with cellular adhesion and myeloid leukocyte activation. Chromatin profiling revealed that the cis-regulatory regions of these silenced genes display a higher level of H3 Lys14 acetylation, and edited K562 cells show diminished H3 mono-methyl Lys4 near these silenced genes, consistent with a role for enhanced LSD1 demethylase activity. These findings illuminate the functional consequences of disconnecting histone modification crosstalk for a key epigenetic enzyme.

The effect of an aiming device on the accuracy of humeral transcondylar screw placement.

OBJECTIVES: (1) To evaluate the accuracy of an aiming device on placement of humeral transcondylar screws compared to fluoroscopic methods. (2) To compare experience level on outcome. STUDY DESIGN: Randomized, match pair, prospective ex-vivo study. SAMPLE POPULATION: A total of 68 dogs. METHODS: Canine cadaveric forelimbs were randomly assigned to either aiming device or fluoroscopic-guided groups, and to diplomate or resident. Digital radiography was used to evaluate screw trajectory deviation and eccentricity on the humeral condyle. Procedure time, outcome based on experience, and complications were recorded. RESULTS: The aiming device screw trajectory angle was decreased in the right limb (1.9 ± 1.1°) compared with the left (3.6 ± 1.1°, p = .0178), and compared to fluoroscopy (3.4 ± 1.1° p = .0128). There was no difference between leg laterality with fluoroscopy (p = .9979). Trajectory angle was increased with resident versus diplomate (3.4 ± 1.1° and 2.5 ± 1.1° respectively, p = .0366). Eccentricity deviation was decreased using fluoroscopy versus aiming device (3.1 ± 0.36 mm, 4.2 ± 0.36 mm, respectively, p = .0017). The risk of joint involvement was 8 times greater in aiming device groups, though not significant (p = .0575). Significant complications included increased drill attempts in fluoroscopic groups (p = .0237). CONCLUSION: The aiming device provided accurate placement of transcondylar screws, in terms of both position on the condyle and trajectory angle. Results were similar to fluoroscopic-guided method. CLINICAL SIGNIFICANCE: An aiming device is an acceptable means of placing humeral transcondylar screws. The use of the aiming device had an eight times increased risk of joint involvement compared to fluoroscopy.

Creation and implementation of a pharmacy-led meds-to-beds program at a large teaching hospital.

BACKGROUND: "Meds-to-beds" programs are a quality improvement intervention that is gaining wider implementation throughout the United States. The University of Oklahoma hospital system did not have this program and sought to implement one. There are sufficient data on the benefits of meds-to-beds programs, but there is a lack of literature on describing the development and implementation process. OBJECTIVES: The objective of this article is to describe the planning process, implementation, and barriers encountered during the organization of a pharmacy-led meds-to-beds program operating within 2 large teaching hospitals. PRACTICE DESCRIPTION: The University of Oklahoma Health Sciences Center campus has 7 colleges, multiple primary care and specialty clinics, and 2 hospitals. In addition, there are 3 on-campus outpatient pharmacies operated by the University of Oklahoma College of Pharmacy (OUCOP). PRACTICE INNOVATION: The college implemented a meds-to-beds program primarily serving 2 on-campus hospitals, The Oklahoma Children's Hospital and University of Oklahoma College of Pharmacy Medical Center. The program operated out of The Children's Pharmacy, an outpatient pharmacy located within the Children's Hospital. EVALUATION METHODS: A Plan-Do-Study-Act model was used, which allowed for adaptation in response to barriers encountered throughout the process. Frequent meetings among stakeholders were held to continuously evaluate progress (e.g., awareness and utilization of the program and prescription counts) and make necessary changes. RESULTS: Implementation of the program required changes in workflow both within the pharmacy and within the registration and discharge processes of medical teams. In addition, after the initiation of the meds-to-beds program, the daily prescription count more than doubled. The program averages 40 deliveries per day and 3 prescriptions per delivery and continues to grow, providing evidence of a successful meds-to-beds implementation. CONCLUSION: The Plan-Do-Study-Act model allowed for many adjustments to be made throughout the process, including the conversion from an opt-in to an opt-out model to increase program utilization.

Sleep and neighborhood socioeconomic status: a micro longitudinal study of chronic low-back pain and pain-free individuals.

Individuals with chronic low back pain (cLBP) frequently report sleep disturbances. Living in a neighborhood characterized by low-socioeconomic status (SES) is associated with a variety of negative health outcomes, including poor sleep. Whether low-neighborhood SES exacerbates sleep disturbances of people with cLBP, relative to pain-free individuals, has not previously been observed. This study compared associations between neighborhood-level SES, pain-status (cLBP vs. pain-free), and daily sleep metrics in 117 adults (cLBP = 82, pain-free = 35). Neighborhood-level SES was gathered from Neighborhood Atlas, which provides a composite measurement of overall neighborhood deprivation (e.g. area deprivation index). Individuals completed home sleep monitoring for 7-consecutive days/nights. Neighborhood SES and pain-status were tested as predictors of actigraphic sleep variables (e.g., sleep efficiency). Analyses revealed neighborhood-level SES and neighborhood-level SES*pain-status interaction significantly impacted objective sleep quality. These findings provide initial support for the negative impact of low neighborhood-level SES and chronic pain on sleep quality.

Shot of a lifetime: How pharmacists stay ahead of the season.

OBJECTIVES: The profession of pharmacy has long advocated for the advancement of practice through increased clinical responsibility. Provision of immunization related services has been one service pharmacists have been able to provide to add to their existing responsibilities. A universal influenza vaccination has been under investigation and is nearing success. While other clinical services should be considered, now more than ever, development of the universal vaccine should provide a pause for the profession and consideration of not only the impact on student learning opportunities but also pharmacy revenue. SUMMARY: The development of the universal influenza vaccination poses a potential challenge to existing service-related revenue models for community pharmacies. There are many other opportunities pharmacists can capitalize on including, but not limited to, travel and other vaccinations, point-of-care testing, and transitions-of-care. In addition, through initiatives such as "Flip the Pharmacy" and Community Pharmacy Enhanced Service Network, pharmacists are in a great position to be innovative with clinical services while continuing to provide learners with training opportunities. CONCLUSION: Many opportunities exist for pharmacists to expand services that lean into their clinical training and add other vaccination opportunities. These opportunities can augment revenue streams and still provide learners with training.

Pharmacotherapeutic Management Strategies for Thyroid Disease-Induced Pericarditis.

Objective: To describe the various pharmacotherapeutic strategies in managing thyroid disease-induced pericarditis (TDIP). Considerations for both hypothyroid-induced and hyperthyroid-induced pericarditis will be discussed. Data Sources: A literature search of MEDLINE, including PubMed, was performed inclusive of all years, using the following search terms: thyroid disease, pericardial diseases, pericarditis, acute pericarditis, cholesterol pericarditis, hypothyroidism, hyperthyroidism, colchicine, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, methimazole, propylthiouracil, and P-glycoprotein. Product monographs were reviewed as well. Study Selection and Data Extraction: Relevant English-language studies and data as well as the most current guidelines for diagnosis and management of thyroid and pericardial diseases were considered. Because of limited data regarding the subject matter, no date range limits were established during literature search. Data Synthesis: It is well documented that thyroid dysfunction can adversely affect cardiovascular function. Additionally, there are published guidelines on the diagnosis and management of pericarditis and, separately, thyroid disease. There are limited data, however, on managing TDIP. The sequela of untreated TDIP can be detrimental. Relevance to Patient Care and Clinical Practice: Strategies on managing TDIP are scarcely reported in the literature. This review provides clinicians with a single reference source for treatment strategies toward managing hypothyroidism-induced and hyperthyroidism-induced pericarditis as well as significant drug interactions that can potentially confound the management of hypothyroidism- and hyperthyroidism-induced pericarditis. Conclusions: Treatment of TDIP involves addressing both the thyroid disease as well as the pericarditis. Along with treatment strategies, clinicians should also consider potential drug-drug and drug-disease interactions that can potentially worsen clinical outcomes.

Interventions to improve dissemination and implementation of Hepatitis B vaccination in patients with diabetes.

OBJECTIVE: The purpose of this study was to assess provider awareness of routine vaccinations recommended for patients with diabetes and to determine whether pharmacist-led interventions are associated with increased provider implementation of recommendations for hepatitis B vaccination. METHODS: This study was conducted in 3 phases at 2 outpatient clinics affiliated with an academic institution. In phase 1, adults with diabetes who visited the clinics between January and November 2012 and who were eligible for the hepatitis B vaccine were identified. In phase 2, medical residents were surveyed twice for vaccine recommendations and reasons for (not) recommending the hepatitis B vaccine, specifically. Residents were then provided a pharmacist-led in-service about hepatitis B vaccine recommendations. The third phase was initiated in April 2013, following postintervention observation from December 2012 through March 2013. RESULTS: Forty-eight of 100 (48%) medical residents attended the in-service and completed both surveys, with 77% indicating they did not recommend the hepatitis B vaccine. During phase 1, 1441 patients were identified, 0.6% (n = 8) of whom had received at least the first dose of the series. In phase 3, 946 patients were identified with 1.7% (n = 16) having received at least the first dose (P = 0.007). CONCLUSION: An attempt to disseminate updated recommendations to providers via educational in-service was successful in increasing the percentage of eligible patients vaccinated with the hepatitis B vaccine.

Effectiveness of a modified open airways curriculum.

OBJECTIVE: Open Airways for Schools is an asthma education program that has proven to be effective in decreasing the number of asthma attacks in children and increasing their confidence in self-management. It is taught to 8-11 year olds in six 40-min sessions. Due to financial and scheduling constraints, many schools have difficulty implementing the program. The Tulsa Health Department created a modified version of the program, which is taught in ten 20-min sessions over lunch. The same topics are covered in a different order and fewer activities are utilized. This study aimed to pilot the effectiveness of the modified program. METHODS: In both versions, a pre-questionnaire is given to participating students on the first day of the program. At the end of the program, the same questionnaire is administered to assess knowledge gained. This is a retrospective review comparing pre- and post-questionnaire data from the two versions of the program. Descriptive statistics and t-tests were used to compare the results of the questionnaires from the modified program to results from the original program. RESULTS: Twenty students completed the original curriculum and 45 completed the modified program. Both versions were found to improve children's knowledge of how to manage asthma triggers and symptoms, as well as to improve inhaler technique. CONCLUSIONS: The modified curriculum is effective at increasing asthma knowledge. Schools may use the modified program as an alternate delivery approach to reduce the scheduling burden and to allow more children to benefit from the educational program.

Nontraditional Considerations With Insulin Needle Length Selection.

Ensuring the correct delivery of insulin is essential in the treatment of diabetes. Both proper injection technique and needle length are important considerations for adequate insulin delivery. There have been several studies demonstrating that BMI does not affect efficacy or insulin leakage with shorter pen needles (e.g., 4 or 5 mm vs. 12.7 mm). Additionally, the International Scientific Advisory Board for the Third Injection Technique Workshop released recommendations in 2010 on best practices for injection technique for patients with diabetes, which, with regard to needle length, concluded that 4-mm pen needles were efficacious in all patients regardless of BMI. However, regardless of patients' BMI, insulin injection technique should always be assessed and physically disabling comorbid conditions taken into consideration when choosing a needle length that will be manageable for patients. The purpose of this article is to raise awareness of unique patient circumstances that may warrant the use of the longer 12.7-mm needle.

Management of a prediabetes case with the DPP-4 inhibitor sitagliptin.

OBJECTIVE: It is important to prevent or slow the progression of prediabetes to type 2 diabetes and, therefore, reduce the risk of long-term complications. New therapeutic options will allow more patients to be effectively managed. Although theorized to be effective for prediabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors have not been studied in this population. The purpose of this article is to report the results of a case in which a patient with prediabetes was treated with the DPP-4 inhibitor, sitagliptin. CASE SUMMARY: A 56-year-old woman was diagnosed with prediabetes at a hemoglobin A1C (A1C) of 6.2%. After 6 months of consistent lifestyle modifications, her A1C was 6.3%, and she wanted to start a medication to prevent disease progression. Because of anticipated risk or intolerability with standard prediabetes treatments, she was started on sitagliptin 100 mg daily; 6 weeks later, she noted improvements in glucometer readings. After 18 months on sitagliptin, her A1C had improved to 5.8% without further lifestyle improvements, and by 32 months, her A1C had improved to 5.6%. Her A1C was maintained within or below the prediabetes range of 5.7% to 6.4% over 3 years of treatment with sitagliptin. DISCUSSION: Although human studies with DPP-4 inhibitors are lacking, the available studies have shown improvements in ß-cell function and postprandial and fasting glucose levels. Furthermore, animal studies have shown a delay in progression of prediabetes. No case reports have been found regarding DPP-4 inhibitor use in prediabetes. CONCLUSION: Sitagliptin may have a role in treating prediabetes and should be further studied.

Identification of essential genes that support fitness of Acinetobacter baumannii efflux pump overproducers in the presence of fluoroquinolone.

Acinetobacter baumannii is a nosocomial pathogen often associated with multidrug resistance (MDR) infections. Fluoroquinolone resistance (FQR) due to drug target site mutations and elevated expression of RND drug transporters is common among clinical isolates. We describe here a CRISPRi platform that identifies hypomorphic mutations that preferentially altered drug sensitivity in RND pump overproducers. An sgRNA library against essential genes of A. baumannii was constructed with single and double nucleotide mutations that produced titratable knockdown efficiencies and introduced into multiple strain backgrounds. Other than nusG depletions, there were few candidates in the absence of drug treatment that showed lowered fitness specifically in strains overexpressing clinically relevant RND efflux pumps AdeAB, AdeIJK, or AdeFGH. In the presence of ciprofloxacin, the hypomorphs causing hypersensitivity were predicted to result in outer membrane dysfunction, to which the AdeFGH overproducer appeared particularly sensitive. Depletions of either the outer membrane assembly BAM complex, LOS biogenesis proteins, or Lpt proteins involved in LOS transport to the outer membrane caused drug hypersensitivity in at least two of the three pump overproducers. On the other hand, depletions of translation-associated proteins, as well as components of the proton-pumping ATP synthase pump resulted in fitness benefits for at least two pump-overproducing strains in the presence of the drug. Therefore, pump overproduction exacerbated stress caused by defective outer membrane integrity, while the efficacy of drug resistance in efflux overproducers was enhanced by slowed translation or defects in ATP synthesis linked to the control of proton movement across the bacterial membrane.

Diabetes and Hearing Impairment: Knowledge, Attitudes, and Practices Among Providers and Patients.

PURPOSE: The purpose of this study was to assess the knowledge, attitudes, and practices among providers and patients regarding hearing impairment and screening referrals in people with diabetes. METHODS: A cross-sectional survey design among health care providers and patients at an academic medical center in Oklahoma was used to gather knowledge, attitudes, and practices data. RESULTS: Only 25.6% of providers selected hearing impairment as a complication of diabetes, whereas 96.7% selected retinopathy, kidney dysfunction, and foot infection. Reported barriers to referring patients for hearing impairment screenings were being unfamiliar with recommended screening frequency (57.3%) and existence of higher priorities (35.4%). When asked to select parts of the body affected by diabetes, 21.0% of patients surveyed selected ears, 88.0% selected feet, and 85.0% selected eyes and kidneys. Fewer patients reported being told hearing impairment is a complication of diabetes compared to retinopathy (8.1% vs 85.9%). Additionally, 24.2% of patients reported having a hearing impairment screening, and 96.0% reported having a dilated eye exam. CONCLUSIONS: Most providers and patients at an academic medical center are unaware of the relationship between diabetes and hearing impairment. Providers reported there are several barriers that need to be overcome to refer patients to audiologists.

Report of the 2023-2024 Strategic Engagement Standing Committee.

The American Association of Colleges of Pharmacy has long emphasized the value of strategic engagement, recognizing that it is critical to the success of pharmacy education, contributing to the expansion of pharmacy and public health practice, the fulfillment of institutional missions, and the meeting of programmatic needs. The 2023-2024 Strategic Engagement Committee was charged with operationalizing advocacy champions, creating an advocacy resource guide to support advocacy champions in their engagement with diverse public and private stakeholders, offering formal training to advocacy champions in the form of a new connect community and webinar series, and conducting focus groups at the 2024 Annual Meeting to determine strengths of the advocacy guide and opportunities to support advocacy champions further.

AACP Strategic Engagement Committee Report: Report of the 2022-2023 Strategic Engagement Standing Committee.

The American Association of Colleges of Pharmacy recognizes strategic engagement as critical to the success of pharmacy education, contributing to the expansion of pharmacy and public health practice, the fulfillment of institutional missions, and the meeting of programmatic needs. The 2022-2023 Strategic Engagement Committee or the Committee was charged with identifying ways professional advocacy is being emphasized in Doctor of Pharmacy and graduate education curricula to optimize active student engagement and share new resources for the ongoing resource guide being developed by the association. The Committee was also tasked with identifying advocacy champions at each member institution, integrating them into the work of the American Association of Colleges of Pharmacy Policy Advisory Task Force, and identifying strong advocacy partnerships between colleges and schools of pharmacy and state pharmacy organizations that can be replicated to advance the legislative or regulatory priorities of the profession. The Committee conducted a 2-part, sequential advocacy survey to identify advocacy champions at member institutions and to gain better insight into the breadth and depth of current advocacy efforts within pharmacy programs. The Committee also developed suggestions for the advocacy activities that should be required in pharmacy curricula, as well as exemplary activities identified through surveying advocacy champions.

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

Prescriber and employee utilization of a health sciences center campus outpatient pharmacy: A qualitative analysis.

PURPOSE: The college of pharmacy has operated pharmacies on campus for over 26 years. Employees and patients are users of the pharmacies; however, utilization across the campus has been limited. This paper describes a process, as well as results, that was used to gather input from employees on a large university health sciences center campus on pharmacy needs and related behaviors on campus pharmacy utilization. METHODS: Two focus groups of staff and 4 focus groups of prescribers were conducted over 1 month. Participants were selected through purposive sampling via email within an academic health sciences center campus over a 1-month period. The sessions were moderated by one investigator using a preconstructed discussion guide and lasted 1 hour. Two additional investigators observed sessions for nonverbal communication; all sessions were audio recorded for subsequent transcription. An open-coding process was performed on verbatim transcripts using NVivo12. The investigator team then developed, refined, and grouped themes during subsequent group discussions. RESULTS: A total of 44 participants took part in 6 focus groups. Participants included prescribers (physicians, nurses, physician assistants) and staff (nonprescribers). Two major themes identified were (1) factors related to on-campus pharmacies and (2) qualities valued in a pharmacy. There was an equal split (8% for each group) on awareness of the on-campus pharmacies. Almost 11% of participants commented on the accessibility of a pharmacy being a quality valued in a pharmacy. CONCLUSION: Focus groups provided insights for the administration team regarding additional value-added services that would be helpful for the campus community, as well as various approaches to increase utilization of the on-campus pharmacies. Focus group methodology is an effective approach to engage employees of a large university campus to garner new ideas to enhance existing policies or services, as well as to gather thoughts on preliminary strategic plans before implementation.

The Report of the 2021-2022 Professional Affairs Standing Committee: Resource Guide for the Integration of Clinical Pharmacy Faculty in Professional Practice Settings.

The 2021-22 Professional Affairs Committee was charged to (1) Develop a resource guide for member institutions and faculty regarding payment for the practice-related activities of pharmacy faculty; (2) Nominate at least one person for an elected AACP or Council Office; and (3) Consider ways that AACP can improve its financial health. This report describes the methodology and content utilized for the development of an online resource guide for member institutions, faculty, and practice sites regarding the integration of clinical faculties' patient care services into patient care settings, including models for payment and value-based payment structures that can be utilized to support the practice-related activities of faculty. The committee offers a revision to a current association policy statement, a proposed policy statement as well as recommendations to AACP and suggestions to colleges and schools of pharmacy pertaining to the committee charges.

Evaluation of a Fixed-Angle Wedge Osteotomy Guide.

OBJECTIVE: The aim of this study was to evaluate a fixed-angle cutting guide designed to aid in the performance of coplanar wedge osteotomies using a proximal tibial cranial closing wedge ostectomy model. STUDY DESIGN: A 30-degree cranial closing wedge ostectomy was created using canine tibia models with either a standard template (method T) or a wedge osteotomy guide (method G) by two surgeons. One surgeon was experienced with both procedures, and one surgeon had no previous experience with the wedge guide. The ostectomy wedges were evaluated for wedge angle, using a digital protractor, and coplanarity by using digital photographs and screen-measuring software. RESULTS: The mean (standard deviation) wedge angles of the T and G groups were 28.16 (1.33) and 28.4 degrees (1.46) respectively. The mean (standard deviation) divergence angles of the T and G groups were 3.21 (1.86) and 2.22 degrees (1.69) respectively. The measured reference angles of the template and cut guides were 31.27 and 29.60 degrees respectively. Individual and cross-surgeon analysis of outcomes found no significant differences when comparing wedge angle or coplanarity with either method regardless of surgeon experience. However, mean wedge angle of group G was significantly closer to the measured reference angles than group T (p < 0.01). CONCLUSION: Use of a fixed-angle surgical wedge guide was successful in consistently producing accurate closing wedge ostectomies regardless of surgeon experience. These results show that use of the guide is a valid method for performing wedge ostectomies.